AVAHO

For patients with cancer, the determining factor in whether they pursue mental health services is often whether their oncologist explicitly says it is a good idea, a psychologist said during the July Association of VA Hematology and Oncology (AVAHO) seminar in Long Beach, California, on treating veterans with renal cell carcinoma (RCC).

Kysa Christie, PhD, of the West Los Angeles Veterans Affairs Medical Center, presented findings from a 2018 study in which researchers asked Swiss patients with cancer whether their oncologist discussed their emotional health with them. 

In terms of boosting intake, it did not matter if oncologists acknowledged distress or pointed out that psychosocial services existed. Instead, a direct recommendation made a difference, increasing the likelihood of using the services over a 4-month period after initial assessment (odds ratio, 6.27).

“What it took was, ‘I really recommend this. This is something that I would want you to try,’” Christie said. 

Oncologists are crucial links between patients and mental health services, Christie said: “If people don’t ask about [distress], you’re not going to see it, but it’s there. Distress is the norm, right? It is not a weakness. It is something that we expect to see.”

Christie noted that an estimated 20% of cancer patients have major depressive disorder, and 35% to 40% have a diagnosable psychiatric condition. RCC shows disproportionately high rates of mental strain. According to Christie, research suggests that about three-fourths of the population report elevated levels of distress as evidenced by patients who scored ≥ 5 on the NCCN Distress Thermometer. Patients with cancer have an estimated 20% higher risk of suicide, especially during the first 12 months after diagnosis and at end of life, she added.

“Early during a diagnosis phase, where you’re having a lot of tests being done, you know something is happening. But you don’t know what,” Christie said. “It could be very serious. That’s just a lot of stress to hold and not know how to plan for.”

After diagnosis, routine could set in and lower distress, she said. Then terminal illness may spike it back up again. Does mental health treatment work in patients with cancer?

“There’s a really strong body of evidence-based treatments for depression, anxiety, adjustment disorders, and coping with different cancers,” Christie said. But it is a step too far to expect patients to ask for help while they are juggling appointments, tests, infusions, and more. “It’s a big ask, right? It’s setting people up for failure.”

To help, Christie said she is embedded with a medical oncology team and routinely talks with the staff about which patients may need help. “One thing I like to do is try to have brief visits with veterans and introduce myself when they come to clinic. I treat it like an opt-out rather than an opt-in program: I’ll just pop into the exam room. They don’t have to ask to see me.”

Christie focuses on open-ended questions and talks about resources ranging from support groups and brief appointments to extensive individual therapy. 

Another approach is a strategy known as the “warm handoff,” when an oncologist directly introduces a patient to a mental health professional. “It’s a transfer of care in front of the veteran: It’s much more time-efficient than putting in a referral.”

Christie explained how this can work. A clinician will ask her to meet with a patient during an appointment, perhaps in a couple minutes.

“Then I pop into the room, and the oncologist says, ‘Thanks for joining us. This is Mr. Jones. He has been experiencing feelings of anxiety and sadness, and we’d appreciate your help in exploring some options that might help.’  I turn to the patient and ask, ‘What more would you add?’ Then I either take Mr. Jones back to my office or stay in clinic, and we’re off to the races.”

Christie reported no disclosures.

For patients with cancer, the determining factor in whether they pursue mental health services is often whether their oncologist explicitly says it is a good idea, a psychologist said during the July Association of VA Hematology and Oncology (AVAHO) seminar in Long Beach, California, on treating veterans with renal cell carcinoma (RCC).

Kysa Christie, PhD, of the West Los Angeles Veterans Affairs Medical Center, presented findings from a 2018 study in which researchers asked Swiss patients with cancer whether their oncologist discussed their emotional health with them. 

In terms of boosting intake, it did not matter if oncologists acknowledged distress or pointed out that psychosocial services existed. Instead, a direct recommendation made a difference, increasing the likelihood of using the services over a 4-month period after initial assessment (odds ratio, 6.27).

“What it took was, ‘I really recommend this. This is something that I would want you to try,’” Christie said. 

Oncologists are crucial links between patients and mental health services, Christie said: “If people don’t ask about [distress], you’re not going to see it, but it’s there. Distress is the norm, right? It is not a weakness. It is something that we expect to see.”

Christie noted that an estimated 20% of cancer patients have major depressive disorder, and 35% to 40% have a diagnosable psychiatric condition. RCC shows disproportionately high rates of mental strain. According to Christie, research suggests that about three-fourths of the population report elevated levels of distress as evidenced by patients who scored ≥ 5 on the NCCN Distress Thermometer. Patients with cancer have an estimated 20% higher risk of suicide, especially during the first 12 months after diagnosis and at end of life, she added.

“Early during a diagnosis phase, where you’re having a lot of tests being done, you know something is happening. But you don’t know what,” Christie said. “It could be very serious. That’s just a lot of stress to hold and not know how to plan for.”

After diagnosis, routine could set in and lower distress, she said. Then terminal illness may spike it back up again. Does mental health treatment work in patients with cancer?

“There’s a really strong body of evidence-based treatments for depression, anxiety, adjustment disorders, and coping with different cancers,” Christie said. But it is a step too far to expect patients to ask for help while they are juggling appointments, tests, infusions, and more. “It’s a big ask, right? It’s setting people up for failure.”

To help, Christie said she is embedded with a medical oncology team and routinely talks with the staff about which patients may need help. “One thing I like to do is try to have brief visits with veterans and introduce myself when they come to clinic. I treat it like an opt-out rather than an opt-in program: I’ll just pop into the exam room. They don’t have to ask to see me.”

Christie focuses on open-ended questions and talks about resources ranging from support groups and brief appointments to extensive individual therapy. 

Another approach is a strategy known as the “warm handoff,” when an oncologist directly introduces a patient to a mental health professional. “It’s a transfer of care in front of the veteran: It’s much more time-efficient than putting in a referral.”

Christie explained how this can work. A clinician will ask her to meet with a patient during an appointment, perhaps in a couple minutes.

“Then I pop into the room, and the oncologist says, ‘Thanks for joining us. This is Mr. Jones. He has been experiencing feelings of anxiety and sadness, and we’d appreciate your help in exploring some options that might help.’  I turn to the patient and ask, ‘What more would you add?’ Then I either take Mr. Jones back to my office or stay in clinic, and we’re off to the races.”

Christie reported no disclosures.

For patients with cancer, the determining factor in whether they pursue mental health services is often whether their oncologist explicitly says it is a good idea, a psychologist said during the July Association of VA Hematology and Oncology (AVAHO) seminar in Long Beach, California, on treating veterans with renal cell carcinoma (RCC).

Kysa Christie, PhD, of the West Los Angeles Veterans Affairs Medical Center, presented findings from a 2018 study in which researchers asked Swiss patients with cancer whether their oncologist discussed their emotional health with them. 

In terms of boosting intake, it did not matter if oncologists acknowledged distress or pointed out that psychosocial services existed. Instead, a direct recommendation made a difference, increasing the likelihood of using the services over a 4-month period after initial assessment (odds ratio, 6.27).

“What it took was, ‘I really recommend this. This is something that I would want you to try,’” Christie said. 

Oncologists are crucial links between patients and mental health services, Christie said: “If people don’t ask about [distress], you’re not going to see it, but it’s there. Distress is the norm, right? It is not a weakness. It is something that we expect to see.”

Christie noted that an estimated 20% of cancer patients have major depressive disorder, and 35% to 40% have a diagnosable psychiatric condition. RCC shows disproportionately high rates of mental strain. According to Christie, research suggests that about three-fourths of the population report elevated levels of distress as evidenced by patients who scored ≥ 5 on the NCCN Distress Thermometer. Patients with cancer have an estimated 20% higher risk of suicide, especially during the first 12 months after diagnosis and at end of life, she added.

“Early during a diagnosis phase, where you’re having a lot of tests being done, you know something is happening. But you don’t know what,” Christie said. “It could be very serious. That’s just a lot of stress to hold and not know how to plan for.”

After diagnosis, routine could set in and lower distress, she said. Then terminal illness may spike it back up again. Does mental health treatment work in patients with cancer?

“There’s a really strong body of evidence-based treatments for depression, anxiety, adjustment disorders, and coping with different cancers,” Christie said. But it is a step too far to expect patients to ask for help while they are juggling appointments, tests, infusions, and more. “It’s a big ask, right? It’s setting people up for failure.”

To help, Christie said she is embedded with a medical oncology team and routinely talks with the staff about which patients may need help. “One thing I like to do is try to have brief visits with veterans and introduce myself when they come to clinic. I treat it like an opt-out rather than an opt-in program: I’ll just pop into the exam room. They don’t have to ask to see me.”

Christie focuses on open-ended questions and talks about resources ranging from support groups and brief appointments to extensive individual therapy. 

Another approach is a strategy known as the “warm handoff,” when an oncologist directly introduces a patient to a mental health professional. “It’s a transfer of care in front of the veteran: It’s much more time-efficient than putting in a referral.”

Christie explained how this can work. A clinician will ask her to meet with a patient during an appointment, perhaps in a couple minutes.

“Then I pop into the room, and the oncologist says, ‘Thanks for joining us. This is Mr. Jones. He has been experiencing feelings of anxiety and sadness, and we’d appreciate your help in exploring some options that might help.’  I turn to the patient and ask, ‘What more would you add?’ Then I either take Mr. Jones back to my office or stay in clinic, and we’re off to the races.”

Christie reported no disclosures.

TOPLINE:

Patients living in rural areas and those aged ≥ 65 y had increased odds of receiving mental health care exclusively by phone.

METHODOLOGY:

• Researchers explored factors linked to receiving phone-only mental health care among patients within the Department of Veterans Affairs.
• They included data for 1,156,146 veteran patients with at least one mental health-specific outpatient encounter between October 2021 and September 2022 and at least one between October 2022 and September 2023.
• Patients were categorized as those who received care through phone only (n = 49,125) and those who received care through other methods (n = 1,107,021. Care was received exclusively through video (6.39%), in-person (6.63%), or a combination of in-person, video, and/or phone (86.98%).
• Demographic and clinical predictors, including rurality, age, sex, race, ethnicity, and the number of mental health diagnoses (< 3 vs ≥ 3), were evaluated.

TAKEAWAY:

• The phone-only group had a mean of 6.27 phone visits, whereas those who received care through other methods had a mean of 4.79 phone visits.
• Highly rural patients had 1.50 times higher odds of receiving phone-only mental health care than their urban counterparts (adjusted odds ratio [aOR], 1.50; P < .0001).
• Patients aged 65 years or older were more than twice as likely to receive phone-only care than those younger than 30 years (aOR, ≥ 2.17; P < .0001).
• Having fewer than three mental health diagnoses and more than 50% of mental health visits conducted by medical providers was associated with higher odds of receiving mental health care exclusively by phone (aORs, 2.03 and 1.87, respectively; P < .0001).

IN PRACTICE:

“The results of this work help to characterize the phone-only patient population and can serve to inform future implementation efforts to ensure that patients are receiving care via the modality that best meets their needs,” the authors wrote.

SOURCE:

This study was led by Samantha L. Connolly, PhD, at the VA Boston Healthcare System in Boston. It was published online in The Journal of Rural Health.

LIMITATIONS:

This study focused on a veteran population which may limit the generalizability of the findings to other groups. Additionally, its cross-sectional design restricted the ability to determine cause-and-effect relationships between factors and phone-only care.

DISCLOSURES:

This study was supported by the US Department of Veterans Affairs. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients living in rural areas and those aged ≥ 65 y had increased odds of receiving mental health care exclusively by phone.

METHODOLOGY:

• Researchers explored factors linked to receiving phone-only mental health care among patients within the Department of Veterans Affairs.
• They included data for 1,156,146 veteran patients with at least one mental health-specific outpatient encounter between October 2021 and September 2022 and at least one between October 2022 and September 2023.
• Patients were categorized as those who received care through phone only (n = 49,125) and those who received care through other methods (n = 1,107,021. Care was received exclusively through video (6.39%), in-person (6.63%), or a combination of in-person, video, and/or phone (86.98%).
• Demographic and clinical predictors, including rurality, age, sex, race, ethnicity, and the number of mental health diagnoses (< 3 vs ≥ 3), were evaluated.

TAKEAWAY:

• The phone-only group had a mean of 6.27 phone visits, whereas those who received care through other methods had a mean of 4.79 phone visits.
• Highly rural patients had 1.50 times higher odds of receiving phone-only mental health care than their urban counterparts (adjusted odds ratio [aOR], 1.50; P < .0001).
• Patients aged 65 years or older were more than twice as likely to receive phone-only care than those younger than 30 years (aOR, ≥ 2.17; P < .0001).
• Having fewer than three mental health diagnoses and more than 50% of mental health visits conducted by medical providers was associated with higher odds of receiving mental health care exclusively by phone (aORs, 2.03 and 1.87, respectively; P < .0001).

IN PRACTICE:

“The results of this work help to characterize the phone-only patient population and can serve to inform future implementation efforts to ensure that patients are receiving care via the modality that best meets their needs,” the authors wrote.

SOURCE:

This study was led by Samantha L. Connolly, PhD, at the VA Boston Healthcare System in Boston. It was published online in The Journal of Rural Health.

LIMITATIONS:

This study focused on a veteran population which may limit the generalizability of the findings to other groups. Additionally, its cross-sectional design restricted the ability to determine cause-and-effect relationships between factors and phone-only care.

DISCLOSURES:

This study was supported by the US Department of Veterans Affairs. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients living in rural areas and those aged ≥ 65 y had increased odds of receiving mental health care exclusively by phone.

METHODOLOGY:

• Researchers explored factors linked to receiving phone-only mental health care among patients within the Department of Veterans Affairs.
• They included data for 1,156,146 veteran patients with at least one mental health-specific outpatient encounter between October 2021 and September 2022 and at least one between October 2022 and September 2023.
• Patients were categorized as those who received care through phone only (n = 49,125) and those who received care through other methods (n = 1,107,021. Care was received exclusively through video (6.39%), in-person (6.63%), or a combination of in-person, video, and/or phone (86.98%).
• Demographic and clinical predictors, including rurality, age, sex, race, ethnicity, and the number of mental health diagnoses (< 3 vs ≥ 3), were evaluated.

TAKEAWAY:

• The phone-only group had a mean of 6.27 phone visits, whereas those who received care through other methods had a mean of 4.79 phone visits.
• Highly rural patients had 1.50 times higher odds of receiving phone-only mental health care than their urban counterparts (adjusted odds ratio [aOR], 1.50; P < .0001).
• Patients aged 65 years or older were more than twice as likely to receive phone-only care than those younger than 30 years (aOR, ≥ 2.17; P < .0001).
• Having fewer than three mental health diagnoses and more than 50% of mental health visits conducted by medical providers was associated with higher odds of receiving mental health care exclusively by phone (aORs, 2.03 and 1.87, respectively; P < .0001).

IN PRACTICE:

“The results of this work help to characterize the phone-only patient population and can serve to inform future implementation efforts to ensure that patients are receiving care via the modality that best meets their needs,” the authors wrote.

SOURCE:

This study was led by Samantha L. Connolly, PhD, at the VA Boston Healthcare System in Boston. It was published online in The Journal of Rural Health.

LIMITATIONS:

This study focused on a veteran population which may limit the generalizability of the findings to other groups. Additionally, its cross-sectional design restricted the ability to determine cause-and-effect relationships between factors and phone-only care.

DISCLOSURES:

This study was supported by the US Department of Veterans Affairs. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths in the United States, with an estimated 52,550 deaths in 2023.¹ However, the disease burden varies among different segments of the population.² While both CRC incidence and mortality have been decreasing due to screening and advances in treatment, there are disparities in incidence and mortality across the sociodemographic spectrum including race, ethnicity, education, and income.^1-4 While CRC incidence is decreasing for older adults, it is increasing among those aged < 55 years.⁵ The incidence of CRC in adults aged 40 to 54 years has increased by 0.5% to 1.3% annually since the mid-1990s.⁶ The US Preventive Services Task Force now recommends starting CRC screening at age 45 years for asymptomatic adults with average risk.⁷

Disparities also exist across geographical boundaries and living environment. Rural Americans faces additional challenges in health and lifestyle that can affect CRC outcomes. Compared to their urban counterparts, rural residents are more likely to be older, have lower levels of education, higher levels of poverty, lack health insurance, and less access to health care practitioners (HCPs).^8-10 Geographic proximity, defined as travel time or physical distance to a health facility, has been recognized as a predictor of inferior outcomes.¹¹ These aspects of rural living may pose challenges for accessing care for CRC screening and treatment.^11-13 National and local studies have shown disparities in CRC screening rates, incidence, and mortality between rural and urban populations.^14-16

It is unclear whether rural/urban disparities persist under the Veterans Health Administration (VHA) health care delivery model. This study examined differences in baseline characteristics and mortality between rural and urban veterans newly diagnosed with CRC. We also focused on a subpopulation aged ≤ 45 years.

Methods

This study extracted national data from the US Department of Veterans Affairs (VA) Corporate Data Warehouse (CDW) hosted in the VA Informatics and Computing Infrastructure (VINCI) environment. VINCI is an initiative to improve access to VA data and facilitate the analysis of these data while ensuring veterans’ privacy and data security.¹⁷ CDW is the VHA business intelligence information repository, which extracts data from clinical and nonclinical sources following prescribed and validated protocols. Data extracted included demographics, diagnosis, and procedure codes for both inpatient and outpatient encounters, vital signs, and vital status. This study used data previously extracted from a national cohort of veterans that encompassed all patients who received a group of commonly prescribed medications, such as statins, proton pump inhibitors, histamine-2 blockers, acetaminophen-containing products, and hydrocortisone-containing skin applications. This cohort encompassed 8,648,754 veterans, from whom 2,460,727 had encounters during fiscal years (FY) 2016 to 2021 (study period). The cohort was used to ensure that subjects were VHA patients, allowing them to adequately capture their clinical profiles.

