‘Reasonable’ to Advise Men Who Have Had Vasectomies That They Have a Small Increased Risk for Lethal Prostate Cancers


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Mohummad Minhaj Siddiqui, MD

Louis R. Kavoussi, MD

James M. McKiernan, MD

The risk [of lethal prostate cancer associated with vasectomy] is pretty small in the grand scheme of things…. Having that discussion [with concerned patients] is probably good, but only in the context of the magnitude of the risk that is discussed.

—Mohummad Minhaj Siddiqui, MD

Long-term results from the Health Professionals Follow-up Health Study have shown a 20% increased risk of advanced prostate cancer and a 19% increased risk of lethal prostate cancer among men who had vasectomies.1 According to the study’s lead author, Mohummad Minhaj Siddiqui, MD, it is “reasonable” to advise men of the association between vasectomy and prostate cancer, but that should be in the context of their overall risk.

“The thing to keep in mind,” Dr. Siddiqui said in an interview with The ASCO Post, “is that although there is an increase of 10% in overall prostate cancer risk, and 19% in the lethal cancer subset, the absolute incidence of lethal prostate cancer within the overall population was relatively rare—1.6%. So if you have a 19% increase on 1.6%, that translates essentially to a 0.3% increase overall,” he explained.

“The risk is pretty small in the grand scheme of things,” he continued. “If a physician senses that some patients are really worried about prostate cancer, those patients may appreciate being advised that there is a small increased risk from vasectomy that may be present,” Dr. Siddiqui said. “Having that discussion is probably good, but only in the context of the magnitude of the risk that is discussed.”

Dr. Siddiqui is Director of Urologic Robotic Surgery, and Assistant Professor of Surgery-Urology, at the University of Maryland School of Medicine in Baltimore, although his work on the study was conducted while he was completing his residency training at Massachusetts General Hospital in Boston. The study coauthors are affiliated with Massachusetts General, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard School of Public Health, all in Boston.

Major Study Findings

The findings, published ahead of print online by the Journal of Clinical Oncology,1 involved 49,405 men in the Health Professionals Follow-up Study who were aged 40 to 75 years old at baseline in 1986 and were followed for up to 24 years. The vasectomy status of the men was updated every 2 years, and 12,321 men (25%) reported having vasectomies by the year 2000. During the study period, 6,023 men were diagnosed with prostate cancer, including 811 lethal prostate cancers.

Multivariate analysis showed a 10% increased risk of prostate cancer overall in men who had a vasectomy. Vasectomy was not significantly associated with risk of low-grade prostate cancer, but the procedure was associated with a 20% increased risk of advanced-stage prostate cancer and a 19% increased risk of lethal prostate cancer.

“We defined advanced prostate cancer as stage T3b, T4, N1, or M1 at diagnosis; development of lymph node or distant metastasis; or death as a result of prostate cancer before the end of follow-up. Lethal cancers, a subset of advanced cancers, were those that caused death or metastasis to bone or other organs before the end of follow-up,” the authors explained.

“There was a suggestion that the increased risk was more pronounced among men who were younger at the time of vasectomy,” the investigators reported, but “this pattern was not apparent when we examined age at vasectomy in quartiles,” they added. “The relative risk seems slightly higher, but it is not statistically significant,” Dr. Siddiqui said. “That story seems to have picked up a little bit of traction, but I don’t think it is something to emphasize, and I think it is actually incorrectly being emphasized.”

An earlier 1993 report from the Health Professionals Follow-up Study also found an increased risk of prostate cancer in men with vasectomies, although it was based on only 300 new cases of the disease from 1986 to 1990 (age-adjusted relative risk = 1.66; 95% confidence interval = 1.25–2.21; P = .0004).2 The recently updated data include 19 additional years of follow-up.

Not Decision-Changing

Dr. Siddiqui agreed with comments in some news reports that the study findings should not be considered practice-changing. A CBS News report quoted Louis R. Kavoussi, MD, Chairman of Urology at North Shore–LIJ Health System, New Hyde Park, New York, as saying, “I would be cautious about applying these findings to clinical practice right now. This is not like cigarette smoking causing a large number of people to develop lung cancer. This is a small increase in the risk of prostate cancer.”3

James M. McKiernan, MD, Interim Chairman of the Department of Urology at New York Presbyterian Hospital/Columbia University Medical Center, commented in The New York Times,4 “If someone asked for a vasectomy, I would have to tell them that there is this new data in this regard, but it’s not enough for me to change the standard of care. I would not say that you should avoid vasectomy.”

The study authors concluded: “The decision to opt for a vasectomy remains a highly personal one in which the potential risks and benefits must be considered.” For men contemplating a vasectomy, it “would be reasonable,” to consider the association between vasectomy and prostate cancer as one of the many potential risks and benefits, Dr. Siddiqui told The ASCO Post, although it should also be noted that no biologic explanation for that association has yet been found.

Biologic Mechanisms

“If we can figure out the biologic mechanisms” for the association between vasectomy and lethal prostate cancer, “that may actually have wider implications beyond vasectomy. The increased risk associated with vasectomy itself is probably modest and not decision-changing for most patients, although it may be for some,” Dr. Siddiqui added.

