For men diagnosed with G8-10 disease facing a treatment decision, I highly recommend these recent papers. The first is a recent review article that also discusses quality of life. The second is a statistical emulation of a clinical trial for high-grade, localized PCa coauthored by Dr. A. D'Amico, a leading radiation oncologist and Chief of Genitourinary Radiation Oncology at Dana Farber.
(BCR rates are not a very good stand-in for overall survival and are used for newer treatments when OS data is scant.)Comparing Radiotherapy to Prostatectomy for High-Risk Prostate Cancer: A Narrative Review of Mortality and Quality-of-Life Outcomes
There is currently a lack of level 1 evidence regarding the relative efficacy of radical prostatectomy compared with radiotherapy combined with androgen deprivation therapy for high-risk prostate cancer. There has recently been an improved optimization of treatment, achieving superior biochemical outcomes and cancer-specific mortality through the use of combined modality therapy strategies. Combined modality therapies have also increasingly incorporated brachytherapy boost. Although available observational data must be interpreted with caution because of the effects of potential residual confounding, we present here a narrative review of recent advances in understanding the relative efficacy of the principal combined modality approaches for treating high-risk prostate cancer. As the trend has demonstrated approaching equivalence between well-selected combined modality therapies, an increasing emphasis should be placed on selecting therapy tailored toward a patient's goals regarding quality of life. We present here an outline of efforts to date to understand the implications of treatment on functional outcomes and quality-of-life endpoints."
---------------------------------------------EMULATING A CLINICAL TRIAL OF RADICAL PROSTATECTOMY VERSUS EXTERNAL BEAM RADIATION THERAPY FOR HIGH-GRADE, CLINICALLY LOCALIZED PROSTATE CANCER
INTRODUCTION AND OBJECTIVE:
The comparative effectiveness of surgery and radiation therapy for clinically localized prostate cancer remains a seminal,
open question in urology. It represents a particularly important evidence gap for men with high-grade prostate cancer, where no randomized controlled trials exist to inform clinical practice.
We therefore emulated a hypothetical target clinical trial of radical prostatectomy (RP) versus external beam radiotherapy (EBRT) for high-grade, clinically localized prostate cancer.
We conducted observational analyses to emulate a target clinical trial of men aged 55-69 years with cT1-3 cN0 cM0, PSA <20 ng/mL, Gleason 8-10 prostate adenocarcinoma treated with RP or 75-81 Gy EBRT with androgen deprivation therapy (ADT) using the National Cancer Database (NCDB) from 2006-2015. A pr
opensity score for treatment was estimated using logistic regression, and the associations of treatment with overall survival (OS) were evaluated after adjusting with inverse probability of treatment weights (IPW).
A total of 26,806 men formed the study cohort, including 23,990 treated with RP and 2,816 with EBRT+ADT. Mean age at diagnosis was 63 years, and median PSA was 6.4 (IQR 4.8-9.3) ng/mL. Gleason score was 8 in 62%, 9 in 36%, and 10 in 2% of patients. Baseline characteristics were well-balanced after IPW-adjustment. Median follow-up was 48 (IQR 26-76) months. During follow-up, a total of 2,272 patients died. After IPW-reweighting, RP was associated with improved OS compared to EBRT+ADT (HR 0.54; p<0.001), with 5- and 10-year OS of 93% vs 87%, and 76% vs 60%, respectively. RP was associated with improved OS across all categories of Gleason score, PSA, cT stage, age, and Charlson index examined (Figure 1).
In observational analyses designed to emulate a target clinical trial of men with high-grade, clinically localized prostate cancer, RP was associated with improved OS compared with EBRT+ADT."
My point is not
that RP is superior to RT, but rather that it can be a perfectly good choice and is not inferior
to RT by our current understanding. Of course men with identical pathologies and statuses can make different choices according to their preferences. High-grade disease requires very different considerations than G6-7, which are, fortunately, the majority of cases.
For those with a good chance of having prostate-confined disease, RP has the advantage that the decision whether maxRP is necessary or not is made after
surgery, whereas the maxRT decision is made before primary treatment starts.