Patients were identified as rural or urban based on their residence address at the date of their first diagnosis of CRC. The Geospatial Service Support Center (GSSC) aggregates and updates veterans’ residence address records for all enrolled veterans from the National Change of Address database. The data contain 1 record per enrollee. GSSC Geocoded Enrollee File contains enrollee addresses and their rurality indicators, categorized as urban, rural, or highly rural.¹⁸ Rurality is defined by the Rural Urban Commuting Area (RUCA) categories developed by the Department of Agriculture and the Health Resources and Services Administration of the US Department of Health and Human Services.¹⁹ Urban areas had RUCA codes of 1.0 to 1.1, and highly rural areas had RUCA scores of 10.0. All other areas were classified as rural. Since the proportion of veterans from highly rural areas was small, we included residents from highly rural areas in the rural residents’ group.

Inclusion and Exclusion Criteria

All veterans newly diagnosed with CRC from FY 2016 to 2021 were included. We used the ninth and tenth clinical modification revisions of the International Classification of Diseases (ICD-9-CM and ICD-10-CM) to define CRC diagnosis (Supplemental materials).^4,20 To ensure that patients were newly diagnosed with CRC, this study excluded patients with a previous ICD-9-CM code for CRC diagnosis since FY 2003.

Comorbidities were identified using diagnosis and procedure codes from inpatient and outpatient encounters, which were used to calculate the Charlson Comorbidity Index (CCI) at the time of CRC diagnosis using the weighted method described by Schneeweiss et al.²¹ We defined CRC high-risk conditions and CRC screening tests, including flexible sigmoidoscopy and stool tests, as described in previous studies (Supplemental materials).²⁰

The main outcome was total mortality. The date of death was extracted from the VHA Death Ascertainment File, which contains mortality data from the Master Person Index file in CDW and the Social Security Administration Death Master File. We used the date of death from any cause, as cause of death was not available.

A propensity score (PS) was created to match rural (including highly rural) and urban residents at a ratio of 1:1. Using a standard procedure described in prior publications, multivariable logistic regression used all baseline characteristics to estimate the PS and perform nearest-number matching without replacement.^22,23 A caliper of 0.01 maximized the matched cohort size and achieved balance (Supplemental materials). We then examined the balance of baseline characteristics between PS-matched groups.

Analyses

Cox proportional hazards regression analysis estimated the hazard ratio (HR) of death in rural residents compared to urban residents in the PS-matched cohort. The outcome event was the date of death during the study’s follow-up period (defined as period from first CRC diagnosis to death or study end), with censoring at the study’s end date (September 30, 2021). The proportional hazards assumption was assessed by inspecting the Kaplan-Meier curves. Multiple analyses examined the HR of total mortality in the PS-matched cohort, stratified by sex, race, and ethnicity. We also examined the HR of total mortality stratified by duration of follow-up.

Another PS-matching analysis among veterans aged ≤ 45 years was performed using the same techniques described earlier in this article. We performed a Cox proportional hazards regression analysis to compare mortality in PS-matched urban and rural veterans aged ≤ 45 years. The HR of death in all veterans aged ≤ 45 years (before PS-matching) was estimated using Cox proportional hazard regression analysis, adjusting for PS.

Dichotomous variables were compared using X² tests and continuous variables were compared using t tests. Baseline characteristics with missing values were converted into categorical variables and the proportion of subjects with missing values was equalized between treatment groups after PS-matching. For subgroup analysis, we examined the HR of total mortality in each subgroup using separate Cox proportional hazards regression models similar to the primary analysis but adjusted for PS. Due to multiple comparisons in the subgroup analysis, the findings should be considered exploratory. Statistical tests were 2-tailed, and significance was defined as P < .05. Data management and statistical analyses were conducted from June 2022 to January 2023 using STATA, Version 17. The VA Orlando Healthcare System Institutional Review Board approved the study and waived requirements for informed consent because only deidentified data were used.

Results

After excluding 49 patients (Supplemental materials, available at doi:10.12788/fp.0560), we identified 30,219 veterans with newly diagnosed CRC between FY 2016 to 2021 (Table 1). Of these, 19,422 (64.3%) resided in urban areas and 10,797 (35.7%) resided in rural areas (Table 2). The mean (SD) duration from the first CRC diagnosis to death or study end was 832 (640) days, and the median (IQR) was 723 (246–1330) days. Overall, incident CRC diagnoses were numerically highest in FY 2016 and lowest in FY 2020 (Figure 1). Patients with CRC in rural areas vs urban areas were significantly older (mean, 71.2 years vs 70.8 years, respectively; P < .001), more likely to be male (96.7% vs 95.7%, respectively; P < .001), more likely to be White (83.6% vs 67.8%, respectively; P < .001) and more likely to be non-Hispanic (92.2% vs 87.5%, respectively; P < .001). In terms of general health, rural veterans with CRC were more likely to be overweight or obese (81.5% rural vs 78.5% urban; P < .001) but had fewer mean comorbidities as measured by CCI (5.66 rural vs 5.90 urban; P < .001). A higher proportion of rural veterans with CRC had received stool-based (fecal occult blood test or fecal immunochemical test) CRC screening tests (61.6% rural vs 57.2% urban; P < .001). Fewer rural patients presented with systemic symptoms or signs within 1 year of CRC diagnosis (54.4% rural vs 57.5% urban, P < .001). Among urban patients with CRC, 6959 (35.8%) deaths were observed, compared with 3766 (34.9%) among rural patients (P = .10).

There were 21,568 PS-matched veterans: 10,784 in each group. In the PS-matched cohort, baseline characteristics were similar between veterans in urban and rural communities, including age, sex, race/ethnicity, body mass index, and comorbidities. Among rural patients with CRC, 3763 deaths (34.9%) were observed compared with 3702 (34.3%) among urban veterans. There was no significant difference in the HR of mortality between rural and urban CRC residents (HR, 1.01; 95% CI, 0.97-1.06; P = .53) (Figure 2).

Among veterans aged ≤ 45 years, 551 were diagnosed with CRC (391 urban and 160 rural). We PS-matched 142 pairs of urban and rural veterans without residual differences in baseline characteristics (Table 3). There was no significant difference in the HR of mortality between rural and urban veterans aged ≤ 45 years (HR, 0.97; 95% CI, 0.57-1.63; P = .90) (Figure 2). Similarly, no difference in mortality was observed adjusting for PS between all rural and urban veterans aged ≤ 45 years (HR, 1.03; 95% CI, 0.67-1.59; P = .88).

There was no difference in total mortality between rural and urban veterans in any subgroup except for American Indian or Alaska Native veterans (HR, 2.41; 95% CI, 1.29-4.50; P = .006) (Table 4).

Discussion

This study examined characteristics of patients with CRC between urban and rural areas among veterans who were VHA patients. Similar to other studies, rural veterans with CRC were older, more likely to be White, and were obese, but exhibited fewer comorbidities (lower CCI and lower incidence of congestive heart failure, dementia, hemiplegia, kidney diseases, liver diseases and AIDS, but higher incidence of chronic obstructive lung disease).^8,16 The incidence of CRC in this study population was lowest in FY 2020, which was reported by the Centers for Disease Control and Prevention and is attributed to COVID-19 pandemic disruption of health services.²⁴ The overall mortality in this study was similar to rates reported in other studies from the VA Central Cancer Registry.⁴ In the PS-matched cohort, where baseline characteristics were similar between urban and rural patients with CRC, we found no disparities in CRC-specific mortality between veterans in rural and urban areas. Additionally, when analysis was restricted to veterans aged ≤ 45 years, the results remained consistent.

Subgroup analyses showed no significant difference in mortality between rural and urban areas by sex, race or ethnicity, except rural American Indian or Alaska Native veterans who had double the mortality of their urban counterparts (HR, 2.41; 95% CI, 1.29-4.50; P = .006). This finding is difficult to interpret due to the small number of events and the wide CI. While with a Bonferroni correction the adjusted P value was .08, which is not statistically significant, a previous study found that although CRC incidence was lower overall in American Indian or Alaska Native populations compared to non-Hispanic White populations, CRC incidence was higher among American Indian or Alaska Native individuals in some areas such as Alaska and the Northern Plains.^25,26 Studies have noted that rural American Indian/Alaska Native populations experience greater poverty, less access to broadband internet, and limited access to care, contributing to poorer cancer outcomes and lower survival.²⁷ Thus, the finding of disparity in mortality between rural and urban American Indian or Alaska Native veterans warrants further study.

Other studies have raised concerns that CRC disproportionately affects adults in rural areas with higher mortality rates.^14-16 These disparities arise from sociodemographic factors and modifiable risk factors, including physical activity, dietary patterns, access to cancer screening, and gaps in quality treatment resources.^16,28 These factors operate at multiple levels: from individual, local health system, to community and policy.^2,27 For example, a South Carolina study (1996–2016) found that residents in rural areas were more likely to be diagnosed with advanced CRC, possibly indicating lower rates of CRC screening in rural areas. They also had higher likelihood of death from CRC.¹⁵ However, the study did not include any clinical parameters, such as comorbidities or obesity. A statewide, population-based study in Utah showed that rural men experienced a lower CRC survival in their unadjusted analysis.¹⁶ However, the study was small, with only 3948 urban and 712 rural residents. Additionally, there was no difference in total mortality in the whole cohort (HR, 0.96; 95% CI, 0.86-1.07) or in CRC-specific death (HR, 0.93; 95% CI, 0.81-1.08). A nationwide study also showed that CRC mortality rates were 8% higher in nonmetropolitan or rural areas than in the most urbanized areas containing large metropolitan counties.²⁹ However, this study did not include descriptions of clinical confounders, such as comorbidities, making it difficult to ascertain whether the difference in CRC mortality was due to rurality or differences in baseline risk characteristics.

In this study, the lack of CRC-specific mortality disparities may be attributed to the structures and practices of VHA health care. Recent studies have noted that mortality of several chronic medical conditions treated at the VHA was lower than at non-VHA hospitals.^30,31 One study that measured the quality of nonmetastatic CRC care based on National Comprehensive Cancer Network guidelines showed that > 72% of VHA patients received guideline-concordant care for each diagnostic and therapeutic measure, except for follow-up colonoscopy timing, which appear to be similar or superior to that of the private sector.^30,32,33 Some of the VA initiative for CRC screening may bypass the urban-rurality divide such as the mailed fecal immunochemical test program for CRC. This program was implemented at the onset of the COVID-19 pandemic to avoid disruptions of medical care.³⁴ Rural patients are more likely to undergo fecal immunochemical testing when compared to urban patients in this data. Beyond clinical care, the VHA uses processes to tackle social determinants of health such as housing, food security, and transportation, promoting equal access to health care, and promoting cultural competency among HCPs.^35-37

The results suggest that solutions to CRC disparities between rural and urban areas need to consider known barriers to rural health care, including transportation, diminished rural health care workforce, and other social determinants of health.^9,10,27,38 VHA makes considerable efforts to provide equitable care to all enrolled veterans, including specific programs for rural veterans, including ongoing outreach.³⁹ This study demonstrated lack of disparity in CRC-specific mortality in veterans receiving VHA care, highlighting the importance of these efforts.

Strengths and Limitations

This study used the VHA cohort to compare patient characteristics and mortality between patients with CRC residing in rural and urban areas. The study provides nationwide perspectives on CRC across the geographical spectrum and used a longitudinal cohort with prolonged follow-up to account for comorbidities.

However, the study compared a cohort of rural and urban veterans enrolled in the VHA; hence, the results may not reflect CRC outcomes in veterans without access to VHA care. Rurality has been independently associated with decreased likelihood of meeting CRC screening guidelines among veterans and military service members.³⁸ This study lacked sufficient information to compare CRC staging or treatment modalities among veterans. Although the data cannot identify CRC stage, the proportions of patients with metastatic CRC at diagnosis and CRC location were similar between groups. The study did not have information on their care outside of VHA setting.

This study could not ascertain whether disparities existed in CRC treatment modality since rural residence may result in referral to community-based CRC care, which did not appear in the data. To address these limitations, we used death from any cause as the primary outcome, since death is a hard outcome and is not subject to ascertainment bias. The relatively short follow-up time is another limitation, though subgroup analysis by follow-up did not show significant differences. Despite PS matching, residual unmeasured confounding may exist between urban and rural groups. The predominantly White, male VHA population with high CCI may limit the generalizability of the results.

Conclusions

Rural VHA enrollees had similar survival rates after CRC diagnosis compared to their urban counterparts in a PS-matched analysis. The VHA models of care—including mailed CRC screening tools, several socioeconomic determinants of health (housing, food security, and transportation), and promoting equal access to health care, as well as cultural competency among HCPs—HCPs—may help alleviate disparities across the rural-urban spectrum. The VHA should continue efforts to enroll veterans and provide comprehensive coordinated care in community partnerships.

Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths in the United States, with an estimated 52,550 deaths in 2023.¹ However, the disease burden varies among different segments of the population.² While both CRC incidence and mortality have been decreasing due to screening and advances in treatment, there are disparities in incidence and mortality across the sociodemographic spectrum including race, ethnicity, education, and income.^1-4 While CRC incidence is decreasing for older adults, it is increasing among those aged < 55 years.⁵ The incidence of CRC in adults aged 40 to 54 years has increased by 0.5% to 1.3% annually since the mid-1990s.⁶ The US Preventive Services Task Force now recommends starting CRC screening at age 45 years for asymptomatic adults with average risk.⁷

Disparities also exist across geographical boundaries and living environment. Rural Americans faces additional challenges in health and lifestyle that can affect CRC outcomes. Compared to their urban counterparts, rural residents are more likely to be older, have lower levels of education, higher levels of poverty, lack health insurance, and less access to health care practitioners (HCPs).^8-10 Geographic proximity, defined as travel time or physical distance to a health facility, has been recognized as a predictor of inferior outcomes.¹¹ These aspects of rural living may pose challenges for accessing care for CRC screening and treatment.^11-13 National and local studies have shown disparities in CRC screening rates, incidence, and mortality between rural and urban populations.^14-16

It is unclear whether rural/urban disparities persist under the Veterans Health Administration (VHA) health care delivery model. This study examined differences in baseline characteristics and mortality between rural and urban veterans newly diagnosed with CRC. We also focused on a subpopulation aged ≤ 45 years.

Methods

This study extracted national data from the US Department of Veterans Affairs (VA) Corporate Data Warehouse (CDW) hosted in the VA Informatics and Computing Infrastructure (VINCI) environment. VINCI is an initiative to improve access to VA data and facilitate the analysis of these data while ensuring veterans’ privacy and data security.¹⁷ CDW is the VHA business intelligence information repository, which extracts data from clinical and nonclinical sources following prescribed and validated protocols. Data extracted included demographics, diagnosis, and procedure codes for both inpatient and outpatient encounters, vital signs, and vital status. This study used data previously extracted from a national cohort of veterans that encompassed all patients who received a group of commonly prescribed medications, such as statins, proton pump inhibitors, histamine-2 blockers, acetaminophen-containing products, and hydrocortisone-containing skin applications. This cohort encompassed 8,648,754 veterans, from whom 2,460,727 had encounters during fiscal years (FY) 2016 to 2021 (study period). The cohort was used to ensure that subjects were VHA patients, allowing them to adequately capture their clinical profiles.

Patients were identified as rural or urban based on their residence address at the date of their first diagnosis of CRC. The Geospatial Service Support Center (GSSC) aggregates and updates veterans’ residence address records for all enrolled veterans from the National Change of Address database. The data contain 1 record per enrollee. GSSC Geocoded Enrollee File contains enrollee addresses and their rurality indicators, categorized as urban, rural, or highly rural.¹⁸ Rurality is defined by the Rural Urban Commuting Area (RUCA) categories developed by the Department of Agriculture and the Health Resources and Services Administration of the US Department of Health and Human Services.¹⁹ Urban areas had RUCA codes of 1.0 to 1.1, and highly rural areas had RUCA scores of 10.0. All other areas were classified as rural. Since the proportion of veterans from highly rural areas was small, we included residents from highly rural areas in the rural residents’ group.

Inclusion and Exclusion Criteria

All veterans newly diagnosed with CRC from FY 2016 to 2021 were included. We used the ninth and tenth clinical modification revisions of the International Classification of Diseases (ICD-9-CM and ICD-10-CM) to define CRC diagnosis (Supplemental materials).^4,20 To ensure that patients were newly diagnosed with CRC, this study excluded patients with a previous ICD-9-CM code for CRC diagnosis since FY 2003.

Comorbidities were identified using diagnosis and procedure codes from inpatient and outpatient encounters, which were used to calculate the Charlson Comorbidity Index (CCI) at the time of CRC diagnosis using the weighted method described by Schneeweiss et al.²¹ We defined CRC high-risk conditions and CRC screening tests, including flexible sigmoidoscopy and stool tests, as described in previous studies (Supplemental materials).²⁰

The main outcome was total mortality. The date of death was extracted from the VHA Death Ascertainment File, which contains mortality data from the Master Person Index file in CDW and the Social Security Administration Death Master File. We used the date of death from any cause, as cause of death was not available.

A propensity score (PS) was created to match rural (including highly rural) and urban residents at a ratio of 1:1. Using a standard procedure described in prior publications, multivariable logistic regression used all baseline characteristics to estimate the PS and perform nearest-number matching without replacement.^22,23 A caliper of 0.01 maximized the matched cohort size and achieved balance (Supplemental materials). We then examined the balance of baseline characteristics between PS-matched groups.

Analyses

Cox proportional hazards regression analysis estimated the hazard ratio (HR) of death in rural residents compared to urban residents in the PS-matched cohort. The outcome event was the date of death during the study’s follow-up period (defined as period from first CRC diagnosis to death or study end), with censoring at the study’s end date (September 30, 2021). The proportional hazards assumption was assessed by inspecting the Kaplan-Meier curves. Multiple analyses examined the HR of total mortality in the PS-matched cohort, stratified by sex, race, and ethnicity. We also examined the HR of total mortality stratified by duration of follow-up.

Another PS-matching analysis among veterans aged ≤ 45 years was performed using the same techniques described earlier in this article. We performed a Cox proportional hazards regression analysis to compare mortality in PS-matched urban and rural veterans aged ≤ 45 years. The HR of death in all veterans aged ≤ 45 years (before PS-matching) was estimated using Cox proportional hazard regression analysis, adjusting for PS.

