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Colorectal cancer among prostate cancer patients treated with ADT

Posted Nov 11 2010 12:00am

As if it wasn’t long enough already, the list of adverse events “associated with” the use of androgen deprivation therapy (ADT) in the treatment of prostate cancer is growing. Some of these adverse events are common and well understood and widely observed in randomized clinical trials (loss of libido, erectile dysfunction, hot flashes, breast tenderness, loss of energy and strength). Others have been reported based on large, retrospective cohort analysis (metabolic syndrome, type II diabetes, cardiovascular problems). And then there are the ones reported by smaller numbers of patients  (loss of mental acuity, inability to focus or concentrate, depression) that can be devastating when they do occur.

Gillessen et al. have now added to the list of possibilities.

They used the the linked Surveillance, Epidemiology, and End Results (SEER)–Medicare database to identify 107,859 men diagnosed with prostate cancer between 1993 and 2002. Follow-up data on these patients were available through 2004. They used these data to identify men who had a diagnosis of colorectal cancer as a second primary cancer, and they then assessed the potential influence of ADT on the occurrence of colorectal cancer in this cohort of patients.

They report the following results:

  • Unadjusted incidence rates of colorectal cancer were …
  • After adjustment for patient and prostate cancer characteristics,  compared to no use of ADT, the hazard ratios (HRs) for colorectal cancer in these patients was …

The authors conclude that, “Long-term androgen deprivation therapy for prostate cancer is associated with an increased risk of colorectal cancer.” An associated editorial by Lin and Giovannucci , published in the same issue of the Journal of the National Cancer Institute states that, “an elevated risk of colorectal cancer may be an additional consideration to weigh in the risk vs. benefit profile” of ADT when used to treat men with prostate cancer. Those are both fair comments … so long as we carefully note the use of the terms “associated with” and “may.” There is no definitive claim of a cause and effect relationship by the athors or the editorialists. Indeed, in their editorial, Lin and Giovannucci are careful to note that there could be all sorts of other reasons why some men with prostate cancer went on to get colorectal concer that have no direct relationship to the use of ADT. They could, for example, have been less physically active, spent less time outside, and therefore had low levels of vitamin D. These are all factors known to be associated with an increased risk for colorectal cancer.

No one has ever suggested that ADT is a benign form of treatment for prostate cancer. It was initially developed as a method to palliate the pain and suffering of men with extensive, metastatic forms of the disease. And many have suggested that it has been massively over-used in the past 15-20 years as a tool to “palliate fear” in men with a rising PSA after the failure of first- and second-line therapies or as a first-line therapy for some men long before there was any evidence of metastatic disease.

The “New” Prostate Cancer InfoLink has long considered that ADT needs to be used selectively, in men who have the potential to gain significant benefit from use of this type of hormone manipulation, because they have clearly advanced forms of prostate cancer. Furthermore, such patients should be carefully informed and advised of established methods that can be used to manage the known complications of ADT. And, in addition, intermittent hormone therapy as opposed to continuous hormone therapy should be considered seriously under all circumstances to minimize risk from long-term complications of ADT.

Unfortunately there is no long-term, prospectively complied database that allows us to document the time-related complications of ADT with care and accuracy. When you mess in a major way with someone’s  endocrine system (which ADT very definitely does), consequences are inevitable. This was probably acceptable in the men with extensive metastases and severe pain for whom this form of hormonal therapy was originally intended. Today’s prostate cancer patients are a very less advanced set of men, and they may be on ADT for as long as two or three decades. We owe it to these patients to be more astute in when to use such therapies, with what intent, and for how long at a time. 

Conversely, we need to be careful not to over-stress the possible risk for colorectal cancer. If Gillessen et al. are correct in their estimation, the relative increase in risk in risk for colorectal cancer in prostate cancer patients being treated with an LHRH agonist (as compared to men receiving no ADT) certainly appears to be 30-40 percent. However,  the absolute increase  in risk is 0.7/1,000 patient-years which equates to 7 cases in every 1,000 men receiving ADT for 10 years. It isn’t negligible … but it also isn’t an enormous increase in their risk when the base rate is 37 cases/1,000 prostate cancer patients followed for 10  years who had no ADT. The risk associated with orchiectomy may or may not be higher, but orchiectomy is a much less common form of treatment for prostate cancer today than it was back in the early to mid 1990s.

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