Data from a small retrospective study suggest that venetoclax-based regimens may have activity against relapsed or refractory T-lineage acute lymphoblastic leukemia (T-ALL) in children and young adults.

Among seven patients with T-ALL treated with venetoclax (Venclexta) in combination with chemotherapy, four had complete remissions and one had a CR with incomplete recovery of blood counts (CRi), and all four patients had undetectable minimal residual disease (MRD), reported pediatric hematology/oncology fellow Amber Gibson, MD, and colleagues from the University of Texas MD Anderson Cancer Center Children’s Cancer Hospital in Houston.

“This single-institution retrospective review found that venetoclax was safe and well tolerated in combination chemotherapy regimens, thrombocytopenia and neutropenia were the most common toxicities identified, [and] venetoclax should be considered for patients with refractory T-cell ALL and investigated as up-front therapy for this patient population,” they wrote in the abstract accompanying a poster presentation at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Children with relapsed T-ALL and T-lymphoblastic lymphoma (T-LL) have a dismal prognosis, with a 3-year event-free survival rate less than 10%, according to the researchers.

To see whether venetoclax, an inhibitor of the antiapoptotic protein B-cell lymphoma-2 (BCL-2), could improve outcomes for children with ALL, the investigators conducted a retrospective chart review of the safety and efficacy of venetoclax in young patients with relapsed/refractory ALL/LL who received the drug at their center.

They identified 10 patients aged 6-21 years (median, 18), 5 of whom had T-ALL (1 with early T-cell precursor ALL), 2 with T-LL, and 3 with B-lineage ALL (B-ALL).

The median number of prior lines of therapy was 3.5. Three of the 10 patients had received hematopoietic stem cell transplants, and the 3 patients with B-ALL had all received prior CD19-directed chimeric antigen receptor T-cell (CAR T) therapy. One of these patients received a dual CD19/CD22 CAR T product, one received CD19-directed blinotumumab.

There were no new safety signals with venetoclax, no treatment-related deaths, and no deaths within 30 days of starting venetoclax.

All 10 patients had grade 4 thrombocytopenias, 6 had grade 4 neutropenia, 3 had grade 4 febrile neutropenia, 2 had grade 4 anemia, and 1 each had grade 4 sepsis, pneumonia, or coagulopathy.

As noted, there were three CRs and one CRi, all in patients with T-ALL. All four of these patients were MRD negative by flow cytometry at a median of 22 days. The median duration of response was 17.4 months (range, 2-18 months).

At the most recent follow-up five patients were still alive, three without disease, one was still undergoing treatment, and one was alive following an allogeneic HSCT.
 

Early studies

Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, said that there are early studies exploring the use of venetoclax in infants with ALL.

“Venetoclax is a BCL-2 inhibitor that is pretty well tolerated, but you can also have cytopenias with it,” she said.

She noted that it is not typically used in the frontline setting in pediatric populations, but may be considered for patients with difficult-to-treat disease or for whom the relatively good toxicity profile might be appropriate.

The MD Anderson investigators did not report a funding source. The authors and Dr. Shahani reported no relevant conflicts of interest.

Data from a small retrospective study suggest that venetoclax-based regimens may have activity against relapsed or refractory T-lineage acute lymphoblastic leukemia (T-ALL) in children and young adults.

Among seven patients with T-ALL treated with venetoclax (Venclexta) in combination with chemotherapy, four had complete remissions and one had a CR with incomplete recovery of blood counts (CRi), and all four patients had undetectable minimal residual disease (MRD), reported pediatric hematology/oncology fellow Amber Gibson, MD, and colleagues from the University of Texas MD Anderson Cancer Center Children’s Cancer Hospital in Houston.

“This single-institution retrospective review found that venetoclax was safe and well tolerated in combination chemotherapy regimens, thrombocytopenia and neutropenia were the most common toxicities identified, [and] venetoclax should be considered for patients with refractory T-cell ALL and investigated as up-front therapy for this patient population,” they wrote in the abstract accompanying a poster presentation at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Children with relapsed T-ALL and T-lymphoblastic lymphoma (T-LL) have a dismal prognosis, with a 3-year event-free survival rate less than 10%, according to the researchers.

To see whether venetoclax, an inhibitor of the antiapoptotic protein B-cell lymphoma-2 (BCL-2), could improve outcomes for children with ALL, the investigators conducted a retrospective chart review of the safety and efficacy of venetoclax in young patients with relapsed/refractory ALL/LL who received the drug at their center.

They identified 10 patients aged 6-21 years (median, 18), 5 of whom had T-ALL (1 with early T-cell precursor ALL), 2 with T-LL, and 3 with B-lineage ALL (B-ALL).

The median number of prior lines of therapy was 3.5. Three of the 10 patients had received hematopoietic stem cell transplants, and the 3 patients with B-ALL had all received prior CD19-directed chimeric antigen receptor T-cell (CAR T) therapy. One of these patients received a dual CD19/CD22 CAR T product, one received CD19-directed blinotumumab.

There were no new safety signals with venetoclax, no treatment-related deaths, and no deaths within 30 days of starting venetoclax.

All 10 patients had grade 4 thrombocytopenias, 6 had grade 4 neutropenia, 3 had grade 4 febrile neutropenia, 2 had grade 4 anemia, and 1 each had grade 4 sepsis, pneumonia, or coagulopathy.

As noted, there were three CRs and one CRi, all in patients with T-ALL. All four of these patients were MRD negative by flow cytometry at a median of 22 days. The median duration of response was 17.4 months (range, 2-18 months).

At the most recent follow-up five patients were still alive, three without disease, one was still undergoing treatment, and one was alive following an allogeneic HSCT.
 

Early studies

Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, said that there are early studies exploring the use of venetoclax in infants with ALL.