Dichotomous variables were compared using X² tests and continuous variables were compared using t tests. Baseline characteristics with missing values were converted into categorical variables and the proportion of subjects with missing values was equalized between treatment groups after PS-matching. For subgroup analysis, we examined the HR of total mortality in each subgroup using separate Cox proportional hazards regression models similar to the primary analysis but adjusted for PS. Due to multiple comparisons in the subgroup analysis, the findings should be considered exploratory. Statistical tests were 2-tailed, and significance was defined as P < .05. Data management and statistical analyses were conducted from June 2022 to January 2023 using STATA, Version 17. The VA Orlando Healthcare System Institutional Review Board approved the study and waived requirements for informed consent because only deidentified data were used.

Results

After excluding 49 patients (Supplemental materials, available at doi:10.12788/fp.0560), we identified 30,219 veterans with newly diagnosed CRC between FY 2016 to 2021 (Table 1). Of these, 19,422 (64.3%) resided in urban areas and 10,797 (35.7%) resided in rural areas (Table 2). The mean (SD) duration from the first CRC diagnosis to death or study end was 832 (640) days, and the median (IQR) was 723 (246–1330) days. Overall, incident CRC diagnoses were numerically highest in FY 2016 and lowest in FY 2020 (Figure 1). Patients with CRC in rural areas vs urban areas were significantly older (mean, 71.2 years vs 70.8 years, respectively; P < .001), more likely to be male (96.7% vs 95.7%, respectively; P < .001), more likely to be White (83.6% vs 67.8%, respectively; P < .001) and more likely to be non-Hispanic (92.2% vs 87.5%, respectively; P < .001). In terms of general health, rural veterans with CRC were more likely to be overweight or obese (81.5% rural vs 78.5% urban; P < .001) but had fewer mean comorbidities as measured by CCI (5.66 rural vs 5.90 urban; P < .001). A higher proportion of rural veterans with CRC had received stool-based (fecal occult blood test or fecal immunochemical test) CRC screening tests (61.6% rural vs 57.2% urban; P < .001). Fewer rural patients presented with systemic symptoms or signs within 1 year of CRC diagnosis (54.4% rural vs 57.5% urban, P < .001). Among urban patients with CRC, 6959 (35.8%) deaths were observed, compared with 3766 (34.9%) among rural patients (P = .10).

There were 21,568 PS-matched veterans: 10,784 in each group. In the PS-matched cohort, baseline characteristics were similar between veterans in urban and rural communities, including age, sex, race/ethnicity, body mass index, and comorbidities. Among rural patients with CRC, 3763 deaths (34.9%) were observed compared with 3702 (34.3%) among urban veterans. There was no significant difference in the HR of mortality between rural and urban CRC residents (HR, 1.01; 95% CI, 0.97-1.06; P = .53) (Figure 2).

Among veterans aged ≤ 45 years, 551 were diagnosed with CRC (391 urban and 160 rural). We PS-matched 142 pairs of urban and rural veterans without residual differences in baseline characteristics (Table 3). There was no significant difference in the HR of mortality between rural and urban veterans aged ≤ 45 years (HR, 0.97; 95% CI, 0.57-1.63; P = .90) (Figure 2). Similarly, no difference in mortality was observed adjusting for PS between all rural and urban veterans aged ≤ 45 years (HR, 1.03; 95% CI, 0.67-1.59; P = .88).

There was no difference in total mortality between rural and urban veterans in any subgroup except for American Indian or Alaska Native veterans (HR, 2.41; 95% CI, 1.29-4.50; P = .006) (Table 4).

Discussion

This study examined characteristics of patients with CRC between urban and rural areas among veterans who were VHA patients. Similar to other studies, rural veterans with CRC were older, more likely to be White, and were obese, but exhibited fewer comorbidities (lower CCI and lower incidence of congestive heart failure, dementia, hemiplegia, kidney diseases, liver diseases and AIDS, but higher incidence of chronic obstructive lung disease).^8,16 The incidence of CRC in this study population was lowest in FY 2020, which was reported by the Centers for Disease Control and Prevention and is attributed to COVID-19 pandemic disruption of health services.²⁴ The overall mortality in this study was similar to rates reported in other studies from the VA Central Cancer Registry.⁴ In the PS-matched cohort, where baseline characteristics were similar between urban and rural patients with CRC, we found no disparities in CRC-specific mortality between veterans in rural and urban areas. Additionally, when analysis was restricted to veterans aged ≤ 45 years, the results remained consistent.

Subgroup analyses showed no significant difference in mortality between rural and urban areas by sex, race or ethnicity, except rural American Indian or Alaska Native veterans who had double the mortality of their urban counterparts (HR, 2.41; 95% CI, 1.29-4.50; P = .006). This finding is difficult to interpret due to the small number of events and the wide CI. While with a Bonferroni correction the adjusted P value was .08, which is not statistically significant, a previous study found that although CRC incidence was lower overall in American Indian or Alaska Native populations compared to non-Hispanic White populations, CRC incidence was higher among American Indian or Alaska Native individuals in some areas such as Alaska and the Northern Plains.^25,26 Studies have noted that rural American Indian/Alaska Native populations experience greater poverty, less access to broadband internet, and limited access to care, contributing to poorer cancer outcomes and lower survival.²⁷ Thus, the finding of disparity in mortality between rural and urban American Indian or Alaska Native veterans warrants further study.

Other studies have raised concerns that CRC disproportionately affects adults in rural areas with higher mortality rates.^14-16 These disparities arise from sociodemographic factors and modifiable risk factors, including physical activity, dietary patterns, access to cancer screening, and gaps in quality treatment resources.^16,28 These factors operate at multiple levels: from individual, local health system, to community and policy.^2,27 For example, a South Carolina study (1996–2016) found that residents in rural areas were more likely to be diagnosed with advanced CRC, possibly indicating lower rates of CRC screening in rural areas. They also had higher likelihood of death from CRC.¹⁵ However, the study did not include any clinical parameters, such as comorbidities or obesity. A statewide, population-based study in Utah showed that rural men experienced a lower CRC survival in their unadjusted analysis.¹⁶ However, the study was small, with only 3948 urban and 712 rural residents. Additionally, there was no difference in total mortality in the whole cohort (HR, 0.96; 95% CI, 0.86-1.07) or in CRC-specific death (HR, 0.93; 95% CI, 0.81-1.08). A nationwide study also showed that CRC mortality rates were 8% higher in nonmetropolitan or rural areas than in the most urbanized areas containing large metropolitan counties.²⁹ However, this study did not include descriptions of clinical confounders, such as comorbidities, making it difficult to ascertain whether the difference in CRC mortality was due to rurality or differences in baseline risk characteristics.

In this study, the lack of CRC-specific mortality disparities may be attributed to the structures and practices of VHA health care. Recent studies have noted that mortality of several chronic medical conditions treated at the VHA was lower than at non-VHA hospitals.^30,31 One study that measured the quality of nonmetastatic CRC care based on National Comprehensive Cancer Network guidelines showed that > 72% of VHA patients received guideline-concordant care for each diagnostic and therapeutic measure, except for follow-up colonoscopy timing, which appear to be similar or superior to that of the private sector.^30,32,33 Some of the VA initiative for CRC screening may bypass the urban-rurality divide such as the mailed fecal immunochemical test program for CRC. This program was implemented at the onset of the COVID-19 pandemic to avoid disruptions of medical care.³⁴ Rural patients are more likely to undergo fecal immunochemical testing when compared to urban patients in this data. Beyond clinical care, the VHA uses processes to tackle social determinants of health such as housing, food security, and transportation, promoting equal access to health care, and promoting cultural competency among HCPs.^35-37

The results suggest that solutions to CRC disparities between rural and urban areas need to consider known barriers to rural health care, including transportation, diminished rural health care workforce, and other social determinants of health.^9,10,27,38 VHA makes considerable efforts to provide equitable care to all enrolled veterans, including specific programs for rural veterans, including ongoing outreach.³⁹ This study demonstrated lack of disparity in CRC-specific mortality in veterans receiving VHA care, highlighting the importance of these efforts.

Strengths and Limitations

This study used the VHA cohort to compare patient characteristics and mortality between patients with CRC residing in rural and urban areas. The study provides nationwide perspectives on CRC across the geographical spectrum and used a longitudinal cohort with prolonged follow-up to account for comorbidities.

However, the study compared a cohort of rural and urban veterans enrolled in the VHA; hence, the results may not reflect CRC outcomes in veterans without access to VHA care. Rurality has been independently associated with decreased likelihood of meeting CRC screening guidelines among veterans and military service members.³⁸ This study lacked sufficient information to compare CRC staging or treatment modalities among veterans. Although the data cannot identify CRC stage, the proportions of patients with metastatic CRC at diagnosis and CRC location were similar between groups. The study did not have information on their care outside of VHA setting.

This study could not ascertain whether disparities existed in CRC treatment modality since rural residence may result in referral to community-based CRC care, which did not appear in the data. To address these limitations, we used death from any cause as the primary outcome, since death is a hard outcome and is not subject to ascertainment bias. The relatively short follow-up time is another limitation, though subgroup analysis by follow-up did not show significant differences. Despite PS matching, residual unmeasured confounding may exist between urban and rural groups. The predominantly White, male VHA population with high CCI may limit the generalizability of the results.

Conclusions

Rural VHA enrollees had similar survival rates after CRC diagnosis compared to their urban counterparts in a PS-matched analysis. The VHA models of care—including mailed CRC screening tools, several socioeconomic determinants of health (housing, food security, and transportation), and promoting equal access to health care, as well as cultural competency among HCPs—HCPs—may help alleviate disparities across the rural-urban spectrum. The VHA should continue efforts to enroll veterans and provide comprehensive coordinated care in community partnerships.

Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths in the United States, with an estimated 52,550 deaths in 2023.¹ However, the disease burden varies among different segments of the population.² While both CRC incidence and mortality have been decreasing due to screening and advances in treatment, there are disparities in incidence and mortality across the sociodemographic spectrum including race, ethnicity, education, and income.^1-4 While CRC incidence is decreasing for older adults, it is increasing among those aged < 55 years.⁵ The incidence of CRC in adults aged 40 to 54 years has increased by 0.5% to 1.3% annually since the mid-1990s.⁶ The US Preventive Services Task Force now recommends starting CRC screening at age 45 years for asymptomatic adults with average risk.⁷

Disparities also exist across geographical boundaries and living environment. Rural Americans faces additional challenges in health and lifestyle that can affect CRC outcomes. Compared to their urban counterparts, rural residents are more likely to be older, have lower levels of education, higher levels of poverty, lack health insurance, and less access to health care practitioners (HCPs).^8-10 Geographic proximity, defined as travel time or physical distance to a health facility, has been recognized as a predictor of inferior outcomes.¹¹ These aspects of rural living may pose challenges for accessing care for CRC screening and treatment.^11-13 National and local studies have shown disparities in CRC screening rates, incidence, and mortality between rural and urban populations.^14-16

It is unclear whether rural/urban disparities persist under the Veterans Health Administration (VHA) health care delivery model. This study examined differences in baseline characteristics and mortality between rural and urban veterans newly diagnosed with CRC. We also focused on a subpopulation aged ≤ 45 years.

Methods

This study extracted national data from the US Department of Veterans Affairs (VA) Corporate Data Warehouse (CDW) hosted in the VA Informatics and Computing Infrastructure (VINCI) environment. VINCI is an initiative to improve access to VA data and facilitate the analysis of these data while ensuring veterans’ privacy and data security.¹⁷ CDW is the VHA business intelligence information repository, which extracts data from clinical and nonclinical sources following prescribed and validated protocols. Data extracted included demographics, diagnosis, and procedure codes for both inpatient and outpatient encounters, vital signs, and vital status. This study used data previously extracted from a national cohort of veterans that encompassed all patients who received a group of commonly prescribed medications, such as statins, proton pump inhibitors, histamine-2 blockers, acetaminophen-containing products, and hydrocortisone-containing skin applications. This cohort encompassed 8,648,754 veterans, from whom 2,460,727 had encounters during fiscal years (FY) 2016 to 2021 (study period). The cohort was used to ensure that subjects were VHA patients, allowing them to adequately capture their clinical profiles.

Patients were identified as rural or urban based on their residence address at the date of their first diagnosis of CRC. The Geospatial Service Support Center (GSSC) aggregates and updates veterans’ residence address records for all enrolled veterans from the National Change of Address database. The data contain 1 record per enrollee. GSSC Geocoded Enrollee File contains enrollee addresses and their rurality indicators, categorized as urban, rural, or highly rural.¹⁸ Rurality is defined by the Rural Urban Commuting Area (RUCA) categories developed by the Department of Agriculture and the Health Resources and Services Administration of the US Department of Health and Human Services.¹⁹ Urban areas had RUCA codes of 1.0 to 1.1, and highly rural areas had RUCA scores of 10.0. All other areas were classified as rural. Since the proportion of veterans from highly rural areas was small, we included residents from highly rural areas in the rural residents’ group.

Inclusion and Exclusion Criteria

All veterans newly diagnosed with CRC from FY 2016 to 2021 were included. We used the ninth and tenth clinical modification revisions of the International Classification of Diseases (ICD-9-CM and ICD-10-CM) to define CRC diagnosis (Supplemental materials).^4,20 To ensure that patients were newly diagnosed with CRC, this study excluded patients with a previous ICD-9-CM code for CRC diagnosis since FY 2003.

Comorbidities were identified using diagnosis and procedure codes from inpatient and outpatient encounters, which were used to calculate the Charlson Comorbidity Index (CCI) at the time of CRC diagnosis using the weighted method described by Schneeweiss et al.²¹ We defined CRC high-risk conditions and CRC screening tests, including flexible sigmoidoscopy and stool tests, as described in previous studies (Supplemental materials).²⁰

The main outcome was total mortality. The date of death was extracted from the VHA Death Ascertainment File, which contains mortality data from the Master Person Index file in CDW and the Social Security Administration Death Master File. We used the date of death from any cause, as cause of death was not available.

A propensity score (PS) was created to match rural (including highly rural) and urban residents at a ratio of 1:1. Using a standard procedure described in prior publications, multivariable logistic regression used all baseline characteristics to estimate the PS and perform nearest-number matching without replacement.^22,23 A caliper of 0.01 maximized the matched cohort size and achieved balance (Supplemental materials). We then examined the balance of baseline characteristics between PS-matched groups.

Analyses

Cox proportional hazards regression analysis estimated the hazard ratio (HR) of death in rural residents compared to urban residents in the PS-matched cohort. The outcome event was the date of death during the study’s follow-up period (defined as period from first CRC diagnosis to death or study end), with censoring at the study’s end date (September 30, 2021). The proportional hazards assumption was assessed by inspecting the Kaplan-Meier curves. Multiple analyses examined the HR of total mortality in the PS-matched cohort, stratified by sex, race, and ethnicity. We also examined the HR of total mortality stratified by duration of follow-up.

Another PS-matching analysis among veterans aged ≤ 45 years was performed using the same techniques described earlier in this article. We performed a Cox proportional hazards regression analysis to compare mortality in PS-matched urban and rural veterans aged ≤ 45 years. The HR of death in all veterans aged ≤ 45 years (before PS-matching) was estimated using Cox proportional hazard regression analysis, adjusting for PS.

Dichotomous variables were compared using X² tests and continuous variables were compared using t tests. Baseline characteristics with missing values were converted into categorical variables and the proportion of subjects with missing values was equalized between treatment groups after PS-matching. For subgroup analysis, we examined the HR of total mortality in each subgroup using separate Cox proportional hazards regression models similar to the primary analysis but adjusted for PS. Due to multiple comparisons in the subgroup analysis, the findings should be considered exploratory. Statistical tests were 2-tailed, and significance was defined as P < .05. Data management and statistical analyses were conducted from June 2022 to January 2023 using STATA, Version 17. The VA Orlando Healthcare System Institutional Review Board approved the study and waived requirements for informed consent because only deidentified data were used.

Results

After excluding 49 patients (Supplemental materials, available at doi:10.12788/fp.0560), we identified 30,219 veterans with newly diagnosed CRC between FY 2016 to 2021 (Table 1). Of these, 19,422 (64.3%) resided in urban areas and 10,797 (35.7%) resided in rural areas (Table 2). The mean (SD) duration from the first CRC diagnosis to death or study end was 832 (640) days, and the median (IQR) was 723 (246–1330) days. Overall, incident CRC diagnoses were numerically highest in FY 2016 and lowest in FY 2020 (Figure 1). Patients with CRC in rural areas vs urban areas were significantly older (mean, 71.2 years vs 70.8 years, respectively; P < .001), more likely to be male (96.7% vs 95.7%, respectively; P < .001), more likely to be White (83.6% vs 67.8%, respectively; P < .001) and more likely to be non-Hispanic (92.2% vs 87.5%, respectively; P < .001). In terms of general health, rural veterans with CRC were more likely to be overweight or obese (81.5% rural vs 78.5% urban; P < .001) but had fewer mean comorbidities as measured by CCI (5.66 rural vs 5.90 urban; P < .001). A higher proportion of rural veterans with CRC had received stool-based (fecal occult blood test or fecal immunochemical test) CRC screening tests (61.6% rural vs 57.2% urban; P < .001). Fewer rural patients presented with systemic symptoms or signs within 1 year of CRC diagnosis (54.4% rural vs 57.5% urban, P < .001). Among urban patients with CRC, 6959 (35.8%) deaths were observed, compared with 3766 (34.9%) among rural patients (P = .10).

There were 21,568 PS-matched veterans: 10,784 in each group. In the PS-matched cohort, baseline characteristics were similar between veterans in urban and rural communities, including age, sex, race/ethnicity, body mass index, and comorbidities. Among rural patients with CRC, 3763 deaths (34.9%) were observed compared with 3702 (34.3%) among urban veterans. There was no significant difference in the HR of mortality between rural and urban CRC residents (HR, 1.01; 95% CI, 0.97-1.06; P = .53) (Figure 2).

Among veterans aged ≤ 45 years, 551 were diagnosed with CRC (391 urban and 160 rural). We PS-matched 142 pairs of urban and rural veterans without residual differences in baseline characteristics (Table 3). There was no significant difference in the HR of mortality between rural and urban veterans aged ≤ 45 years (HR, 0.97; 95% CI, 0.57-1.63; P = .90) (Figure 2). Similarly, no difference in mortality was observed adjusting for PS between all rural and urban veterans aged ≤ 45 years (HR, 1.03; 95% CI, 0.67-1.59; P = .88).

