Improved Survival Outcomes after Local Therapy in Men with Metastatic and Non-Metastatic cT4 Prostate Cancer Presenting with Obstructive Urinary Symptoms

Abstract

<h3>Purpose/Objective(s)</h3> Patients with <i>de novo</i> clinical T4 (cT4) prostate cancer represent a heterogenous and understudied population. The advanced nature of their local disease often results in obstructive urinary symptoms that lead to significant morbidity and mortality. We analyzed the effects of definitive local therapy on the outcomes of patients with cT4 prostate cancer. <h3>Materials/Methods</h3> We retrospectively reviewed 155 patients with <i>de novo</i> cT4 prostate cancer, treated at a single institution between 1996 and 2020. Baseline obstructive symptoms were defined as lower urinary tract symptoms (LUTS, AUA_SI>20 on flomax), urinary retention requiring foley, or acute renal failure (ARF). The association between baseline and treatment characteristics with outcomes were analyzed using Cox regression univariable analysis (UVA) and multivariable analysis (MVA), p<0.05 was considered significant. <h3>Results</h3> Analysis included 155 men, with median follow-up of 71 mos. Most patients had adenocarcinoma (88%), Gleason 9-10 (77%), and median baseline PSA of 19.9ng/ml (range, 0.5-1110). The majority of patients had T4NanyM1 disease (54%), followed by T4N1M0 (24%), and T4N0M0 (22%), as defined by conventional imaging studies. All men received systemic therapy with ADT (80%), ADT+abiraterone (12%), ADT+chemo (4%) or chemotherapy alone (4%). Local therapy was delivered with radiation (RT) (n=44), surgery (n=28), or both (n=9). Median prostate RT dose was 78Gy (IQR, 70-78) in 2Gy fractions. Patients did not receive definitive RT to their metastatic disease. Seventy-two (47%) men presented with obstructive symptoms with 36 (25%) being catheter dependent. For patients with obstructive symptoms, local therapy was associated with improved overall survival (OS: HR 0.33, p=0.001), freedom from local recurrence (FFLR:HR 0.19, p=0.003), and freedom from castration resistance (FFCR:HR 0.28, p=0.002). Patients who received local therapy were less likely to have local progression (HR 0.23, p=0.01), obstructive symptoms with progression (HR 0.21, p=0.03), or die with local disease (HR 0.15, p=0.001). On MVA local therapy improved OS (HR 0.45, p=0.03). OS was also affected by Gleason 10 and M1 disease (HR 15.58, p=0.02, HR 2.99, p=0.004; respectively). Conversely, in men who did not present with obstructive symptoms (n=83), there was no improvement in OS (HR=0.63, P=0.15). <h3>Conclusion</h3> Men with cT4 prostate cancer commonly present with obstructive symptoms due to local disease burden, representing a source of significant morbidity and potential mortality. Even among patients with metastatic disease, definitive local therapy is associated with improved patient outcomes including OS. Pending prospective evaluation, these data support the use of local therapy in men with cT4 disease presenting with obstructive urinary symptoms, irrespective of the presence of metastatic disease.