Surgical Oncology

PHOENIX – Improving cancer-specific survival after resection for colorectal cancer may be as simple as ordering preoperative mechanical bowel preparation, according to an analysis of data from a randomized trial conducted in Sweden and Germany.

Roughly half of the 841 patients studied had such preparation before their operation. The actuarial 5-year rate of cancer-specific survival was about 8% higher in this group, first author Dr. Åsa Collin of Uppsala University reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

An analysis of cancer stage at the time of surgery suggested that the two groups were well matched on this measure. Preparation did not significantly decrease the rate of recurrence or increase the rate of overall survival.

Session attendee Dr. J. Daniel Stanley of University Surgical Associates in Chattanooga, Tenn., questioned whether the patients might have differed on other factors that influenced whether they underwent mechanical bowel preparation.

"Were some of them obstructed, which might indicate a different tumor biology than was reflected in the staging?" he asked.

"These were all elective surgeries, and there was no patient who we actually decided that they shouldn’t have preparation," Dr. Collin replied.

In an interview, session comoderator Dr. David Maron, a colorectal surgeon at the Cleveland Clinic in Weston, Fla., said, "What was interesting was that they didn’t show a significant difference in cancer recurrence, although it was close to significance. So the question remains, is it in fact the mechanical bowel prep, or could there be differences in the postoperative follow-up and even the postoperative treatment of those patients who developed recurrence?"

Guidelines leave preparation up to the treating surgeon, and several studies have found no benefit at least in the short term, he noted. "This is one of the first studies that have shown that perhaps from a long-term standpoint in patients with cancer, that there may be some benefit to preoperative preparation of the bowel, although again, it’s preliminary and there’s a lot of unknowns out there."

Dr. Collin and her colleagues analyzed data from a trial among patients who underwent an elective resection for cancer, adenoma, or diverticular disease of the colon at 21 hospitals in Sweden and Germany between 1999 and 2005.

Earlier results for the entire trial population, previously reported, showed no significant reduction in 30-day rates of complications with mechanical bowel preparation (Br. J. Surg. 2007;94:689-95).

The new, long-term results for just the 841 patients with colorectal cancer – 53% of whom had a mechanical bowel preparation before their surgery – indicated those undergoing this preparation had a higher actuarial 5-year rate of cancer-specific survival (90% vs. 82%; P = .03).

The two groups were similar in terms of the 5-year rate of recurrence (80% vs. 89%, P = .08) and overall survival, Dr. Collin said.

"We looked at tumor stage to see if the explanation for patients having no mechanical bowel preparation having poorer cancer-specific survival was that they had more advanced tumors, and there was no difference in the stages" between groups, she said, with the majority of patients in both groups having stage II or III disease.

Dr. Collin disclosed no conflicts of interest related to the research.

PHOENIX – Improving cancer-specific survival after resection for colorectal cancer may be as simple as ordering preoperative mechanical bowel preparation, according to an analysis of data from a randomized trial conducted in Sweden and Germany.

Roughly half of the 841 patients studied had such preparation before their operation. The actuarial 5-year rate of cancer-specific survival was about 8% higher in this group, first author Dr. Åsa Collin of Uppsala University reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

An analysis of cancer stage at the time of surgery suggested that the two groups were well matched on this measure. Preparation did not significantly decrease the rate of recurrence or increase the rate of overall survival.

Session attendee Dr. J. Daniel Stanley of University Surgical Associates in Chattanooga, Tenn., questioned whether the patients might have differed on other factors that influenced whether they underwent mechanical bowel preparation.

"Were some of them obstructed, which might indicate a different tumor biology than was reflected in the staging?" he asked.

"These were all elective surgeries, and there was no patient who we actually decided that they shouldn’t have preparation," Dr. Collin replied.

In an interview, session comoderator Dr. David Maron, a colorectal surgeon at the Cleveland Clinic in Weston, Fla., said, "What was interesting was that they didn’t show a significant difference in cancer recurrence, although it was close to significance. So the question remains, is it in fact the mechanical bowel prep, or could there be differences in the postoperative follow-up and even the postoperative treatment of those patients who developed recurrence?"

Guidelines leave preparation up to the treating surgeon, and several studies have found no benefit at least in the short term, he noted. "This is one of the first studies that have shown that perhaps from a long-term standpoint in patients with cancer, that there may be some benefit to preoperative preparation of the bowel, although again, it’s preliminary and there’s a lot of unknowns out there."

Dr. Collin and her colleagues analyzed data from a trial among patients who underwent an elective resection for cancer, adenoma, or diverticular disease of the colon at 21 hospitals in Sweden and Germany between 1999 and 2005.

Earlier results for the entire trial population, previously reported, showed no significant reduction in 30-day rates of complications with mechanical bowel preparation (Br. J. Surg. 2007;94:689-95).

The new, long-term results for just the 841 patients with colorectal cancer – 53% of whom had a mechanical bowel preparation before their surgery – indicated those undergoing this preparation had a higher actuarial 5-year rate of cancer-specific survival (90% vs. 82%; P = .03).

The two groups were similar in terms of the 5-year rate of recurrence (80% vs. 89%, P = .08) and overall survival, Dr. Collin said.

"We looked at tumor stage to see if the explanation for patients having no mechanical bowel preparation having poorer cancer-specific survival was that they had more advanced tumors, and there was no difference in the stages" between groups, she said, with the majority of patients in both groups having stage II or III disease.

Dr. Collin disclosed no conflicts of interest related to the research.

PHOENIX – Improving cancer-specific survival after resection for colorectal cancer may be as simple as ordering preoperative mechanical bowel preparation, according to an analysis of data from a randomized trial conducted in Sweden and Germany.

Roughly half of the 841 patients studied had such preparation before their operation. The actuarial 5-year rate of cancer-specific survival was about 8% higher in this group, first author Dr. Åsa Collin of Uppsala University reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

An analysis of cancer stage at the time of surgery suggested that the two groups were well matched on this measure. Preparation did not significantly decrease the rate of recurrence or increase the rate of overall survival.

Session attendee Dr. J. Daniel Stanley of University Surgical Associates in Chattanooga, Tenn., questioned whether the patients might have differed on other factors that influenced whether they underwent mechanical bowel preparation.

"Were some of them obstructed, which might indicate a different tumor biology than was reflected in the staging?" he asked.

"These were all elective surgeries, and there was no patient who we actually decided that they shouldn’t have preparation," Dr. Collin replied.

In an interview, session comoderator Dr. David Maron, a colorectal surgeon at the Cleveland Clinic in Weston, Fla., said, "What was interesting was that they didn’t show a significant difference in cancer recurrence, although it was close to significance. So the question remains, is it in fact the mechanical bowel prep, or could there be differences in the postoperative follow-up and even the postoperative treatment of those patients who developed recurrence?"

Guidelines leave preparation up to the treating surgeon, and several studies have found no benefit at least in the short term, he noted. "This is one of the first studies that have shown that perhaps from a long-term standpoint in patients with cancer, that there may be some benefit to preoperative preparation of the bowel, although again, it’s preliminary and there’s a lot of unknowns out there."

Dr. Collin and her colleagues analyzed data from a trial among patients who underwent an elective resection for cancer, adenoma, or diverticular disease of the colon at 21 hospitals in Sweden and Germany between 1999 and 2005.

Earlier results for the entire trial population, previously reported, showed no significant reduction in 30-day rates of complications with mechanical bowel preparation (Br. J. Surg. 2007;94:689-95).

The new, long-term results for just the 841 patients with colorectal cancer – 53% of whom had a mechanical bowel preparation before their surgery – indicated those undergoing this preparation had a higher actuarial 5-year rate of cancer-specific survival (90% vs. 82%; P = .03).

The two groups were similar in terms of the 5-year rate of recurrence (80% vs. 89%, P = .08) and overall survival, Dr. Collin said.

"We looked at tumor stage to see if the explanation for patients having no mechanical bowel preparation having poorer cancer-specific survival was that they had more advanced tumors, and there was no difference in the stages" between groups, she said, with the majority of patients in both groups having stage II or III disease.

Dr. Collin disclosed no conflicts of interest related to the research.

A new practice guideline released at the American Urological Association annual meeting presents the clinical framework to help weigh the risks and benefits of providing adjuvant and salvage radiation therapy after prostatectomy.

"There is now a document that guides us in offering the best clinical practices for anyone who undergoes radical prostatectomy regarding their follow-up care with radiotherapy," said Dr. Richard K. Valicenti of the department of radiation oncology at the University of California, Davis.

One practice standard in the guideline advises physicians to offer adjuvant radiotherapy to patients with adverse pathologic findings at prostatectomy, because studies have shown that this therapy can result in reductions in prostate-specific antigen (PSA) recurrence, local recurrence, and clinical progression. The adverse findings that would warrant this therapy include seminal vesicle invasion, positive surgical margins, or extraprostatic extension.

"The data are overwhelmingly consistent that it [radiotherapy] will improve on tumor control rates, as well as progression-free survival," Dr. Valicenti said, adding that these patients should also experience improved quality of life.

In addition to the above practice standard, the guideline, issued jointly by the American Society for Radiation Oncology (ASTRO) and the American Urological Association (AUA), made the following recommendations:

• Inform patients with localized prostate cancer considering radical prostatectomy about the possibility that the pathologic findings will predict a higher risk of cancer recurrence.

• Advise patients with adverse pathologic findings, including seminal vesicle invasion, positive surgical margins, and extraprostatic extension, that adjuvant radiation therapy compared with radical prostatectomy only reduces the risk of PSA recurrence, local recurrence, and clinical progression of cancer;

• Warn patients that they are a higher risk of developing metastatic prostate cancer or death from the disease if there is a PSA recurrence after surgery;

• Define biochemical recurrence as a detectable or rising PSA value after surgery that is greater than or equal to 0.2 ng/mL with a second confirmatory level greater than or equal to 0.2 ng/mL.

• Consider a restaging evaluation in patients with a PSA recurrence.

• Offer salvage radiation therapy to patients with PSA or local recurrence after radical prostatectomy in whom there is no evidence of distant metastatic disease.

• Inform patients that the effectiveness of radiation therapy for PSA recurrence is greatest when given at lower levels of PSA. and

• Inform patients that in addition to the benefits of controlling disease recurrence, radiation therapy could produce possible short- and long-term urinary, bowel, and sexual side effects.

Before recommending adjuvant or salvage radiotherapy, "look at the patients’ biological information obtained from the radical prostatectomy specimen, and balance that with the overall health status of the patients [and] concerns about certain aspects of quality of life, whether it be sexual activity or urinary function. They also need to balance that with any other medical conditions or previous treatments that would preclude the use of radiation therapy," Dr. Valicenti said.

"The Adjuvant and Salvage Radiotherapy After Prostatectomy: ASTRO/AUA Guideline" is a comprehensive review of 324 research articles on patients with detectable and undetectable PSA levels, toxicity, optimal imaging strategies, and the impact on quality of life to determine the appropriateness of radiation therapy in patients suspected of recurrence. Only studies in which PSA data were provided for at least 75% of patients were included in the guideline. The panel was led by Dr. Valicenti and Dr. Ian M. Thompson of the University of Texas Health Science Center.

The guideline is available at www.redjournal.org and www.auanet.org.

Dr. Valicenti reported no relevant disclosures.

A new practice guideline released at the American Urological Association annual meeting presents the clinical framework to help weigh the risks and benefits of providing adjuvant and salvage radiation therapy after prostatectomy.

"There is now a document that guides us in offering the best clinical practices for anyone who undergoes radical prostatectomy regarding their follow-up care with radiotherapy," said Dr. Richard K. Valicenti of the department of radiation oncology at the University of California, Davis.

One practice standard in the guideline advises physicians to offer adjuvant radiotherapy to patients with adverse pathologic findings at prostatectomy, because studies have shown that this therapy can result in reductions in prostate-specific antigen (PSA) recurrence, local recurrence, and clinical progression. The adverse findings that would warrant this therapy include seminal vesicle invasion, positive surgical margins, or extraprostatic extension.

"The data are overwhelmingly consistent that it [radiotherapy] will improve on tumor control rates, as well as progression-free survival," Dr. Valicenti said, adding that these patients should also experience improved quality of life.

In addition to the above practice standard, the guideline, issued jointly by the American Society for Radiation Oncology (ASTRO) and the American Urological Association (AUA), made the following recommendations:

• Inform patients with localized prostate cancer considering radical prostatectomy about the possibility that the pathologic findings will predict a higher risk of cancer recurrence.

• Advise patients with adverse pathologic findings, including seminal vesicle invasion, positive surgical margins, and extraprostatic extension, that adjuvant radiation therapy compared with radical prostatectomy only reduces the risk of PSA recurrence, local recurrence, and clinical progression of cancer;

• Warn patients that they are a higher risk of developing metastatic prostate cancer or death from the disease if there is a PSA recurrence after surgery;

• Define biochemical recurrence as a detectable or rising PSA value after surgery that is greater than or equal to 0.2 ng/mL with a second confirmatory level greater than or equal to 0.2 ng/mL.