There was no difference in total mortality between rural and urban veterans in any subgroup except for American Indian or Alaska Native veterans (HR, 2.41; 95% CI, 1.29-4.50; P = .006) (Table 4).

Discussion

This study examined characteristics of patients with CRC between urban and rural areas among veterans who were VHA patients. Similar to other studies, rural veterans with CRC were older, more likely to be White, and were obese, but exhibited fewer comorbidities (lower CCI and lower incidence of congestive heart failure, dementia, hemiplegia, kidney diseases, liver diseases and AIDS, but higher incidence of chronic obstructive lung disease).^8,16 The incidence of CRC in this study population was lowest in FY 2020, which was reported by the Centers for Disease Control and Prevention and is attributed to COVID-19 pandemic disruption of health services.²⁴ The overall mortality in this study was similar to rates reported in other studies from the VA Central Cancer Registry.⁴ In the PS-matched cohort, where baseline characteristics were similar between urban and rural patients with CRC, we found no disparities in CRC-specific mortality between veterans in rural and urban areas. Additionally, when analysis was restricted to veterans aged ≤ 45 years, the results remained consistent.

Subgroup analyses showed no significant difference in mortality between rural and urban areas by sex, race or ethnicity, except rural American Indian or Alaska Native veterans who had double the mortality of their urban counterparts (HR, 2.41; 95% CI, 1.29-4.50; P = .006). This finding is difficult to interpret due to the small number of events and the wide CI. While with a Bonferroni correction the adjusted P value was .08, which is not statistically significant, a previous study found that although CRC incidence was lower overall in American Indian or Alaska Native populations compared to non-Hispanic White populations, CRC incidence was higher among American Indian or Alaska Native individuals in some areas such as Alaska and the Northern Plains.^25,26 Studies have noted that rural American Indian/Alaska Native populations experience greater poverty, less access to broadband internet, and limited access to care, contributing to poorer cancer outcomes and lower survival.²⁷ Thus, the finding of disparity in mortality between rural and urban American Indian or Alaska Native veterans warrants further study.

Other studies have raised concerns that CRC disproportionately affects adults in rural areas with higher mortality rates.^14-16 These disparities arise from sociodemographic factors and modifiable risk factors, including physical activity, dietary patterns, access to cancer screening, and gaps in quality treatment resources.^16,28 These factors operate at multiple levels: from individual, local health system, to community and policy.^2,27 For example, a South Carolina study (1996–2016) found that residents in rural areas were more likely to be diagnosed with advanced CRC, possibly indicating lower rates of CRC screening in rural areas. They also had higher likelihood of death from CRC.¹⁵ However, the study did not include any clinical parameters, such as comorbidities or obesity. A statewide, population-based study in Utah showed that rural men experienced a lower CRC survival in their unadjusted analysis.¹⁶ However, the study was small, with only 3948 urban and 712 rural residents. Additionally, there was no difference in total mortality in the whole cohort (HR, 0.96; 95% CI, 0.86-1.07) or in CRC-specific death (HR, 0.93; 95% CI, 0.81-1.08). A nationwide study also showed that CRC mortality rates were 8% higher in nonmetropolitan or rural areas than in the most urbanized areas containing large metropolitan counties.²⁹ However, this study did not include descriptions of clinical confounders, such as comorbidities, making it difficult to ascertain whether the difference in CRC mortality was due to rurality or differences in baseline risk characteristics.

In this study, the lack of CRC-specific mortality disparities may be attributed to the structures and practices of VHA health care. Recent studies have noted that mortality of several chronic medical conditions treated at the VHA was lower than at non-VHA hospitals.^30,31 One study that measured the quality of nonmetastatic CRC care based on National Comprehensive Cancer Network guidelines showed that > 72% of VHA patients received guideline-concordant care for each diagnostic and therapeutic measure, except for follow-up colonoscopy timing, which appear to be similar or superior to that of the private sector.^30,32,33 Some of the VA initiative for CRC screening may bypass the urban-rurality divide such as the mailed fecal immunochemical test program for CRC. This program was implemented at the onset of the COVID-19 pandemic to avoid disruptions of medical care.³⁴ Rural patients are more likely to undergo fecal immunochemical testing when compared to urban patients in this data. Beyond clinical care, the VHA uses processes to tackle social determinants of health such as housing, food security, and transportation, promoting equal access to health care, and promoting cultural competency among HCPs.^35-37

The results suggest that solutions to CRC disparities between rural and urban areas need to consider known barriers to rural health care, including transportation, diminished rural health care workforce, and other social determinants of health.^9,10,27,38 VHA makes considerable efforts to provide equitable care to all enrolled veterans, including specific programs for rural veterans, including ongoing outreach.³⁹ This study demonstrated lack of disparity in CRC-specific mortality in veterans receiving VHA care, highlighting the importance of these efforts.

Strengths and Limitations

This study used the VHA cohort to compare patient characteristics and mortality between patients with CRC residing in rural and urban areas. The study provides nationwide perspectives on CRC across the geographical spectrum and used a longitudinal cohort with prolonged follow-up to account for comorbidities.

However, the study compared a cohort of rural and urban veterans enrolled in the VHA; hence, the results may not reflect CRC outcomes in veterans without access to VHA care. Rurality has been independently associated with decreased likelihood of meeting CRC screening guidelines among veterans and military service members.³⁸ This study lacked sufficient information to compare CRC staging or treatment modalities among veterans. Although the data cannot identify CRC stage, the proportions of patients with metastatic CRC at diagnosis and CRC location were similar between groups. The study did not have information on their care outside of VHA setting.

This study could not ascertain whether disparities existed in CRC treatment modality since rural residence may result in referral to community-based CRC care, which did not appear in the data. To address these limitations, we used death from any cause as the primary outcome, since death is a hard outcome and is not subject to ascertainment bias. The relatively short follow-up time is another limitation, though subgroup analysis by follow-up did not show significant differences. Despite PS matching, residual unmeasured confounding may exist between urban and rural groups. The predominantly White, male VHA population with high CCI may limit the generalizability of the results.

Conclusions

Rural VHA enrollees had similar survival rates after CRC diagnosis compared to their urban counterparts in a PS-matched analysis. The VHA models of care—including mailed CRC screening tools, several socioeconomic determinants of health (housing, food security, and transportation), and promoting equal access to health care, as well as cultural competency among HCPs—HCPs—may help alleviate disparities across the rural-urban spectrum. The VHA should continue efforts to enroll veterans and provide comprehensive coordinated care in community partnerships.

The annual issue of Cancer Data Trends, produced in collaboration with the Association of VA Hematology/Oncology (AVAHO), highlights the latest research in some of the top cancers impacting US veterans. 

In this issue: 

1. Access, Race, and "Colon Age": Improving CRC Screening
2. Lung Cancer: Mortality Trends in Veterans and New Treatments
3. Racial Disparities, Germline Testing, and Improved Overall Survival in Prostate Cancer
4. Breast and Uterine Cancer: Screening Guidelines, Genetic Testing, and Mortality Trends
5. HCC Updates: Quality Care Framework and Risk Stratification Data
6. Rising Kidney Cancer Cases and Emerging Treatments for Veterans
7. Advances in Blood Cancer Care for Veterans
8. AI-Based Risk Stratification for Oropharyngeal Carcinomas: AIROC
9. Brain Cancer: Epidemiology, TBI, and New Treatments

The annual issue of Cancer Data Trends, produced in collaboration with the Association of VA Hematology/Oncology (AVAHO), highlights the latest research in some of the top cancers impacting US veterans. 

In this issue: 

1. Access, Race, and "Colon Age": Improving CRC Screening
2. Lung Cancer: Mortality Trends in Veterans and New Treatments
3. Racial Disparities, Germline Testing, and Improved Overall Survival in Prostate Cancer
4. Breast and Uterine Cancer: Screening Guidelines, Genetic Testing, and Mortality Trends
5. HCC Updates: Quality Care Framework and Risk Stratification Data
6. Rising Kidney Cancer Cases and Emerging Treatments for Veterans
7. Advances in Blood Cancer Care for Veterans
8. AI-Based Risk Stratification for Oropharyngeal Carcinomas: AIROC
9. Brain Cancer: Epidemiology, TBI, and New Treatments

The annual issue of Cancer Data Trends, produced in collaboration with the Association of VA Hematology/Oncology (AVAHO), highlights the latest research in some of the top cancers impacting US veterans. 

In this issue: 

1. Access, Race, and "Colon Age": Improving CRC Screening
2. Lung Cancer: Mortality Trends in Veterans and New Treatments
3. Racial Disparities, Germline Testing, and Improved Overall Survival in Prostate Cancer
4. Breast and Uterine Cancer: Screening Guidelines, Genetic Testing, and Mortality Trends
5. HCC Updates: Quality Care Framework and Risk Stratification Data
6. Rising Kidney Cancer Cases and Emerging Treatments for Veterans
7. Advances in Blood Cancer Care for Veterans
8. AI-Based Risk Stratification for Oropharyngeal Carcinomas: AIROC
9. Brain Cancer: Epidemiology, TBI, and New Treatments

Pulmonary embolism (PE) is a common cause of morbidity and mortality in the general population.¹ The incidence of PE has been reported to range from 39 to 115 per 100,000 persons per year and has remained stable.² Although mortality rates have declined, they remain high.³ The clinical presentation is nonspecific, making diagnosis and management challenging. A crucial and difficult aspect in the management of patients with PE is weighing the risks vs benefits of treatment, including thrombolytic therapy and other invasive procedures, which carry inherent risks. These factors have led to the development of PE response teams (PERTs) in some hospitals to implement effective multidisciplinary protocols that facilitate prompt diagnosis, management, and follow-up.⁴

CASE PRESENTATIONS

Case 1

New onset seizures and cardiac arrest in the treatment of saddle PE. A 54-year-old male who worked as a draftsman and truck driver with a history of hypertension and nephrolithiasis presented to the emergency department (ED) with progressive shortness of breath for 2 weeks. On the morning of ED presentation the patient experienced an episode of severe shortness of breath, lightheadedness, and chest pressure. He reported no other symptoms such as palpitations, nausea, vomiting, abdominal discomfort, or extremity pain or swelling. He reported no recent travel, immunization, falls, or surgery. Upon evaluation, the patient was found to be in no acute distress, with stable vital signs and laboratory results except for 2 elevated results: > 20 μg/mL D-dimer (reference range, < 0.5 μg/mL) and N-terminal prohormone brain natriuretic peptide (proBNP) level, 3455 pg/mL (reference range, < 125 pg/mL for patients aged < 75 years). Electrocardiogram showed T-wave inversions in leads V2 to V4. Imaging revealed a saddle PE and left popliteal deep venous thrombosis (Figure 1). The patient received an anticoagulation loading dose and was started on heparin drip upon admission to the medical intensive care unit (MICU) for further management and monitoring. The Interventional Radiology Service recommended full anticoagulation with consideration of reperfusion therapies if deterioration developed.

While in the MICU, point-of-care ultrasound findings were confirmed with official echocardiogram by the cardiology service, which demonstrated a preserved ejection fraction of 60% to 65%, a D-shaped left ventricle with septal wall hypokinesis secondary to right heart strain (Figure 2), a markedly elevated right ventricular systolic pressure (RVSP) of 73 mm Hg, and a mean pulmonary artery pressure (mPAP) of 38 mm Hg. The patient’s blood pressure progressively decreased, heart rate increased, and he required increased oxygen supplementation. The case was discussed with the Pharmacy Service, and since the patient had no contraindications to thrombolytic therapy, the appropriate dosage was calculated and 100 mg intravenous (IV) tissue plasminogen activator (tPA) was administered over 2 hours.

About 40 minutes into tPA infusion, the patient suddenly experienced marked shortness of breath, diaphoresis, and anxiety with seizure-like involuntary movements; as a result, the infusion was stopped. He also had episodes of posturing, mental status decline, and briefly going in and out of consciousness, which lasted about 3 minutes before he lost consciousness and pulse. High-quality advanced cardiac life support was initiated, followed by endotracheal intubation. Despite a secured airway and return of spontaneous circulation, the patient remained hypotensive and continued to have seizure-like activity.

The patient was administered a total of 8 mg of lorazepam, sedated with propofol, initiated at 5 μg/kg/min, titrated to stop seizure activity at 15μg/kg/min, and later maintained at 10 μg/kg/min, for a RASS of -1, and started on norepinephrine 0.1 μg/kg/min for acute stabilization. Head computed tomography without contrast showed no acute intracranial pathology as etiology of seizures. Seizure etiology differential at this time was broad; however, hypoxemia due to PE and medication adverse effects were strongly suspected.

The patient’s condition improved, and vasopressor therapy was tapered off the next day. Four days later, the patient was weaned from mechanical ventilation and transferred to the step-down unit. Echocardiogram obtained 48 hours after tPA infusion showed essentially normal left ventricular function (60%-65%), a RVSP of 17 mm Hg and mPAP of 13 mm Hg. The patient’s ProBNP levels markedly decreased to 137 pg/mL. Postextubation, the neurologic examination was at baseline. The Neurology Service recommended temporary treatment with levetiracetam, 1000 mg every 12 hours, and the Hematology Service recommended transitioning to direct oral anticoagulation with follow-up. The patient presented significant clinical and respiratory improvement and was referred for home-based physical rehabilitation as recommended by the physical medicine and rehabilitation service before being discharged.

Case 2

Localized tPA infusion for bilateral PEs via infusion catheters. A 91-year-old male with no history of smoking and a medical history of hypertension, diabetes mellitus, prostate cancer (> 20 years postradiotherapy) and severe osteoarthritis was receiving treatment in the medical ward for medication-induced liver injury secondary to an antibiotic for a urinary tract infection. During the night the patient developed hypotension (86/46 mm Hg), shortness of breath, tachypnea, desaturation, nonradiating retrosternal chest pain, and tachycardia. The hypotension resolved after a 500-mL 0.9 normal saline bolus, and hypoxemia improved with supplemental oxygen via Venturi mask. Chest computed tomography angiography was performed immediately and revealed extensive bilateral acute PE, located most proximally in the right main pulmonary artery (PA) and on the left in the proximal lobar branches, with associated right heart strain. The patient was started on IV heparin with a bolus of 5000 units (80 u/kg) followed by a drip with a partial thromboplastin time goal of 62-103 seconds and transferred to MICU.

Laboratory findings were notable for proBNP that increased from 115 pg/mL to 4470 pg/mL (reference range, < 450 pg/mL for patients aged 75 years) and elevated troponin levels at 218 ng/L to 295 ng/L (reference range, < 22 ng/L), exhibiting chemical evidence of right heart strain. Initial echocardiogram showed mid-right ventricular free wall akinesis with a hypercontractile apex, suggestive of PE (McConnell’s sign) (Figure 3). Interventional Radiology Service was consulted and recommended tPA infusion given that the patient had bilateral PEs and stable blood pressure.

Pulmonary angiogram showed elevated pressures in the right PA of 64/21 mm Hg and the left PA pressures of 63/20 mm Hg. Mechanical disruption of the larger right lower PA thrombus was achieved via a pigtail catheter followed by bilateral catheter bolus infusions of 2 mg tPA (alteplase) and a continuous tPA infusion 0.5 mg/h for 24 hours, in conjunction with a heparin infusion.

After 24 hours of tPA infusion, the catheters were removed, with posttreatment pulmonary angiography demonstrating right and left PA pressures of 42/15 mm Hg and 40/16 mm Hg, respectively. Pre- and postlocalized tPA infusion treatment images are provided for visual comparison (Figure 4). An echocardiogram performed after tPA infusion showed no signs of pulmonary hypertension. The Hematology Service provided recommendations regarding anticoagulation, and after completion of tPA infusion, the patient was transitioned to an unfractioned heparin infusion and subsequently to direct oral anticoagulation prior to transfer back to the medical ward, hemodynamically stable and asymptomatic.

DISCUSSION

PE management can be a straightforward decision when the patient meets criteria for hemodynamic instability, or with small PE burden. In contrast, management can be more challenging in intermediate-risk (submassive) PE when patients remain hemodynamically stable but show signs of cardiopulmonary stress, such as right heart strain, elevated troponins, or increased proBNP levels.² In these situations, case-by- case evaluation is warranted. A PERT can assess the most beneficial treatment approach by considering factors such as right ventricular dysfunction, hemodynamic status, clot burden, and clinical deterioration despite appropriate anticoagulation. The evidence supporting the benefits these organized teams can provide is growing. These case reports emphasize the need for a multidisciplinary and systematic approach in these complex cases, especially in the management of intermediate-risk PE patients.

Currently, the Veterans Affairs Caribbean Healthcare System does not have an organized PERT, although a multidisciplinary approach was applied in the management of these patients. A systematic, structured team could have decreased time to interventions and alleviated the burden of physician decision-making. Having such a team would streamline the diagnostic pathway for patients presenting from a ward or emergency department with suspected PE.

We present 2 cases of patients found to have a high clot burden from PEs. The patients were initially hemodynamically stable (intermediate-risk PE), but later required systemic or localized thrombolysis due to hemodynamic deterioration despite adequate anticoagulation. Despite similar diagnoses and etiologies, these patients were successfully managed using different approaches, yielding positive outcomes. This reflects the complexity and variability in diagnosing and managing intermediate-risk PE in patients with different comorbidities and clot burden effects. In Case 1, our multidisciplinary approach was obtained via consults to selected services such as interventional radiology, cardiology, and direct involvement of pharmacy. An organized PERT conceivably would have allowed quicker discussions among these services, including hematology, to provide recommendations and collaborative support upon the patient’s arrival to the ED. Additionally, with a PERT team, a systematic approach to these patients could have allowed for an earlier official echocardiogram report for evaluation of right heart strain and develop an adequate therapeutic plan in a timely manner.

In Case 2, consultation with the Interventional Radiology Service yielded a better therapeutic plan, utilizing localized tPA infusion for this older adult patient with increased risk of bleeding with systemic tPA infusion. Having a PERT presents an opportunity to optimize PE management through early recognition, diagnosis, and treatment by institutional consensus from an interdisciplinary team.^5,6 These response teams may improve outcomes and prognosis for patients with PE, especially where diagnosis and management is not clear.

