COMMENTARY

New Interest in Local Therapy for Metastatic Prostate Cancer

David L. Graham, MD

Disclosures

November 11, 2016

In August, I spent time reviewing the impact of cytoreductive nephrectomy in renal cell carcinoma. Keeping on the theme, a recent article in the Journal of Clinical Oncology by Rusthoven and colleagues[1] reports a retrospective review of the National Cancer Database, looking at the impact of radiation therapy (RT) on androgen deprivation (ADT) as initial therapy for prostate cancer.

Their review included 6382 men treated from 2004-2012. Of those 6382 men, 538 (8.4%) received RT as well. Looking at the highest level, the addition of RT to ADT at the time of diagnosis improved overall survival in every way described. Median survival was nearly doubled (52 vs 29 months). Overall survival was significantly better at 3, 5, and 8 years. The benefit of RT persisted on multivariate analysis. The only group that did not show benefit with the addition of RT was the very high-risk group of men with a Gleason score of 9 or 10 and T4 disease.

The impact of this report was felt to be high enough to warrant an editorial by Christopher Logothetis, MD, chair of Genitourinary Medical Oncology at MD Anderson Cancer Center.[2] One of the more surprising aspects of the editorial was a review of previous reports describing these same results. Several retrospective reviews have been published. I'll not review them all, but I would like to present a flavor of the previous literature.

Culp and colleagues[3] reported a review of the Surveillance, Epidemiology, and End Results Program (SEER) database from 2004-2010, looking at the addition of either prostatectomy or brachytherapy to ADT. It included 8185 men and showed a significant increase in overall survival and disease-specific survival at 5 years with the addition of definitive treatment.

A very similar review of the SEER database from 2004-2009 was reported by Satkunasivam and colleagues[4] in 2015. They looked at the addition of prostatectomy, intensity-modulated RT (IMRT), or conformal RT to ADT. Their review described a benefit with prostatectomy or IMRT, but no benefit was seen with the addition of conformal RT.

One issue with all of these studies are the comparison groups. The total numbers of each report sound impressive, but the numbers of men receiving local therapy are small. In Culp and colleagues' review,[3] only 374 of the 8185 men received the local therapy. Satkunasivam and colleagues' report[4] included only 242 of the 4069 men receiving local therapy. The groups showing benefit—men receiving either prostatectomy or IMRT—consisted of 47 and 88 men, respectively. As a result, even though the statistics look impressive, you have to wonder whether the men receiving the local therapy may have been favorably selected in the clinical setting.

Our most convincing evidence for a question such as this is always the randomized, phase 3 trial. A randomized German trial begun last year is looking at the addition of prostatectomy to ADT in men with limited bone metastases.[5] The trial does allow the use of taxanes with ADT or before prostatectomy.

In their editorial, Logothetis and Aparicio[2] state that the addition of prostate RT to the primary therapy in metastatic prostate cancer should be considered only to alleviate symptoms or as part of a clinical trial. The main question, then, is whether a randomized clinical trial can be mounted and completed, either in the United States or as part of an international effort. Short of that, I would say that it may be worth a discussion with your patient as well as your local radiation therapists.

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