Pancreatic Cancer Risk Not Confined to IPMN Target Cyst

SAN FRANCISCO – A small proportion of patients with a lower-risk intraductal papillary mucinous neoplasm go on to develop pancreatic ductal adenocarcinoma in an entirely separate region of the gland, an outcome that raises questions about the surveillance strategy for these patients.

Dr. Jennifer LaFemina and her colleagues at the Memorial Sloan-Kettering Cancer Center, New York, retrospectively examined data for 158 patients who were seen at the center in 1989-2010 and who had intraductal papillary mucinous neoplasms (IPMNs) with favorable enough initial features that they were followed with radiographic surveillance for at least 6 months after diagnosis, instead of being taken right to surgery.

Five patients (3.2%) developed pancreatic cancer in a different part of the gland, she reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology. In all cases, the cancer was stage 2A or 2B at diagnosis and was resected with negative margins; however, with a median follow-up of just 1 year, three of the five patients have died.

Dr. LaFemina noted that several published studies have shown that IPMN represents a field defect of ductal instability, and although many have focused on the risk of developing malignancy in the IPMN cyst itself, "the risk of developing a cancer in a region of the pancreas separate from the target cyst that we are monitoring is poorly defined."

In her study, 97 of the 158 patients eventually underwent resection at a median of 16 months after IPMN diagnosis because of a worrisome change either in the IPMN target cyst or elsewhere in the pancreas (J. Clin. Oncol. 2012;30 [suppl 4]:abstract 152). "Five patients ultimately came to surgery not because of the target cyst but because of a ductal adenocarcinoma without IPMN that developed while we were watching them," Dr. LaFemina explained. (In all, 13 of the patients having resection were found to have cancer at the IPMN target cyst.)

In four of these five cases of a separate cancer, the IPMN that had been under surveillance was of the branched-duct subtype and was smaller, measuring no more than 1.6 cm. And in three cases, the time from diagnosis of the IPMN to diagnosis of the separate cancer was fairly short, just 16 months or less.

"Diagnostic, operative, and surveillance strategies should consider the cancer risk not only to the [IPMN] target cyst that we are presented with, but also to the entire gland," Dr. LaFemina recommended. Although the center has not changed its surveillance strategy for these patients, she said that this new information raises some concerns.

The findings also bring up the question of whether to recommend total pancreatectomy for patients who undergo resection, to be on the safe side. "At this point, we are not endorsing total pancreatectomy for a number of reasons," she said – notably because of the difficulty of predicting preoperatively what is actually going on in the gland.

A key question is to determine what is different about patients who develop an adenocarcinoma separate from the IPMN. "Can we identify them and watch them [more closely]? We don’t have that answer yet," Dr. LaFemina noted.

The study "has really thrown us a curve ball in terms of how we deal with these patients," commented session cochair Dr. Mitchell Posner, a surgical oncologist at the University of Chicago Medical Center.

"It’s scary, because the criteria we are using to decide not to operate on patients – which I think are appropriate – unfortunately aren’t definitively ruling out patients who will develop a pancreatic cancer in a relatively short period of time," he said in an interview. Furthermore, he noted, it’s tricky to decide whether to operate (because of the morbidity and mortality risks associated with a pancreatic resection) or to risk letting a patient develop a pancreatic cancer, knowing that an intervention potentially could have changed the outcome.

"So it is very frightening that we unfortunately don’t have the tools to identify patients accurately at this point. And we are detecting these lesions [IPMNs] at a very high frequency, so it’s a problem," Dr. Posner said. The lesions’ molecular signatures likely hold the key to identifying the bad actors, which may help target pancreatectomy to the patients who need it, he proposed.

Dr. LaFemina and Dr. Posner disclosed that they had no relevant conflicts of interest.

SAN FRANCISCO – A small proportion of patients with a lower-risk intraductal papillary mucinous neoplasm go on to develop pancreatic ductal adenocarcinoma in an entirely separate region of the gland, an outcome that raises questions about the surveillance strategy for these patients.

Dr. Jennifer LaFemina and her colleagues at the Memorial Sloan-Kettering Cancer Center, New York, retrospectively examined data for 158 patients who were seen at the center in 1989-2010 and who had intraductal papillary mucinous neoplasms (IPMNs) with favorable enough initial features that they were followed with radiographic surveillance for at least 6 months after diagnosis, instead of being taken right to surgery.

Five patients (3.2%) developed pancreatic cancer in a different part of the gland, she reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology. In all cases, the cancer was stage 2A or 2B at diagnosis and was resected with negative margins; however, with a median follow-up of just 1 year, three of the five patients have died.

Dr. LaFemina noted that several published studies have shown that IPMN represents a field defect of ductal instability, and although many have focused on the risk of developing malignancy in the IPMN cyst itself, "the risk of developing a cancer in a region of the pancreas separate from the target cyst that we are monitoring is poorly defined."

In her study, 97 of the 158 patients eventually underwent resection at a median of 16 months after IPMN diagnosis because of a worrisome change either in the IPMN target cyst or elsewhere in the pancreas (J. Clin. Oncol. 2012;30 [suppl 4]:abstract 152). "Five patients ultimately came to surgery not because of the target cyst but because of a ductal adenocarcinoma without IPMN that developed while we were watching them," Dr. LaFemina explained. (In all, 13 of the patients having resection were found to have cancer at the IPMN target cyst.)

In four of these five cases of a separate cancer, the IPMN that had been under surveillance was of the branched-duct subtype and was smaller, measuring no more than 1.6 cm. And in three cases, the time from diagnosis of the IPMN to diagnosis of the separate cancer was fairly short, just 16 months or less.