The definite etiology of seizure activity in the first case pre- and postcardiac arrest, in the context of no acute intracranial process, remains unknown. Reports have emerged about postreperfusion seizures in acute ischemic stroke, as well as cases of seizures masquerading as PE as the primary presentation. ^7,8 However, there were no reports of patients developing seizures post tPA infusion for the treatment of PE. This report may shed light into possible complications secondary to tPA infusion, raising awareness among physicians and encouraging further investigation into its possible etiologies.

CONCLUSIONS

Management of PE can be challenging in patients that meet criteria for intermediate risk. PERTs are a tool that allow for a multidisciplinary, standardized and systematic approach with a diagnostic and treatment algorithm that conceivably would result in a better consensus and therapeutic approach.

Pulmonary embolism (PE) is a common cause of morbidity and mortality in the general population.¹ The incidence of PE has been reported to range from 39 to 115 per 100,000 persons per year and has remained stable.² Although mortality rates have declined, they remain high.³ The clinical presentation is nonspecific, making diagnosis and management challenging. A crucial and difficult aspect in the management of patients with PE is weighing the risks vs benefits of treatment, including thrombolytic therapy and other invasive procedures, which carry inherent risks. These factors have led to the development of PE response teams (PERTs) in some hospitals to implement effective multidisciplinary protocols that facilitate prompt diagnosis, management, and follow-up.⁴

CASE PRESENTATIONS

Case 1

New onset seizures and cardiac arrest in the treatment of saddle PE. A 54-year-old male who worked as a draftsman and truck driver with a history of hypertension and nephrolithiasis presented to the emergency department (ED) with progressive shortness of breath for 2 weeks. On the morning of ED presentation the patient experienced an episode of severe shortness of breath, lightheadedness, and chest pressure. He reported no other symptoms such as palpitations, nausea, vomiting, abdominal discomfort, or extremity pain or swelling. He reported no recent travel, immunization, falls, or surgery. Upon evaluation, the patient was found to be in no acute distress, with stable vital signs and laboratory results except for 2 elevated results: > 20 μg/mL D-dimer (reference range, < 0.5 μg/mL) and N-terminal prohormone brain natriuretic peptide (proBNP) level, 3455 pg/mL (reference range, < 125 pg/mL for patients aged < 75 years). Electrocardiogram showed T-wave inversions in leads V2 to V4. Imaging revealed a saddle PE and left popliteal deep venous thrombosis (Figure 1). The patient received an anticoagulation loading dose and was started on heparin drip upon admission to the medical intensive care unit (MICU) for further management and monitoring. The Interventional Radiology Service recommended full anticoagulation with consideration of reperfusion therapies if deterioration developed.

While in the MICU, point-of-care ultrasound findings were confirmed with official echocardiogram by the cardiology service, which demonstrated a preserved ejection fraction of 60% to 65%, a D-shaped left ventricle with septal wall hypokinesis secondary to right heart strain (Figure 2), a markedly elevated right ventricular systolic pressure (RVSP) of 73 mm Hg, and a mean pulmonary artery pressure (mPAP) of 38 mm Hg. The patient’s blood pressure progressively decreased, heart rate increased, and he required increased oxygen supplementation. The case was discussed with the Pharmacy Service, and since the patient had no contraindications to thrombolytic therapy, the appropriate dosage was calculated and 100 mg intravenous (IV) tissue plasminogen activator (tPA) was administered over 2 hours.

About 40 minutes into tPA infusion, the patient suddenly experienced marked shortness of breath, diaphoresis, and anxiety with seizure-like involuntary movements; as a result, the infusion was stopped. He also had episodes of posturing, mental status decline, and briefly going in and out of consciousness, which lasted about 3 minutes before he lost consciousness and pulse. High-quality advanced cardiac life support was initiated, followed by endotracheal intubation. Despite a secured airway and return of spontaneous circulation, the patient remained hypotensive and continued to have seizure-like activity.

The patient was administered a total of 8 mg of lorazepam, sedated with propofol, initiated at 5 μg/kg/min, titrated to stop seizure activity at 15μg/kg/min, and later maintained at 10 μg/kg/min, for a RASS of -1, and started on norepinephrine 0.1 μg/kg/min for acute stabilization. Head computed tomography without contrast showed no acute intracranial pathology as etiology of seizures. Seizure etiology differential at this time was broad; however, hypoxemia due to PE and medication adverse effects were strongly suspected.

The patient’s condition improved, and vasopressor therapy was tapered off the next day. Four days later, the patient was weaned from mechanical ventilation and transferred to the step-down unit. Echocardiogram obtained 48 hours after tPA infusion showed essentially normal left ventricular function (60%-65%), a RVSP of 17 mm Hg and mPAP of 13 mm Hg. The patient’s ProBNP levels markedly decreased to 137 pg/mL. Postextubation, the neurologic examination was at baseline. The Neurology Service recommended temporary treatment with levetiracetam, 1000 mg every 12 hours, and the Hematology Service recommended transitioning to direct oral anticoagulation with follow-up. The patient presented significant clinical and respiratory improvement and was referred for home-based physical rehabilitation as recommended by the physical medicine and rehabilitation service before being discharged.

Case 2

Localized tPA infusion for bilateral PEs via infusion catheters. A 91-year-old male with no history of smoking and a medical history of hypertension, diabetes mellitus, prostate cancer (> 20 years postradiotherapy) and severe osteoarthritis was receiving treatment in the medical ward for medication-induced liver injury secondary to an antibiotic for a urinary tract infection. During the night the patient developed hypotension (86/46 mm Hg), shortness of breath, tachypnea, desaturation, nonradiating retrosternal chest pain, and tachycardia. The hypotension resolved after a 500-mL 0.9 normal saline bolus, and hypoxemia improved with supplemental oxygen via Venturi mask. Chest computed tomography angiography was performed immediately and revealed extensive bilateral acute PE, located most proximally in the right main pulmonary artery (PA) and on the left in the proximal lobar branches, with associated right heart strain. The patient was started on IV heparin with a bolus of 5000 units (80 u/kg) followed by a drip with a partial thromboplastin time goal of 62-103 seconds and transferred to MICU.

Laboratory findings were notable for proBNP that increased from 115 pg/mL to 4470 pg/mL (reference range, < 450 pg/mL for patients aged 75 years) and elevated troponin levels at 218 ng/L to 295 ng/L (reference range, < 22 ng/L), exhibiting chemical evidence of right heart strain. Initial echocardiogram showed mid-right ventricular free wall akinesis with a hypercontractile apex, suggestive of PE (McConnell’s sign) (Figure 3). Interventional Radiology Service was consulted and recommended tPA infusion given that the patient had bilateral PEs and stable blood pressure.

Pulmonary angiogram showed elevated pressures in the right PA of 64/21 mm Hg and the left PA pressures of 63/20 mm Hg. Mechanical disruption of the larger right lower PA thrombus was achieved via a pigtail catheter followed by bilateral catheter bolus infusions of 2 mg tPA (alteplase) and a continuous tPA infusion 0.5 mg/h for 24 hours, in conjunction with a heparin infusion.

After 24 hours of tPA infusion, the catheters were removed, with posttreatment pulmonary angiography demonstrating right and left PA pressures of 42/15 mm Hg and 40/16 mm Hg, respectively. Pre- and postlocalized tPA infusion treatment images are provided for visual comparison (Figure 4). An echocardiogram performed after tPA infusion showed no signs of pulmonary hypertension. The Hematology Service provided recommendations regarding anticoagulation, and after completion of tPA infusion, the patient was transitioned to an unfractioned heparin infusion and subsequently to direct oral anticoagulation prior to transfer back to the medical ward, hemodynamically stable and asymptomatic.

DISCUSSION

PE management can be a straightforward decision when the patient meets criteria for hemodynamic instability, or with small PE burden. In contrast, management can be more challenging in intermediate-risk (submassive) PE when patients remain hemodynamically stable but show signs of cardiopulmonary stress, such as right heart strain, elevated troponins, or increased proBNP levels.² In these situations, case-by- case evaluation is warranted. A PERT can assess the most beneficial treatment approach by considering factors such as right ventricular dysfunction, hemodynamic status, clot burden, and clinical deterioration despite appropriate anticoagulation. The evidence supporting the benefits these organized teams can provide is growing. These case reports emphasize the need for a multidisciplinary and systematic approach in these complex cases, especially in the management of intermediate-risk PE patients.

Currently, the Veterans Affairs Caribbean Healthcare System does not have an organized PERT, although a multidisciplinary approach was applied in the management of these patients. A systematic, structured team could have decreased time to interventions and alleviated the burden of physician decision-making. Having such a team would streamline the diagnostic pathway for patients presenting from a ward or emergency department with suspected PE.

We present 2 cases of patients found to have a high clot burden from PEs. The patients were initially hemodynamically stable (intermediate-risk PE), but later required systemic or localized thrombolysis due to hemodynamic deterioration despite adequate anticoagulation. Despite similar diagnoses and etiologies, these patients were successfully managed using different approaches, yielding positive outcomes. This reflects the complexity and variability in diagnosing and managing intermediate-risk PE in patients with different comorbidities and clot burden effects. In Case 1, our multidisciplinary approach was obtained via consults to selected services such as interventional radiology, cardiology, and direct involvement of pharmacy. An organized PERT conceivably would have allowed quicker discussions among these services, including hematology, to provide recommendations and collaborative support upon the patient’s arrival to the ED. Additionally, with a PERT team, a systematic approach to these patients could have allowed for an earlier official echocardiogram report for evaluation of right heart strain and develop an adequate therapeutic plan in a timely manner.

In Case 2, consultation with the Interventional Radiology Service yielded a better therapeutic plan, utilizing localized tPA infusion for this older adult patient with increased risk of bleeding with systemic tPA infusion. Having a PERT presents an opportunity to optimize PE management through early recognition, diagnosis, and treatment by institutional consensus from an interdisciplinary team.^5,6 These response teams may improve outcomes and prognosis for patients with PE, especially where diagnosis and management is not clear.

The definite etiology of seizure activity in the first case pre- and postcardiac arrest, in the context of no acute intracranial process, remains unknown. Reports have emerged about postreperfusion seizures in acute ischemic stroke, as well as cases of seizures masquerading as PE as the primary presentation. ^7,8 However, there were no reports of patients developing seizures post tPA infusion for the treatment of PE. This report may shed light into possible complications secondary to tPA infusion, raising awareness among physicians and encouraging further investigation into its possible etiologies.

CONCLUSIONS

Management of PE can be challenging in patients that meet criteria for intermediate risk. PERTs are a tool that allow for a multidisciplinary, standardized and systematic approach with a diagnostic and treatment algorithm that conceivably would result in a better consensus and therapeutic approach.

Pulmonary embolism (PE) is a common cause of morbidity and mortality in the general population.¹ The incidence of PE has been reported to range from 39 to 115 per 100,000 persons per year and has remained stable.² Although mortality rates have declined, they remain high.³ The clinical presentation is nonspecific, making diagnosis and management challenging. A crucial and difficult aspect in the management of patients with PE is weighing the risks vs benefits of treatment, including thrombolytic therapy and other invasive procedures, which carry inherent risks. These factors have led to the development of PE response teams (PERTs) in some hospitals to implement effective multidisciplinary protocols that facilitate prompt diagnosis, management, and follow-up.⁴

CASE PRESENTATIONS

Case 1

New onset seizures and cardiac arrest in the treatment of saddle PE. A 54-year-old male who worked as a draftsman and truck driver with a history of hypertension and nephrolithiasis presented to the emergency department (ED) with progressive shortness of breath for 2 weeks. On the morning of ED presentation the patient experienced an episode of severe shortness of breath, lightheadedness, and chest pressure. He reported no other symptoms such as palpitations, nausea, vomiting, abdominal discomfort, or extremity pain or swelling. He reported no recent travel, immunization, falls, or surgery. Upon evaluation, the patient was found to be in no acute distress, with stable vital signs and laboratory results except for 2 elevated results: > 20 μg/mL D-dimer (reference range, < 0.5 μg/mL) and N-terminal prohormone brain natriuretic peptide (proBNP) level, 3455 pg/mL (reference range, < 125 pg/mL for patients aged < 75 years). Electrocardiogram showed T-wave inversions in leads V2 to V4. Imaging revealed a saddle PE and left popliteal deep venous thrombosis (Figure 1). The patient received an anticoagulation loading dose and was started on heparin drip upon admission to the medical intensive care unit (MICU) for further management and monitoring. The Interventional Radiology Service recommended full anticoagulation with consideration of reperfusion therapies if deterioration developed.

While in the MICU, point-of-care ultrasound findings were confirmed with official echocardiogram by the cardiology service, which demonstrated a preserved ejection fraction of 60% to 65%, a D-shaped left ventricle with septal wall hypokinesis secondary to right heart strain (Figure 2), a markedly elevated right ventricular systolic pressure (RVSP) of 73 mm Hg, and a mean pulmonary artery pressure (mPAP) of 38 mm Hg. The patient’s blood pressure progressively decreased, heart rate increased, and he required increased oxygen supplementation. The case was discussed with the Pharmacy Service, and since the patient had no contraindications to thrombolytic therapy, the appropriate dosage was calculated and 100 mg intravenous (IV) tissue plasminogen activator (tPA) was administered over 2 hours.

About 40 minutes into tPA infusion, the patient suddenly experienced marked shortness of breath, diaphoresis, and anxiety with seizure-like involuntary movements; as a result, the infusion was stopped. He also had episodes of posturing, mental status decline, and briefly going in and out of consciousness, which lasted about 3 minutes before he lost consciousness and pulse. High-quality advanced cardiac life support was initiated, followed by endotracheal intubation. Despite a secured airway and return of spontaneous circulation, the patient remained hypotensive and continued to have seizure-like activity.

The patient was administered a total of 8 mg of lorazepam, sedated with propofol, initiated at 5 μg/kg/min, titrated to stop seizure activity at 15μg/kg/min, and later maintained at 10 μg/kg/min, for a RASS of -1, and started on norepinephrine 0.1 μg/kg/min for acute stabilization. Head computed tomography without contrast showed no acute intracranial pathology as etiology of seizures. Seizure etiology differential at this time was broad; however, hypoxemia due to PE and medication adverse effects were strongly suspected.

The patient’s condition improved, and vasopressor therapy was tapered off the next day. Four days later, the patient was weaned from mechanical ventilation and transferred to the step-down unit. Echocardiogram obtained 48 hours after tPA infusion showed essentially normal left ventricular function (60%-65%), a RVSP of 17 mm Hg and mPAP of 13 mm Hg. The patient’s ProBNP levels markedly decreased to 137 pg/mL. Postextubation, the neurologic examination was at baseline. The Neurology Service recommended temporary treatment with levetiracetam, 1000 mg every 12 hours, and the Hematology Service recommended transitioning to direct oral anticoagulation with follow-up. The patient presented significant clinical and respiratory improvement and was referred for home-based physical rehabilitation as recommended by the physical medicine and rehabilitation service before being discharged.

Case 2

Localized tPA infusion for bilateral PEs via infusion catheters. A 91-year-old male with no history of smoking and a medical history of hypertension, diabetes mellitus, prostate cancer (> 20 years postradiotherapy) and severe osteoarthritis was receiving treatment in the medical ward for medication-induced liver injury secondary to an antibiotic for a urinary tract infection. During the night the patient developed hypotension (86/46 mm Hg), shortness of breath, tachypnea, desaturation, nonradiating retrosternal chest pain, and tachycardia. The hypotension resolved after a 500-mL 0.9 normal saline bolus, and hypoxemia improved with supplemental oxygen via Venturi mask. Chest computed tomography angiography was performed immediately and revealed extensive bilateral acute PE, located most proximally in the right main pulmonary artery (PA) and on the left in the proximal lobar branches, with associated right heart strain. The patient was started on IV heparin with a bolus of 5000 units (80 u/kg) followed by a drip with a partial thromboplastin time goal of 62-103 seconds and transferred to MICU.

Laboratory findings were notable for proBNP that increased from 115 pg/mL to 4470 pg/mL (reference range, < 450 pg/mL for patients aged 75 years) and elevated troponin levels at 218 ng/L to 295 ng/L (reference range, < 22 ng/L), exhibiting chemical evidence of right heart strain. Initial echocardiogram showed mid-right ventricular free wall akinesis with a hypercontractile apex, suggestive of PE (McConnell’s sign) (Figure 3). Interventional Radiology Service was consulted and recommended tPA infusion given that the patient had bilateral PEs and stable blood pressure.

Pulmonary angiogram showed elevated pressures in the right PA of 64/21 mm Hg and the left PA pressures of 63/20 mm Hg. Mechanical disruption of the larger right lower PA thrombus was achieved via a pigtail catheter followed by bilateral catheter bolus infusions of 2 mg tPA (alteplase) and a continuous tPA infusion 0.5 mg/h for 24 hours, in conjunction with a heparin infusion.

After 24 hours of tPA infusion, the catheters were removed, with posttreatment pulmonary angiography demonstrating right and left PA pressures of 42/15 mm Hg and 40/16 mm Hg, respectively. Pre- and postlocalized tPA infusion treatment images are provided for visual comparison (Figure 4). An echocardiogram performed after tPA infusion showed no signs of pulmonary hypertension. The Hematology Service provided recommendations regarding anticoagulation, and after completion of tPA infusion, the patient was transitioned to an unfractioned heparin infusion and subsequently to direct oral anticoagulation prior to transfer back to the medical ward, hemodynamically stable and asymptomatic.

DISCUSSION

PE management can be a straightforward decision when the patient meets criteria for hemodynamic instability, or with small PE burden. In contrast, management can be more challenging in intermediate-risk (submassive) PE when patients remain hemodynamically stable but show signs of cardiopulmonary stress, such as right heart strain, elevated troponins, or increased proBNP levels.² In these situations, case-by- case evaluation is warranted. A PERT can assess the most beneficial treatment approach by considering factors such as right ventricular dysfunction, hemodynamic status, clot burden, and clinical deterioration despite appropriate anticoagulation. The evidence supporting the benefits these organized teams can provide is growing. These case reports emphasize the need for a multidisciplinary and systematic approach in these complex cases, especially in the management of intermediate-risk PE patients.

