Tuesday, January 31, 2012

Dutasteride vs Low Grade Prostate Cancer

Low grade cancer is a very difficult concept for most people to consider.  To the average layperson, cancer is binary and digital.  It's either present or not.  However, to the clinician, especially the oncologist, cancer is really analog; in other words, there are lesser evils.  For instance, if I had to have a cancer but was also given the opportunity to choose which kind of cancer, I'd pick a simple basal cell carcinoma since they're easy to eradicate and very rarely metastasize (spread) rather than melanoma which has the opposite characteristics.

For most men, when we hear about prostate cancer, all we can think of is dying a slow & painful death from bone metastases & bladder obstruction, or something like that.  However, as my colleagues know, there are various grades of prostate cancer as denoted by Gleason score.  And in fact, localized (not yet having spread) prostate cancer with a low Gleason score can often be actively monitored (otherwise known as watchful waiting) without any loss of continence, erectile function, or quality-adjusted life years.

Which brings me to a randomized, double-blind, placebo-controlled study published last week in Lancet which concluded that dutasteride taken daily for 3 years compared to placebo could decrease the risk of low grade prostate cancer from progressing onward to high grade disease.  Specifically, the authors noted that only 38% of those randomized to the 5 alpha reductase inhibitor progressed while 48% randomized to placebo had biopsy proven progression.  As expected, those randomized to dutasteride (24%) complained more of side effects such as decrease in libido, breast enlargement, and/or nipple sensitivity than those randomized to placebo (15%).  

While the above study might make the use of dutasteride as chemoprophlaxis against prostate cancer, let's not forget another study published almost 2 years ago in NEJM in which it appears that dutasteride might increase the risk for high grade cancer, even while lowering one's risk for low grade disease.  Of course, the editorial for this latest study brought up the question of why even screen if there is no benefit to be gained.  After all, the recent analysis of the ongoing PLCO trial demonstrated no mortality benefit after 13 years of annual screening for prostate cancer.

Clearly, there is no easy answer.  Each man will need to assess his risk aversion vs tolerance in order to make an informed decision with the assistance of his family physician.



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