• Consider a restaging evaluation in patients with a PSA recurrence.

• Offer salvage radiation therapy to patients with PSA or local recurrence after radical prostatectomy in whom there is no evidence of distant metastatic disease.

• Inform patients that the effectiveness of radiation therapy for PSA recurrence is greatest when given at lower levels of PSA. and

• Inform patients that in addition to the benefits of controlling disease recurrence, radiation therapy could produce possible short- and long-term urinary, bowel, and sexual side effects.

Before recommending adjuvant or salvage radiotherapy, "look at the patients’ biological information obtained from the radical prostatectomy specimen, and balance that with the overall health status of the patients [and] concerns about certain aspects of quality of life, whether it be sexual activity or urinary function. They also need to balance that with any other medical conditions or previous treatments that would preclude the use of radiation therapy," Dr. Valicenti said.

"The Adjuvant and Salvage Radiotherapy After Prostatectomy: ASTRO/AUA Guideline" is a comprehensive review of 324 research articles on patients with detectable and undetectable PSA levels, toxicity, optimal imaging strategies, and the impact on quality of life to determine the appropriateness of radiation therapy in patients suspected of recurrence. Only studies in which PSA data were provided for at least 75% of patients were included in the guideline. The panel was led by Dr. Valicenti and Dr. Ian M. Thompson of the University of Texas Health Science Center.

The guideline is available at www.redjournal.org and www.auanet.org.

Dr. Valicenti reported no relevant disclosures.

A new practice guideline released at the American Urological Association annual meeting presents the clinical framework to help weigh the risks and benefits of providing adjuvant and salvage radiation therapy after prostatectomy.

"There is now a document that guides us in offering the best clinical practices for anyone who undergoes radical prostatectomy regarding their follow-up care with radiotherapy," said Dr. Richard K. Valicenti of the department of radiation oncology at the University of California, Davis.

One practice standard in the guideline advises physicians to offer adjuvant radiotherapy to patients with adverse pathologic findings at prostatectomy, because studies have shown that this therapy can result in reductions in prostate-specific antigen (PSA) recurrence, local recurrence, and clinical progression. The adverse findings that would warrant this therapy include seminal vesicle invasion, positive surgical margins, or extraprostatic extension.

"The data are overwhelmingly consistent that it [radiotherapy] will improve on tumor control rates, as well as progression-free survival," Dr. Valicenti said, adding that these patients should also experience improved quality of life.

In addition to the above practice standard, the guideline, issued jointly by the American Society for Radiation Oncology (ASTRO) and the American Urological Association (AUA), made the following recommendations:

• Inform patients with localized prostate cancer considering radical prostatectomy about the possibility that the pathologic findings will predict a higher risk of cancer recurrence.

• Advise patients with adverse pathologic findings, including seminal vesicle invasion, positive surgical margins, and extraprostatic extension, that adjuvant radiation therapy compared with radical prostatectomy only reduces the risk of PSA recurrence, local recurrence, and clinical progression of cancer;

• Warn patients that they are a higher risk of developing metastatic prostate cancer or death from the disease if there is a PSA recurrence after surgery;

• Define biochemical recurrence as a detectable or rising PSA value after surgery that is greater than or equal to 0.2 ng/mL with a second confirmatory level greater than or equal to 0.2 ng/mL.

• Consider a restaging evaluation in patients with a PSA recurrence.

• Offer salvage radiation therapy to patients with PSA or local recurrence after radical prostatectomy in whom there is no evidence of distant metastatic disease.

• Inform patients that the effectiveness of radiation therapy for PSA recurrence is greatest when given at lower levels of PSA. and

• Inform patients that in addition to the benefits of controlling disease recurrence, radiation therapy could produce possible short- and long-term urinary, bowel, and sexual side effects.

Before recommending adjuvant or salvage radiotherapy, "look at the patients’ biological information obtained from the radical prostatectomy specimen, and balance that with the overall health status of the patients [and] concerns about certain aspects of quality of life, whether it be sexual activity or urinary function. They also need to balance that with any other medical conditions or previous treatments that would preclude the use of radiation therapy," Dr. Valicenti said.

"The Adjuvant and Salvage Radiotherapy After Prostatectomy: ASTRO/AUA Guideline" is a comprehensive review of 324 research articles on patients with detectable and undetectable PSA levels, toxicity, optimal imaging strategies, and the impact on quality of life to determine the appropriateness of radiation therapy in patients suspected of recurrence. Only studies in which PSA data were provided for at least 75% of patients were included in the guideline. The panel was led by Dr. Valicenti and Dr. Ian M. Thompson of the University of Texas Health Science Center.

The guideline is available at www.redjournal.org and www.auanet.org.

Dr. Valicenti reported no relevant disclosures.

MINNEAPOLIS – Sublobar resection and lobectomy resulted in equivalent lung cancer survival and overall recurrence rates in a screen-detected cohort of 348 stage IA non–small-cell lung cancer patients.

In all, 7% of patients (4/54) who underwent sublobar resection and 10% of those (29/294) who underwent lobectomy died of lung cancer after a median follow-up of 73 months (P = .64).

All-cause mortality was also statistically similar at 17% and 22%, said Dr. Nasser Altorki, professor of cardiothoracic surgery and director of thoracic surgery at New York Presbyterian–Weill Cornell Medical Center in New York.

Although lobectomy has been the standard of care for resection of early-stage non–small-cell lung cancer since 1994, several studies support sublobar resection in patients with small peripheral tumors and the elderly with compromised pulmonary reserve.

The best surgical treatment for younger patients with adequate cardiopulmonary function remains controversial, with two large, ongoing trials in the U.S. and Japan evaluating lobar vs. sublobar resection in this setting. A recent best evidence paper (Interact. CardioVasc. Thorac. Surg. 2012;14:816-20) concluded that lobectomy is still the best surgical option for these patients, citing evidence of lower survival and higher recurrence rates with wedge resections than with anatomic segmentectomies. The two sublobar techniques are often lumped together in comparisons with lobectomy, but are not technically or oncologically the same.

Wedge resection in the current study seemed to be associated with a higher rate of recurrence than segmentectomy, Dr. Altorki said at the annual meeting of the American Association for Thoracic Surgery.

Recurrence occurred in 32 patients after lobectomy and 8 after sublobar resection (11% vs. 15%; P = .40), with all of the sublobar resection recurrences occurring after wedge resection (8/38 or 21% vs. 0%).

"I don’t want to say this is a practice-changing study; however, it is a study that calls for more technical equipoise in our approach to the [surgical] treatment of lung cancer," he said during a discussion of the results. "Clearly, we can apply this operation to patients who would be candidates for both lobectomy and sublobar resection, but it does not extend to those patients, for example, that would have been poor candidates for any surgical resection."

The 348 patients had c1A non–small-cell lung cancer that presented as a solid nodule on computed tomography screening and underwent surgery as part of the International Early Lung Cancer Action Program from 1993 to 2011. Comorbidities were similar among the lobectomy and sublobar patients including cardiac disease (6% vs. 11%), chronic obstructive pulmonary disease (15% vs. 26%) and diabetes (9% vs. 7%). Their median age was 63 vs. 65 years, and the median number of pack-years of smoking was 48 vs. 49, respectively.

The lobectomy group had significantly larger tumors (13 mm vs. 11 mm), more frequent sampling of mediastinal nodes (78% vs. 56%) and more resected lymph nodes (mean 8 vs. 5).

The overall rate of hospital mortality in the multicenter study was low at 0.9% (3/348) and "represents what is achievable in screening centers of excellence," Dr. Altorki said.

Ten-year survival was 88% with lobectomy and 90% with sublobar resection (log rank P = .64). There was no difference in patients with tumors less than 2 cm (88% vs. 89%), who represented the majority or 86% of the cohort.

Cox regression analysis, adjusted for the above potential confounders, showed that only age (hazard ratio, 2.9; P less than .0001) and severe emphysema (HR, 4.2; P = .005) significantly predicted survival, whereas sublobar resection did not (HR, 0.8; P = .60), he said.

Invited discussant Dr. Joseph S. Friedberg, chief of thoracic surgery at the University of Pennsylvania Health System-Presbyterian in Philadelphia, expressed surprise that despite undergoing surgery by highly qualified general thoracic surgeons, 70% of sublobar resections were performed as wedge and not segmentectomies, and that more than 40% of sublobar resection patients and nearly a quarter of lobectomy patients did not have one mediastinal node biopsied.

"One would expect, based on the Lung Cancer Study Group analysis and common sense, that some of these patients, especially sublobar resection patients, were understaged and/or undertreated and yet the results are as good as anything in the literature," he said. "How do you reconcile that?"

Dr. Altorki said assessment of the mediastinal field was disappointing and that further education is needed on the prognostic and therapeutic benefits of such assessment, but that the rate far exceeds what is in the published literature. He also speculated that most of the patients were done by video-assisted thoracic surgery and that mediastinal node assessment may not be as straightforward with VATS as it is with open surgery.

Dr. Altorki said that, going in, many of the surgeons may have thought that a 1- to 1.2-cm tumor may be equally resected with wedge resection and anatomic segmentectomy, and that this "is a job we have to address in ongoing randomized trials."

Dr. Altorki reported no relevant financial disclosures.

[email protected]

MINNEAPOLIS – Sublobar resection and lobectomy resulted in equivalent lung cancer survival and overall recurrence rates in a screen-detected cohort of 348 stage IA non–small-cell lung cancer patients.

In all, 7% of patients (4/54) who underwent sublobar resection and 10% of those (29/294) who underwent lobectomy died of lung cancer after a median follow-up of 73 months (P = .64).

All-cause mortality was also statistically similar at 17% and 22%, said Dr. Nasser Altorki, professor of cardiothoracic surgery and director of thoracic surgery at New York Presbyterian–Weill Cornell Medical Center in New York.

Although lobectomy has been the standard of care for resection of early-stage non–small-cell lung cancer since 1994, several studies support sublobar resection in patients with small peripheral tumors and the elderly with compromised pulmonary reserve.

The best surgical treatment for younger patients with adequate cardiopulmonary function remains controversial, with two large, ongoing trials in the U.S. and Japan evaluating lobar vs. sublobar resection in this setting. A recent best evidence paper (Interact. CardioVasc. Thorac. Surg. 2012;14:816-20) concluded that lobectomy is still the best surgical option for these patients, citing evidence of lower survival and higher recurrence rates with wedge resections than with anatomic segmentectomies. The two sublobar techniques are often lumped together in comparisons with lobectomy, but are not technically or oncologically the same.

Wedge resection in the current study seemed to be associated with a higher rate of recurrence than segmentectomy, Dr. Altorki said at the annual meeting of the American Association for Thoracic Surgery.

Recurrence occurred in 32 patients after lobectomy and 8 after sublobar resection (11% vs. 15%; P = .40), with all of the sublobar resection recurrences occurring after wedge resection (8/38 or 21% vs. 0%).

"I don’t want to say this is a practice-changing study; however, it is a study that calls for more technical equipoise in our approach to the [surgical] treatment of lung cancer," he said during a discussion of the results. "Clearly, we can apply this operation to patients who would be candidates for both lobectomy and sublobar resection, but it does not extend to those patients, for example, that would have been poor candidates for any surgical resection."

The 348 patients had c1A non–small-cell lung cancer that presented as a solid nodule on computed tomography screening and underwent surgery as part of the International Early Lung Cancer Action Program from 1993 to 2011. Comorbidities were similar among the lobectomy and sublobar patients including cardiac disease (6% vs. 11%), chronic obstructive pulmonary disease (15% vs. 26%) and diabetes (9% vs. 7%). Their median age was 63 vs. 65 years, and the median number of pack-years of smoking was 48 vs. 49, respectively.

The lobectomy group had significantly larger tumors (13 mm vs. 11 mm), more frequent sampling of mediastinal nodes (78% vs. 56%) and more resected lymph nodes (mean 8 vs. 5).

The overall rate of hospital mortality in the multicenter study was low at 0.9% (3/348) and "represents what is achievable in screening centers of excellence," Dr. Altorki said.

Ten-year survival was 88% with lobectomy and 90% with sublobar resection (log rank P = .64). There was no difference in patients with tumors less than 2 cm (88% vs. 89%), who represented the majority or 86% of the cohort.

Cox regression analysis, adjusted for the above potential confounders, showed that only age (hazard ratio, 2.9; P less than .0001) and severe emphysema (HR, 4.2; P = .005) significantly predicted survival, whereas sublobar resection did not (HR, 0.8; P = .60), he said.