“Venetoclax is a BCL-2 inhibitor that is pretty well tolerated, but you can also have cytopenias with it,” she said.

She noted that it is not typically used in the frontline setting in pediatric populations, but may be considered for patients with difficult-to-treat disease or for whom the relatively good toxicity profile might be appropriate.

The MD Anderson investigators did not report a funding source. The authors and Dr. Shahani reported no relevant conflicts of interest.

Data from a small retrospective study suggest that venetoclax-based regimens may have activity against relapsed or refractory T-lineage acute lymphoblastic leukemia (T-ALL) in children and young adults.

Among seven patients with T-ALL treated with venetoclax (Venclexta) in combination with chemotherapy, four had complete remissions and one had a CR with incomplete recovery of blood counts (CRi), and all four patients had undetectable minimal residual disease (MRD), reported pediatric hematology/oncology fellow Amber Gibson, MD, and colleagues from the University of Texas MD Anderson Cancer Center Children’s Cancer Hospital in Houston.

“This single-institution retrospective review found that venetoclax was safe and well tolerated in combination chemotherapy regimens, thrombocytopenia and neutropenia were the most common toxicities identified, [and] venetoclax should be considered for patients with refractory T-cell ALL and investigated as up-front therapy for this patient population,” they wrote in the abstract accompanying a poster presentation at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Children with relapsed T-ALL and T-lymphoblastic lymphoma (T-LL) have a dismal prognosis, with a 3-year event-free survival rate less than 10%, according to the researchers.

To see whether venetoclax, an inhibitor of the antiapoptotic protein B-cell lymphoma-2 (BCL-2), could improve outcomes for children with ALL, the investigators conducted a retrospective chart review of the safety and efficacy of venetoclax in young patients with relapsed/refractory ALL/LL who received the drug at their center.

They identified 10 patients aged 6-21 years (median, 18), 5 of whom had T-ALL (1 with early T-cell precursor ALL), 2 with T-LL, and 3 with B-lineage ALL (B-ALL).

The median number of prior lines of therapy was 3.5. Three of the 10 patients had received hematopoietic stem cell transplants, and the 3 patients with B-ALL had all received prior CD19-directed chimeric antigen receptor T-cell (CAR T) therapy. One of these patients received a dual CD19/CD22 CAR T product, one received CD19-directed blinotumumab.

There were no new safety signals with venetoclax, no treatment-related deaths, and no deaths within 30 days of starting venetoclax.

All 10 patients had grade 4 thrombocytopenias, 6 had grade 4 neutropenia, 3 had grade 4 febrile neutropenia, 2 had grade 4 anemia, and 1 each had grade 4 sepsis, pneumonia, or coagulopathy.

As noted, there were three CRs and one CRi, all in patients with T-ALL. All four of these patients were MRD negative by flow cytometry at a median of 22 days. The median duration of response was 17.4 months (range, 2-18 months).

At the most recent follow-up five patients were still alive, three without disease, one was still undergoing treatment, and one was alive following an allogeneic HSCT.
 

Early studies

Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, said that there are early studies exploring the use of venetoclax in infants with ALL.

“Venetoclax is a BCL-2 inhibitor that is pretty well tolerated, but you can also have cytopenias with it,” she said.

She noted that it is not typically used in the frontline setting in pediatric populations, but may be considered for patients with difficult-to-treat disease or for whom the relatively good toxicity profile might be appropriate.

The MD Anderson investigators did not report a funding source. The authors and Dr. Shahani reported no relevant conflicts of interest.

A reduced dose of prednisolone plus rituximab was as effective as a conventionally high dose in treating patients with newly diagnosed antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, according to a new Japanese study, along with significantly fewer adverse events as well.

“To our knowledge, this is the first trial in ANCA-associated vasculitis showing that a lower glucocorticoid dose may reduce serious adverse events,” wrote Shunsuke Furuta, MD, PhD, of the department of allergy and clinical immunology at Chiba (Japan) University Hospital, and colleagues. The study was published June 1, 2021, in JAMA.

To determine the most effective and safe dose of glucocorticoids for treating this specific subset of patients with vasculitis, the researchers launched an open-label noninferiority clinical trial at 21 hospitals in Japan. A group of 140 patients with new-onset ANCA-associated vasculitis (AAV) without severe glomerulonephritis or alveolar hemorrhage were enrolled and split evenly into two treatment subgroups: reduced-dose prednisolone (0.5 mg/kg per day) plus four doses of rituximab (375 mg/m² per week) or high-dose prednisolone (1 mg/kg per day) plus rituximab. The median age for all enrolled patients was 73, and approximately 58% were women.

Of the 140 original patients, 134 (95.7%) completed the trial. After 6 months, 49 participants in the reduced-dose group (71%) and 45 in the high-dose group (69.2%) achieved remission, as assessed via the Birmingham Vasculitis Activity Score. The difference between the two groups – 1.8 percentage points (one-sided 97.5% confidence interval, –13.7 to infinity) – met the prespecified margin of –20 percentage points for noninferiority (P = .003 for noninferiority). Relapse within 6 months occurred in three participants in the reduced-dose group and zero in the high-dose group, frequencies that the researchers identified as not statistically different (difference, 4.3%; 95% CI, –0.5% to 9.3%; P = .24).

Serious adverse events occurred less frequently in the reduced-dose group (21 events in 13 patients, 18.8%), compared with the high-dose group (41 events in 24 patients, 36.9%), as did serious infections in the reduced-dose group (7 events in 5 patients, 7.2%) versus the high-dose group (20 events in 13 patients, 20%). Two patients died in the reduced-dose group and three died in the high-dose group; those frequencies were noted as not statistically different (difference, –1.7%; 95% CI, –4.7% to 8.2%; P = .67). Causes of death included subarachnoid hemorrhage in a 58-year-old in the reduced-dose group, along with a case of sepsis in an 80-year-old and two gastrointestinal bleedings in a 75-year-old and an 85-year-old in the high-dose group.

