Experts Advocate Salpingectomy Trial in Ovarian Cancer Prevention

VANCOUVER – A clinical trial is needed to assess the risk-benefit profile of salpingectomy for ovarian cancer prevention, said Dr. Barry Rosen.

A recent, serendipitous discovery, resulting from pathology examination of tissues removed during prophylactic salpingo-oophorectomy in patients with BRCA mutations, was that serous "ovarian" cancers actually arise from the fimbriae of the fallopian tubes.

"We didn’t know it when we started doing [the surgery]," Dr. Rosen explained at the annual meeting of the Society of Obstetricians and Gynaecologists of Canada. "We sort of all of a sudden started to identify cancers, and most of them were in the tube. ... All of a sudden, there has been a shift in the understanding that serous carcinomas do come from the tube."

In the wake of this new information, the Society of Gynecologic Oncology of Canada (GOC) issued two key recommendations, according to Dr. Rosen, professor of ob.gyn. and head of gynecologic oncology at the University of Toronto.

First, the GOC recommends that physicians discuss the risk-benefit profile of salpingectomy with women who are already having a hysterectomy or seeking irreversible contraception. "We don’t come out and say ‘Do it,’ " he noted. "But we are coming out to say that it makes sense, and you should discuss it, and in that discussion, if it makes sense, that you should go ahead and proceed to do it."

Second, the GOC recommends that, given the lack of evidence, a national study of ovarian cancer prevention through salpingectomy be a priority of the society. "We want to collect the evidence to support this, and we want to be sure that the evidence supports it before we really jump in and say everybody should be doing this," Dr. Rosen said.

"I don’t think there’s any question that salpingectomy makes sense. Serous carcinoma is the worst [ovarian] cancer, it’s the most common cancer, [and] it causes more deaths than any," he commented. "So if you can prevent this cancer, you are probably going to have the biggest impact on ovarian cancer that we have today. Bigger than screening, for sure – we know [screening] doesn’t work. But bigger than any treatment and any of the fancy treatments that are coming out that are really very expensive treatments."

Adding salpingectomy to other, planned surgeries could potentially provide preventive benefit to tens of thousands of women annually in Canada alone. For starters, roughly 47,000 Canadian women undergo hysterectomy nationally each year. Removal of the ovaries and tubes at the same time is fairly standard for those who are postmenopausal. "But it’s the premenopausal women for whom you would have the benefit of taking out the tubes and leaving the ovaries so that they could continue to have their hormone function," he noted.

And the procedure could be offered even more widely. For example, approximately 10,100 new cases of colon cancer are diagnosed annually among Canadian women, many of whom undergo pelvic surgery as a result.

There are many "other situations where urologists or general surgeons are doing surgery, so I don’t think we have to limit this discussion to gynecologists," commented Dr. Rosen. "We need to expand it to all disciplines that may operate in the pelvis, because a surgeon can take out the tubes as well as we can."

When asked by an attendee whether it might perhaps be better to recommend simpler distal salpingectomy instead of total salpingectomy, he expressed reservations.

"While the belief is that most of these cancers arise in the fimbriated end, there are some that do arise further up the tube." Additionally, "we have to be careful if we put in the word ‘distal.’ We also have to define what distal is. So it’s trickier than you think."

Dr. Rosen offered a few notes of caution from his own perspective. "Salpingectomy at open hysterectomy is different than at laparoscopic hysterectomy or tubal ligation," he said. "It’s pretty simple if you have an open case to be able to put your favorite clamp across the tube and remove it; laparascopically, [for some it may be] a little bit more difficult. ... When doing the procedure, you need to treat this as a surgical procedure, and not just think, ‘Oh yeah, we’ll just take out the tubes,’ and find yourself in some trouble with bleeding or an injury of some sort."

Also, the medical profession must decide what level of complications is acceptable. "I don’t know the answer to that, but we need to know what the complication rate is, and we do know that there will be complications," he said.

Finally, the new recommendations are currently based on a hypothesis, not on evidence. "There are other situations in our history in medicine where physicians really believed something very strongly and proceeded with limited information," he noted, citing by way of example the use of diethylstilbestrol in the 1940s and 1950s to prevent miscarriage, and its subsequent linkage to cancer. "We need to be sure that we get the evidence. I believe that we need to evaluate this in some form of clinical trial."