Invited discussant Dr. Joseph S. Friedberg, chief of thoracic surgery at the University of Pennsylvania Health System-Presbyterian in Philadelphia, expressed surprise that despite undergoing surgery by highly qualified general thoracic surgeons, 70% of sublobar resections were performed as wedge and not segmentectomies, and that more than 40% of sublobar resection patients and nearly a quarter of lobectomy patients did not have one mediastinal node biopsied.

"One would expect, based on the Lung Cancer Study Group analysis and common sense, that some of these patients, especially sublobar resection patients, were understaged and/or undertreated and yet the results are as good as anything in the literature," he said. "How do you reconcile that?"

Dr. Altorki said assessment of the mediastinal field was disappointing and that further education is needed on the prognostic and therapeutic benefits of such assessment, but that the rate far exceeds what is in the published literature. He also speculated that most of the patients were done by video-assisted thoracic surgery and that mediastinal node assessment may not be as straightforward with VATS as it is with open surgery.

Dr. Altorki said that, going in, many of the surgeons may have thought that a 1- to 1.2-cm tumor may be equally resected with wedge resection and anatomic segmentectomy, and that this "is a job we have to address in ongoing randomized trials."

Dr. Altorki reported no relevant financial disclosures.

[email protected]

MINNEAPOLIS – Sublobar resection and lobectomy resulted in equivalent lung cancer survival and overall recurrence rates in a screen-detected cohort of 348 stage IA non–small-cell lung cancer patients.

In all, 7% of patients (4/54) who underwent sublobar resection and 10% of those (29/294) who underwent lobectomy died of lung cancer after a median follow-up of 73 months (P = .64).

All-cause mortality was also statistically similar at 17% and 22%, said Dr. Nasser Altorki, professor of cardiothoracic surgery and director of thoracic surgery at New York Presbyterian–Weill Cornell Medical Center in New York.

Although lobectomy has been the standard of care for resection of early-stage non–small-cell lung cancer since 1994, several studies support sublobar resection in patients with small peripheral tumors and the elderly with compromised pulmonary reserve.

The best surgical treatment for younger patients with adequate cardiopulmonary function remains controversial, with two large, ongoing trials in the U.S. and Japan evaluating lobar vs. sublobar resection in this setting. A recent best evidence paper (Interact. CardioVasc. Thorac. Surg. 2012;14:816-20) concluded that lobectomy is still the best surgical option for these patients, citing evidence of lower survival and higher recurrence rates with wedge resections than with anatomic segmentectomies. The two sublobar techniques are often lumped together in comparisons with lobectomy, but are not technically or oncologically the same.

Wedge resection in the current study seemed to be associated with a higher rate of recurrence than segmentectomy, Dr. Altorki said at the annual meeting of the American Association for Thoracic Surgery.

Recurrence occurred in 32 patients after lobectomy and 8 after sublobar resection (11% vs. 15%; P = .40), with all of the sublobar resection recurrences occurring after wedge resection (8/38 or 21% vs. 0%).

"I don’t want to say this is a practice-changing study; however, it is a study that calls for more technical equipoise in our approach to the [surgical] treatment of lung cancer," he said during a discussion of the results. "Clearly, we can apply this operation to patients who would be candidates for both lobectomy and sublobar resection, but it does not extend to those patients, for example, that would have been poor candidates for any surgical resection."

The 348 patients had c1A non–small-cell lung cancer that presented as a solid nodule on computed tomography screening and underwent surgery as part of the International Early Lung Cancer Action Program from 1993 to 2011. Comorbidities were similar among the lobectomy and sublobar patients including cardiac disease (6% vs. 11%), chronic obstructive pulmonary disease (15% vs. 26%) and diabetes (9% vs. 7%). Their median age was 63 vs. 65 years, and the median number of pack-years of smoking was 48 vs. 49, respectively.

The lobectomy group had significantly larger tumors (13 mm vs. 11 mm), more frequent sampling of mediastinal nodes (78% vs. 56%) and more resected lymph nodes (mean 8 vs. 5).

The overall rate of hospital mortality in the multicenter study was low at 0.9% (3/348) and "represents what is achievable in screening centers of excellence," Dr. Altorki said.

Ten-year survival was 88% with lobectomy and 90% with sublobar resection (log rank P = .64). There was no difference in patients with tumors less than 2 cm (88% vs. 89%), who represented the majority or 86% of the cohort.

Cox regression analysis, adjusted for the above potential confounders, showed that only age (hazard ratio, 2.9; P less than .0001) and severe emphysema (HR, 4.2; P = .005) significantly predicted survival, whereas sublobar resection did not (HR, 0.8; P = .60), he said.

Invited discussant Dr. Joseph S. Friedberg, chief of thoracic surgery at the University of Pennsylvania Health System-Presbyterian in Philadelphia, expressed surprise that despite undergoing surgery by highly qualified general thoracic surgeons, 70% of sublobar resections were performed as wedge and not segmentectomies, and that more than 40% of sublobar resection patients and nearly a quarter of lobectomy patients did not have one mediastinal node biopsied.

"One would expect, based on the Lung Cancer Study Group analysis and common sense, that some of these patients, especially sublobar resection patients, were understaged and/or undertreated and yet the results are as good as anything in the literature," he said. "How do you reconcile that?"

Dr. Altorki said assessment of the mediastinal field was disappointing and that further education is needed on the prognostic and therapeutic benefits of such assessment, but that the rate far exceeds what is in the published literature. He also speculated that most of the patients were done by video-assisted thoracic surgery and that mediastinal node assessment may not be as straightforward with VATS as it is with open surgery.

Dr. Altorki said that, going in, many of the surgeons may have thought that a 1- to 1.2-cm tumor may be equally resected with wedge resection and anatomic segmentectomy, and that this "is a job we have to address in ongoing randomized trials."

Dr. Altorki reported no relevant financial disclosures.

[email protected]

Data show that African Americans present with colon cancer at an earlier age than whites. But there's debate about the appropriate screening age. Should all African American patients be screened at age 40? Dr. Byron Cryer, professor of medicine at the University of Texas Southwestern Medical Center, discusses the pros and cons of earlier screening and shares his opinion on the issue.

Data show that African Americans present with colon cancer at an earlier age than whites. But there's debate about the appropriate screening age. Should all African American patients be screened at age 40? Dr. Byron Cryer, professor of medicine at the University of Texas Southwestern Medical Center, discusses the pros and cons of earlier screening and shares his opinion on the issue.

Data show that African Americans present with colon cancer at an earlier age than whites. But there's debate about the appropriate screening age. Should all African American patients be screened at age 40? Dr. Byron Cryer, professor of medicine at the University of Texas Southwestern Medical Center, discusses the pros and cons of earlier screening and shares his opinion on the issue.

PHOENIX – The standard sequential approach to treatment of patients with isolated synchronous liver metastases of colorectal cancer, entailing up-front removal of the primary tumor, is associated with growth of the metastases, according to results from a retrospective cohort study.

A team led by Dr. Alistair Slesser, a surgical registrar at the Royal Marsden Hospital in London, studied 114 patients with colorectal cancer who had synchronous liver metastases, meaning ones identified within a year of the cancer diagnosis, and no other metastases.

Results showed that patients whose initial treatment was resection of the colorectal primary tumor had ninefold higher odds of progression of their liver metastases at 3 months, compared with patients whose initial treatment was chemotherapy, he reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

Although liver metastases showed regression during 3-6 months of treatment in both groups, the rate was somewhat slower in the primary tumor resection group.

"Our findings suggest that an up-front primary tumor resection is actually an adverse prognostic factor. Indeed, our results have demonstrated that up-front primary tumor resection seemed to negate the effects of the adjuvant therapy on the treatment of the liver metastasis," Dr. Slesser commented.

"How does this apply clinically? We would recommend that patients who have limited metastatic disease, instead of having an up-front primary tumor resection perhaps [they should] be treated with neoadjuvant chemotherapy first. Or perhaps another surgical approach, like a simultaneous resection, should be considered to negate the adverse effects of a primary tumor resection on the metastatic disease," he said.

"When patients have lesions which are suspicious for liver metastases, we would recommend that these patients [be] thoroughly investigated, and if metastatic disease is confirmed, then again, we would recommend that they have chemotherapy prior to any subsequent intervention," he added.

The mechanism leading to growth of liver metastases after primary tumor resection is unknown, according to Dr. Slesser. "There is possibly an association for ... biological reasons. The other reason is that perhaps when a patient has an up-front primary tumor resection, there is a delay in getting chemotherapy, and that can cause the progression that we see."

Session attendee Dr. Gary Dunn, of the University of Oklahoma, Oklahoma City, asked how much time elapsed between up-front resection and receipt of adjuvant chemotherapy in that group, and the variance in this measure, noting, "That will significantly affect your outcome, if some patients started at 6 weeks and some patients started at 12 weeks postop."

"Usually, patients waited 6 weeks before they started chemotherapy postoperatively," Dr. Slesser explained. "The majority of patients who had primary tumor resection had the adjuvant chemotherapy after the postoperative scan; the 3-month scan tends to be the postoperative scan."

Dr. Dunn further wondered about the comparability between groups of the chemotherapy received, asking what agents were used.

"At the Royal Marsden, the chemotherapy regimes tend to be quite uniform," Dr. Slesser replied. "Generally, all patients are on capecitabine [Xeloda] and oxaliplatin, with a monoclonal agent such as bevacizumab [Avastin]. They tend to get that when they have neoadjuvant chemotherapy."

Another attendee said, "Excellent paper, very well presented data, particularly considering there are a lot of retrospective series out there that are showing the up-front resection as a favorable prognostic indicator, which I don’t believe. ... But I would like to see a little more information about how the patients were treated subsequently. Were these patients who they were planning to get to surgery for resection, or were these patients who were treated for palliative intent? Did they have symptomatic primaries?"

"In the majority of these patients, the intent was curative surgery," Dr. Slesser replied. "We tried to exclude patients who were clearly referred for palliative treatment because we really wanted to assess patients who were referred for curative treatment."

Attendee Dr. David Shibata, of the Moffitt Cancer Center in Tampa, commented, "I think a critical question is that you have done a primary tumor resection and the liver tumor has tended to grow, which is not entirely surprising, but then in those cases, how many became unresectable from a liver standpoint?"

"About 60% ended up having hepatectomies," Dr. Slesser said, noting that the data reported looked only at the short-term time frame. "We do have further results, which will be in the paper, pertaining to survival. But the real aim of this study was to look at initial radiological progression of disease, because we thought that the primary tumor resection may be associated with a sudden increase in the size of metastasis."

The finding of a better liver outcome with initial chemotherapy "makes sense," session comoderator Dr. Marylise Boutros, of McGill University in Montreal, said in an interview. "That’s something that we would expect, that you can treat the largest burden of the disease, which is the metastasis – it’s a systemic disease – with chemotherapy up-front."

"But it’s definitely a smaller study, and this needs to be looked at in a larger subset and in a prospective fashion," she added.

Giving some background to the research, Dr. Slesser noted that "the mainstay of surgical treatment for these patients with limited metastatic disease is a sequential resection. Patients tend to have an up-front primary tumor resection, followed by adjuvant chemotherapy, followed by hepatic resection if feasible. On the other hand, patients who have extensive metastatic disease tend to have neoadjuvant chemotherapy prior to a surgical intervention."

He and his coinvestigators studied patients with isolated synchronous colorectal liver metastases who were referred to the Royal Marsden Hospital for treatment between 2005 and 2010 and had imaging done at baseline, 3 months, and 6 months.

The mean age of the cohort was 64 years, and the ratio of men to women was about 2:1. In terms of treatment, 51% of the patients underwent primary tumor resection, while the other 49% received neoadjuvant chemotherapy.

In univariate analysis, the factor most strongly associated with progression of liver metastases – defined as an increase in their cumulative diameter of at least 20% – at 3 months was a primary tumor resection, according to Dr. Slesser.

In a multivariate analysis, relative to their counterparts in the neoadjuvant chemotherapy group, patients undergoing primary tumor resection had dramatically elevated odds of progression of liver metastases (odds ratio, 9.0; P = .001).

Additionally, metastatic burden showed an upward trend between baseline and 6 months in the group undergoing primary tumor resection (from 40 to 51 mm; P = .19), whereas it decreased significantly in the neoadjuvant chemotherapy group (from 96 to 52 mm; P = .001).

Overall, 93% of patients having a primary tumor resection went on to receive adjuvant chemotherapy, according to Dr. Slesser.

Comparing baseline to 3 months versus 3 months to 6 months, liver metastases began regressing in the primary tumor resection group, with the growth rate changing from 4.0 to –3.0 mm/month (P less than .001), reflecting the effect of the adjuvant chemotherapy, he said. Liver metastases in the neoadjuvant chemotherapy group continued to regress, albeit also at a slower pace, with the growth rate changing from –5.6 to –4.0 mm/month (P = .003).

Dr. Slesser disclosed no relevant conflicts of interest.