End-stage kidney disease (ESKD) occurred in one patient in the high-dose group and none in the reduced-dose group. Cumulative survival rates at 6 months were not significantly different between the reduced-dose (97.1%) and the high-dose (95.3%) groups (95% CI, –4.7% to 8.2%; P = .58).

Less glucocorticoids makes sense for subset of patients with milder vasculitis

“We always worry about how much steroids we’re giving our patients,” said Anisha B. Dua, MD, an associate professor of rheumatology at Northwestern University, Chicago. “And it’s not a shock to find out that we can use less. That’s been the theme of many studies across vasculitities that have been coming out: ‘Maybe we are using too much steroids.’ It’s really important to have actual data supporting that, though, so clinicians can feel more confident and figure out what population it applies to.”

M. Alexander Otto

She added that, because the study focused on patients with milder disease, it’s no surprise that remission was achieved with a lesser dose.

“I see a lot of vasculitis patients, and this gives me more confidence in a subset of them – new ANCA vasculitis, MPO positive, not very severe disease – to get away with using less steroids up front,” she said.

To apply these findings more broadly across vasculitis patients, Dr. Dua stressed the need for a follow-up study, preferably a randomized, controlled trial, with an expanded population and a longer duration.

“There were 3 relapses in the low-dose group and zero in the high-dose group in the first 6 months,” she said. “I’d be interested to know when those happened and also, over time, whether the low-dose regiment up front impacts the rate of relapse in the long term.”

The authors acknowledged the study’s limitations, including the necessity of an open-label trial because of the inevitable visible effects of high-dose glucocorticoid on patients. They also addressed the potential subjectivity of the Birmingham Vasculitis Activity Score, though they added that “other endpoints, including death, ESKD, and serious adverse events, were objective.” Finally, they acknowledged that their study was nationwide but not international, with disease phenotypes that were typical of Japanese patients with AAV. That said, “previous studies have shown that treatment responses are similar between Japan and other countries,” they wrote.

The study was funded by an intramural competitive grant from Chiba University Hospital. The authors reported numerous potential conflicts of interest, including receiving grant support, lecture fees, and personal fees from various pharmaceutical companies.

A reduced dose of prednisolone plus rituximab was as effective as a conventionally high dose in treating patients with newly diagnosed antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, according to a new Japanese study, along with significantly fewer adverse events as well.

“To our knowledge, this is the first trial in ANCA-associated vasculitis showing that a lower glucocorticoid dose may reduce serious adverse events,” wrote Shunsuke Furuta, MD, PhD, of the department of allergy and clinical immunology at Chiba (Japan) University Hospital, and colleagues. The study was published June 1, 2021, in JAMA.

To determine the most effective and safe dose of glucocorticoids for treating this specific subset of patients with vasculitis, the researchers launched an open-label noninferiority clinical trial at 21 hospitals in Japan. A group of 140 patients with new-onset ANCA-associated vasculitis (AAV) without severe glomerulonephritis or alveolar hemorrhage were enrolled and split evenly into two treatment subgroups: reduced-dose prednisolone (0.5 mg/kg per day) plus four doses of rituximab (375 mg/m² per week) or high-dose prednisolone (1 mg/kg per day) plus rituximab. The median age for all enrolled patients was 73, and approximately 58% were women.

Of the 140 original patients, 134 (95.7%) completed the trial. After 6 months, 49 participants in the reduced-dose group (71%) and 45 in the high-dose group (69.2%) achieved remission, as assessed via the Birmingham Vasculitis Activity Score. The difference between the two groups – 1.8 percentage points (one-sided 97.5% confidence interval, –13.7 to infinity) – met the prespecified margin of –20 percentage points for noninferiority (P = .003 for noninferiority). Relapse within 6 months occurred in three participants in the reduced-dose group and zero in the high-dose group, frequencies that the researchers identified as not statistically different (difference, 4.3%; 95% CI, –0.5% to 9.3%; P = .24).

Serious adverse events occurred less frequently in the reduced-dose group (21 events in 13 patients, 18.8%), compared with the high-dose group (41 events in 24 patients, 36.9%), as did serious infections in the reduced-dose group (7 events in 5 patients, 7.2%) versus the high-dose group (20 events in 13 patients, 20%). Two patients died in the reduced-dose group and three died in the high-dose group; those frequencies were noted as not statistically different (difference, –1.7%; 95% CI, –4.7% to 8.2%; P = .67). Causes of death included subarachnoid hemorrhage in a 58-year-old in the reduced-dose group, along with a case of sepsis in an 80-year-old and two gastrointestinal bleedings in a 75-year-old and an 85-year-old in the high-dose group.

End-stage kidney disease (ESKD) occurred in one patient in the high-dose group and none in the reduced-dose group. Cumulative survival rates at 6 months were not significantly different between the reduced-dose (97.1%) and the high-dose (95.3%) groups (95% CI, –4.7% to 8.2%; P = .58).

Less glucocorticoids makes sense for subset of patients with milder vasculitis

“We always worry about how much steroids we’re giving our patients,” said Anisha B. Dua, MD, an associate professor of rheumatology at Northwestern University, Chicago. “And it’s not a shock to find out that we can use less. That’s been the theme of many studies across vasculitities that have been coming out: ‘Maybe we are using too much steroids.’ It’s really important to have actual data supporting that, though, so clinicians can feel more confident and figure out what population it applies to.”

M. Alexander Otto

She added that, because the study focused on patients with milder disease, it’s no surprise that remission was achieved with a lesser dose.

“I see a lot of vasculitis patients, and this gives me more confidence in a subset of them – new ANCA vasculitis, MPO positive, not very severe disease – to get away with using less steroids up front,” she said.