Should salpingectomy prove to be effective and adequately safe for preventing ovarian cancer, it would constitute a major turning point in a disease that still has a poor prognosis, according to Dr. Rosen.

To be sure, treatments have improved steadily over the past 25 years, prolonging life and improving its quality. "We can continue to expect improvements, but I think they are going to be gradual and they are going to be small," he said. "I don’t think anybody would say that there are any home runs out there right now."

Efforts to detect the cancer early through screening have thus far not panned out. Three large screening studies were initiated in 1985-2001, one each in the United Kingdom, Japan, and the United States.

Results from the last – the PLCO (Prostate, Lung, Colorectal, and Ovarian) trial, which tested screening with cancer antigen 125 (CA 125) and transvaginal ultrasound – were recently reported (JAMA 2011;305:2295-303). They showed that 20 surgeries had to be performed to detect one cancer, and the rate of major complications was 20% among patients who underwent surgery. And at the end of the day, there was no reduction in ovarian cancer mortality.

"This is a big study, it is very well done, [and] it has a very long follow-up," Dr. Rosen commented. "And I think this pretty much conclusively says that ultrasound and CA 125 [screening] just don’t work." Results of the U.K. study, which is using a different, serial multimodality approach to screening, are expected in the 2014 timeframe.

Prevention efforts up to this point have been limited to birth control pills and to BRCA testing with prophylactic surgery for carriers, but this group makes up only about a tenth of all patients with ovarian cancer, he noted.

Dr. Rosen said he had no relevant financial disclosures.

VANCOUVER – A clinical trial is needed to assess the risk-benefit profile of salpingectomy for ovarian cancer prevention, said Dr. Barry Rosen.

A recent, serendipitous discovery, resulting from pathology examination of tissues removed during prophylactic salpingo-oophorectomy in patients with BRCA mutations, was that serous "ovarian" cancers actually arise from the fimbriae of the fallopian tubes.

"We didn’t know it when we started doing [the surgery]," Dr. Rosen explained at the annual meeting of the Society of Obstetricians and Gynaecologists of Canada. "We sort of all of a sudden started to identify cancers, and most of them were in the tube. ... All of a sudden, there has been a shift in the understanding that serous carcinomas do come from the tube."

In the wake of this new information, the Society of Gynecologic Oncology of Canada (GOC) issued two key recommendations, according to Dr. Rosen, professor of ob.gyn. and head of gynecologic oncology at the University of Toronto.

First, the GOC recommends that physicians discuss the risk-benefit profile of salpingectomy with women who are already having a hysterectomy or seeking irreversible contraception. "We don’t come out and say ‘Do it,’ " he noted. "But we are coming out to say that it makes sense, and you should discuss it, and in that discussion, if it makes sense, that you should go ahead and proceed to do it."

Second, the GOC recommends that, given the lack of evidence, a national study of ovarian cancer prevention through salpingectomy be a priority of the society. "We want to collect the evidence to support this, and we want to be sure that the evidence supports it before we really jump in and say everybody should be doing this," Dr. Rosen said.

"I don’t think there’s any question that salpingectomy makes sense. Serous carcinoma is the worst [ovarian] cancer, it’s the most common cancer, [and] it causes more deaths than any," he commented. "So if you can prevent this cancer, you are probably going to have the biggest impact on ovarian cancer that we have today. Bigger than screening, for sure – we know [screening] doesn’t work. But bigger than any treatment and any of the fancy treatments that are coming out that are really very expensive treatments."

Adding salpingectomy to other, planned surgeries could potentially provide preventive benefit to tens of thousands of women annually in Canada alone. For starters, roughly 47,000 Canadian women undergo hysterectomy nationally each year. Removal of the ovaries and tubes at the same time is fairly standard for those who are postmenopausal. "But it’s the premenopausal women for whom you would have the benefit of taking out the tubes and leaving the ovaries so that they could continue to have their hormone function," he noted.

And the procedure could be offered even more widely. For example, approximately 10,100 new cases of colon cancer are diagnosed annually among Canadian women, many of whom undergo pelvic surgery as a result.

There are many "other situations where urologists or general surgeons are doing surgery, so I don’t think we have to limit this discussion to gynecologists," commented Dr. Rosen. "We need to expand it to all disciplines that may operate in the pelvis, because a surgeon can take out the tubes as well as we can."