PHOENIX – The standard sequential approach to treatment of patients with isolated synchronous liver metastases of colorectal cancer, entailing up-front removal of the primary tumor, is associated with growth of the metastases, according to results from a retrospective cohort study.

A team led by Dr. Alistair Slesser, a surgical registrar at the Royal Marsden Hospital in London, studied 114 patients with colorectal cancer who had synchronous liver metastases, meaning ones identified within a year of the cancer diagnosis, and no other metastases.

Results showed that patients whose initial treatment was resection of the colorectal primary tumor had ninefold higher odds of progression of their liver metastases at 3 months, compared with patients whose initial treatment was chemotherapy, he reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

Although liver metastases showed regression during 3-6 months of treatment in both groups, the rate was somewhat slower in the primary tumor resection group.

"Our findings suggest that an up-front primary tumor resection is actually an adverse prognostic factor. Indeed, our results have demonstrated that up-front primary tumor resection seemed to negate the effects of the adjuvant therapy on the treatment of the liver metastasis," Dr. Slesser commented.

"How does this apply clinically? We would recommend that patients who have limited metastatic disease, instead of having an up-front primary tumor resection perhaps [they should] be treated with neoadjuvant chemotherapy first. Or perhaps another surgical approach, like a simultaneous resection, should be considered to negate the adverse effects of a primary tumor resection on the metastatic disease," he said.

"When patients have lesions which are suspicious for liver metastases, we would recommend that these patients [be] thoroughly investigated, and if metastatic disease is confirmed, then again, we would recommend that they have chemotherapy prior to any subsequent intervention," he added.

The mechanism leading to growth of liver metastases after primary tumor resection is unknown, according to Dr. Slesser. "There is possibly an association for ... biological reasons. The other reason is that perhaps when a patient has an up-front primary tumor resection, there is a delay in getting chemotherapy, and that can cause the progression that we see."

Session attendee Dr. Gary Dunn, of the University of Oklahoma, Oklahoma City, asked how much time elapsed between up-front resection and receipt of adjuvant chemotherapy in that group, and the variance in this measure, noting, "That will significantly affect your outcome, if some patients started at 6 weeks and some patients started at 12 weeks postop."

"Usually, patients waited 6 weeks before they started chemotherapy postoperatively," Dr. Slesser explained. "The majority of patients who had primary tumor resection had the adjuvant chemotherapy after the postoperative scan; the 3-month scan tends to be the postoperative scan."

Dr. Dunn further wondered about the comparability between groups of the chemotherapy received, asking what agents were used.

"At the Royal Marsden, the chemotherapy regimes tend to be quite uniform," Dr. Slesser replied. "Generally, all patients are on capecitabine [Xeloda] and oxaliplatin, with a monoclonal agent such as bevacizumab [Avastin]. They tend to get that when they have neoadjuvant chemotherapy."

Another attendee said, "Excellent paper, very well presented data, particularly considering there are a lot of retrospective series out there that are showing the up-front resection as a favorable prognostic indicator, which I don’t believe. ... But I would like to see a little more information about how the patients were treated subsequently. Were these patients who they were planning to get to surgery for resection, or were these patients who were treated for palliative intent? Did they have symptomatic primaries?"

"In the majority of these patients, the intent was curative surgery," Dr. Slesser replied. "We tried to exclude patients who were clearly referred for palliative treatment because we really wanted to assess patients who were referred for curative treatment."

Attendee Dr. David Shibata, of the Moffitt Cancer Center in Tampa, commented, "I think a critical question is that you have done a primary tumor resection and the liver tumor has tended to grow, which is not entirely surprising, but then in those cases, how many became unresectable from a liver standpoint?"

"About 60% ended up having hepatectomies," Dr. Slesser said, noting that the data reported looked only at the short-term time frame. "We do have further results, which will be in the paper, pertaining to survival. But the real aim of this study was to look at initial radiological progression of disease, because we thought that the primary tumor resection may be associated with a sudden increase in the size of metastasis."

The finding of a better liver outcome with initial chemotherapy "makes sense," session comoderator Dr. Marylise Boutros, of McGill University in Montreal, said in an interview. "That’s something that we would expect, that you can treat the largest burden of the disease, which is the metastasis – it’s a systemic disease – with chemotherapy up-front."

"But it’s definitely a smaller study, and this needs to be looked at in a larger subset and in a prospective fashion," she added.

Giving some background to the research, Dr. Slesser noted that "the mainstay of surgical treatment for these patients with limited metastatic disease is a sequential resection. Patients tend to have an up-front primary tumor resection, followed by adjuvant chemotherapy, followed by hepatic resection if feasible. On the other hand, patients who have extensive metastatic disease tend to have neoadjuvant chemotherapy prior to a surgical intervention."

He and his coinvestigators studied patients with isolated synchronous colorectal liver metastases who were referred to the Royal Marsden Hospital for treatment between 2005 and 2010 and had imaging done at baseline, 3 months, and 6 months.

The mean age of the cohort was 64 years, and the ratio of men to women was about 2:1. In terms of treatment, 51% of the patients underwent primary tumor resection, while the other 49% received neoadjuvant chemotherapy.

In univariate analysis, the factor most strongly associated with progression of liver metastases – defined as an increase in their cumulative diameter of at least 20% – at 3 months was a primary tumor resection, according to Dr. Slesser.

In a multivariate analysis, relative to their counterparts in the neoadjuvant chemotherapy group, patients undergoing primary tumor resection had dramatically elevated odds of progression of liver metastases (odds ratio, 9.0; P = .001).

Additionally, metastatic burden showed an upward trend between baseline and 6 months in the group undergoing primary tumor resection (from 40 to 51 mm; P = .19), whereas it decreased significantly in the neoadjuvant chemotherapy group (from 96 to 52 mm; P = .001).

Overall, 93% of patients having a primary tumor resection went on to receive adjuvant chemotherapy, according to Dr. Slesser.

Comparing baseline to 3 months versus 3 months to 6 months, liver metastases began regressing in the primary tumor resection group, with the growth rate changing from 4.0 to –3.0 mm/month (P less than .001), reflecting the effect of the adjuvant chemotherapy, he said. Liver metastases in the neoadjuvant chemotherapy group continued to regress, albeit also at a slower pace, with the growth rate changing from –5.6 to –4.0 mm/month (P = .003).

Dr. Slesser disclosed no relevant conflicts of interest.

PHOENIX – The standard sequential approach to treatment of patients with isolated synchronous liver metastases of colorectal cancer, entailing up-front removal of the primary tumor, is associated with growth of the metastases, according to results from a retrospective cohort study.

A team led by Dr. Alistair Slesser, a surgical registrar at the Royal Marsden Hospital in London, studied 114 patients with colorectal cancer who had synchronous liver metastases, meaning ones identified within a year of the cancer diagnosis, and no other metastases.

Results showed that patients whose initial treatment was resection of the colorectal primary tumor had ninefold higher odds of progression of their liver metastases at 3 months, compared with patients whose initial treatment was chemotherapy, he reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

Although liver metastases showed regression during 3-6 months of treatment in both groups, the rate was somewhat slower in the primary tumor resection group.

"Our findings suggest that an up-front primary tumor resection is actually an adverse prognostic factor. Indeed, our results have demonstrated that up-front primary tumor resection seemed to negate the effects of the adjuvant therapy on the treatment of the liver metastasis," Dr. Slesser commented.

"How does this apply clinically? We would recommend that patients who have limited metastatic disease, instead of having an up-front primary tumor resection perhaps [they should] be treated with neoadjuvant chemotherapy first. Or perhaps another surgical approach, like a simultaneous resection, should be considered to negate the adverse effects of a primary tumor resection on the metastatic disease," he said.

"When patients have lesions which are suspicious for liver metastases, we would recommend that these patients [be] thoroughly investigated, and if metastatic disease is confirmed, then again, we would recommend that they have chemotherapy prior to any subsequent intervention," he added.

The mechanism leading to growth of liver metastases after primary tumor resection is unknown, according to Dr. Slesser. "There is possibly an association for ... biological reasons. The other reason is that perhaps when a patient has an up-front primary tumor resection, there is a delay in getting chemotherapy, and that can cause the progression that we see."

Session attendee Dr. Gary Dunn, of the University of Oklahoma, Oklahoma City, asked how much time elapsed between up-front resection and receipt of adjuvant chemotherapy in that group, and the variance in this measure, noting, "That will significantly affect your outcome, if some patients started at 6 weeks and some patients started at 12 weeks postop."

"Usually, patients waited 6 weeks before they started chemotherapy postoperatively," Dr. Slesser explained. "The majority of patients who had primary tumor resection had the adjuvant chemotherapy after the postoperative scan; the 3-month scan tends to be the postoperative scan."

Dr. Dunn further wondered about the comparability between groups of the chemotherapy received, asking what agents were used.

"At the Royal Marsden, the chemotherapy regimes tend to be quite uniform," Dr. Slesser replied. "Generally, all patients are on capecitabine [Xeloda] and oxaliplatin, with a monoclonal agent such as bevacizumab [Avastin]. They tend to get that when they have neoadjuvant chemotherapy."

Another attendee said, "Excellent paper, very well presented data, particularly considering there are a lot of retrospective series out there that are showing the up-front resection as a favorable prognostic indicator, which I don’t believe. ... But I would like to see a little more information about how the patients were treated subsequently. Were these patients who they were planning to get to surgery for resection, or were these patients who were treated for palliative intent? Did they have symptomatic primaries?"

"In the majority of these patients, the intent was curative surgery," Dr. Slesser replied. "We tried to exclude patients who were clearly referred for palliative treatment because we really wanted to assess patients who were referred for curative treatment."

Attendee Dr. David Shibata, of the Moffitt Cancer Center in Tampa, commented, "I think a critical question is that you have done a primary tumor resection and the liver tumor has tended to grow, which is not entirely surprising, but then in those cases, how many became unresectable from a liver standpoint?"

"About 60% ended up having hepatectomies," Dr. Slesser said, noting that the data reported looked only at the short-term time frame. "We do have further results, which will be in the paper, pertaining to survival. But the real aim of this study was to look at initial radiological progression of disease, because we thought that the primary tumor resection may be associated with a sudden increase in the size of metastasis."

The finding of a better liver outcome with initial chemotherapy "makes sense," session comoderator Dr. Marylise Boutros, of McGill University in Montreal, said in an interview. "That’s something that we would expect, that you can treat the largest burden of the disease, which is the metastasis – it’s a systemic disease – with chemotherapy up-front."

"But it’s definitely a smaller study, and this needs to be looked at in a larger subset and in a prospective fashion," she added.

Giving some background to the research, Dr. Slesser noted that "the mainstay of surgical treatment for these patients with limited metastatic disease is a sequential resection. Patients tend to have an up-front primary tumor resection, followed by adjuvant chemotherapy, followed by hepatic resection if feasible. On the other hand, patients who have extensive metastatic disease tend to have neoadjuvant chemotherapy prior to a surgical intervention."

He and his coinvestigators studied patients with isolated synchronous colorectal liver metastases who were referred to the Royal Marsden Hospital for treatment between 2005 and 2010 and had imaging done at baseline, 3 months, and 6 months.

The mean age of the cohort was 64 years, and the ratio of men to women was about 2:1. In terms of treatment, 51% of the patients underwent primary tumor resection, while the other 49% received neoadjuvant chemotherapy.

In univariate analysis, the factor most strongly associated with progression of liver metastases – defined as an increase in their cumulative diameter of at least 20% – at 3 months was a primary tumor resection, according to Dr. Slesser.

In a multivariate analysis, relative to their counterparts in the neoadjuvant chemotherapy group, patients undergoing primary tumor resection had dramatically elevated odds of progression of liver metastases (odds ratio, 9.0; P = .001).

Additionally, metastatic burden showed an upward trend between baseline and 6 months in the group undergoing primary tumor resection (from 40 to 51 mm; P = .19), whereas it decreased significantly in the neoadjuvant chemotherapy group (from 96 to 52 mm; P = .001).

Overall, 93% of patients having a primary tumor resection went on to receive adjuvant chemotherapy, according to Dr. Slesser.

Comparing baseline to 3 months versus 3 months to 6 months, liver metastases began regressing in the primary tumor resection group, with the growth rate changing from 4.0 to –3.0 mm/month (P less than .001), reflecting the effect of the adjuvant chemotherapy, he said. Liver metastases in the neoadjuvant chemotherapy group continued to regress, albeit also at a slower pace, with the growth rate changing from –5.6 to –4.0 mm/month (P = .003).

Dr. Slesser disclosed no relevant conflicts of interest.

SAN DIEGO – A blood test that detects the –2proPSA isoform of prostate-specific antigen may provide a way to reduce the number of unneeded prostate biopsies, results from a multicenter study showed.