Currently, the Veterans Affairs Caribbean Healthcare System does not have an organized PERT, although a multidisciplinary approach was applied in the management of these patients. A systematic, structured team could have decreased time to interventions and alleviated the burden of physician decision-making. Having such a team would streamline the diagnostic pathway for patients presenting from a ward or emergency department with suspected PE.

We present 2 cases of patients found to have a high clot burden from PEs. The patients were initially hemodynamically stable (intermediate-risk PE), but later required systemic or localized thrombolysis due to hemodynamic deterioration despite adequate anticoagulation. Despite similar diagnoses and etiologies, these patients were successfully managed using different approaches, yielding positive outcomes. This reflects the complexity and variability in diagnosing and managing intermediate-risk PE in patients with different comorbidities and clot burden effects. In Case 1, our multidisciplinary approach was obtained via consults to selected services such as interventional radiology, cardiology, and direct involvement of pharmacy. An organized PERT conceivably would have allowed quicker discussions among these services, including hematology, to provide recommendations and collaborative support upon the patient’s arrival to the ED. Additionally, with a PERT team, a systematic approach to these patients could have allowed for an earlier official echocardiogram report for evaluation of right heart strain and develop an adequate therapeutic plan in a timely manner.

In Case 2, consultation with the Interventional Radiology Service yielded a better therapeutic plan, utilizing localized tPA infusion for this older adult patient with increased risk of bleeding with systemic tPA infusion. Having a PERT presents an opportunity to optimize PE management through early recognition, diagnosis, and treatment by institutional consensus from an interdisciplinary team.^5,6 These response teams may improve outcomes and prognosis for patients with PE, especially where diagnosis and management is not clear.

The definite etiology of seizure activity in the first case pre- and postcardiac arrest, in the context of no acute intracranial process, remains unknown. Reports have emerged about postreperfusion seizures in acute ischemic stroke, as well as cases of seizures masquerading as PE as the primary presentation. ^7,8 However, there were no reports of patients developing seizures post tPA infusion for the treatment of PE. This report may shed light into possible complications secondary to tPA infusion, raising awareness among physicians and encouraging further investigation into its possible etiologies.

CONCLUSIONS

Management of PE can be challenging in patients that meet criteria for intermediate risk. PERTs are a tool that allow for a multidisciplinary, standardized and systematic approach with a diagnostic and treatment algorithm that conceivably would result in a better consensus and therapeutic approach.

ATHENS, Greece — At the 11th World Congress of Melanoma and 21st EADO Congress 2025, experts presented divergent perspectives on the merits of population-wide skin cancer screening programs vs more targeted approaches. The debate highlighted concerns about healthcare resource allocation, overdiagnosis, and the true impact of mass skin cancer screening on mortality.

Arguing against widespread screening, particularly in low-to-medium incidence countries like Spain, was Susana Puig, MD, the head of Dermatology at Hospital Clínic de Barcelona, University of Barcelona, and a dermatologist at Barnaclínic+, Barcelona, Spain.

“It’s not efficient. We visit too many healthy individuals to detect melanoma,” she said. “We need to focus on treating patients, not checking healthy people without any risk.”

Championing for population-wide screening was Peter Mohr, MD, a dermatologist at the Clinic of Dermatology in Elbe Klinikum Buxtehude, Buxtehude, Germany, who noted a disproportionate focus on treatment rather than prevention. “The ultimate goal of screening,” he said, “is to prevent advanced disease and reduce melanoma-specific mortality.”

 

Avoid Population-Based Screening

Presenting data from Germany, Puig noted that population-based screening starting at any age requires examining more than 600 people and performing over 24 excisions to detect one melanoma. When setting screening to start at the age of 35 years, the number of people needed to screen to detect one melanoma decreased slightly to 559. 

These findings highlight that population-based screening will include many people who don’t need it and can increase the potential for overdiagnosis, she argued.

Studies and guidelines from the United States align with Puig’s concern about broad-based screening likely leading to overdiagnosis. “The incidence of melanoma has risen sixfold in the past 40 years in the United States, while mortality has remained largely flat, an epidemiological signature consistent with overdiagnosis,” according to Adewole Adamson, MD, an assistant professor of internal medicine, in the Division of Dermatology at Dell Medical School at The University of Texas at Austin, Texas, who published findings to this effect in 2022.

“We cannot saturate the system with healthy people,” Puig said. Instead, “we need to use strategies to identify high-risk patients.” She proposed being more selective about who to screen by identifying those at higher risk of developing melanoma.

Identifying risk factors, such as the presence of atypical nevi and a personal or family history of melanoma, can help hone who is screened, she explained. Patients with a personal history of melanoma, in particular, face a higher risk of developing subsequent melanomas. Data show that patients with two or more primary melanomas had almost three times the risk of developing a subsequent one than those with one prior melanoma — 25.7% vs 8.6%. Puig also pointed out the significant correlation between age and melanoma risk, with people over 70 years exhibiting a 93-fold higher probability of diagnosis than those younger than 30 years.

Citing the German data, she noted that screening people 20 years and older with one risk factor reduced the number needed to screen by more than threefold — from more than 600 to 178.

Puig suggested dedicated surveillance programs for high-risk individuals alongside opportunistic screening during routine medical encounters.

“This would lead to a more efficient allocation of healthcare resources and better outcomes for those most vulnerable to melanoma,” Puig concluded.

 

Perform Population-Based Screening

In contrast, Mohr presented a defense of population-based skin cancer screening. Skin cancer is the most common cancer diagnosed in the United States and is prevalent worldwide, with more than 1.5 million new cases diagnosed globally in 2022.

Screening people and identifying the disease in its earliest stages is important, he said.

Mohr highlighted a recent study exploring biennial skin cancer screening in Germany and found that 4.2% of those screened had a skin cancer finding, but the number of interval melanomas was similar in both screened and unscreened populations.

However, a large retrospective cohort study from Germany involving about 1.4 million people showed a decrease in locoregional metastasis (from 13% to 4%), distant metastases (from 8% to 4%), and systemic treatments (from 21% to 11%) in screened vs unscreened people, as well as better overall survival rates in the screened population.

Mohr highlighted how Germany, in particular, is well-equipped for more broad-based, preventative screening.

Germany has had long-standing primary prevention programs, which have existed for about 24 years and involve extensive public awareness campaigns. Access to dermatologists is significantly better in Germany compared with the Netherlands, with an average waiting time for screening of around 6 weeks and only 1.2 weeks for suspicious lesions, compared with 14 weeks and 3.5 weeks, respectively, in the Netherlands. This access may make a broader screening strategy more feasible in a country like Germany.

However, Mohr did note that there are “no large, randomized trials to show us the value of skin cancer screening.”

 

A Role for Primary Care Physicians?

Although they disagreed about the utility of screening, both Puig and Mohr agreed on the important role primary care physicians play in improving early melanoma detection. “We cannot do it alone, and general practitioners are really fundamental,” Puig said.

Mohr said that continuous education for primary care physicians can dramatically improve their diagnostic skills. In Germany, an 8-hour training session significantly improved their ability to detect basal cell carcinoma and melanomas. However, he cautioned that this improved accuracy tended to wane within a year.

In Spain, Puig highlighted the successful implementation of teledermatology to support general practitioners. “We train them with dermoscopy, and we answer all teledermatology requests in 1 week, reducing in-person visits by 50%,” she explained. This approach allows general practitioners to assess potential skin cancer efficiently and streamline referrals.

Puig reported being on advisory boards for Almirall, Bristol Myers Squibb (BMS), ISDIN, La Roche-Posay, Leo Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi, and Sun Pharma. She conducts research and trials with AbbVie, Almirall, Amgen, BMS, Biofrontera, Canfield, Cantabria, Fotofinder, GSK, ISDIN, La Roche-Posay, Leo Pharma, MSD, MEDA, Novartis, Pfizer, Polychem, Sanofi, Roche, and Regeneron. She is involved with Athena Technology Solutions and Dermavision Solutions. Mohr reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

ATHENS, Greece — At the 11th World Congress of Melanoma and 21st EADO Congress 2025, experts presented divergent perspectives on the merits of population-wide skin cancer screening programs vs more targeted approaches. The debate highlighted concerns about healthcare resource allocation, overdiagnosis, and the true impact of mass skin cancer screening on mortality.

Arguing against widespread screening, particularly in low-to-medium incidence countries like Spain, was Susana Puig, MD, the head of Dermatology at Hospital Clínic de Barcelona, University of Barcelona, and a dermatologist at Barnaclínic+, Barcelona, Spain.

“It’s not efficient. We visit too many healthy individuals to detect melanoma,” she said. “We need to focus on treating patients, not checking healthy people without any risk.”

Championing for population-wide screening was Peter Mohr, MD, a dermatologist at the Clinic of Dermatology in Elbe Klinikum Buxtehude, Buxtehude, Germany, who noted a disproportionate focus on treatment rather than prevention. “The ultimate goal of screening,” he said, “is to prevent advanced disease and reduce melanoma-specific mortality.”

 

Avoid Population-Based Screening

Presenting data from Germany, Puig noted that population-based screening starting at any age requires examining more than 600 people and performing over 24 excisions to detect one melanoma. When setting screening to start at the age of 35 years, the number of people needed to screen to detect one melanoma decreased slightly to 559. 

These findings highlight that population-based screening will include many people who don’t need it and can increase the potential for overdiagnosis, she argued.

Studies and guidelines from the United States align with Puig’s concern about broad-based screening likely leading to overdiagnosis. “The incidence of melanoma has risen sixfold in the past 40 years in the United States, while mortality has remained largely flat, an epidemiological signature consistent with overdiagnosis,” according to Adewole Adamson, MD, an assistant professor of internal medicine, in the Division of Dermatology at Dell Medical School at The University of Texas at Austin, Texas, who published findings to this effect in 2022.

“We cannot saturate the system with healthy people,” Puig said. Instead, “we need to use strategies to identify high-risk patients.” She proposed being more selective about who to screen by identifying those at higher risk of developing melanoma.

Identifying risk factors, such as the presence of atypical nevi and a personal or family history of melanoma, can help hone who is screened, she explained. Patients with a personal history of melanoma, in particular, face a higher risk of developing subsequent melanomas. Data show that patients with two or more primary melanomas had almost three times the risk of developing a subsequent one than those with one prior melanoma — 25.7% vs 8.6%. Puig also pointed out the significant correlation between age and melanoma risk, with people over 70 years exhibiting a 93-fold higher probability of diagnosis than those younger than 30 years.

Citing the German data, she noted that screening people 20 years and older with one risk factor reduced the number needed to screen by more than threefold — from more than 600 to 178.

Puig suggested dedicated surveillance programs for high-risk individuals alongside opportunistic screening during routine medical encounters.

“This would lead to a more efficient allocation of healthcare resources and better outcomes for those most vulnerable to melanoma,” Puig concluded.

 

Perform Population-Based Screening

In contrast, Mohr presented a defense of population-based skin cancer screening. Skin cancer is the most common cancer diagnosed in the United States and is prevalent worldwide, with more than 1.5 million new cases diagnosed globally in 2022.

Screening people and identifying the disease in its earliest stages is important, he said.

Mohr highlighted a recent study exploring biennial skin cancer screening in Germany and found that 4.2% of those screened had a skin cancer finding, but the number of interval melanomas was similar in both screened and unscreened populations.

However, a large retrospective cohort study from Germany involving about 1.4 million people showed a decrease in locoregional metastasis (from 13% to 4%), distant metastases (from 8% to 4%), and systemic treatments (from 21% to 11%) in screened vs unscreened people, as well as better overall survival rates in the screened population.

Mohr highlighted how Germany, in particular, is well-equipped for more broad-based, preventative screening.

Germany has had long-standing primary prevention programs, which have existed for about 24 years and involve extensive public awareness campaigns. Access to dermatologists is significantly better in Germany compared with the Netherlands, with an average waiting time for screening of around 6 weeks and only 1.2 weeks for suspicious lesions, compared with 14 weeks and 3.5 weeks, respectively, in the Netherlands. This access may make a broader screening strategy more feasible in a country like Germany.

However, Mohr did note that there are “no large, randomized trials to show us the value of skin cancer screening.”

 

A Role for Primary Care Physicians?

Although they disagreed about the utility of screening, both Puig and Mohr agreed on the important role primary care physicians play in improving early melanoma detection. “We cannot do it alone, and general practitioners are really fundamental,” Puig said.

Mohr said that continuous education for primary care physicians can dramatically improve their diagnostic skills. In Germany, an 8-hour training session significantly improved their ability to detect basal cell carcinoma and melanomas. However, he cautioned that this improved accuracy tended to wane within a year.

In Spain, Puig highlighted the successful implementation of teledermatology to support general practitioners. “We train them with dermoscopy, and we answer all teledermatology requests in 1 week, reducing in-person visits by 50%,” she explained. This approach allows general practitioners to assess potential skin cancer efficiently and streamline referrals.

Puig reported being on advisory boards for Almirall, Bristol Myers Squibb (BMS), ISDIN, La Roche-Posay, Leo Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi, and Sun Pharma. She conducts research and trials with AbbVie, Almirall, Amgen, BMS, Biofrontera, Canfield, Cantabria, Fotofinder, GSK, ISDIN, La Roche-Posay, Leo Pharma, MSD, MEDA, Novartis, Pfizer, Polychem, Sanofi, Roche, and Regeneron. She is involved with Athena Technology Solutions and Dermavision Solutions. Mohr reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

ATHENS, Greece — At the 11th World Congress of Melanoma and 21st EADO Congress 2025, experts presented divergent perspectives on the merits of population-wide skin cancer screening programs vs more targeted approaches. The debate highlighted concerns about healthcare resource allocation, overdiagnosis, and the true impact of mass skin cancer screening on mortality.

Arguing against widespread screening, particularly in low-to-medium incidence countries like Spain, was Susana Puig, MD, the head of Dermatology at Hospital Clínic de Barcelona, University of Barcelona, and a dermatologist at Barnaclínic+, Barcelona, Spain.

“It’s not efficient. We visit too many healthy individuals to detect melanoma,” she said. “We need to focus on treating patients, not checking healthy people without any risk.”

Championing for population-wide screening was Peter Mohr, MD, a dermatologist at the Clinic of Dermatology in Elbe Klinikum Buxtehude, Buxtehude, Germany, who noted a disproportionate focus on treatment rather than prevention. “The ultimate goal of screening,” he said, “is to prevent advanced disease and reduce melanoma-specific mortality.”

 

Avoid Population-Based Screening

Presenting data from Germany, Puig noted that population-based screening starting at any age requires examining more than 600 people and performing over 24 excisions to detect one melanoma. When setting screening to start at the age of 35 years, the number of people needed to screen to detect one melanoma decreased slightly to 559. 

These findings highlight that population-based screening will include many people who don’t need it and can increase the potential for overdiagnosis, she argued.

Studies and guidelines from the United States align with Puig’s concern about broad-based screening likely leading to overdiagnosis. “The incidence of melanoma has risen sixfold in the past 40 years in the United States, while mortality has remained largely flat, an epidemiological signature consistent with overdiagnosis,” according to Adewole Adamson, MD, an assistant professor of internal medicine, in the Division of Dermatology at Dell Medical School at The University of Texas at Austin, Texas, who published findings to this effect in 2022.

“We cannot saturate the system with healthy people,” Puig said. Instead, “we need to use strategies to identify high-risk patients.” She proposed being more selective about who to screen by identifying those at higher risk of developing melanoma.

Identifying risk factors, such as the presence of atypical nevi and a personal or family history of melanoma, can help hone who is screened, she explained. Patients with a personal history of melanoma, in particular, face a higher risk of developing subsequent melanomas. Data show that patients with two or more primary melanomas had almost three times the risk of developing a subsequent one than those with one prior melanoma — 25.7% vs 8.6%. Puig also pointed out the significant correlation between age and melanoma risk, with people over 70 years exhibiting a 93-fold higher probability of diagnosis than those younger than 30 years.

Citing the German data, she noted that screening people 20 years and older with one risk factor reduced the number needed to screen by more than threefold — from more than 600 to 178.

Puig suggested dedicated surveillance programs for high-risk individuals alongside opportunistic screening during routine medical encounters.

“This would lead to a more efficient allocation of healthcare resources and better outcomes for those most vulnerable to melanoma,” Puig concluded.

 

Perform Population-Based Screening

In contrast, Mohr presented a defense of population-based skin cancer screening. Skin cancer is the most common cancer diagnosed in the United States and is prevalent worldwide, with more than 1.5 million new cases diagnosed globally in 2022.

Screening people and identifying the disease in its earliest stages is important, he said.

Mohr highlighted a recent study exploring biennial skin cancer screening in Germany and found that 4.2% of those screened had a skin cancer finding, but the number of interval melanomas was similar in both screened and unscreened populations.

However, a large retrospective cohort study from Germany involving about 1.4 million people showed a decrease in locoregional metastasis (from 13% to 4%), distant metastases (from 8% to 4%), and systemic treatments (from 21% to 11%) in screened vs unscreened people, as well as better overall survival rates in the screened population.

Mohr highlighted how Germany, in particular, is well-equipped for more broad-based, preventative screening.

Germany has had long-standing primary prevention programs, which have existed for about 24 years and involve extensive public awareness campaigns. Access to dermatologists is significantly better in Germany compared with the Netherlands, with an average waiting time for screening of around 6 weeks and only 1.2 weeks for suspicious lesions, compared with 14 weeks and 3.5 weeks, respectively, in the Netherlands. This access may make a broader screening strategy more feasible in a country like Germany.

However, Mohr did note that there are “no large, randomized trials to show us the value of skin cancer screening.”

 

A Role for Primary Care Physicians?

Although they disagreed about the utility of screening, both Puig and Mohr agreed on the important role primary care physicians play in improving early melanoma detection. “We cannot do it alone, and general practitioners are really fundamental,” Puig said.

Mohr said that continuous education for primary care physicians can dramatically improve their diagnostic skills. In Germany, an 8-hour training session significantly improved their ability to detect basal cell carcinoma and melanomas. However, he cautioned that this improved accuracy tended to wane within a year.