To apply these findings more broadly across vasculitis patients, Dr. Dua stressed the need for a follow-up study, preferably a randomized, controlled trial, with an expanded population and a longer duration.

“There were 3 relapses in the low-dose group and zero in the high-dose group in the first 6 months,” she said. “I’d be interested to know when those happened and also, over time, whether the low-dose regiment up front impacts the rate of relapse in the long term.”

The authors acknowledged the study’s limitations, including the necessity of an open-label trial because of the inevitable visible effects of high-dose glucocorticoid on patients. They also addressed the potential subjectivity of the Birmingham Vasculitis Activity Score, though they added that “other endpoints, including death, ESKD, and serious adverse events, were objective.” Finally, they acknowledged that their study was nationwide but not international, with disease phenotypes that were typical of Japanese patients with AAV. That said, “previous studies have shown that treatment responses are similar between Japan and other countries,” they wrote.

The study was funded by an intramural competitive grant from Chiba University Hospital. The authors reported numerous potential conflicts of interest, including receiving grant support, lecture fees, and personal fees from various pharmaceutical companies.

A reduced dose of prednisolone plus rituximab was as effective as a conventionally high dose in treating patients with newly diagnosed antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, according to a new Japanese study, along with significantly fewer adverse events as well.

“To our knowledge, this is the first trial in ANCA-associated vasculitis showing that a lower glucocorticoid dose may reduce serious adverse events,” wrote Shunsuke Furuta, MD, PhD, of the department of allergy and clinical immunology at Chiba (Japan) University Hospital, and colleagues. The study was published June 1, 2021, in JAMA.

To determine the most effective and safe dose of glucocorticoids for treating this specific subset of patients with vasculitis, the researchers launched an open-label noninferiority clinical trial at 21 hospitals in Japan. A group of 140 patients with new-onset ANCA-associated vasculitis (AAV) without severe glomerulonephritis or alveolar hemorrhage were enrolled and split evenly into two treatment subgroups: reduced-dose prednisolone (0.5 mg/kg per day) plus four doses of rituximab (375 mg/m² per week) or high-dose prednisolone (1 mg/kg per day) plus rituximab. The median age for all enrolled patients was 73, and approximately 58% were women.

Of the 140 original patients, 134 (95.7%) completed the trial. After 6 months, 49 participants in the reduced-dose group (71%) and 45 in the high-dose group (69.2%) achieved remission, as assessed via the Birmingham Vasculitis Activity Score. The difference between the two groups – 1.8 percentage points (one-sided 97.5% confidence interval, –13.7 to infinity) – met the prespecified margin of –20 percentage points for noninferiority (P = .003 for noninferiority). Relapse within 6 months occurred in three participants in the reduced-dose group and zero in the high-dose group, frequencies that the researchers identified as not statistically different (difference, 4.3%; 95% CI, –0.5% to 9.3%; P = .24).

Serious adverse events occurred less frequently in the reduced-dose group (21 events in 13 patients, 18.8%), compared with the high-dose group (41 events in 24 patients, 36.9%), as did serious infections in the reduced-dose group (7 events in 5 patients, 7.2%) versus the high-dose group (20 events in 13 patients, 20%). Two patients died in the reduced-dose group and three died in the high-dose group; those frequencies were noted as not statistically different (difference, –1.7%; 95% CI, –4.7% to 8.2%; P = .67). Causes of death included subarachnoid hemorrhage in a 58-year-old in the reduced-dose group, along with a case of sepsis in an 80-year-old and two gastrointestinal bleedings in a 75-year-old and an 85-year-old in the high-dose group.

End-stage kidney disease (ESKD) occurred in one patient in the high-dose group and none in the reduced-dose group. Cumulative survival rates at 6 months were not significantly different between the reduced-dose (97.1%) and the high-dose (95.3%) groups (95% CI, –4.7% to 8.2%; P = .58).

Less glucocorticoids makes sense for subset of patients with milder vasculitis

“We always worry about how much steroids we’re giving our patients,” said Anisha B. Dua, MD, an associate professor of rheumatology at Northwestern University, Chicago. “And it’s not a shock to find out that we can use less. That’s been the theme of many studies across vasculitities that have been coming out: ‘Maybe we are using too much steroids.’ It’s really important to have actual data supporting that, though, so clinicians can feel more confident and figure out what population it applies to.”

M. Alexander Otto

She added that, because the study focused on patients with milder disease, it’s no surprise that remission was achieved with a lesser dose.

“I see a lot of vasculitis patients, and this gives me more confidence in a subset of them – new ANCA vasculitis, MPO positive, not very severe disease – to get away with using less steroids up front,” she said.

To apply these findings more broadly across vasculitis patients, Dr. Dua stressed the need for a follow-up study, preferably a randomized, controlled trial, with an expanded population and a longer duration.

“There were 3 relapses in the low-dose group and zero in the high-dose group in the first 6 months,” she said. “I’d be interested to know when those happened and also, over time, whether the low-dose regiment up front impacts the rate of relapse in the long term.”

The authors acknowledged the study’s limitations, including the necessity of an open-label trial because of the inevitable visible effects of high-dose glucocorticoid on patients. They also addressed the potential subjectivity of the Birmingham Vasculitis Activity Score, though they added that “other endpoints, including death, ESKD, and serious adverse events, were objective.” Finally, they acknowledged that their study was nationwide but not international, with disease phenotypes that were typical of Japanese patients with AAV. That said, “previous studies have shown that treatment responses are similar between Japan and other countries,” they wrote.

The study was funded by an intramural competitive grant from Chiba University Hospital. The authors reported numerous potential conflicts of interest, including receiving grant support, lecture fees, and personal fees from various pharmaceutical companies.