Using a Prostate Health Index (phi) level of 27 as a threshold for selecting men for prostate cancer could eliminate unnecessary biopsies in 26% of men when total PSA is 4-10 ng/mL, said Dr. Martin G. Sanda, chief of urology at Emory University in Atlanta, during a press briefing at the annual meeting of the American Urological Association.

"This is a substantial portion of the population who may undergo PSA testing. [The index] would allow the ability to detect aggressive prostate cancer while having an acceptable false-negative rate. The Prostate Health Index has the potential to mitigate harms of overdetection/overtreatment of indolent cancers while retaining benefits of detecting aggressive prostate cancer which warrants treatment," he said.

The Prostate Health Index (phi), developed by Beckman Coulter and granted premarket approval from the Food and Drug Administration in June 2012, is a simple, noninvasive blood test that is 2.5 times more specific in detecting prostate cancer than PSA in patients with PSA values in the 4- to 10-ng/mL range and is shown to reduce the number of prostate biopsies.

"The Achilles’ heel of PSA detection in its current form is the overdetection and subsequently the downstream overtreatment of indolent prostate cancers," Dr. Sanda said. "The phi is a manner of reporting the detection of the –2proPSA isoform of PSA. This is a small subset of the PSA molecules, as opposed to the routine total PSA test that we are familiar with."

For the current study Dr. Sanda and his associates investigated whether the use of phi, compared with total PSA and the ratio of free to total PSA (%fPSA), could reduce unnecessary biopsies and overdetection of indolent prostate cancer while improving the detection of aggressive prostate cancer. He reported results from 658 men whose PSA was 4-10 ng/mL. Of these 658 men, 324 had prostate cancer. Among these 324 cancers, 160 were aggressive (meaning a Gleason score of 7 or greater) and 164 were indolent cancers.

Dr. Sanda reported that at 90% sensitivity, the specificity of phi was 31.1%, compared with 19.8% for %fPSA (P = .024) and 10.8% for PSA (P less than .001). When the phi ranged from 0 to 26.9, the probability of significant prostate cancer was 3.9% and rose sequentially with increasing range of phi. Specifically, the probability of significant prostate cancer was 8.5% for those with a phi of 27.0-35.9, 14.4% for those in the range of 36.0-54.9, and 28.9% for those with a phi level of 55 or higher.

"When phi is less than 27, the probability of one of these cancers being a Gleason score of 7 or higher was under 4%," said Dr. Sanda, who also directs the university’s Prostate Cancer Center. "With that particular threshold, we would be able to retain the benefits of being able to detect aggressive cancers in patients who had a biopsy when their phi was higher than 27 while avoiding unnecessary [biopsies] in about 26% of the men, substantially reducing the number of indolent cancers diagnosed and the number of unnecessary biopsies performed."

The false-positive rate was "in an acceptable range," he added. Only 4 out of 109 Gleason 3 + 4 cancers were missed (3.7%), and only 1 out of 35 Gleason 4 + 3 cancers was missed (2.9%).

"Because this is a straightforward serum assay, phi does have the potential to have a favorable cost profile relative to some of the genetic marker testing that’s coming down the pipeline," Dr. Sanda commented. "The next step is to validate these findings in a larger and separate cohort." That effort is currently underway with the Early Detection Research Network, a cohort study funded by the National Cancer Institute.

The study was funded by Beckman Coulter. Dr. Sanda disclosed that he is an investigator for the company. He also reported affiliations with Medicametrix, Accuray, and other companies.

[email protected]

SAN DIEGO – A blood test that detects the –2proPSA isoform of prostate-specific antigen may provide a way to reduce the number of unneeded prostate biopsies, results from a multicenter study showed.

Using a Prostate Health Index (phi) level of 27 as a threshold for selecting men for prostate cancer could eliminate unnecessary biopsies in 26% of men when total PSA is 4-10 ng/mL, said Dr. Martin G. Sanda, chief of urology at Emory University in Atlanta, during a press briefing at the annual meeting of the American Urological Association.

"This is a substantial portion of the population who may undergo PSA testing. [The index] would allow the ability to detect aggressive prostate cancer while having an acceptable false-negative rate. The Prostate Health Index has the potential to mitigate harms of overdetection/overtreatment of indolent cancers while retaining benefits of detecting aggressive prostate cancer which warrants treatment," he said.

The Prostate Health Index (phi), developed by Beckman Coulter and granted premarket approval from the Food and Drug Administration in June 2012, is a simple, noninvasive blood test that is 2.5 times more specific in detecting prostate cancer than PSA in patients with PSA values in the 4- to 10-ng/mL range and is shown to reduce the number of prostate biopsies.

"The Achilles’ heel of PSA detection in its current form is the overdetection and subsequently the downstream overtreatment of indolent prostate cancers," Dr. Sanda said. "The phi is a manner of reporting the detection of the –2proPSA isoform of PSA. This is a small subset of the PSA molecules, as opposed to the routine total PSA test that we are familiar with."

For the current study Dr. Sanda and his associates investigated whether the use of phi, compared with total PSA and the ratio of free to total PSA (%fPSA), could reduce unnecessary biopsies and overdetection of indolent prostate cancer while improving the detection of aggressive prostate cancer. He reported results from 658 men whose PSA was 4-10 ng/mL. Of these 658 men, 324 had prostate cancer. Among these 324 cancers, 160 were aggressive (meaning a Gleason score of 7 or greater) and 164 were indolent cancers.

Dr. Sanda reported that at 90% sensitivity, the specificity of phi was 31.1%, compared with 19.8% for %fPSA (P = .024) and 10.8% for PSA (P less than .001). When the phi ranged from 0 to 26.9, the probability of significant prostate cancer was 3.9% and rose sequentially with increasing range of phi. Specifically, the probability of significant prostate cancer was 8.5% for those with a phi of 27.0-35.9, 14.4% for those in the range of 36.0-54.9, and 28.9% for those with a phi level of 55 or higher.

"When phi is less than 27, the probability of one of these cancers being a Gleason score of 7 or higher was under 4%," said Dr. Sanda, who also directs the university’s Prostate Cancer Center. "With that particular threshold, we would be able to retain the benefits of being able to detect aggressive cancers in patients who had a biopsy when their phi was higher than 27 while avoiding unnecessary [biopsies] in about 26% of the men, substantially reducing the number of indolent cancers diagnosed and the number of unnecessary biopsies performed."

The false-positive rate was "in an acceptable range," he added. Only 4 out of 109 Gleason 3 + 4 cancers were missed (3.7%), and only 1 out of 35 Gleason 4 + 3 cancers was missed (2.9%).

"Because this is a straightforward serum assay, phi does have the potential to have a favorable cost profile relative to some of the genetic marker testing that’s coming down the pipeline," Dr. Sanda commented. "The next step is to validate these findings in a larger and separate cohort." That effort is currently underway with the Early Detection Research Network, a cohort study funded by the National Cancer Institute.

The study was funded by Beckman Coulter. Dr. Sanda disclosed that he is an investigator for the company. He also reported affiliations with Medicametrix, Accuray, and other companies.

[email protected]

SAN DIEGO – A blood test that detects the –2proPSA isoform of prostate-specific antigen may provide a way to reduce the number of unneeded prostate biopsies, results from a multicenter study showed.

Using a Prostate Health Index (phi) level of 27 as a threshold for selecting men for prostate cancer could eliminate unnecessary biopsies in 26% of men when total PSA is 4-10 ng/mL, said Dr. Martin G. Sanda, chief of urology at Emory University in Atlanta, during a press briefing at the annual meeting of the American Urological Association.

"This is a substantial portion of the population who may undergo PSA testing. [The index] would allow the ability to detect aggressive prostate cancer while having an acceptable false-negative rate. The Prostate Health Index has the potential to mitigate harms of overdetection/overtreatment of indolent cancers while retaining benefits of detecting aggressive prostate cancer which warrants treatment," he said.

The Prostate Health Index (phi), developed by Beckman Coulter and granted premarket approval from the Food and Drug Administration in June 2012, is a simple, noninvasive blood test that is 2.5 times more specific in detecting prostate cancer than PSA in patients with PSA values in the 4- to 10-ng/mL range and is shown to reduce the number of prostate biopsies.

"The Achilles’ heel of PSA detection in its current form is the overdetection and subsequently the downstream overtreatment of indolent prostate cancers," Dr. Sanda said. "The phi is a manner of reporting the detection of the –2proPSA isoform of PSA. This is a small subset of the PSA molecules, as opposed to the routine total PSA test that we are familiar with."

For the current study Dr. Sanda and his associates investigated whether the use of phi, compared with total PSA and the ratio of free to total PSA (%fPSA), could reduce unnecessary biopsies and overdetection of indolent prostate cancer while improving the detection of aggressive prostate cancer. He reported results from 658 men whose PSA was 4-10 ng/mL. Of these 658 men, 324 had prostate cancer. Among these 324 cancers, 160 were aggressive (meaning a Gleason score of 7 or greater) and 164 were indolent cancers.

Dr. Sanda reported that at 90% sensitivity, the specificity of phi was 31.1%, compared with 19.8% for %fPSA (P = .024) and 10.8% for PSA (P less than .001). When the phi ranged from 0 to 26.9, the probability of significant prostate cancer was 3.9% and rose sequentially with increasing range of phi. Specifically, the probability of significant prostate cancer was 8.5% for those with a phi of 27.0-35.9, 14.4% for those in the range of 36.0-54.9, and 28.9% for those with a phi level of 55 or higher.

"When phi is less than 27, the probability of one of these cancers being a Gleason score of 7 or higher was under 4%," said Dr. Sanda, who also directs the university’s Prostate Cancer Center. "With that particular threshold, we would be able to retain the benefits of being able to detect aggressive cancers in patients who had a biopsy when their phi was higher than 27 while avoiding unnecessary [biopsies] in about 26% of the men, substantially reducing the number of indolent cancers diagnosed and the number of unnecessary biopsies performed."

The false-positive rate was "in an acceptable range," he added. Only 4 out of 109 Gleason 3 + 4 cancers were missed (3.7%), and only 1 out of 35 Gleason 4 + 3 cancers was missed (2.9%).

"Because this is a straightforward serum assay, phi does have the potential to have a favorable cost profile relative to some of the genetic marker testing that’s coming down the pipeline," Dr. Sanda commented. "The next step is to validate these findings in a larger and separate cohort." That effort is currently underway with the Early Detection Research Network, a cohort study funded by the National Cancer Institute.

The study was funded by Beckman Coulter. Dr. Sanda disclosed that he is an investigator for the company. He also reported affiliations with Medicametrix, Accuray, and other companies.

[email protected]

ORLANDO – Patients with unresectable pancreatic cancer may be safely spared from endoscopic sphincterotomy prior to stent placement, investigators said at the annual Digestive Disease Week.

Among patients undergoing placement of a self-expanding, 10-mm-diameter stent into the bile duct*, there were no differences in the rates of early or late complications between patients randomized to receive endoscopic sphincterotomy (ES) before stent placement and those who underwent stent placement alone, reported Dr. Tsuyoshi Hayashi from Sapporo Medical University in Japan.

"ES had no effect on not only the incidence of complications but also SEMS [self-expanding metal stent] patency and patient survival. ES is an unnecessary pretreatment prior to SEMS placement for distal biliary obstruction due to pancreatic cancer," Dr. Hayashi said.

Although endoscopic sphincterotomy is intended to prevent potential pancreatitis from the expansion forces of the stent on the opening of the pancreatic duct, it adds significantly to operative time and carries the risk of bleeding or perforation, Dr. Hayashi said.

To see whether the endoscopist could safely forego sphincterotomy, investigators in 25 hospitals on Japan’s northern island of Hokkaido enrolled a total of 200 patients into a randomized trial and assigned them to stent placement with or without sphincterotomy. Four patients assigned to sphincterotomy and two assigned to stenting alone were unable to undergo biliary cannulation, leaving 96 and 98 patients, respectively, for the analysis.

The authors found that sphincterotomy added significantly to the procedural time, at a mean of 577 (plus or minus 310) seconds, compared with 388 (plus or minus 203) seconds for the no-sphincterotomy procedures.

But when they looked at early complications (within 30 days of the procedure), they found that there were no significant between-group differences in the rates of mild to severe pancreatitis, moderate bleeding, mild perforation, moderate hepatic abscess, pain, or vomiting.

In addition, there were no significant between-group differences in late complications, including either mild to severe cholecystitis, pancreatitis, bleeding, or duodenal ulcer. Similarly, there were no significant differences between the sphincterotomy group and the no-sphincterotomy group in either median time to stent dysfunction (170.5 vs. 148.0 days, respectively) or median overall survival (242 vs. 202 days).

Causes of stent dysfunction, which occurred in 25 patients in each group, included food impaction, sludge formation, intestinal obstruction, migration, and tumor ingrowth or overgrowth, but there were no significant between-group differences in the causes.

