Local Therapy Improves Survival in Metastatic Prostate Cancer

Background Treatment of the primary, termed local therapy (LT), may improve survival in metastatic prostate cancer (mPCa) versus no local therapy (NLT). Objective To assess cancer-specific mortality (CSM) after LT versus NLT in mPCa. Design, setting, and participants Within the Surveillance, Epidemiology and End Results database (2004–2013), 13 692 mPCa patients were treated with LT (radical prostatectomy [RP] or radiation therapy [RT]) or NLT. Outcome measurements and statistical analysis Multivariable competing risk regression analyses (MVA CRR) tested CSM after propensity score matching (PSM) in two analyses, (1) NLT versus LT and (2) RP versus RT, and were complemented with interaction, sensitivity, unmeasured confounder, and landmark analyses. Results and limitations Of 13 692 mPCa patients, 474 received LT: 313 underwent RP and 161 RT. In MVA CRR, after PSM, LT (n = 474) results in lower CSM (subhazard ratio [SHR] 0.40, 95% confidence interval [CI] 0.32–0.50) versus NLT (n = 1896). In MVA CRR after PSM, RP (n = 161) results in lower CSM (SHR 0.59, 95% CI 0.35–0.99) versus RT (n = 161). Invariably, lowest CSM rates were recorded for Gleason ≤7, ≤cT3, and M1a substage. Interaction and sensitivity analyses confirmed the robustness of results, and landmark analyses rejected the bias favouring LT. A strong unmeasured confounder (HR = 5), affecting 30% of NLT patients, could obliterate LT benefit. Data were retrospective. Conclusions In mPCa, LT results in lower mortality relative to NLT. Within LT, lower mortality is recorded after RP than RT. Patients with most favourable grade, local stage, and metastatic substage derive most benefit from LT. They also derive most benefit from RP, when LT types are compared (RP vs RT). It is important to consider study limitations until ongoing clinical trials confirm the proposed benefits. Patient summary Individuals with prostate cancer that spreads outside of the prostate might still benefit from prostate-directed treatments, such as radiation or surgery, in addition to receiving androgen deprivation therapy.