When asked by an attendee whether it might perhaps be better to recommend simpler distal salpingectomy instead of total salpingectomy, he expressed reservations.

"While the belief is that most of these cancers arise in the fimbriated end, there are some that do arise further up the tube." Additionally, "we have to be careful if we put in the word ‘distal.’ We also have to define what distal is. So it’s trickier than you think."

Dr. Rosen offered a few notes of caution from his own perspective. "Salpingectomy at open hysterectomy is different than at laparoscopic hysterectomy or tubal ligation," he said. "It’s pretty simple if you have an open case to be able to put your favorite clamp across the tube and remove it; laparascopically, [for some it may be] a little bit more difficult. ... When doing the procedure, you need to treat this as a surgical procedure, and not just think, ‘Oh yeah, we’ll just take out the tubes,’ and find yourself in some trouble with bleeding or an injury of some sort."

Also, the medical profession must decide what level of complications is acceptable. "I don’t know the answer to that, but we need to know what the complication rate is, and we do know that there will be complications," he said.

Finally, the new recommendations are currently based on a hypothesis, not on evidence. "There are other situations in our history in medicine where physicians really believed something very strongly and proceeded with limited information," he noted, citing by way of example the use of diethylstilbestrol in the 1940s and 1950s to prevent miscarriage, and its subsequent linkage to cancer. "We need to be sure that we get the evidence. I believe that we need to evaluate this in some form of clinical trial."

Should salpingectomy prove to be effective and adequately safe for preventing ovarian cancer, it would constitute a major turning point in a disease that still has a poor prognosis, according to Dr. Rosen.

To be sure, treatments have improved steadily over the past 25 years, prolonging life and improving its quality. "We can continue to expect improvements, but I think they are going to be gradual and they are going to be small," he said. "I don’t think anybody would say that there are any home runs out there right now."

Efforts to detect the cancer early through screening have thus far not panned out. Three large screening studies were initiated in 1985-2001, one each in the United Kingdom, Japan, and the United States.

Results from the last – the PLCO (Prostate, Lung, Colorectal, and Ovarian) trial, which tested screening with cancer antigen 125 (CA 125) and transvaginal ultrasound – were recently reported (JAMA 2011;305:2295-303). They showed that 20 surgeries had to be performed to detect one cancer, and the rate of major complications was 20% among patients who underwent surgery. And at the end of the day, there was no reduction in ovarian cancer mortality.

"This is a big study, it is very well done, [and] it has a very long follow-up," Dr. Rosen commented. "And I think this pretty much conclusively says that ultrasound and CA 125 [screening] just don’t work." Results of the U.K. study, which is using a different, serial multimodality approach to screening, are expected in the 2014 timeframe.

Prevention efforts up to this point have been limited to birth control pills and to BRCA testing with prophylactic surgery for carriers, but this group makes up only about a tenth of all patients with ovarian cancer, he noted.

Dr. Rosen said he had no relevant financial disclosures.

VANCOUVER – A clinical trial is needed to assess the risk-benefit profile of salpingectomy for ovarian cancer prevention, said Dr. Barry Rosen.

A recent, serendipitous discovery, resulting from pathology examination of tissues removed during prophylactic salpingo-oophorectomy in patients with BRCA mutations, was that serous "ovarian" cancers actually arise from the fimbriae of the fallopian tubes.

"We didn’t know it when we started doing [the surgery]," Dr. Rosen explained at the annual meeting of the Society of Obstetricians and Gynaecologists of Canada. "We sort of all of a sudden started to identify cancers, and most of them were in the tube. ... All of a sudden, there has been a shift in the understanding that serous carcinomas do come from the tube."

In the wake of this new information, the Society of Gynecologic Oncology of Canada (GOC) issued two key recommendations, according to Dr. Rosen, professor of ob.gyn. and head of gynecologic oncology at the University of Toronto.

First, the GOC recommends that physicians discuss the risk-benefit profile of salpingectomy with women who are already having a hysterectomy or seeking irreversible contraception. "We don’t come out and say ‘Do it,’ " he noted. "But we are coming out to say that it makes sense, and you should discuss it, and in that discussion, if it makes sense, that you should go ahead and proceed to do it."

Second, the GOC recommends that, given the lack of evidence, a national study of ovarian cancer prevention through salpingectomy be a priority of the society. "We want to collect the evidence to support this, and we want to be sure that the evidence supports it before we really jump in and say everybody should be doing this," Dr. Rosen said.