The study funding source was not disclosed. Dr. Hayashi and his colleagues reported having no financial disclosures.

*Correction 7/25/2013: An earlier version of this story missnamed this duct and stent.

ORLANDO – Patients with unresectable pancreatic cancer may be safely spared from endoscopic sphincterotomy prior to stent placement, investigators said at the annual Digestive Disease Week.

Among patients undergoing placement of a self-expanding, 10-mm-diameter stent into the bile duct*, there were no differences in the rates of early or late complications between patients randomized to receive endoscopic sphincterotomy (ES) before stent placement and those who underwent stent placement alone, reported Dr. Tsuyoshi Hayashi from Sapporo Medical University in Japan.

"ES had no effect on not only the incidence of complications but also SEMS [self-expanding metal stent] patency and patient survival. ES is an unnecessary pretreatment prior to SEMS placement for distal biliary obstruction due to pancreatic cancer," Dr. Hayashi said.

Although endoscopic sphincterotomy is intended to prevent potential pancreatitis from the expansion forces of the stent on the opening of the pancreatic duct, it adds significantly to operative time and carries the risk of bleeding or perforation, Dr. Hayashi said.

To see whether the endoscopist could safely forego sphincterotomy, investigators in 25 hospitals on Japan’s northern island of Hokkaido enrolled a total of 200 patients into a randomized trial and assigned them to stent placement with or without sphincterotomy. Four patients assigned to sphincterotomy and two assigned to stenting alone were unable to undergo biliary cannulation, leaving 96 and 98 patients, respectively, for the analysis.

The authors found that sphincterotomy added significantly to the procedural time, at a mean of 577 (plus or minus 310) seconds, compared with 388 (plus or minus 203) seconds for the no-sphincterotomy procedures.

But when they looked at early complications (within 30 days of the procedure), they found that there were no significant between-group differences in the rates of mild to severe pancreatitis, moderate bleeding, mild perforation, moderate hepatic abscess, pain, or vomiting.

In addition, there were no significant between-group differences in late complications, including either mild to severe cholecystitis, pancreatitis, bleeding, or duodenal ulcer. Similarly, there were no significant differences between the sphincterotomy group and the no-sphincterotomy group in either median time to stent dysfunction (170.5 vs. 148.0 days, respectively) or median overall survival (242 vs. 202 days).

Causes of stent dysfunction, which occurred in 25 patients in each group, included food impaction, sludge formation, intestinal obstruction, migration, and tumor ingrowth or overgrowth, but there were no significant between-group differences in the causes.

The study funding source was not disclosed. Dr. Hayashi and his colleagues reported having no financial disclosures.

*Correction 7/25/2013: An earlier version of this story missnamed this duct and stent.

ORLANDO – Patients with unresectable pancreatic cancer may be safely spared from endoscopic sphincterotomy prior to stent placement, investigators said at the annual Digestive Disease Week.

Among patients undergoing placement of a self-expanding, 10-mm-diameter stent into the bile duct*, there were no differences in the rates of early or late complications between patients randomized to receive endoscopic sphincterotomy (ES) before stent placement and those who underwent stent placement alone, reported Dr. Tsuyoshi Hayashi from Sapporo Medical University in Japan.

"ES had no effect on not only the incidence of complications but also SEMS [self-expanding metal stent] patency and patient survival. ES is an unnecessary pretreatment prior to SEMS placement for distal biliary obstruction due to pancreatic cancer," Dr. Hayashi said.

Although endoscopic sphincterotomy is intended to prevent potential pancreatitis from the expansion forces of the stent on the opening of the pancreatic duct, it adds significantly to operative time and carries the risk of bleeding or perforation, Dr. Hayashi said.

To see whether the endoscopist could safely forego sphincterotomy, investigators in 25 hospitals on Japan’s northern island of Hokkaido enrolled a total of 200 patients into a randomized trial and assigned them to stent placement with or without sphincterotomy. Four patients assigned to sphincterotomy and two assigned to stenting alone were unable to undergo biliary cannulation, leaving 96 and 98 patients, respectively, for the analysis.

The authors found that sphincterotomy added significantly to the procedural time, at a mean of 577 (plus or minus 310) seconds, compared with 388 (plus or minus 203) seconds for the no-sphincterotomy procedures.

But when they looked at early complications (within 30 days of the procedure), they found that there were no significant between-group differences in the rates of mild to severe pancreatitis, moderate bleeding, mild perforation, moderate hepatic abscess, pain, or vomiting.

In addition, there were no significant between-group differences in late complications, including either mild to severe cholecystitis, pancreatitis, bleeding, or duodenal ulcer. Similarly, there were no significant differences between the sphincterotomy group and the no-sphincterotomy group in either median time to stent dysfunction (170.5 vs. 148.0 days, respectively) or median overall survival (242 vs. 202 days).

Causes of stent dysfunction, which occurred in 25 patients in each group, included food impaction, sludge formation, intestinal obstruction, migration, and tumor ingrowth or overgrowth, but there were no significant between-group differences in the causes.

The study funding source was not disclosed. Dr. Hayashi and his colleagues reported having no financial disclosures.

*Correction 7/25/2013: An earlier version of this story missnamed this duct and stent.

ORLANDO – Combining surgical resection of primary carcinoid and neuroendocrine tumors with cytoreductive surgery of liver metastases is safe in select patients and can produce outcomes similar to those seen with surgery and adjuvant therapy, said investigators at the annual Digestive Disease Week.

Among 47 patients with carcinoid and neuroendocrine tumors (CNET), 22 of whom underwent simultaneous resection of primary tumors and surgical reduction of metastatic tumor burden with partial or near-total surgical cytoreduction (CR), and 25 of whom had resection of the primary with additional therapies, the 5-year survival rate was 82%, reported Dr. Nicholas N. Nissen of the Cedars-Sinai Medical Center in Los Angeles.

In addition, no patients who had near-total CR required a repeat hepatic intervention within 1 year of surgery, compared with 18 of 25 patients (72%) who had surgery followed by additional hepatic therapy, Dr. Nissen said.

"While most patients progress over time, overall survival is excellent, and we admit very freely that this reflects the growing and evolving multimodal therapies that are available to these patients," Dr. Nissen said.

"We would propose that simultaneous removal of the primary tumor and liver metastases may in fact be primarily beneficial as it consolidates procedures and allows some patients to delay or perhaps even avoid other locoregional hepatic therapies," he added.

The authors took a retrospective look at records of 51 patients, 47 of whom were available for the overall survival analysis. The patients all underwent resection of hepatic masses simultaneously with surgery to remove either small bowel carcinoid (32 patients) or pancreatic neuroendocrine tumor (15 patients). In all, 27 patients had partial surgical cytoreduction of metastases, and 22 had planned near-total surgical CR.

Of the 19 patients with carcinoid syndrome, all had what Dr. Nissen described as "dramatic improvement," and 11 had complete resolution of symptoms following surgery.

There were no deaths within 30 days of surgery. There were eight complications greater than Clavien grade 2, including two instances of bile leak requiring endoscopic retrograde cholangiopancreatography, and four cases requiring repeat laparotomy.

Overall survival for 47 patients with at least 5 years of data was 95% at 1 year, and 82% at years 3 and 5 of follow-up. Overall 5-year survival among those patients who had near-total CR was 88%, compared with 72% of those who had subtotal CR, but the difference was not statistically significant.

The respective progression-free survival rates were 77%, 37%, and 28%. Broken down by treatment type, 5-year PFS was 40% among patients who had near total CR, compared with 22% for those who had subtotal cytoreduction, but this difference was also not significant.

However, the seven patients who had no additional hepatic therapy had a more-than-threefold risk for progression, compared with either near total CR (hazard ratio [HR], 3.10; P = .044) or partial CR with additional liver treatment (HR, 3.37; P =.029).

No demographic or disease-related variables appeared to predict survival, but progression-free survival was significantly associated with poor differentiation (P = .022) and with large tumors (P = .044).

Dr. Carlos Corvera, a gastrointestinal surgeon at the University of California at San Francisco, who was not involved in the study, commented that the worse progression-free survival seen in the seven patients who did not receive adjuvant hepatic therapies suggested a benefit for additional cytoreduction, regardless of whether the patients are having symptoms.

"What do you tell your medical oncology colleagues who argue that disease-specific survival is really the most important thing, and that we end up predisposing these patients to possible [surgical] complications in situations where there’s really no significant survival benefit shown in asymptomatic patients?" he asked

Dr. Nissen replied that with the availability of new targeted systemic and locoregional therapies, in the near future the question may no longer when to operate and with what additional therapies, but "whether to operate."

The study sponsor was not disclosed. Dr. Nissen and Dr. Corvera reported having no relevant financial disclosures.

ORLANDO – Combining surgical resection of primary carcinoid and neuroendocrine tumors with cytoreductive surgery of liver metastases is safe in select patients and can produce outcomes similar to those seen with surgery and adjuvant therapy, said investigators at the annual Digestive Disease Week.

Among 47 patients with carcinoid and neuroendocrine tumors (CNET), 22 of whom underwent simultaneous resection of primary tumors and surgical reduction of metastatic tumor burden with partial or near-total surgical cytoreduction (CR), and 25 of whom had resection of the primary with additional therapies, the 5-year survival rate was 82%, reported Dr. Nicholas N. Nissen of the Cedars-Sinai Medical Center in Los Angeles.

In addition, no patients who had near-total CR required a repeat hepatic intervention within 1 year of surgery, compared with 18 of 25 patients (72%) who had surgery followed by additional hepatic therapy, Dr. Nissen said.

"While most patients progress over time, overall survival is excellent, and we admit very freely that this reflects the growing and evolving multimodal therapies that are available to these patients," Dr. Nissen said.

"We would propose that simultaneous removal of the primary tumor and liver metastases may in fact be primarily beneficial as it consolidates procedures and allows some patients to delay or perhaps even avoid other locoregional hepatic therapies," he added.

The authors took a retrospective look at records of 51 patients, 47 of whom were available for the overall survival analysis. The patients all underwent resection of hepatic masses simultaneously with surgery to remove either small bowel carcinoid (32 patients) or pancreatic neuroendocrine tumor (15 patients). In all, 27 patients had partial surgical cytoreduction of metastases, and 22 had planned near-total surgical CR.

Of the 19 patients with carcinoid syndrome, all had what Dr. Nissen described as "dramatic improvement," and 11 had complete resolution of symptoms following surgery.

There were no deaths within 30 days of surgery. There were eight complications greater than Clavien grade 2, including two instances of bile leak requiring endoscopic retrograde cholangiopancreatography, and four cases requiring repeat laparotomy.

Overall survival for 47 patients with at least 5 years of data was 95% at 1 year, and 82% at years 3 and 5 of follow-up. Overall 5-year survival among those patients who had near-total CR was 88%, compared with 72% of those who had subtotal CR, but the difference was not statistically significant.

The respective progression-free survival rates were 77%, 37%, and 28%. Broken down by treatment type, 5-year PFS was 40% among patients who had near total CR, compared with 22% for those who had subtotal cytoreduction, but this difference was also not significant.

However, the seven patients who had no additional hepatic therapy had a more-than-threefold risk for progression, compared with either near total CR (hazard ratio [HR], 3.10; P = .044) or partial CR with additional liver treatment (HR, 3.37; P =.029).

No demographic or disease-related variables appeared to predict survival, but progression-free survival was significantly associated with poor differentiation (P = .022) and with large tumors (P = .044).

Dr. Carlos Corvera, a gastrointestinal surgeon at the University of California at San Francisco, who was not involved in the study, commented that the worse progression-free survival seen in the seven patients who did not receive adjuvant hepatic therapies suggested a benefit for additional cytoreduction, regardless of whether the patients are having symptoms.

"What do you tell your medical oncology colleagues who argue that disease-specific survival is really the most important thing, and that we end up predisposing these patients to possible [surgical] complications in situations where there’s really no significant survival benefit shown in asymptomatic patients?" he asked

Dr. Nissen replied that with the availability of new targeted systemic and locoregional therapies, in the near future the question may no longer when to operate and with what additional therapies, but "whether to operate."

The study sponsor was not disclosed. Dr. Nissen and Dr. Corvera reported having no relevant financial disclosures.

ORLANDO – Combining surgical resection of primary carcinoid and neuroendocrine tumors with cytoreductive surgery of liver metastases is safe in select patients and can produce outcomes similar to those seen with surgery and adjuvant therapy, said investigators at the annual Digestive Disease Week.

Among 47 patients with carcinoid and neuroendocrine tumors (CNET), 22 of whom underwent simultaneous resection of primary tumors and surgical reduction of metastatic tumor burden with partial or near-total surgical cytoreduction (CR), and 25 of whom had resection of the primary with additional therapies, the 5-year survival rate was 82%, reported Dr. Nicholas N. Nissen of the Cedars-Sinai Medical Center in Los Angeles.