In Spain, Puig highlighted the successful implementation of teledermatology to support general practitioners. “We train them with dermoscopy, and we answer all teledermatology requests in 1 week, reducing in-person visits by 50%,” she explained. This approach allows general practitioners to assess potential skin cancer efficiently and streamline referrals.

Puig reported being on advisory boards for Almirall, Bristol Myers Squibb (BMS), ISDIN, La Roche-Posay, Leo Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi, and Sun Pharma. She conducts research and trials with AbbVie, Almirall, Amgen, BMS, Biofrontera, Canfield, Cantabria, Fotofinder, GSK, ISDIN, La Roche-Posay, Leo Pharma, MSD, MEDA, Novartis, Pfizer, Polychem, Sanofi, Roche, and Regeneron. She is involved with Athena Technology Solutions and Dermavision Solutions. Mohr reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

About 15,000 veterans are annually diagnosed with prostate cancer. Fortunately, those veterans enrolled in the US Department of Veterans Affairs (VA) Million Veteran Program (MVP) provide researchers with a deep pool of genetic data that can help identify causes, aid diagnosis, and guide targeted treatments.

More than 1,000,000 veterans have enrolled in MVP and donated their anonymized DNA to foster research. It is also one of the most genetically diverse health-related databases: 20% of participants identify as Black, 8% as Hispanic, 2% as Asian American, and 1% as Native American. 

Ethnically and racially diverse data are particularly important for advancing the treatment of underserved groups. In a 2020 review, researchers found a number of areas where Black veterans differed from White veterans, including prostate-specific antigen (PSA) levels, incidence (almost 60% higher), clinical course, and mortality rate (2 to 3 times greater). To facilitate research, the MVP developed the “DNA chip,” a custom-designed tool that tests for > 750,000 genetic variants, including > 300,000 that are more common in minority populations.

“The whole thing about understanding genetics and diversity is like a circular feedback loop,” Director of MVP Dr. Sumitra Muralidhar said in a VA news article. “The more people you have represented from different racial and ethnic backgrounds, the more we’ll be able to discover genetic variants that contribute to their health. The more we discover, the more we can help that group. It’s a complete circular feedback loop.”

In addition to veterans’ blood samples and 600,000-plus baseline surveys on lifestyle, military service, and health, the MVP has collected upwards of 825,000 germline DNA samples, which have helped inform research into prostate cancer, the most commonly diagnosed solid tumor among veterans. By mining these data, researchers have built more evidence of how genes add to risk and disease progression.

In one study preprint that has not been peer reviewed, VA researchers investigated the significance of high polygenic hazard scores. The scores are strongly associated with age at diagnosis of any prostate cancer, as well as lifetime risk of metastatic and fatal prostate cancer. However, because they’re associated with any prostate cancer, the researchers say, there is concern that screening men with high polygenic risk could increase overdiagnosis of indolent cancers.

The researchers analyzed genetic and phenotypic data from 69,901 men in the MVP who have been diagnosed with prostate cancer (6413 metastatic). They found their hypothesis to be correct: Among men eventually diagnosed with prostate cancer, those with higher polygenic risk were more likely to develop metastatic disease. 

Genetic risk scores like PHS601, a 601-variant polygenic score, can be performed on a saliva sample at any time during a person’s life, the researchers note. Thus, the scores provide the earliest information about age-specific risk of developing aggressive prostate cancer. These scores might be useful, they suggest, to support clinical decisions not only about whom to screen but also at what age.

Another study led by Stanford University researchers and published in Nature Genetics aimed to make screening more targeted, in this case prostate specific antigen screening. Estimates about PSA heritability vary from 40% to 45%, with genome-wide evaluations putting it at 25% to 30%, suggesting that incorporating genetic factors could improve screening. 

This study involved 296,754 men (211,342 with European ancestry, 58,236 with African ancestry, 23,546 with Hispanic/Latino ancestry, and 3630 with Asian ancestry; 96.5% of participants were from MVP)—a sample size more than triple that in previous work. 

The researchers detected 448 genome-wide significant variants, including 295 that were novel (to the best of their knowledge). The variance explained by genome-wide polygenic risk scores ranged from 11.6% to 16.6% for European ancestry, 5.5% to 9.5% for African ancestry, 13.5% to 18.2% for Hispanic/Latino ancestry, and 8.6% to 15.3% for Asian ancestry, and decreased with increasing age. Midlife genetically adjusted PSA levels were more strongly associated with overall and aggressive prostate cancer than unadjusted PSA levels.

The researchers say their study highlights how including higher proportions of participants from underrepresented populations can improve genetic prediction of PSA levels, offering the potential to personalize prostate cancer screening. Adjusting PSA for individuals’ predispositions in the absence of prostate cancer could improve the specificity (to reduce overdiagnosis) and sensitivity (to prevent more deaths) of screening.

Their findings, the researchers suggest, also explain additional variation in PSA, especially among men of African heritage, who experience the highest prostate cancer morbidity and mortality. They note that this work “moved us closer to leveraging genetic information to personalize PSA and substantially improved our understanding of PSA across diverse ancestries.”

A third study from a team at the VA Tennessee Valley Healthcare System also investigated the risk of inheriting a predisposition to prostate cancer. These researchers explored pathogenic variants using both genome-wide single-allele and identity-by-descent analytic approaches. They then tested their candidate variants for replication across independent biobanks, including MVP.

The researchers discovered the gene WNT9B E152K more than doubled the risk of familial prostate cancer. Meta-analysis, collectively encompassing 500,000 patients, confirmed the genome-wide significance. The researchers say WNT9B shares an “unexpected commonality” with the previously established prostate cancer risk genes HOXB13 and HNF1B: Each are required for embryonic prostate development. Based on that finding, the researchers also evaluated 2 additional genes, KMT2D and DHCR7, which are known to cause Mendelian genitourinary developmental defects. They, too, were nominally associated with prostate cancer under meta-analyses.

Tens of thousands of participants in MVP have had prostate cancer. The genetic research they participate in advances detection, prediction, and treatment for themselves and others, and science in general. The research is not only about finding causes, but what to do if the cancer develops. An “acting on MVP prostate cancer findings” study at VA Puget Sound Health Care System is testing how communicating with veterans about MVP prostate cancer results will affect their care. Those with prostate cancer will be screened to determine genetic contributions to their cancers. Those found to have a gene-based cancer diagnosis will be offered genetic counseling. Their immediate family will also be offered screening to test for inherited prostate cancer risk.

In 2016, the VA partnered with the Prostate Cancer Foundation to establish the Precision Oncology Program for Cancer of the Prostate (POPCaP). In collaboration with MVP and the Genomic Medicine Service, the program uses genetic information to individualize treatments for veterans with advanced prostate cancer. 

US Army Veteran James Perry is one of the beneficiaries of the program. First diagnosed with prostate cancer in 2001, he was initially treated with radiation therapy, but the cancer recurred and spread to his lung. The John J. Cochran Veterans Hospital in St. Louis sent a sample of Perry's lung tumor to the laboratory for genetic testing, where they discovered he had a BRCA1 gene mutation.

His oncologist, Dr. Martin Schoen, recommended Perry enroll in AMPLITUDE, a clinical trial testing the effectiveness of poly-ADP ribose polymerase inhibitors, a new class of drugs to treat hormone-sensitive prostate cancer. One year later, Perry’s lung tumor could barely be seen on computed tomography, and his PSA levels were undetectable.

"I would highly recommend enrolling in a trial," Perry told VA Research Currents. “If a veteran has that opportunity, I would encourage it—anything that is going to give you a few more days is worth it.” In the interview, Perry said he enjoyed being part of the trial because he knows he is getting the most advanced care possible and is proud to help others like himself.

"We are honored to support VA's work to improve the lives of veterans who are living with advanced prostate cancer," Vice President and National Director of the PCF Veterans Health Initiative Rebecca Levine said. "Clinical trials play a vital role in bringing new treatments to patients who need them most. Mr. Perry's experience illustrates VA's commitment to provide state-of-the-art cancer care to all veterans who need it."

About 15,000 veterans are annually diagnosed with prostate cancer. Fortunately, those veterans enrolled in the US Department of Veterans Affairs (VA) Million Veteran Program (MVP) provide researchers with a deep pool of genetic data that can help identify causes, aid diagnosis, and guide targeted treatments.

More than 1,000,000 veterans have enrolled in MVP and donated their anonymized DNA to foster research. It is also one of the most genetically diverse health-related databases: 20% of participants identify as Black, 8% as Hispanic, 2% as Asian American, and 1% as Native American. 

Ethnically and racially diverse data are particularly important for advancing the treatment of underserved groups. In a 2020 review, researchers found a number of areas where Black veterans differed from White veterans, including prostate-specific antigen (PSA) levels, incidence (almost 60% higher), clinical course, and mortality rate (2 to 3 times greater). To facilitate research, the MVP developed the “DNA chip,” a custom-designed tool that tests for > 750,000 genetic variants, including > 300,000 that are more common in minority populations.

“The whole thing about understanding genetics and diversity is like a circular feedback loop,” Director of MVP Dr. Sumitra Muralidhar said in a VA news article. “The more people you have represented from different racial and ethnic backgrounds, the more we’ll be able to discover genetic variants that contribute to their health. The more we discover, the more we can help that group. It’s a complete circular feedback loop.”

In addition to veterans’ blood samples and 600,000-plus baseline surveys on lifestyle, military service, and health, the MVP has collected upwards of 825,000 germline DNA samples, which have helped inform research into prostate cancer, the most commonly diagnosed solid tumor among veterans. By mining these data, researchers have built more evidence of how genes add to risk and disease progression.

In one study preprint that has not been peer reviewed, VA researchers investigated the significance of high polygenic hazard scores. The scores are strongly associated with age at diagnosis of any prostate cancer, as well as lifetime risk of metastatic and fatal prostate cancer. However, because they’re associated with any prostate cancer, the researchers say, there is concern that screening men with high polygenic risk could increase overdiagnosis of indolent cancers.

The researchers analyzed genetic and phenotypic data from 69,901 men in the MVP who have been diagnosed with prostate cancer (6413 metastatic). They found their hypothesis to be correct: Among men eventually diagnosed with prostate cancer, those with higher polygenic risk were more likely to develop metastatic disease. 

Genetic risk scores like PHS601, a 601-variant polygenic score, can be performed on a saliva sample at any time during a person’s life, the researchers note. Thus, the scores provide the earliest information about age-specific risk of developing aggressive prostate cancer. These scores might be useful, they suggest, to support clinical decisions not only about whom to screen but also at what age.

Another study led by Stanford University researchers and published in Nature Genetics aimed to make screening more targeted, in this case prostate specific antigen screening. Estimates about PSA heritability vary from 40% to 45%, with genome-wide evaluations putting it at 25% to 30%, suggesting that incorporating genetic factors could improve screening. 

This study involved 296,754 men (211,342 with European ancestry, 58,236 with African ancestry, 23,546 with Hispanic/Latino ancestry, and 3630 with Asian ancestry; 96.5% of participants were from MVP)—a sample size more than triple that in previous work. 

The researchers detected 448 genome-wide significant variants, including 295 that were novel (to the best of their knowledge). The variance explained by genome-wide polygenic risk scores ranged from 11.6% to 16.6% for European ancestry, 5.5% to 9.5% for African ancestry, 13.5% to 18.2% for Hispanic/Latino ancestry, and 8.6% to 15.3% for Asian ancestry, and decreased with increasing age. Midlife genetically adjusted PSA levels were more strongly associated with overall and aggressive prostate cancer than unadjusted PSA levels.

The researchers say their study highlights how including higher proportions of participants from underrepresented populations can improve genetic prediction of PSA levels, offering the potential to personalize prostate cancer screening. Adjusting PSA for individuals’ predispositions in the absence of prostate cancer could improve the specificity (to reduce overdiagnosis) and sensitivity (to prevent more deaths) of screening.

Their findings, the researchers suggest, also explain additional variation in PSA, especially among men of African heritage, who experience the highest prostate cancer morbidity and mortality. They note that this work “moved us closer to leveraging genetic information to personalize PSA and substantially improved our understanding of PSA across diverse ancestries.”

A third study from a team at the VA Tennessee Valley Healthcare System also investigated the risk of inheriting a predisposition to prostate cancer. These researchers explored pathogenic variants using both genome-wide single-allele and identity-by-descent analytic approaches. They then tested their candidate variants for replication across independent biobanks, including MVP.

The researchers discovered the gene WNT9B E152K more than doubled the risk of familial prostate cancer. Meta-analysis, collectively encompassing 500,000 patients, confirmed the genome-wide significance. The researchers say WNT9B shares an “unexpected commonality” with the previously established prostate cancer risk genes HOXB13 and HNF1B: Each are required for embryonic prostate development. Based on that finding, the researchers also evaluated 2 additional genes, KMT2D and DHCR7, which are known to cause Mendelian genitourinary developmental defects. They, too, were nominally associated with prostate cancer under meta-analyses.

Tens of thousands of participants in MVP have had prostate cancer. The genetic research they participate in advances detection, prediction, and treatment for themselves and others, and science in general. The research is not only about finding causes, but what to do if the cancer develops. An “acting on MVP prostate cancer findings” study at VA Puget Sound Health Care System is testing how communicating with veterans about MVP prostate cancer results will affect their care. Those with prostate cancer will be screened to determine genetic contributions to their cancers. Those found to have a gene-based cancer diagnosis will be offered genetic counseling. Their immediate family will also be offered screening to test for inherited prostate cancer risk.

In 2016, the VA partnered with the Prostate Cancer Foundation to establish the Precision Oncology Program for Cancer of the Prostate (POPCaP). In collaboration with MVP and the Genomic Medicine Service, the program uses genetic information to individualize treatments for veterans with advanced prostate cancer. 

US Army Veteran James Perry is one of the beneficiaries of the program. First diagnosed with prostate cancer in 2001, he was initially treated with radiation therapy, but the cancer recurred and spread to his lung. The John J. Cochran Veterans Hospital in St. Louis sent a sample of Perry's lung tumor to the laboratory for genetic testing, where they discovered he had a BRCA1 gene mutation.

His oncologist, Dr. Martin Schoen, recommended Perry enroll in AMPLITUDE, a clinical trial testing the effectiveness of poly-ADP ribose polymerase inhibitors, a new class of drugs to treat hormone-sensitive prostate cancer. One year later, Perry’s lung tumor could barely be seen on computed tomography, and his PSA levels were undetectable.

"I would highly recommend enrolling in a trial," Perry told VA Research Currents. “If a veteran has that opportunity, I would encourage it—anything that is going to give you a few more days is worth it.” In the interview, Perry said he enjoyed being part of the trial because he knows he is getting the most advanced care possible and is proud to help others like himself.

"We are honored to support VA's work to improve the lives of veterans who are living with advanced prostate cancer," Vice President and National Director of the PCF Veterans Health Initiative Rebecca Levine said. "Clinical trials play a vital role in bringing new treatments to patients who need them most. Mr. Perry's experience illustrates VA's commitment to provide state-of-the-art cancer care to all veterans who need it."

About 15,000 veterans are annually diagnosed with prostate cancer. Fortunately, those veterans enrolled in the US Department of Veterans Affairs (VA) Million Veteran Program (MVP) provide researchers with a deep pool of genetic data that can help identify causes, aid diagnosis, and guide targeted treatments.

More than 1,000,000 veterans have enrolled in MVP and donated their anonymized DNA to foster research. It is also one of the most genetically diverse health-related databases: 20% of participants identify as Black, 8% as Hispanic, 2% as Asian American, and 1% as Native American. 

Ethnically and racially diverse data are particularly important for advancing the treatment of underserved groups. In a 2020 review, researchers found a number of areas where Black veterans differed from White veterans, including prostate-specific antigen (PSA) levels, incidence (almost 60% higher), clinical course, and mortality rate (2 to 3 times greater). To facilitate research, the MVP developed the “DNA chip,” a custom-designed tool that tests for > 750,000 genetic variants, including > 300,000 that are more common in minority populations.

“The whole thing about understanding genetics and diversity is like a circular feedback loop,” Director of MVP Dr. Sumitra Muralidhar said in a VA news article. “The more people you have represented from different racial and ethnic backgrounds, the more we’ll be able to discover genetic variants that contribute to their health. The more we discover, the more we can help that group. It’s a complete circular feedback loop.”

In addition to veterans’ blood samples and 600,000-plus baseline surveys on lifestyle, military service, and health, the MVP has collected upwards of 825,000 germline DNA samples, which have helped inform research into prostate cancer, the most commonly diagnosed solid tumor among veterans. By mining these data, researchers have built more evidence of how genes add to risk and disease progression.

In one study preprint that has not been peer reviewed, VA researchers investigated the significance of high polygenic hazard scores. The scores are strongly associated with age at diagnosis of any prostate cancer, as well as lifetime risk of metastatic and fatal prostate cancer. However, because they’re associated with any prostate cancer, the researchers say, there is concern that screening men with high polygenic risk could increase overdiagnosis of indolent cancers.

The researchers analyzed genetic and phenotypic data from 69,901 men in the MVP who have been diagnosed with prostate cancer (6413 metastatic). They found their hypothesis to be correct: Among men eventually diagnosed with prostate cancer, those with higher polygenic risk were more likely to develop metastatic disease. 

Genetic risk scores like PHS601, a 601-variant polygenic score, can be performed on a saliva sample at any time during a person’s life, the researchers note. Thus, the scores provide the earliest information about age-specific risk of developing aggressive prostate cancer. These scores might be useful, they suggest, to support clinical decisions not only about whom to screen but also at what age.

Another study led by Stanford University researchers and published in Nature Genetics aimed to make screening more targeted, in this case prostate specific antigen screening. Estimates about PSA heritability vary from 40% to 45%, with genome-wide evaluations putting it at 25% to 30%, suggesting that incorporating genetic factors could improve screening. 

This study involved 296,754 men (211,342 with European ancestry, 58,236 with African ancestry, 23,546 with Hispanic/Latino ancestry, and 3630 with Asian ancestry; 96.5% of participants were from MVP)—a sample size more than triple that in previous work. 