“We have been working on trying to see what kind of biologic explanations there might be. There are a lot of theories, but nothing has been proven,” Dr. Siddiqui stated. “Vasectomy leads to hormonal changes and changes in the contents of semen, such as different proteins that are present in the semen, and even immune changes in the body. It is feasible—and it has been shown in other studies—that these changes could be linked to prostate cancer pathogenesis, but it has not been definitively shown with vasectomy.”

As the study report states, “the challenge lies in the fact that there is usually a 20- to 30-year interval between vasectomy and detection of prostate cancer.” The study group is continuing to look at the data and at underlying biologic reasons. “We have some good gene-expression data on subsets of patients, and we are trying to study differences in the different groups.” Dr. Siddiqui said

Impact of PSA Testing

The study report estimates that about 15% of men now get vasectomies, although the rate for the study population was 25%. Dr. Siddiqui said that the research team suspects the reason for the higher rate in the study population was that the men were all health professionals and relatively well off. “It is possible that with that background,” he speculated, “more of them opted for vasectomy as their method of birth control. This is a unique subset of patients; that is important to remember.”

They were also more likely to have had PSA testing during the study years, 1986 to 2010. “Having said that, since PSA testing is so closely related to prostate cancer diagnosis, we controlled for PSA testing using multiple methods. We controlled for that in the baseline analysis, but we also did subanalyses of only patients with highly screened behaviors,” Dr. Siddiqui explained. In a cohort of 13,901 “highly screened men”—those getting PSA testing on a regular basis—27% reported having had a vasectomy by the year 2000, and “the overall findings were essentially the same as in the general cohort,” Dr. Siddiqui reported.

“That is one of the issues that has been historically challenging,” Dr. Siddiqui stated. “Patients who get vasectomies may be more plugged into their medical care. They have a relationship with a urologist, and they may be more likely to undergo prostate cancer screening than patients who do not get a vasectomy. So the detection of prostate cancer could be biased by the fact that you are checking for prostate cancer more often in men with vasectomy vs those who do not have vasectomy. The way to control for that is to look at all men who are regularly checking for prostate cancer, and exclude the ones who don’t look for prostate cancer as regularly. That was a new dimension to this study that built on previous studies.”

Effect of 2012 Screening Recommendations

The study follow-up ended in 2010, which was 2 years before the U.S. Preventive Services Task Force updated its prostate cancer screening recommendation—the Task Force now advocates against PSA-based screening for prostate cancer.5

“It is unclear” what if any effect this updated recommendation will have on PSA screening among men who have had vasectomies. Follow-up is continuing, but the recommendation probably won’t affect men in the study because “many of them have already been getting PSA tested for a while,” Dr. Siddiqui noted. “These are men who were enrolled in the 1980s and 1990s; we are not enrolling additional men now. So there won’t be many men who are getting PSA testing in 2012 for the first time. Most of them have already passed the point at which they were going to get PSA testing anyway.”

Dr. Siddiqui said that while “it is a subjective finding,” he thinks that the routine administration of PSA testing “has really dropped off.” Among urologists, “we see fewer and fewer people coming in with elevated PSAs as the primary complaint,” he said. “Men with a family history or some other reason for concern about prostate cancer are not denied PSA testing,” he said. “It is just not a routine part of a yearly physical exam anymore.”

Confounding Factors Unlikely

The study also notes that confounding by infections or cancer treatment is unlikely. “Studies have actually shown that prostate cancer is associated with sexually transmitted infections, in particular, Trichomonas vaginalis and herpesvirus,” Dr. Siddiqui explained. “Some people suggest that perhaps men with vasectomy are more prone to sexually transmitted infections because of behavioral changes, so that could be a reason for the increased risk of prostate cancer. But we didn’t see any association with infections in our study, and we had pretty good data on histories of sexually transmitted infections.”

Cancer treatments were considered as confounding factors because of concerns that differing treatments could affect whether particular cases were lethal or not. “Perhaps some men are getting lethal prostate cancer because they are getting treated differently…. Theoretically, it is possible that men with vasectomies have relationships with their urologists, so maybe they prefer treatments that the urologist offers, such as surgery, as opposed to men who haven’t had a vasectomy,” Dr. Siddiqui explained.

“Maybe those men fear surgery in general and so they opt for radiation or other treatments,” he continued. “But what we found was that there was no difference in the vasectomy and nonvasectomy group with regard to what treatments were used to treat the prostate cancer. So that does not explain the observed risk either.” ■

Disclosure: Dr. Siddiqui reported no potential conflicts of interest.

References

1. Siddiqui MM, Wilson KM, Epstein MM, et al: Vasectomy and risk of aggressive prostate cancer. J Clin Oncol. July 7, 2014 (early release online).

2. Giovannucci E, Ascherio A, Rimm EB, et al: A prospective cohort study of vasectomy and prostate cancer in US men. JAMA 269:873-877, 1993.

3. Preidt R: Vasectomy linked to aggressive prostate cancer. Available at www.cbsnews.com. Posted July 11, 2014. Accessed July 14, 2014.

4. Bakalar N: A vasectomy may increase prostate cancer risk. New York Times, July 17, 2014.

5. U.S. Preventive Services Task Force: Screening for prostate cancer. Available at http://www.uspreventiveservicestaskforce.org/prostatecancerscreening.htm. Accessed July 17, 2014.


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