Due to the heterogeneity of outcomes and study designs, consensus on definitive prostate cancer risk assessment has been somewhat elusive. Differences in outcomes based on ethnicity and race have been observed, but much data on risk has originally been obtained in populations with lower ethnic and racial diversity, complicating extrapolation to larger populations. Huynh-Le et al developed an updated polygenic hazard score (PHS₂) based on a single nucleotide polymorphism (SNP) panel (46 total SNPs) for prostate cancer patients with multiple ethnicities (African, Asian, and European ancestries). This updated PHS₂ score stratified men into higher and lower risks for any, aggressive, and fatal prostate cancers in a statistically significant way. Camargo et al took a different approach and evaluated whether 2 SNPs were prognostic in prostate cancer: rs1834306 corresponding to microRNA 100 (miR 100) and rs2910164 from miR 146a. There were no differences in miR 100 or miR 156a between patients with local prostate cancer or a control group of men without prostate cancer. In addition, there were no differences in the chance of particular genotypes between the 2 groups. There was an association between lower presence of rs1834306 (miR 100) and patients with PSA > 10 mg/mL and between a higher amount of the polymorphic allele for rs2910164 (miR 146A).

The 3 studies summarized here demonstrate the ongoing challenges in how to identify nuances that will affect clinical decision-making in PSA screening and to identify prognostic features that associate with particular outcomes. The study by Bergengren confirmed the current state of PSA screening in that balancing diagnosis and potential overtreatment with modest survival outcomes is challenging. While the studies by Huynh-Le  et al and Camargo et al have interesting findings, the use of SNPs and miR in prostate cancer prognosis is still not ready for routine clinical use in prostate cancer management.

Due to the heterogeneity of outcomes and study designs, consensus on definitive prostate cancer risk assessment has been somewhat elusive. Differences in outcomes based on ethnicity and race have been observed, but much data on risk has originally been obtained in populations with lower ethnic and racial diversity, complicating extrapolation to larger populations. Huynh-Le et al developed an updated polygenic hazard score (PHS₂) based on a single nucleotide polymorphism (SNP) panel (46 total SNPs) for prostate cancer patients with multiple ethnicities (African, Asian, and European ancestries). This updated PHS₂ score stratified men into higher and lower risks for any, aggressive, and fatal prostate cancers in a statistically significant way. Camargo et al took a different approach and evaluated whether 2 SNPs were prognostic in prostate cancer: rs1834306 corresponding to microRNA 100 (miR 100) and rs2910164 from miR 146a. There were no differences in miR 100 or miR 156a between patients with local prostate cancer or a control group of men without prostate cancer. In addition, there were no differences in the chance of particular genotypes between the 2 groups. There was an association between lower presence of rs1834306 (miR 100) and patients with PSA > 10 mg/mL and between a higher amount of the polymorphic allele for rs2910164 (miR 146A).

The 3 studies summarized here demonstrate the ongoing challenges in how to identify nuances that will affect clinical decision-making in PSA screening and to identify prognostic features that associate with particular outcomes. The study by Bergengren confirmed the current state of PSA screening in that balancing diagnosis and potential overtreatment with modest survival outcomes is challenging. While the studies by Huynh-Le  et al and Camargo et al have interesting findings, the use of SNPs and miR in prostate cancer prognosis is still not ready for routine clinical use in prostate cancer management.

Due to the heterogeneity of outcomes and study designs, consensus on definitive prostate cancer risk assessment has been somewhat elusive. Differences in outcomes based on ethnicity and race have been observed, but much data on risk has originally been obtained in populations with lower ethnic and racial diversity, complicating extrapolation to larger populations. Huynh-Le et al developed an updated polygenic hazard score (PHS₂) based on a single nucleotide polymorphism (SNP) panel (46 total SNPs) for prostate cancer patients with multiple ethnicities (African, Asian, and European ancestries). This updated PHS₂ score stratified men into higher and lower risks for any, aggressive, and fatal prostate cancers in a statistically significant way. Camargo et al took a different approach and evaluated whether 2 SNPs were prognostic in prostate cancer: rs1834306 corresponding to microRNA 100 (miR 100) and rs2910164 from miR 146a. There were no differences in miR 100 or miR 156a between patients with local prostate cancer or a control group of men without prostate cancer. In addition, there were no differences in the chance of particular genotypes between the 2 groups. There was an association between lower presence of rs1834306 (miR 100) and patients with PSA > 10 mg/mL and between a higher amount of the polymorphic allele for rs2910164 (miR 146A).

The 3 studies summarized here demonstrate the ongoing challenges in how to identify nuances that will affect clinical decision-making in PSA screening and to identify prognostic features that associate with particular outcomes. The study by Bergengren confirmed the current state of PSA screening in that balancing diagnosis and potential overtreatment with modest survival outcomes is challenging. While the studies by Huynh-Le  et al and Camargo et al have interesting findings, the use of SNPs and miR in prostate cancer prognosis is still not ready for routine clinical use in prostate cancer management.

Key clinical point: Single nucleotide polymorphisms (SNP) can serve as prognostic factors for prostate cancer

Major finding: In patients with prostate cancer, SNP rs2910164 of miR146a was more common in patients with a Gleason score of 7 or higher than those with a Gleason score of less than 7 (P=0.043); in addition, SNP rs1834306 of miR100 was overexpressed in those with pT3 staging compared to pT2 (P = 0.004).

Study details: The data come from a review of 100 patients with clinically localized prostate cancer who underwent radical prostatectomy and 68 controls without prostate cancer.

Disclosures: The study was supported in part by a grant from the Sao Paulo Research Foundation. The researchers had no financial conflicts to disclose.

Source: Camargo JA et al. Int J Biol Markers. 2021 May 25. doi: 10.1177/172460082199746.

