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Treatment of Prostate Cancer in Obese Patients: Review 1

Treatment of Prostate Cancer in Obese Patients: Review 1

In the article entitled "Treatment of Prostate Cancer in Obese Patients," the authors propose that prostate cancer occurring in obese men should be treated differently than that occurring in nonobese men. This proposal is based upon the observation that treatment outcomes in very obese men, to date, are worse than those in men of lesser body mass index (BMI). This may be, in part, due to the technical difficulties encountered in treatment, but is more likely due to a more aggressive disease biology.

Impact of Obesity on Prostate Cancer

The effects of obesity on both prostate carcinogenesis and prostate cancer progression have been the focus of many studies in recent years. Several studies have suggested that very obese men (generally defined as BMI > 35 kg/m2) are more likely to develop prostate cancer,[1,2] but an equal number of studies have suggested the reverse (references 7 and 8 in the article by Mitsuyama et al). In fact, the timing of obesity (and secondary hypogonadism) in a man's life may make a big difference in the effects of obesity on carcinogenesis. Early in life, obesity may be protective, whereas later in life, it may promote a higher risk of prostate cancer (reference 7 in the article).

While the effects of obesity on prostate carcinogenesis remain to be fully understood, it is generally agreed by most investigators that prostate cancer occurring in obese men has a more aggressive natural history. Surgical series have demonstrated higher grade, more advanced local stage, and higher likelihood of metastasis among obese men, even when correcting for pretreatment clinical parameters (reference 35 in the article). Cancer-specific mortality rates are higher among obese men developing prostate cancer as well.[3]

As the authors have pointed out, the potential mechanisms underlying the effect of obesity on prostate cancer are multiple. At the core of the potential mechanistic avenues is a significant hormonal dysregulation including decreased testosterone, increased estrogen, and altered fat metabolism. As such, to simply imply that surgery fails in obese men because it is technically more difficult is an oversimplification of a complex biologic process, and it demonstrates a relative naivete regarding prostate cancer therapy.

Diagnosis in Obese Men

The authors suggest technical difficulties of prostate cancer diagnosis in men with obesity. In general, transrectal imaging and needle placement are not greatly affected by obesity. The article by Presti et al referenced by the authors (their reference 27) demonstrated a reduction in cancer detection among obese men with elevated prostate-specific antigen (PSA). Later, however, a reevaluation of the same dataset by Freedland et al demonstrated that when correcting for prostate volume, cancer detection rates were actually higher among obese men.[4]

Obese (and hypogonadal) men with elevated PSA either have a very large prostate or prostate cancer underlying their PSA elevation.[4] They may, in fact, need to be biopsied at lower PSA values in order to overcome the effects of lower testosterone on serum PSA. This illustrates that the outcomes of the Presti study are more likely affected by the biology of obesity than by the technical difficulties of biopsy in the obese.

Prostatectomy

Observations regarding perineal prostatectomy are probably of historical significance only, given the infrequency with which this procedure is performed in contemporary practice. Observations regarding length of operation and blood loss do not translate to clinically significant parameters in measuring morbidity or, more importantly, cancer outcome. Finally, functional outcomes such as continence and potency are highly operator-dependent.

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