In addition, no patients who had near-total CR required a repeat hepatic intervention within 1 year of surgery, compared with 18 of 25 patients (72%) who had surgery followed by additional hepatic therapy, Dr. Nissen said.

"While most patients progress over time, overall survival is excellent, and we admit very freely that this reflects the growing and evolving multimodal therapies that are available to these patients," Dr. Nissen said.

"We would propose that simultaneous removal of the primary tumor and liver metastases may in fact be primarily beneficial as it consolidates procedures and allows some patients to delay or perhaps even avoid other locoregional hepatic therapies," he added.

The authors took a retrospective look at records of 51 patients, 47 of whom were available for the overall survival analysis. The patients all underwent resection of hepatic masses simultaneously with surgery to remove either small bowel carcinoid (32 patients) or pancreatic neuroendocrine tumor (15 patients). In all, 27 patients had partial surgical cytoreduction of metastases, and 22 had planned near-total surgical CR.

Of the 19 patients with carcinoid syndrome, all had what Dr. Nissen described as "dramatic improvement," and 11 had complete resolution of symptoms following surgery.

There were no deaths within 30 days of surgery. There were eight complications greater than Clavien grade 2, including two instances of bile leak requiring endoscopic retrograde cholangiopancreatography, and four cases requiring repeat laparotomy.

Overall survival for 47 patients with at least 5 years of data was 95% at 1 year, and 82% at years 3 and 5 of follow-up. Overall 5-year survival among those patients who had near-total CR was 88%, compared with 72% of those who had subtotal CR, but the difference was not statistically significant.

The respective progression-free survival rates were 77%, 37%, and 28%. Broken down by treatment type, 5-year PFS was 40% among patients who had near total CR, compared with 22% for those who had subtotal cytoreduction, but this difference was also not significant.

However, the seven patients who had no additional hepatic therapy had a more-than-threefold risk for progression, compared with either near total CR (hazard ratio [HR], 3.10; P = .044) or partial CR with additional liver treatment (HR, 3.37; P =.029).

No demographic or disease-related variables appeared to predict survival, but progression-free survival was significantly associated with poor differentiation (P = .022) and with large tumors (P = .044).

Dr. Carlos Corvera, a gastrointestinal surgeon at the University of California at San Francisco, who was not involved in the study, commented that the worse progression-free survival seen in the seven patients who did not receive adjuvant hepatic therapies suggested a benefit for additional cytoreduction, regardless of whether the patients are having symptoms.

"What do you tell your medical oncology colleagues who argue that disease-specific survival is really the most important thing, and that we end up predisposing these patients to possible [surgical] complications in situations where there’s really no significant survival benefit shown in asymptomatic patients?" he asked

Dr. Nissen replied that with the availability of new targeted systemic and locoregional therapies, in the near future the question may no longer when to operate and with what additional therapies, but "whether to operate."

The study sponsor was not disclosed. Dr. Nissen and Dr. Corvera reported having no relevant financial disclosures.

INDIANAPOLIS – Robotic-assisted major pancreatic resection is safe, feasible, reliable, and versatile, according to the findings of the largest reported single-center series of such procedures.

That being said, the next and absolutely critical step needs to be comparative effectiveness studies pitting robotic versus laparoscopic or open pancreatic resections, Dr. Herbert J. Zeh III reported at the annual meeting of the American Surgical Association.

He noted that there was a considerable learning curve with the procedure in this single-center series of 250 consecutive robotic-assisted major pancreatic resections. "If we had compared our first 30, 40, or even 60 cases, we would have been comparing an innovative procedure to one that’s been refined continuously since 1937," noted Dr. Zeh of the University of Pittsburgh.

Discussants praised Dr. Zeh and his coinvestigators as innovators who are taking a rigorously scientific and cautious approach in investigating the applicability of robotic techniques to major pancreatic surgery. But some discussants were concerned that the growing dissemination of robotic surgery is based largely upon what they consider to be marketing hype and competitive pressure.

Dr. Zeh explained that he and his coworkers have undertaken the study of robotic-assisted major pancreatic resections because they believe that a minimally invasive approach will reduce the substantial morbidity traditionally associated with open procedures, and that laparoscopic techniques aren’t the answer in these complex resections, which often require resuturing the pancreas to the GI tract.

"It was our perception as a group of dedicated pancreatic surgeons that we could not utilize the laparoscopic technology to adhere to the standard principles of open surgery that we thought were important for safe performance of pancreatic resections. These include meticulous dissection, safe control of major vascular structures, and precise suturing," he said.

The 250 consecutive robotic-assisted major pancreatic resections in this series included the full range of complex pancreatic operations. The two most common procedures were pancreaticoduodenectomy, also known as the Whipple procedure, in 132 patients and distal pancreatectomy in 83.

Overall 30- and 90-day mortality rates were 0.8% and 2.0%, respectively. All deaths were in pancreaticoduodenectomy patients, with 30- and 90-day mortality rates of 1.5% and 3.8%.

Clinically significant complications occurred in 21% of patients. The most common was intra-abdominal fluid collection requiring drainage via interventional radiology. Morbidity rates were similar to those reported in large series of open and laparoscopic pancreatic resections.

Estimated blood loss in pancreaticoduodenectomy averaged 499 mL in the first one-third of patients who had the robotic procedure; thereafter, the blood loss improved to 401 mL.

Rates of conversion from robotic to open surgery also improved over time, from 18.2% in the first third of the patient series to 3.4% in the latter two-thirds.

Mean operative time was 529 minutes for pancreaticoduodenectomy and 256 minutes for distal pancreatectomy. These times have dropped steadily with experience such that mean operative time in the last 50 pancreaticoduodenectomies was 444 minutes, while in the last 50 distal pancreatectomies it was 222 minutes, which approaches reported times for laparoscopic and open operations, Dr. Zeh noted.

The median length of stay was 10 days for pancreaticoduodenectomy patients and 6 days for those undergoing distal pancreatectomy. As a precautionary measure, surgeons kept patients treated early in the series in the hospital longer than was probably necessary. Length of stay has come down over time, although this trend hasn’t yet reached statistical significance.

The readmission rate was 24% in pancreaticoduodenectomy patients and 28% in distal pancreatectomy patients; 2% of patients required a reoperation.

As experience has grown, the group’s criteria for selecting patients for the robotic approach have loosened considerably. Many recent patients have been obese or superobese.

"Currently the only absolute contraindication is some sort of vascular involvement that would entail resecting a vein and reanastomosing it using a minimally invasive approach. That’s really the only frontier we haven’t crossed," said Dr. Zeh.

The potential advantages of the robotic platform that drew the researchers’ interest include greater range of motion for the robotic needle driver and other tools, compared with what is achievable laparoscopically; enhanced visualization with magnification; computerized smoothing of a surgeon’s tremor; and the ability to see structures in three dimensions, unlike in laparoscopy.

"I think the real advantage is the computer," he added. "Robotic surgery is probably misnamed; it’s really computer-assisted surgery. What this is going to allow us to do is to take the skill sets that we have to the next level. Pilots couldn’t control fighter jets without a computer between them and the plane. In the end, I think the addition of the computer between us and the patient is going to allow us to do things that we haven’t even thought about."

He reported having received an honorarium from Medtronic on a single occasion for participation in a symposium on minimally invasive pancreatic surgery.

INDIANAPOLIS – Robotic-assisted major pancreatic resection is safe, feasible, reliable, and versatile, according to the findings of the largest reported single-center series of such procedures.

That being said, the next and absolutely critical step needs to be comparative effectiveness studies pitting robotic versus laparoscopic or open pancreatic resections, Dr. Herbert J. Zeh III reported at the annual meeting of the American Surgical Association.

He noted that there was a considerable learning curve with the procedure in this single-center series of 250 consecutive robotic-assisted major pancreatic resections. "If we had compared our first 30, 40, or even 60 cases, we would have been comparing an innovative procedure to one that’s been refined continuously since 1937," noted Dr. Zeh of the University of Pittsburgh.

Discussants praised Dr. Zeh and his coinvestigators as innovators who are taking a rigorously scientific and cautious approach in investigating the applicability of robotic techniques to major pancreatic surgery. But some discussants were concerned that the growing dissemination of robotic surgery is based largely upon what they consider to be marketing hype and competitive pressure.

Dr. Zeh explained that he and his coworkers have undertaken the study of robotic-assisted major pancreatic resections because they believe that a minimally invasive approach will reduce the substantial morbidity traditionally associated with open procedures, and that laparoscopic techniques aren’t the answer in these complex resections, which often require resuturing the pancreas to the GI tract.

"It was our perception as a group of dedicated pancreatic surgeons that we could not utilize the laparoscopic technology to adhere to the standard principles of open surgery that we thought were important for safe performance of pancreatic resections. These include meticulous dissection, safe control of major vascular structures, and precise suturing," he said.

The 250 consecutive robotic-assisted major pancreatic resections in this series included the full range of complex pancreatic operations. The two most common procedures were pancreaticoduodenectomy, also known as the Whipple procedure, in 132 patients and distal pancreatectomy in 83.

Overall 30- and 90-day mortality rates were 0.8% and 2.0%, respectively. All deaths were in pancreaticoduodenectomy patients, with 30- and 90-day mortality rates of 1.5% and 3.8%.

Clinically significant complications occurred in 21% of patients. The most common was intra-abdominal fluid collection requiring drainage via interventional radiology. Morbidity rates were similar to those reported in large series of open and laparoscopic pancreatic resections.

Estimated blood loss in pancreaticoduodenectomy averaged 499 mL in the first one-third of patients who had the robotic procedure; thereafter, the blood loss improved to 401 mL.

Rates of conversion from robotic to open surgery also improved over time, from 18.2% in the first third of the patient series to 3.4% in the latter two-thirds.

Mean operative time was 529 minutes for pancreaticoduodenectomy and 256 minutes for distal pancreatectomy. These times have dropped steadily with experience such that mean operative time in the last 50 pancreaticoduodenectomies was 444 minutes, while in the last 50 distal pancreatectomies it was 222 minutes, which approaches reported times for laparoscopic and open operations, Dr. Zeh noted.

The median length of stay was 10 days for pancreaticoduodenectomy patients and 6 days for those undergoing distal pancreatectomy. As a precautionary measure, surgeons kept patients treated early in the series in the hospital longer than was probably necessary. Length of stay has come down over time, although this trend hasn’t yet reached statistical significance.

The readmission rate was 24% in pancreaticoduodenectomy patients and 28% in distal pancreatectomy patients; 2% of patients required a reoperation.

As experience has grown, the group’s criteria for selecting patients for the robotic approach have loosened considerably. Many recent patients have been obese or superobese.

"Currently the only absolute contraindication is some sort of vascular involvement that would entail resecting a vein and reanastomosing it using a minimally invasive approach. That’s really the only frontier we haven’t crossed," said Dr. Zeh.

The potential advantages of the robotic platform that drew the researchers’ interest include greater range of motion for the robotic needle driver and other tools, compared with what is achievable laparoscopically; enhanced visualization with magnification; computerized smoothing of a surgeon’s tremor; and the ability to see structures in three dimensions, unlike in laparoscopy.

"I think the real advantage is the computer," he added. "Robotic surgery is probably misnamed; it’s really computer-assisted surgery. What this is going to allow us to do is to take the skill sets that we have to the next level. Pilots couldn’t control fighter jets without a computer between them and the plane. In the end, I think the addition of the computer between us and the patient is going to allow us to do things that we haven’t even thought about."

He reported having received an honorarium from Medtronic on a single occasion for participation in a symposium on minimally invasive pancreatic surgery.

INDIANAPOLIS – Robotic-assisted major pancreatic resection is safe, feasible, reliable, and versatile, according to the findings of the largest reported single-center series of such procedures.

That being said, the next and absolutely critical step needs to be comparative effectiveness studies pitting robotic versus laparoscopic or open pancreatic resections, Dr. Herbert J. Zeh III reported at the annual meeting of the American Surgical Association.

He noted that there was a considerable learning curve with the procedure in this single-center series of 250 consecutive robotic-assisted major pancreatic resections. "If we had compared our first 30, 40, or even 60 cases, we would have been comparing an innovative procedure to one that’s been refined continuously since 1937," noted Dr. Zeh of the University of Pittsburgh.

Discussants praised Dr. Zeh and his coinvestigators as innovators who are taking a rigorously scientific and cautious approach in investigating the applicability of robotic techniques to major pancreatic surgery. But some discussants were concerned that the growing dissemination of robotic surgery is based largely upon what they consider to be marketing hype and competitive pressure.

Dr. Zeh explained that he and his coworkers have undertaken the study of robotic-assisted major pancreatic resections because they believe that a minimally invasive approach will reduce the substantial morbidity traditionally associated with open procedures, and that laparoscopic techniques aren’t the answer in these complex resections, which often require resuturing the pancreas to the GI tract.