Key clinical point: Single nucleotide polymorphisms (SNP) can serve as prognostic factors for prostate cancer

Major finding: In patients with prostate cancer, SNP rs2910164 of miR146a was more common in patients with a Gleason score of 7 or higher than those with a Gleason score of less than 7 (P=0.043); in addition, SNP rs1834306 of miR100 was overexpressed in those with pT3 staging compared to pT2 (P = 0.004).

Study details: The data come from a review of 100 patients with clinically localized prostate cancer who underwent radical prostatectomy and 68 controls without prostate cancer.

Disclosures: The study was supported in part by a grant from the Sao Paulo Research Foundation. The researchers had no financial conflicts to disclose.

Source: Camargo JA et al. Int J Biol Markers. 2021 May 25. doi: 10.1177/172460082199746.

Key clinical point: Single nucleotide polymorphisms (SNP) can serve as prognostic factors for prostate cancer

Major finding: In patients with prostate cancer, SNP rs2910164 of miR146a was more common in patients with a Gleason score of 7 or higher than those with a Gleason score of less than 7 (P=0.043); in addition, SNP rs1834306 of miR100 was overexpressed in those with pT3 staging compared to pT2 (P = 0.004).

Study details: The data come from a review of 100 patients with clinically localized prostate cancer who underwent radical prostatectomy and 68 controls without prostate cancer.

Disclosures: The study was supported in part by a grant from the Sao Paulo Research Foundation. The researchers had no financial conflicts to disclose.

Source: Camargo JA et al. Int J Biol Markers. 2021 May 25. doi: 10.1177/172460082199746.

Key clinical point: Increased bone involvement was negatively correlated with overall survival after radioligand therapy for prostate cancer.

Major finding: The median overall survival for prostate cancer patients with less than 6 bone lesions, 6-20 lesions, more than 20 lesions, and diffuse lesions was 18 months, 13 months, 11 months, and 8 months, respectively.

Study details: The data come from 319 men with progressive metastatic castration-resistant prostate cancer who underwent radioligand therapy with lutetium prostate-specific membrane antigen (Lu-PSMA-617).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Ahmadzadehfar H et al. Eur J Nucl Med Mol Imaging. 2021 May 25. doi: 10.1007/s00259-021-05383-3.

Key clinical point: Increased bone involvement was negatively correlated with overall survival after radioligand therapy for prostate cancer.

Major finding: The median overall survival for prostate cancer patients with less than 6 bone lesions, 6-20 lesions, more than 20 lesions, and diffuse lesions was 18 months, 13 months, 11 months, and 8 months, respectively.

Study details: The data come from 319 men with progressive metastatic castration-resistant prostate cancer who underwent radioligand therapy with lutetium prostate-specific membrane antigen (Lu-PSMA-617).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Ahmadzadehfar H et al. Eur J Nucl Med Mol Imaging. 2021 May 25. doi: 10.1007/s00259-021-05383-3.

Key clinical point: Increased bone involvement was negatively correlated with overall survival after radioligand therapy for prostate cancer.

Major finding: The median overall survival for prostate cancer patients with less than 6 bone lesions, 6-20 lesions, more than 20 lesions, and diffuse lesions was 18 months, 13 months, 11 months, and 8 months, respectively.

Study details: The data come from 319 men with progressive metastatic castration-resistant prostate cancer who underwent radioligand therapy with lutetium prostate-specific membrane antigen (Lu-PSMA-617).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Ahmadzadehfar H et al. Eur J Nucl Med Mol Imaging. 2021 May 25. doi: 10.1007/s00259-021-05383-3.

Key clinical point: The Polygenic Hazard Score (PHS2) was effective for risk-stratifying men for prostate cancer in a large, multiethnic data set.

Major finding: The Polygenic Hazard Score (PHS2) indicated hazard ratios for prostate cancer, aggressive cancer, and prostate cancer-specific death of 5.32, 5.88, and 5.68, respectively, when researchers compared the 80^th and 20^th PHS2 percentiles.

Study details: The data come from 80,491 men enrolled in the OncoArray genetic project; researchers tested the polygenic hazard score (PHS2, adapted for OncoArray) for association with age at diagnosis of any and aggressive prostate cancer.

Disclosures: The study was supported in part by the National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering, the United States Department of Defense, the University of California, the Research Council of Norway, K.G. Jebsen Stiftelsen, and South East Norway Health Authority. Lead author Dr. Huynh-Le had no financial conflicts to disclose.

Source: Huynh-Le M-P et al. Nat Commun. 2021 Feb 23. doi: 10.1038/s41467-021-21287-0.

Key clinical point: The Polygenic Hazard Score (PHS2) was effective for risk-stratifying men for prostate cancer in a large, multiethnic data set.

Major finding: The Polygenic Hazard Score (PHS2) indicated hazard ratios for prostate cancer, aggressive cancer, and prostate cancer-specific death of 5.32, 5.88, and 5.68, respectively, when researchers compared the 80^th and 20^th PHS2 percentiles.

Study details: The data come from 80,491 men enrolled in the OncoArray genetic project; researchers tested the polygenic hazard score (PHS2, adapted for OncoArray) for association with age at diagnosis of any and aggressive prostate cancer.

Disclosures: The study was supported in part by the National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering, the United States Department of Defense, the University of California, the Research Council of Norway, K.G. Jebsen Stiftelsen, and South East Norway Health Authority. Lead author Dr. Huynh-Le had no financial conflicts to disclose.

Source: Huynh-Le M-P et al. Nat Commun. 2021 Feb 23. doi: 10.1038/s41467-021-21287-0.

Key clinical point: The Polygenic Hazard Score (PHS2) was effective for risk-stratifying men for prostate cancer in a large, multiethnic data set.