The researchers detected 448 genome-wide significant variants, including 295 that were novel (to the best of their knowledge). The variance explained by genome-wide polygenic risk scores ranged from 11.6% to 16.6% for European ancestry, 5.5% to 9.5% for African ancestry, 13.5% to 18.2% for Hispanic/Latino ancestry, and 8.6% to 15.3% for Asian ancestry, and decreased with increasing age. Midlife genetically adjusted PSA levels were more strongly associated with overall and aggressive prostate cancer than unadjusted PSA levels.

The researchers say their study highlights how including higher proportions of participants from underrepresented populations can improve genetic prediction of PSA levels, offering the potential to personalize prostate cancer screening. Adjusting PSA for individuals’ predispositions in the absence of prostate cancer could improve the specificity (to reduce overdiagnosis) and sensitivity (to prevent more deaths) of screening.

Their findings, the researchers suggest, also explain additional variation in PSA, especially among men of African heritage, who experience the highest prostate cancer morbidity and mortality. They note that this work “moved us closer to leveraging genetic information to personalize PSA and substantially improved our understanding of PSA across diverse ancestries.”

A third study from a team at the VA Tennessee Valley Healthcare System also investigated the risk of inheriting a predisposition to prostate cancer. These researchers explored pathogenic variants using both genome-wide single-allele and identity-by-descent analytic approaches. They then tested their candidate variants for replication across independent biobanks, including MVP.

The researchers discovered the gene WNT9B E152K more than doubled the risk of familial prostate cancer. Meta-analysis, collectively encompassing 500,000 patients, confirmed the genome-wide significance. The researchers say WNT9B shares an “unexpected commonality” with the previously established prostate cancer risk genes HOXB13 and HNF1B: Each are required for embryonic prostate development. Based on that finding, the researchers also evaluated 2 additional genes, KMT2D and DHCR7, which are known to cause Mendelian genitourinary developmental defects. They, too, were nominally associated with prostate cancer under meta-analyses.

Tens of thousands of participants in MVP have had prostate cancer. The genetic research they participate in advances detection, prediction, and treatment for themselves and others, and science in general. The research is not only about finding causes, but what to do if the cancer develops. An “acting on MVP prostate cancer findings” study at VA Puget Sound Health Care System is testing how communicating with veterans about MVP prostate cancer results will affect their care. Those with prostate cancer will be screened to determine genetic contributions to their cancers. Those found to have a gene-based cancer diagnosis will be offered genetic counseling. Their immediate family will also be offered screening to test for inherited prostate cancer risk.

In 2016, the VA partnered with the Prostate Cancer Foundation to establish the Precision Oncology Program for Cancer of the Prostate (POPCaP). In collaboration with MVP and the Genomic Medicine Service, the program uses genetic information to individualize treatments for veterans with advanced prostate cancer. 

US Army Veteran James Perry is one of the beneficiaries of the program. First diagnosed with prostate cancer in 2001, he was initially treated with radiation therapy, but the cancer recurred and spread to his lung. The John J. Cochran Veterans Hospital in St. Louis sent a sample of Perry's lung tumor to the laboratory for genetic testing, where they discovered he had a BRCA1 gene mutation.

His oncologist, Dr. Martin Schoen, recommended Perry enroll in AMPLITUDE, a clinical trial testing the effectiveness of poly-ADP ribose polymerase inhibitors, a new class of drugs to treat hormone-sensitive prostate cancer. One year later, Perry’s lung tumor could barely be seen on computed tomography, and his PSA levels were undetectable.

"I would highly recommend enrolling in a trial," Perry told VA Research Currents. “If a veteran has that opportunity, I would encourage it—anything that is going to give you a few more days is worth it.” In the interview, Perry said he enjoyed being part of the trial because he knows he is getting the most advanced care possible and is proud to help others like himself.

"We are honored to support VA's work to improve the lives of veterans who are living with advanced prostate cancer," Vice President and National Director of the PCF Veterans Health Initiative Rebecca Levine said. "Clinical trials play a vital role in bringing new treatments to patients who need them most. Mr. Perry's experience illustrates VA's commitment to provide state-of-the-art cancer care to all veterans who need it."

Advocacy for veterans with cancer has always been a central part of the Association for VA Hematology/Oncology (AVAHO) mission, but that advocacy has now taken on a new focus: the fate of US Department of Veterans Affairs (VA) employees. The advocacy portal provides templated letters, a search function to find local Senators and Members of Congress, a search function to find regional media outlets, updates on voting and elections, and information on key legislation relevant to VA health care.

To ensure its members’ concerns are heard, AVAHO is encouraging members, in their own time and as private citizens, to contact their local representatives to inform them about the real impact of recent policy changes on VA employees and the veterans they care for. Members can select any of 4 letters focused on reductions in force, cancellation of VA contracts, the return to office mandate, and the National Institutes of Health’s proposed cap on indirect cost for research grants: “AVAHO recognizes the power of the individual voice. Our members have an important role in shaping the health care services provided to veterans across our nation.”

"The contracts that have been canceled and continue to be canceled included critical services related to cancer care," AVAHO notes on its Advocacy page. "We know these impacted contracts have hindered the VA’s ability to implement research protocols, process and report pharmacogenomic results, manage Electronic Health Record Modernization workgroups responsible for safety improvements, and execute new oncology services through the Close to Me initiative, just to name a few."

Advocacy for veterans with cancer has always been a central part of the Association for VA Hematology/Oncology (AVAHO) mission, but that advocacy has now taken on a new focus: the fate of US Department of Veterans Affairs (VA) employees. The advocacy portal provides templated letters, a search function to find local Senators and Members of Congress, a search function to find regional media outlets, updates on voting and elections, and information on key legislation relevant to VA health care.

To ensure its members’ concerns are heard, AVAHO is encouraging members, in their own time and as private citizens, to contact their local representatives to inform them about the real impact of recent policy changes on VA employees and the veterans they care for. Members can select any of 4 letters focused on reductions in force, cancellation of VA contracts, the return to office mandate, and the National Institutes of Health’s proposed cap on indirect cost for research grants: “AVAHO recognizes the power of the individual voice. Our members have an important role in shaping the health care services provided to veterans across our nation.”

"The contracts that have been canceled and continue to be canceled included critical services related to cancer care," AVAHO notes on its Advocacy page. "We know these impacted contracts have hindered the VA’s ability to implement research protocols, process and report pharmacogenomic results, manage Electronic Health Record Modernization workgroups responsible for safety improvements, and execute new oncology services through the Close to Me initiative, just to name a few."

Advocacy for veterans with cancer has always been a central part of the Association for VA Hematology/Oncology (AVAHO) mission, but that advocacy has now taken on a new focus: the fate of US Department of Veterans Affairs (VA) employees. The advocacy portal provides templated letters, a search function to find local Senators and Members of Congress, a search function to find regional media outlets, updates on voting and elections, and information on key legislation relevant to VA health care.

To ensure its members’ concerns are heard, AVAHO is encouraging members, in their own time and as private citizens, to contact their local representatives to inform them about the real impact of recent policy changes on VA employees and the veterans they care for. Members can select any of 4 letters focused on reductions in force, cancellation of VA contracts, the return to office mandate, and the National Institutes of Health’s proposed cap on indirect cost for research grants: “AVAHO recognizes the power of the individual voice. Our members have an important role in shaping the health care services provided to veterans across our nation.”

"The contracts that have been canceled and continue to be canceled included critical services related to cancer care," AVAHO notes on its Advocacy page. "We know these impacted contracts have hindered the VA’s ability to implement research protocols, process and report pharmacogenomic results, manage Electronic Health Record Modernization workgroups responsible for safety improvements, and execute new oncology services through the Close to Me initiative, just to name a few."

The US Department of Veterans Affairs (VA) is "lowering the burden of proof" for thousands, making acute and chronic leukemias, multiple myelomas, myelodysplastic syndromes, myelofibrosis, urinary bladder, ureter, and related genitourinary cancers presumptive for service connection.

The Jan. 8 decision included Gulf War veterans, those who served in Somalia or the Southwest Asia theater of operations during the Persian Gulf War on or after Aug. 2, 1990; and post-9/11 veterans, those who served in Afghanistan, Iraq, Djibouti, Egypt, Jordan, Lebanon, Syria, Yemen, or Uzbekistan and the airspace above these locations during the Gulf War on or after Sept. 11, 2001. It also includes veterans who served at the Karshi-Khanabad (K2) base in Uzbekistan after Sept. 11, 2001.

Veterans no longer must prove their service caused their condition to receive benefits. This landmark decision allows them access to free health care for that condition.

According to the VA, these steps are also part of a comprehensive effort to ensure that K2 veterans—and their survivors—receive the care and benefits they deserve. K2 veterans have higher claim and approval rates than any other cohort of veterans: 13,002 are enrolled in VA health care, and the average K2 veteran is service connected for 14.6 conditions.

The 2022 PACT Act was the largest expansion of veteran benefits in generations. The VA then made millions of veterans eligible for health care and benefits years earlier than called for by the law. It also launched the largest outreach campaign in the history of the VA to encourage veterans to apply. 

Nearly 890,000 veterans have signed up for VA health care since the bill was signed into law, a nearly 40% increase over the previous equivalent period, and veterans have submitted > 4.8 million applications for VA benefits (a 42% increase over the previous equivalent period and an all-time record). The VA has delivered > $600 billion in earned benefits directly to veterans, their families, and survivors during that time.

The VA encourages all eligible veterans—including those with previously denied claims—to apply for benefits. To apply for benefits, veterans and survivors may visit VA.gov or call 1-800-MYVA411. 

The US Department of Veterans Affairs (VA) is "lowering the burden of proof" for thousands, making acute and chronic leukemias, multiple myelomas, myelodysplastic syndromes, myelofibrosis, urinary bladder, ureter, and related genitourinary cancers presumptive for service connection.

The Jan. 8 decision included Gulf War veterans, those who served in Somalia or the Southwest Asia theater of operations during the Persian Gulf War on or after Aug. 2, 1990; and post-9/11 veterans, those who served in Afghanistan, Iraq, Djibouti, Egypt, Jordan, Lebanon, Syria, Yemen, or Uzbekistan and the airspace above these locations during the Gulf War on or after Sept. 11, 2001. It also includes veterans who served at the Karshi-Khanabad (K2) base in Uzbekistan after Sept. 11, 2001.

Veterans no longer must prove their service caused their condition to receive benefits. This landmark decision allows them access to free health care for that condition.

According to the VA, these steps are also part of a comprehensive effort to ensure that K2 veterans—and their survivors—receive the care and benefits they deserve. K2 veterans have higher claim and approval rates than any other cohort of veterans: 13,002 are enrolled in VA health care, and the average K2 veteran is service connected for 14.6 conditions.

The 2022 PACT Act was the largest expansion of veteran benefits in generations. The VA then made millions of veterans eligible for health care and benefits years earlier than called for by the law. It also launched the largest outreach campaign in the history of the VA to encourage veterans to apply. 

Nearly 890,000 veterans have signed up for VA health care since the bill was signed into law, a nearly 40% increase over the previous equivalent period, and veterans have submitted > 4.8 million applications for VA benefits (a 42% increase over the previous equivalent period and an all-time record). The VA has delivered > $600 billion in earned benefits directly to veterans, their families, and survivors during that time.

The VA encourages all eligible veterans—including those with previously denied claims—to apply for benefits. To apply for benefits, veterans and survivors may visit VA.gov or call 1-800-MYVA411. 

The US Department of Veterans Affairs (VA) is "lowering the burden of proof" for thousands, making acute and chronic leukemias, multiple myelomas, myelodysplastic syndromes, myelofibrosis, urinary bladder, ureter, and related genitourinary cancers presumptive for service connection.

The Jan. 8 decision included Gulf War veterans, those who served in Somalia or the Southwest Asia theater of operations during the Persian Gulf War on or after Aug. 2, 1990; and post-9/11 veterans, those who served in Afghanistan, Iraq, Djibouti, Egypt, Jordan, Lebanon, Syria, Yemen, or Uzbekistan and the airspace above these locations during the Gulf War on or after Sept. 11, 2001. It also includes veterans who served at the Karshi-Khanabad (K2) base in Uzbekistan after Sept. 11, 2001.

Veterans no longer must prove their service caused their condition to receive benefits. This landmark decision allows them access to free health care for that condition.

According to the VA, these steps are also part of a comprehensive effort to ensure that K2 veterans—and their survivors—receive the care and benefits they deserve. K2 veterans have higher claim and approval rates than any other cohort of veterans: 13,002 are enrolled in VA health care, and the average K2 veteran is service connected for 14.6 conditions.

The 2022 PACT Act was the largest expansion of veteran benefits in generations. The VA then made millions of veterans eligible for health care and benefits years earlier than called for by the law. It also launched the largest outreach campaign in the history of the VA to encourage veterans to apply. 

Nearly 890,000 veterans have signed up for VA health care since the bill was signed into law, a nearly 40% increase over the previous equivalent period, and veterans have submitted > 4.8 million applications for VA benefits (a 42% increase over the previous equivalent period and an all-time record). The VA has delivered > $600 billion in earned benefits directly to veterans, their families, and survivors during that time.

The VA encourages all eligible veterans—including those with previously denied claims—to apply for benefits. To apply for benefits, veterans and survivors may visit VA.gov or call 1-800-MYVA411. 

Studies in chronic lymphocytic leukemia (CLL) treatment in frontline and relapsed/refractory settings, presented at the American Society of Hematology (ASH) 2024 Annual Meeting and Exposition, are discussed by Dr Muhammad Jawad Javed of Albany Medical Center and Stratton VA.

Dr Javed begins with the AMPLIFY trial, the first phase 3 study to evaluate a fixed-duration regimen of venetoclax with a second-generation BTK inhibitor. AMPLIFY compares three frontline treatment arms: (1) acalabrutinib plus venetoclax (AV); (2) acalabrutinib plus venetoclax plus obinutuzumab (AVO); and (3) chemoimmunotherapy. Results showed improved progression-free survival (PFS) and overall survival (OS) in the AV and AVO groups.

The next frontline treatment study he discusses examined use of minimal residual disease testing to guide treatment duration of a venetoclax/obinutuzumab regimen. The study found that shorter treatment duration led to PFS comparable to that achieved by longer duration.

Dr Javed next turns to a retrospective analysis of the impact of first-line treatment choice on the risk for other malignancies, using data from the Department of US Veteran Affairs Central Cancer Registry.

In relapsed/refractory disease, Dr Javed highlights the BRUIN CLL-321 study of the noncovalent reversible BTK inhibitor pirtobrutinib. Pirtobrutinib improved PFS compared with chemoimmunotherapy.

Last, he discusses epcoritamab, which yielded encouraging complete response data in heavily pretreated CLL patients.

--

Muhammad Jawad Javed, MBBS, Albany Medical Center/Stratton VA Albany, Department of Medicine; Resident Physician, Department of Internal Medicine, Albany Medical Center, Albany, New York

Muhammad Jawad Javed, MBBS, has disclosed no relevant financial relationships

Studies in chronic lymphocytic leukemia (CLL) treatment in frontline and relapsed/refractory settings, presented at the American Society of Hematology (ASH) 2024 Annual Meeting and Exposition, are discussed by Dr Muhammad Jawad Javed of Albany Medical Center and Stratton VA.

Dr Javed begins with the AMPLIFY trial, the first phase 3 study to evaluate a fixed-duration regimen of venetoclax with a second-generation BTK inhibitor. AMPLIFY compares three frontline treatment arms: (1) acalabrutinib plus venetoclax (AV); (2) acalabrutinib plus venetoclax plus obinutuzumab (AVO); and (3) chemoimmunotherapy. Results showed improved progression-free survival (PFS) and overall survival (OS) in the AV and AVO groups.

The next frontline treatment study he discusses examined use of minimal residual disease testing to guide treatment duration of a venetoclax/obinutuzumab regimen. The study found that shorter treatment duration led to PFS comparable to that achieved by longer duration.

Dr Javed next turns to a retrospective analysis of the impact of first-line treatment choice on the risk for other malignancies, using data from the Department of US Veteran Affairs Central Cancer Registry.

In relapsed/refractory disease, Dr Javed highlights the BRUIN CLL-321 study of the noncovalent reversible BTK inhibitor pirtobrutinib. Pirtobrutinib improved PFS compared with chemoimmunotherapy.

Last, he discusses epcoritamab, which yielded encouraging complete response data in heavily pretreated CLL patients.

--

Muhammad Jawad Javed, MBBS, Albany Medical Center/Stratton VA Albany, Department of Medicine; Resident Physician, Department of Internal Medicine, Albany Medical Center, Albany, New York

Muhammad Jawad Javed, MBBS, has disclosed no relevant financial relationships

Studies in chronic lymphocytic leukemia (CLL) treatment in frontline and relapsed/refractory settings, presented at the American Society of Hematology (ASH) 2024 Annual Meeting and Exposition, are discussed by Dr Muhammad Jawad Javed of Albany Medical Center and Stratton VA.

Dr Javed begins with the AMPLIFY trial, the first phase 3 study to evaluate a fixed-duration regimen of venetoclax with a second-generation BTK inhibitor. AMPLIFY compares three frontline treatment arms: (1) acalabrutinib plus venetoclax (AV); (2) acalabrutinib plus venetoclax plus obinutuzumab (AVO); and (3) chemoimmunotherapy. Results showed improved progression-free survival (PFS) and overall survival (OS) in the AV and AVO groups.

The next frontline treatment study he discusses examined use of minimal residual disease testing to guide treatment duration of a venetoclax/obinutuzumab regimen. The study found that shorter treatment duration led to PFS comparable to that achieved by longer duration.

Dr Javed next turns to a retrospective analysis of the impact of first-line treatment choice on the risk for other malignancies, using data from the Department of US Veteran Affairs Central Cancer Registry.

In relapsed/refractory disease, Dr Javed highlights the BRUIN CLL-321 study of the noncovalent reversible BTK inhibitor pirtobrutinib. Pirtobrutinib improved PFS compared with chemoimmunotherapy.

Last, he discusses epcoritamab, which yielded encouraging complete response data in heavily pretreated CLL patients.

--

Muhammad Jawad Javed, MBBS, Albany Medical Center/Stratton VA Albany, Department of Medicine; Resident Physician, Department of Internal Medicine, Albany Medical Center, Albany, New York

Muhammad Jawad Javed, MBBS, has disclosed no relevant financial relationships