"It was our perception as a group of dedicated pancreatic surgeons that we could not utilize the laparoscopic technology to adhere to the standard principles of open surgery that we thought were important for safe performance of pancreatic resections. These include meticulous dissection, safe control of major vascular structures, and precise suturing," he said.

The 250 consecutive robotic-assisted major pancreatic resections in this series included the full range of complex pancreatic operations. The two most common procedures were pancreaticoduodenectomy, also known as the Whipple procedure, in 132 patients and distal pancreatectomy in 83.

Overall 30- and 90-day mortality rates were 0.8% and 2.0%, respectively. All deaths were in pancreaticoduodenectomy patients, with 30- and 90-day mortality rates of 1.5% and 3.8%.

Clinically significant complications occurred in 21% of patients. The most common was intra-abdominal fluid collection requiring drainage via interventional radiology. Morbidity rates were similar to those reported in large series of open and laparoscopic pancreatic resections.

Estimated blood loss in pancreaticoduodenectomy averaged 499 mL in the first one-third of patients who had the robotic procedure; thereafter, the blood loss improved to 401 mL.

Rates of conversion from robotic to open surgery also improved over time, from 18.2% in the first third of the patient series to 3.4% in the latter two-thirds.

Mean operative time was 529 minutes for pancreaticoduodenectomy and 256 minutes for distal pancreatectomy. These times have dropped steadily with experience such that mean operative time in the last 50 pancreaticoduodenectomies was 444 minutes, while in the last 50 distal pancreatectomies it was 222 minutes, which approaches reported times for laparoscopic and open operations, Dr. Zeh noted.

The median length of stay was 10 days for pancreaticoduodenectomy patients and 6 days for those undergoing distal pancreatectomy. As a precautionary measure, surgeons kept patients treated early in the series in the hospital longer than was probably necessary. Length of stay has come down over time, although this trend hasn’t yet reached statistical significance.

The readmission rate was 24% in pancreaticoduodenectomy patients and 28% in distal pancreatectomy patients; 2% of patients required a reoperation.

As experience has grown, the group’s criteria for selecting patients for the robotic approach have loosened considerably. Many recent patients have been obese or superobese.

"Currently the only absolute contraindication is some sort of vascular involvement that would entail resecting a vein and reanastomosing it using a minimally invasive approach. That’s really the only frontier we haven’t crossed," said Dr. Zeh.

The potential advantages of the robotic platform that drew the researchers’ interest include greater range of motion for the robotic needle driver and other tools, compared with what is achievable laparoscopically; enhanced visualization with magnification; computerized smoothing of a surgeon’s tremor; and the ability to see structures in three dimensions, unlike in laparoscopy.

"I think the real advantage is the computer," he added. "Robotic surgery is probably misnamed; it’s really computer-assisted surgery. What this is going to allow us to do is to take the skill sets that we have to the next level. Pilots couldn’t control fighter jets without a computer between them and the plane. In the end, I think the addition of the computer between us and the patient is going to allow us to do things that we haven’t even thought about."

He reported having received an honorarium from Medtronic on a single occasion for participation in a symposium on minimally invasive pancreatic surgery.

BRUSSELS – When biopsying a primary breast cancer, once is probably not enough based on accumulating evidence of primary-tumor heterogeneity, but despite this evidence, taking multiple biopsies has not yet become routine practice.

"Intra-tumor heterogeneity is one of the causes of variation during genetic profiling" of tumors, Dr. Jorge S. Reis-Fiho said. "Taking multiple biopsies from a primary tumor and putting them all together may mitigate the effect of intra-tumor heterogeneity," but taking multiple biopsies has not yet become standard of care, he said at the conference, which was sponsored by the European Society for Medical Oncology.

Mitchel L. Zoler/IMNG Medical Media

"I think we should start to seriously consider taking more than one biopsy. Quite a few places already do it, and our radiologists will routinely take two or three biopsies," said Dr. Fiho, a surgical pathologist at Memorial Sloan-Kettering Cancer Center in New York. "With only a single, small biopsy of the primary tumor we may not have sufficient information to predict what the metastasis will respond to," he said in an interview.

Results from two studies reported at the meeting added to the evidence favoring multiple biopsies as a way to more precisely characterize primary tumors and target the best therapy.

In one study, Dr. Michal Jarzab and his associates took three core biopsies from the primary tumors of 26 patients and assessed them genetically for estrogen receptor, progesterone receptor, and HER2-receptor mutations. Their sample included some patients with early-stage disease and others with advanced-stage cancer. The results of the three individual biopsy tests showed significant heterogeneity in seven of the 26 tumors (27%), reported Dr. Jarzab, a researcher at the Maria Sklodowska-Curie Cancer Center and Institute of Oncology in Gliwice, Poland.

The intratumor heterogeneity in these seven patients "could negatively impact genomic assessment if done with one specimen," he said.

"If other studies report similar results" on intratumor heterogeneity, "then it could become common practice to evaluate prognostic or predictive breast cancer markers from more than one primary tumour area," Dr. Angelo Di Leo, chairman of oncology at Prato (Italy) Hospital, said in a written statement.

The second study looked at the impact of assessing one, two, or three biopsies on the variance in results from four different single- or multiple-genetic tests in biopsies collected from 51 breast cancer patients. The amount of variance depended on the gene or genes tested, but, overall, using three biopsy specimens rather than one substantially reduced the variance, reported Dr. Rosanna Lau, a researcher at the University of Texas M.D. Anderson Cancer Center in Houston.

"Pooling biopsies from a single tumor reduced outlier results and reduced variance more generally for certain genes," Dr. Lau said. "Pooling biopsies is usually preferable to a single biopsy." The results showed that "we can get a comprehensive picture of the genes being expressed in the tumor by sampling multiple areas of the tumor and pooling the samples together. This increases the precision of the assay and allows us to make more reliable predictions related to the disease," she said in a written statement.

Her study also looked at the scope of analytic variance – variance caused by technical issues – in the biopsies taken from a 20-patient subgroup and found that the extent of analytic variance also varied by gene and was generally of the same magnitude as intratumor heterogeneity. The analytic variance wasn’t helped by pooling multiple biopsies, but data-processing solutions such as normalizing and scaling reduced this part of the variance, Dr. Lau said.

Dr. Reis-Fiho, Dr. Lau, Dr. Jarzab, and Dr. Di Leo had no disclosures.

[email protected]

BRUSSELS – When biopsying a primary breast cancer, once is probably not enough based on accumulating evidence of primary-tumor heterogeneity, but despite this evidence, taking multiple biopsies has not yet become routine practice.

"Intra-tumor heterogeneity is one of the causes of variation during genetic profiling" of tumors, Dr. Jorge S. Reis-Fiho said. "Taking multiple biopsies from a primary tumor and putting them all together may mitigate the effect of intra-tumor heterogeneity," but taking multiple biopsies has not yet become standard of care, he said at the conference, which was sponsored by the European Society for Medical Oncology.

Mitchel L. Zoler/IMNG Medical Media

"I think we should start to seriously consider taking more than one biopsy. Quite a few places already do it, and our radiologists will routinely take two or three biopsies," said Dr. Fiho, a surgical pathologist at Memorial Sloan-Kettering Cancer Center in New York. "With only a single, small biopsy of the primary tumor we may not have sufficient information to predict what the metastasis will respond to," he said in an interview.

Results from two studies reported at the meeting added to the evidence favoring multiple biopsies as a way to more precisely characterize primary tumors and target the best therapy.

In one study, Dr. Michal Jarzab and his associates took three core biopsies from the primary tumors of 26 patients and assessed them genetically for estrogen receptor, progesterone receptor, and HER2-receptor mutations. Their sample included some patients with early-stage disease and others with advanced-stage cancer. The results of the three individual biopsy tests showed significant heterogeneity in seven of the 26 tumors (27%), reported Dr. Jarzab, a researcher at the Maria Sklodowska-Curie Cancer Center and Institute of Oncology in Gliwice, Poland.

The intratumor heterogeneity in these seven patients "could negatively impact genomic assessment if done with one specimen," he said.

"If other studies report similar results" on intratumor heterogeneity, "then it could become common practice to evaluate prognostic or predictive breast cancer markers from more than one primary tumour area," Dr. Angelo Di Leo, chairman of oncology at Prato (Italy) Hospital, said in a written statement.

The second study looked at the impact of assessing one, two, or three biopsies on the variance in results from four different single- or multiple-genetic tests in biopsies collected from 51 breast cancer patients. The amount of variance depended on the gene or genes tested, but, overall, using three biopsy specimens rather than one substantially reduced the variance, reported Dr. Rosanna Lau, a researcher at the University of Texas M.D. Anderson Cancer Center in Houston.

"Pooling biopsies from a single tumor reduced outlier results and reduced variance more generally for certain genes," Dr. Lau said. "Pooling biopsies is usually preferable to a single biopsy." The results showed that "we can get a comprehensive picture of the genes being expressed in the tumor by sampling multiple areas of the tumor and pooling the samples together. This increases the precision of the assay and allows us to make more reliable predictions related to the disease," she said in a written statement.

Her study also looked at the scope of analytic variance – variance caused by technical issues – in the biopsies taken from a 20-patient subgroup and found that the extent of analytic variance also varied by gene and was generally of the same magnitude as intratumor heterogeneity. The analytic variance wasn’t helped by pooling multiple biopsies, but data-processing solutions such as normalizing and scaling reduced this part of the variance, Dr. Lau said.

Dr. Reis-Fiho, Dr. Lau, Dr. Jarzab, and Dr. Di Leo had no disclosures.

[email protected]

BRUSSELS – When biopsying a primary breast cancer, once is probably not enough based on accumulating evidence of primary-tumor heterogeneity, but despite this evidence, taking multiple biopsies has not yet become routine practice.

"Intra-tumor heterogeneity is one of the causes of variation during genetic profiling" of tumors, Dr. Jorge S. Reis-Fiho said. "Taking multiple biopsies from a primary tumor and putting them all together may mitigate the effect of intra-tumor heterogeneity," but taking multiple biopsies has not yet become standard of care, he said at the conference, which was sponsored by the European Society for Medical Oncology.

Mitchel L. Zoler/IMNG Medical Media

"I think we should start to seriously consider taking more than one biopsy. Quite a few places already do it, and our radiologists will routinely take two or three biopsies," said Dr. Fiho, a surgical pathologist at Memorial Sloan-Kettering Cancer Center in New York. "With only a single, small biopsy of the primary tumor we may not have sufficient information to predict what the metastasis will respond to," he said in an interview.

Results from two studies reported at the meeting added to the evidence favoring multiple biopsies as a way to more precisely characterize primary tumors and target the best therapy.

In one study, Dr. Michal Jarzab and his associates took three core biopsies from the primary tumors of 26 patients and assessed them genetically for estrogen receptor, progesterone receptor, and HER2-receptor mutations. Their sample included some patients with early-stage disease and others with advanced-stage cancer. The results of the three individual biopsy tests showed significant heterogeneity in seven of the 26 tumors (27%), reported Dr. Jarzab, a researcher at the Maria Sklodowska-Curie Cancer Center and Institute of Oncology in Gliwice, Poland.

The intratumor heterogeneity in these seven patients "could negatively impact genomic assessment if done with one specimen," he said.

"If other studies report similar results" on intratumor heterogeneity, "then it could become common practice to evaluate prognostic or predictive breast cancer markers from more than one primary tumour area," Dr. Angelo Di Leo, chairman of oncology at Prato (Italy) Hospital, said in a written statement.

The second study looked at the impact of assessing one, two, or three biopsies on the variance in results from four different single- or multiple-genetic tests in biopsies collected from 51 breast cancer patients. The amount of variance depended on the gene or genes tested, but, overall, using three biopsy specimens rather than one substantially reduced the variance, reported Dr. Rosanna Lau, a researcher at the University of Texas M.D. Anderson Cancer Center in Houston.

"Pooling biopsies from a single tumor reduced outlier results and reduced variance more generally for certain genes," Dr. Lau said. "Pooling biopsies is usually preferable to a single biopsy." The results showed that "we can get a comprehensive picture of the genes being expressed in the tumor by sampling multiple areas of the tumor and pooling the samples together. This increases the precision of the assay and allows us to make more reliable predictions related to the disease," she said in a written statement.

Her study also looked at the scope of analytic variance – variance caused by technical issues – in the biopsies taken from a 20-patient subgroup and found that the extent of analytic variance also varied by gene and was generally of the same magnitude as intratumor heterogeneity. The analytic variance wasn’t helped by pooling multiple biopsies, but data-processing solutions such as normalizing and scaling reduced this part of the variance, Dr. Lau said.

Dr. Reis-Fiho, Dr. Lau, Dr. Jarzab, and Dr. Di Leo had no disclosures.

[email protected]