"Diagnostic, operative, and surveillance strategies should consider the cancer risk not only to the [IPMN] target cyst that we are presented with, but also to the entire gland," Dr. LaFemina recommended. Although the center has not changed its surveillance strategy for these patients, she said that this new information raises some concerns.

The findings also bring up the question of whether to recommend total pancreatectomy for patients who undergo resection, to be on the safe side. "At this point, we are not endorsing total pancreatectomy for a number of reasons," she said – notably because of the difficulty of predicting preoperatively what is actually going on in the gland.

A key question is to determine what is different about patients who develop an adenocarcinoma separate from the IPMN. "Can we identify them and watch them [more closely]? We don’t have that answer yet," Dr. LaFemina noted.

The study "has really thrown us a curve ball in terms of how we deal with these patients," commented session cochair Dr. Mitchell Posner, a surgical oncologist at the University of Chicago Medical Center.

"It’s scary, because the criteria we are using to decide not to operate on patients – which I think are appropriate – unfortunately aren’t definitively ruling out patients who will develop a pancreatic cancer in a relatively short period of time," he said in an interview. Furthermore, he noted, it’s tricky to decide whether to operate (because of the morbidity and mortality risks associated with a pancreatic resection) or to risk letting a patient develop a pancreatic cancer, knowing that an intervention potentially could have changed the outcome.

"So it is very frightening that we unfortunately don’t have the tools to identify patients accurately at this point. And we are detecting these lesions [IPMNs] at a very high frequency, so it’s a problem," Dr. Posner said. The lesions’ molecular signatures likely hold the key to identifying the bad actors, which may help target pancreatectomy to the patients who need it, he proposed.

Dr. LaFemina and Dr. Posner disclosed that they had no relevant conflicts of interest.

SAN FRANCISCO – A small proportion of patients with a lower-risk intraductal papillary mucinous neoplasm go on to develop pancreatic ductal adenocarcinoma in an entirely separate region of the gland, an outcome that raises questions about the surveillance strategy for these patients.

Dr. Jennifer LaFemina and her colleagues at the Memorial Sloan-Kettering Cancer Center, New York, retrospectively examined data for 158 patients who were seen at the center in 1989-2010 and who had intraductal papillary mucinous neoplasms (IPMNs) with favorable enough initial features that they were followed with radiographic surveillance for at least 6 months after diagnosis, instead of being taken right to surgery.

Five patients (3.2%) developed pancreatic cancer in a different part of the gland, she reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology. In all cases, the cancer was stage 2A or 2B at diagnosis and was resected with negative margins; however, with a median follow-up of just 1 year, three of the five patients have died.

Dr. LaFemina noted that several published studies have shown that IPMN represents a field defect of ductal instability, and although many have focused on the risk of developing malignancy in the IPMN cyst itself, "the risk of developing a cancer in a region of the pancreas separate from the target cyst that we are monitoring is poorly defined."

In her study, 97 of the 158 patients eventually underwent resection at a median of 16 months after IPMN diagnosis because of a worrisome change either in the IPMN target cyst or elsewhere in the pancreas (J. Clin. Oncol. 2012;30 [suppl 4]:abstract 152). "Five patients ultimately came to surgery not because of the target cyst but because of a ductal adenocarcinoma without IPMN that developed while we were watching them," Dr. LaFemina explained. (In all, 13 of the patients having resection were found to have cancer at the IPMN target cyst.)

In four of these five cases of a separate cancer, the IPMN that had been under surveillance was of the branched-duct subtype and was smaller, measuring no more than 1.6 cm. And in three cases, the time from diagnosis of the IPMN to diagnosis of the separate cancer was fairly short, just 16 months or less.

"Diagnostic, operative, and surveillance strategies should consider the cancer risk not only to the [IPMN] target cyst that we are presented with, but also to the entire gland," Dr. LaFemina recommended. Although the center has not changed its surveillance strategy for these patients, she said that this new information raises some concerns.

The findings also bring up the question of whether to recommend total pancreatectomy for patients who undergo resection, to be on the safe side. "At this point, we are not endorsing total pancreatectomy for a number of reasons," she said – notably because of the difficulty of predicting preoperatively what is actually going on in the gland.

A key question is to determine what is different about patients who develop an adenocarcinoma separate from the IPMN. "Can we identify them and watch them [more closely]? We don’t have that answer yet," Dr. LaFemina noted.

The study "has really thrown us a curve ball in terms of how we deal with these patients," commented session cochair Dr. Mitchell Posner, a surgical oncologist at the University of Chicago Medical Center.

"It’s scary, because the criteria we are using to decide not to operate on patients – which I think are appropriate – unfortunately aren’t definitively ruling out patients who will develop a pancreatic cancer in a relatively short period of time," he said in an interview. Furthermore, he noted, it’s tricky to decide whether to operate (because of the morbidity and mortality risks associated with a pancreatic resection) or to risk letting a patient develop a pancreatic cancer, knowing that an intervention potentially could have changed the outcome.

"So it is very frightening that we unfortunately don’t have the tools to identify patients accurately at this point. And we are detecting these lesions [IPMNs] at a very high frequency, so it’s a problem," Dr. Posner said. The lesions’ molecular signatures likely hold the key to identifying the bad actors, which may help target pancreatectomy to the patients who need it, he proposed.

Dr. LaFemina and Dr. Posner disclosed that they had no relevant conflicts of interest.