Radical Prostatectomy With Adjuvant Radiotherapy vs Radiotherapy Plus ADT in Advanced Prostate Cancer
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
Men with locally advanced prostate cancer (LAPCa) or regionally advanced prostate cancer (RAPCa) are at high risk for death from their disease. Clinical guidelines support multimodal approaches, which include radical prostatectomy (RP) followed by radiotherapy (XRT) and XRT plus androgen deprivation therapy (ADT). However, there are limited data comparing these substantially different treatment approaches. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, this study compared survival outcomes and adverse effects associated with RP plus XRT versus XRT plus ADT in these men.
METHODS
SEER-Medicare data were queried for men with cT3-T4N0M0 (LAPCa) or cT3-T4N1M0 (RAPCa) prostate cancer. Propensity score methods were used to balance cohort characteristics between the treatment arms. Survival analyses were analyzed with the Kaplan-Meier method and Cox proportional hazards models.
RESULTS
From 1992 to 2009, 13,856 men (≥65 years old) were diagnosed with LAPCa or RAPCa: 6.1% received RP plus XRT, and 23.6% received XRT plus ADT. At a median follow-up of 14.6 years, there were 2189 deaths in the cohort, of which 702 were secondary to prostate cancer. Regardless of the tumor stage or the Gleason score, the adjusted 10-year prostate cancer-specific survival and 10-year overall survival favored men who underwent RP plus XRT over men who underwent XRT plus ADT. However, RP plus XRT versus XRT plus ADT was associated with higher rates of erectile dysfunction (28% vs 20%; P = .0212) and urinary incontinence (49% vs 19%; P < .001).
CONCLUSIONS
Men with LAPCa or RAPCa treated initially with RP plus XRT had a lower risk of prostate cancer-specific death and improved overall survival in comparison with those men treated with XRT plus ADT, but they experienced higher rates of erectile dysfunction and urinary incontinence.
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Additional Info
Comparative Effectiveness of Radical Prostatectomy With Adjuvant Radiotherapy Versus Radiotherapy Plus Androgen Deprivation Therapy for Men With Advanced Prostate Cancer
Cancer 2018 Sep 25;[EPub Ahead of Print], TL Jang, N Patel, I Faiena, KD Radadia, DF Moore, SE Elsamra, EA Singer, MN Stein, JA Eastham, PT Scardino, Y Lin, IY Kim, GL Lu-YaoFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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In this article, the authors attempt to address the age-old question in the treatment of prostate cancer—which is better, surgery or radiation therapy? They utilize SEER–Medicare data and limit their analysis to patients with advanced but not metastatic disease. Specifically, they included those men with cT3-T4N0M0 or cT3-T4N1M0 prostate cancer. Despite the limitations of SEER and the observational nature of the study, several interesting findings should be noted. First, a significant number of men are likely undertreated, with 20% receiving no treatment whereas 21% and 18% underwent surgery and radiation alone, respectively. The current evidence would support aggressive and multimodal approaches to locally advanced and/or node-positive disease.
Second, prostatectomy was associated with the expected, increased risk of urinary and sexual morbidity while reducing need for intervention due to local symptoms/disease compared with radiation. However, one wonders whether the risks of bladder neck contractures (38%) would be significantly lower today compared with the study period (1992–2009) due to the widespread adoption of robotic-assisted techniques, which clearly reduce anastomotic strictures. Finally, the bottom-line conclusion is that surgery followed by adjuvant radiotherapy was associated with improved cancer-specific and overall survival at 10 years compared with combined androgen deprivation therapy and radiotherapy. Indeed, the 10-year cancer-specific survival in this advanced cohort was between 72% and 89% after surgery and radiation.
Ultimately, these findings add to the existing, indirect evidence, which may support an aggressive surgical approach for high-risk disease. Clearly, less is more for low-risk disease, where active surveillance may be most appropriate and significant oncologic differences between surgery and radiation therapy are unlikely to be proven. However, as suggested by Cooperberg et al and Zelefsky et al in studies of men with localized disease, surgery may have the greatest impact, compared with radiation, in those with aggressive prostate cancer.1,2 This coincides with current trends towards surgery even in cases of regional or oligometastatic disease, recognizing that surgery alone may not be curative but an important component of a combined modality; removal of the primary tumor within the prostate may have long-term benefits, given the longer natural history and the availability of novel, systemic agents today.
Questions that are not addressed in the study include details regarding duration of androgen deprivation as well as details regarding radiation treatment, such as dose and precise fields, which likely impact the results. Although limited to patients with metastatic disease, we may be able to draw some conclusions from the ongoing trial (NCT03678025) comparing standard systemic therapy with or without definitive therapy (ie, prostatectomy or radiation therapy). Whether we will be able to definitively answer this question in a prospective, randomized trial remains to be determined; but, for now, we should not necessarily dismiss surgery in cases of more aggressive or locally advanced prostate cancer.
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