There is now data from retrospective studies suggesting but not yet proving definitively that removing or radiating the remaining prostate gland may increase overall survival. An unusual approach.
Conventional medical wisdom dictated that standard therapy for patients with prostate cancer with spread from the prostate gland to a distant site such as bone should not undergo prostatectomy or radiation directed to the prostate gland but rather receive androgen deprivation therapy (ADT) aimed at tumor cells wherever they may be hiding. Why? Because in the presence of distant metastatic spread the proverbial “cat is out of the bag”. However, as we see from a new extensive retrospective evaluation of patients with metastatic disease1, surgical removal of or radiation directed to the prostate gland added to ADT in the presence of distant spread (distant metastasis (M1) of tumor was found associated with a significant increase in patient overall survival. They propose that the original source of tumor may still be exerting control of and a source for continued metastatic cell growth. There are several laboratory and a few clinical examples for such in patients undergoing surgery for several other types of malignancies i.e. renal cell cancer.
From 2004 to 2012, 6,382 men with metastatic prostate cancer (mPCa) were identified, including 538 (8.4%) receiving prostate RT. At a median follow-up of 5.1 years, the addition of prostate RT to ADT was associated with improved overall survival (OS) on univariate (P , .001) and multivariate analysis (hazard ratio, 0.624; 95% CI, 0.551 to 0.706; P , .001) adjusted for age, year, race, comorbidity score, PSA level, Gleason score, T stage, N stage, chemotherapy administration, treating facility, and insurance status. Attacking the prostate gland in the presence of distant spread (up to now a medical NO NO) revealed a superior median (55 v 37 months) and 5-year overall patient survival (49% v 33%) with prostate radiation plus androgen deprivation therapy (ADT) compared with ADT alone (P , 0.001). Landmark analyses limited to long-term survivors of ≥1, ≥3, and ≥5 years demonstrated improved OS with prostate RT in all subsets (all P , 0.05). Secondary analyses comparing the survival outcomes for patients treated with therapeutic dose radiation plus ADT versus prostatectomy plus ADT during the same time interval demonstrated no significant differences in OS, whereas both therapies were superior to ADT alone.
Is this a game changer? Possibly, however keep in mind that these results, though a product of expert statisticians, are based on a retrospective look-back. Data for this study was collected from many community hospital-based cancer registries and were provided by several American College of Surgeons-Commission on Cancer accredited facilities. Realizing that there would be an issue with data accuracy the authors of the study stated “We undertook several analytic approaches, including multivariate adjustment, propensity score matching, recursive partitioning, and landmark analyses…” sounds good but remember (junk in = junk out) regardless of the statistics.
In the Journal there is an associated editorial authored by Christopher J. Logothetis and Ana M. Aparicio from MD Anderson Cancer Center in Houston addressing the study findings. In this editorial the authors note that “controlled studies will be required to establish definitive treatment of the primary tumor as an integral part of the standard therapy of men with metastatic prostate cancer. Therefore, controlling the primary tumor should be considered only for men with metastatic prostate cancer to avoid or treatpresumably local symptoms, or as part of a clinical trial. Most importantly, the results serve as an impetus to investigate the role of the primary prostate tumor in metastatic progression and resistance to therapy”.
I personally believe that the gold standard study to confirm these initial findings of increased survival would be a contemporary prospective randomized study carried out by experienced medical research teams. However, the results of this study1 are provocative and should be kept in mind by physicians responsible for treating patients with prostate cancer as we await outcomes from current definitive confirmatory studies.
1) Improved Survival With Prostate Radiation in Addition to Androgen Deprivation Therapy for Men With Newly Diagnosed Metastatic Prostate Cancer Chad G. Rusthoven et al. JCO VOLUME 34 * NUMBER 24 * AUGUST 20, 2016. Corresponding author: Chad G. Rusthoven, MD, University of Colorado School of Medicine, 1665 N. Aurora Court, Suite 1032, Mail Stop F706, Aurora, CO
80045; e-mail: firstname.lastname@example.org
Glenn Tisman, M.D.