Major finding: The Polygenic Hazard Score (PHS2) indicated hazard ratios for prostate cancer, aggressive cancer, and prostate cancer-specific death of 5.32, 5.88, and 5.68, respectively, when researchers compared the 80^th and 20^th PHS2 percentiles.

Study details: The data come from 80,491 men enrolled in the OncoArray genetic project; researchers tested the polygenic hazard score (PHS2, adapted for OncoArray) for association with age at diagnosis of any and aggressive prostate cancer.

Disclosures: The study was supported in part by the National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering, the United States Department of Defense, the University of California, the Research Council of Norway, K.G. Jebsen Stiftelsen, and South East Norway Health Authority. Lead author Dr. Huynh-Le had no financial conflicts to disclose.

Source: Huynh-Le M-P et al. Nat Commun. 2021 Feb 23. doi: 10.1038/s41467-021-21287-0.

Key clinical point: Increased use of PSA testing and diagnostic activity increased the number of men diagnosed with low and intermediate-risk prostate cancer.

Major finding: The number of men diagnosed with prostate cancer increased by 48% in the high diagnostic activity model compared to the low diagnostic activity model (423 cases per 100,000 me per year vs. 286 cases per 100,000 men per year). 

Study details: The data come from a cohort study of 188,884 men aged 64-77 years diagnosed with prostate cancer between 1996 and 2016 in Sweden. The researchers used a simulation model to compare scenarios of high and low diagnostic activity for prostate cancer.

Disclosures: The study was funded by the Swedish Cancer Society. The researchers had no financial conflicts to disclose.

Source: Bergengren O et al. JAMA Netw Open. 2021 May 17. doi: 10.1001/jamanetworkopen.2021.9444.

Key clinical point: Increased use of PSA testing and diagnostic activity increased the number of men diagnosed with low and intermediate-risk prostate cancer.

Major finding: The number of men diagnosed with prostate cancer increased by 48% in the high diagnostic activity model compared to the low diagnostic activity model (423 cases per 100,000 me per year vs. 286 cases per 100,000 men per year). 

Study details: The data come from a cohort study of 188,884 men aged 64-77 years diagnosed with prostate cancer between 1996 and 2016 in Sweden. The researchers used a simulation model to compare scenarios of high and low diagnostic activity for prostate cancer.

Disclosures: The study was funded by the Swedish Cancer Society. The researchers had no financial conflicts to disclose.

Source: Bergengren O et al. JAMA Netw Open. 2021 May 17. doi: 10.1001/jamanetworkopen.2021.9444.

Key clinical point: Increased use of PSA testing and diagnostic activity increased the number of men diagnosed with low and intermediate-risk prostate cancer.

Major finding: The number of men diagnosed with prostate cancer increased by 48% in the high diagnostic activity model compared to the low diagnostic activity model (423 cases per 100,000 me per year vs. 286 cases per 100,000 men per year). 

Study details: The data come from a cohort study of 188,884 men aged 64-77 years diagnosed with prostate cancer between 1996 and 2016 in Sweden. The researchers used a simulation model to compare scenarios of high and low diagnostic activity for prostate cancer.

Disclosures: The study was funded by the Swedish Cancer Society. The researchers had no financial conflicts to disclose.

Source: Bergengren O et al. JAMA Netw Open. 2021 May 17. doi: 10.1001/jamanetworkopen.2021.9444.

Key clinical point: Treatment with lutetium prostate-specific membrane antigen (Lu-PSMA) therapy at 6.0 GBq and 7.4 GBq yielded similar PSA response rates and overall survival for patients with progressive metastatic castrate resistant prostate cancer.

Major finding: The primary endpoint of PSA response of at least a 50% reduction from baseline after 2 treatment cycles was met in 28% of the whole cohort, and 46% and 19%, respectively, for treatment regimens of 6.0 GBq and 7.4 GBq.

Study details: The data come from a prospective, phase II trial of 71 men with progressive, metastatic castrate resistant prostate cancer. The patients were randomized to Lu-PSMA therapy at doses of either 6.0 vs 7.4 GBq.

Disclosures: The original study was supported by Endocyte. The researchers had no financial conflicts to disclose.  

Source: Calais J. et al. J Nucl Med. 2021 May 20. doi: 10.2967/jnumed.121.261982.

Key clinical point: Treatment with lutetium prostate-specific membrane antigen (Lu-PSMA) therapy at 6.0 GBq and 7.4 GBq yielded similar PSA response rates and overall survival for patients with progressive metastatic castrate resistant prostate cancer.

Major finding: The primary endpoint of PSA response of at least a 50% reduction from baseline after 2 treatment cycles was met in 28% of the whole cohort, and 46% and 19%, respectively, for treatment regimens of 6.0 GBq and 7.4 GBq.

Study details: The data come from a prospective, phase II trial of 71 men with progressive, metastatic castrate resistant prostate cancer. The patients were randomized to Lu-PSMA therapy at doses of either 6.0 vs 7.4 GBq.

Disclosures: The original study was supported by Endocyte. The researchers had no financial conflicts to disclose.  

Source: Calais J. et al. J Nucl Med. 2021 May 20. doi: 10.2967/jnumed.121.261982.

Key clinical point: Treatment with lutetium prostate-specific membrane antigen (Lu-PSMA) therapy at 6.0 GBq and 7.4 GBq yielded similar PSA response rates and overall survival for patients with progressive metastatic castrate resistant prostate cancer.

Major finding: The primary endpoint of PSA response of at least a 50% reduction from baseline after 2 treatment cycles was met in 28% of the whole cohort, and 46% and 19%, respectively, for treatment regimens of 6.0 GBq and 7.4 GBq.

Study details: The data come from a prospective, phase II trial of 71 men with progressive, metastatic castrate resistant prostate cancer. The patients were randomized to Lu-PSMA therapy at doses of either 6.0 vs 7.4 GBq.