"I don’t think there’s any question that salpingectomy makes sense. Serous carcinoma is the worst [ovarian] cancer, it’s the most common cancer, [and] it causes more deaths than any," he commented. "So if you can prevent this cancer, you are probably going to have the biggest impact on ovarian cancer that we have today. Bigger than screening, for sure – we know [screening] doesn’t work. But bigger than any treatment and any of the fancy treatments that are coming out that are really very expensive treatments."

Adding salpingectomy to other, planned surgeries could potentially provide preventive benefit to tens of thousands of women annually in Canada alone. For starters, roughly 47,000 Canadian women undergo hysterectomy nationally each year. Removal of the ovaries and tubes at the same time is fairly standard for those who are postmenopausal. "But it’s the premenopausal women for whom you would have the benefit of taking out the tubes and leaving the ovaries so that they could continue to have their hormone function," he noted.

And the procedure could be offered even more widely. For example, approximately 10,100 new cases of colon cancer are diagnosed annually among Canadian women, many of whom undergo pelvic surgery as a result.

There are many "other situations where urologists or general surgeons are doing surgery, so I don’t think we have to limit this discussion to gynecologists," commented Dr. Rosen. "We need to expand it to all disciplines that may operate in the pelvis, because a surgeon can take out the tubes as well as we can."

When asked by an attendee whether it might perhaps be better to recommend simpler distal salpingectomy instead of total salpingectomy, he expressed reservations.

"While the belief is that most of these cancers arise in the fimbriated end, there are some that do arise further up the tube." Additionally, "we have to be careful if we put in the word ‘distal.’ We also have to define what distal is. So it’s trickier than you think."

Dr. Rosen offered a few notes of caution from his own perspective. "Salpingectomy at open hysterectomy is different than at laparoscopic hysterectomy or tubal ligation," he said. "It’s pretty simple if you have an open case to be able to put your favorite clamp across the tube and remove it; laparascopically, [for some it may be] a little bit more difficult. ... When doing the procedure, you need to treat this as a surgical procedure, and not just think, ‘Oh yeah, we’ll just take out the tubes,’ and find yourself in some trouble with bleeding or an injury of some sort."

Also, the medical profession must decide what level of complications is acceptable. "I don’t know the answer to that, but we need to know what the complication rate is, and we do know that there will be complications," he said.

Finally, the new recommendations are currently based on a hypothesis, not on evidence. "There are other situations in our history in medicine where physicians really believed something very strongly and proceeded with limited information," he noted, citing by way of example the use of diethylstilbestrol in the 1940s and 1950s to prevent miscarriage, and its subsequent linkage to cancer. "We need to be sure that we get the evidence. I believe that we need to evaluate this in some form of clinical trial."

Should salpingectomy prove to be effective and adequately safe for preventing ovarian cancer, it would constitute a major turning point in a disease that still has a poor prognosis, according to Dr. Rosen.

To be sure, treatments have improved steadily over the past 25 years, prolonging life and improving its quality. "We can continue to expect improvements, but I think they are going to be gradual and they are going to be small," he said. "I don’t think anybody would say that there are any home runs out there right now."

Efforts to detect the cancer early through screening have thus far not panned out. Three large screening studies were initiated in 1985-2001, one each in the United Kingdom, Japan, and the United States.

Results from the last – the PLCO (Prostate, Lung, Colorectal, and Ovarian) trial, which tested screening with cancer antigen 125 (CA 125) and transvaginal ultrasound – were recently reported (JAMA 2011;305:2295-303). They showed that 20 surgeries had to be performed to detect one cancer, and the rate of major complications was 20% among patients who underwent surgery. And at the end of the day, there was no reduction in ovarian cancer mortality.

"This is a big study, it is very well done, [and] it has a very long follow-up," Dr. Rosen commented. "And I think this pretty much conclusively says that ultrasound and CA 125 [screening] just don’t work." Results of the U.K. study, which is using a different, serial multimodality approach to screening, are expected in the 2014 timeframe.

Prevention efforts up to this point have been limited to birth control pills and to BRCA testing with prophylactic surgery for carriers, but this group makes up only about a tenth of all patients with ovarian cancer, he noted.

Dr. Rosen said he had no relevant financial disclosures.