Disclosures: The original study was supported by Endocyte. The researchers had no financial conflicts to disclose.  

Source: Calais J. et al. J Nucl Med. 2021 May 20. doi: 10.2967/jnumed.121.261982.

Key clinical point: A serum metabolic panel was more effective than prostate-specific antigen at differentiating prostate cancer patients from patients with negative prostate biopsy and healthy controls.

Major finding: The metabolic panel showed a higher diagnostic performance than prostate-specific antigen in distinguishing PCa from control patients, with an area under the curve of 0.823 for the metabolic panel vs. 0.712 for PSA (P <0.001).

Study details: The data come from a logistic regression analysis of 134 individuals, 39 prostate cancer patients, 45 controls with a negative prostate biopsy, and 50 healthy controls.

Disclosures: The study was funded by the National Natural Science Foundation of China, Science and Technology Support Project in the field of biomedicine of Shanghai Science and Technology Action Plan, Clinical Research Project of Shanghai Municipal Commission of Health and Family Planning, Precision Medicine Program of Second Military Medical University, Youth Startup Program of Second Military Medical University, and Jiangsu Provincial Medical Youth Talent. The researchers had no financial conflicts to disclose.

Source: Xu H et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.666320.

Key clinical point: A serum metabolic panel was more effective than prostate-specific antigen at differentiating prostate cancer patients from patients with negative prostate biopsy and healthy controls.

Major finding: The metabolic panel showed a higher diagnostic performance than prostate-specific antigen in distinguishing PCa from control patients, with an area under the curve of 0.823 for the metabolic panel vs. 0.712 for PSA (P <0.001).

Study details: The data come from a logistic regression analysis of 134 individuals, 39 prostate cancer patients, 45 controls with a negative prostate biopsy, and 50 healthy controls.

Disclosures: The study was funded by the National Natural Science Foundation of China, Science and Technology Support Project in the field of biomedicine of Shanghai Science and Technology Action Plan, Clinical Research Project of Shanghai Municipal Commission of Health and Family Planning, Precision Medicine Program of Second Military Medical University, Youth Startup Program of Second Military Medical University, and Jiangsu Provincial Medical Youth Talent. The researchers had no financial conflicts to disclose.

Source: Xu H et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.666320.

Key clinical point: A serum metabolic panel was more effective than prostate-specific antigen at differentiating prostate cancer patients from patients with negative prostate biopsy and healthy controls.

Major finding: The metabolic panel showed a higher diagnostic performance than prostate-specific antigen in distinguishing PCa from control patients, with an area under the curve of 0.823 for the metabolic panel vs. 0.712 for PSA (P <0.001).

Study details: The data come from a logistic regression analysis of 134 individuals, 39 prostate cancer patients, 45 controls with a negative prostate biopsy, and 50 healthy controls.

Disclosures: The study was funded by the National Natural Science Foundation of China, Science and Technology Support Project in the field of biomedicine of Shanghai Science and Technology Action Plan, Clinical Research Project of Shanghai Municipal Commission of Health and Family Planning, Precision Medicine Program of Second Military Medical University, Youth Startup Program of Second Military Medical University, and Jiangsu Provincial Medical Youth Talent. The researchers had no financial conflicts to disclose.

Source: Xu H et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.666320.

Key clinical point: Overall survival among men with castration sensitive prostate cancer was similar whether they were treated with docetaxel or abiraterone, but progression-free survival favored abiraterone patients.

Major finding: Progression-free survival at 12 months was greater among men who received ABI compared to those who received DOC (79.7% vs. 67.1%). Overall survival rates at 12 months were similar between the ABI and DOC groups (92.7% and 98.7%, respectively).

Study details: The data come from a retrospective analysis of 121 men with castration sensitive prostate cancer (mCSPC) who were treated at a single center between December 2014 and March 2021; 79 received docetaxel and 42 received abiraterone in addition to androgen deprivation therapy.

Disclosures: The study was supported by the Joseph and Silvana Melara Cancer Research Fund. Lead author Dr. Briones had no financial conflicts to disclose.

Source: Briones J et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.658331.

Key clinical point: Overall survival among men with castration sensitive prostate cancer was similar whether they were treated with docetaxel or abiraterone, but progression-free survival favored abiraterone patients.

Major finding: Progression-free survival at 12 months was greater among men who received ABI compared to those who received DOC (79.7% vs. 67.1%). Overall survival rates at 12 months were similar between the ABI and DOC groups (92.7% and 98.7%, respectively).

Study details: The data come from a retrospective analysis of 121 men with castration sensitive prostate cancer (mCSPC) who were treated at a single center between December 2014 and March 2021; 79 received docetaxel and 42 received abiraterone in addition to androgen deprivation therapy.

Disclosures: The study was supported by the Joseph and Silvana Melara Cancer Research Fund. Lead author Dr. Briones had no financial conflicts to disclose.

Source: Briones J et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.658331.

Key clinical point: Overall survival among men with castration sensitive prostate cancer was similar whether they were treated with docetaxel or abiraterone, but progression-free survival favored abiraterone patients.

Major finding: Progression-free survival at 12 months was greater among men who received ABI compared to those who received DOC (79.7% vs. 67.1%). Overall survival rates at 12 months were similar between the ABI and DOC groups (92.7% and 98.7%, respectively).

Study details: The data come from a retrospective analysis of 121 men with castration sensitive prostate cancer (mCSPC) who were treated at a single center between December 2014 and March 2021; 79 received docetaxel and 42 received abiraterone in addition to androgen deprivation therapy.

Disclosures: The study was supported by the Joseph and Silvana Melara Cancer Research Fund. Lead author Dr. Briones had no financial conflicts to disclose.

Source: Briones J et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.658331.