Prostate cancer is the second most common cancer among men. Despite advances in diagnosis and management, prostate cancer led to more than 300,000 deaths globally in 2020. Chemotherapy is a cornerstone of therapy for advanced prostate cancer and can prolong survival of patients with both castration-sensitive and castration-resistant disease. Herein, we present a comprehensive review of the data supporting implementation of chemotherapy in the modern treatment of advanced prostate cancer, with special attention to the use of chemotherapy for aggressive variant prostate cancer (e.g., neuroendocrine prostate cancer) and the combination of chemotherapy with androgen signaling inhibitors. As the field of prostate cancer research continues to rapidly evolve yielding novel agents and treatment modalities, chemotherapy continues to play an essential role in prolonging the survival of patients with advanced and metastatic prostate cancer.

Background/Objectives: Total neoadjuvant therapy (TnT) has emerged as a treatment option for locally advanced rectal cancer. Few studies have evaluated specifically the use of chemotherapy and short-course radiation therapy (SCRT) in obtaining a complete clinical response (cCR) or near-complete clinical response (nCR) and offering non-operative management (NOM). This phase II study sequences FOLFOX followed by SCRT with the primary aim of evaluating the rate of cCR or nCR. Methods: Treatment-naïve adults with non-metastatic clinical T2-3N0 or T1-3 with N1-2a rectal adenocarcinoma deemed candidates for total mesorectal excision (TME) were eligible for this open-label, single-arm clinical trial. This trial evaluated TnT with 5-fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) followed by SCRT. The primary endpoint was the rate of cCR or nCR. Those with cCR or nCR after TnT were offered NOM and close surveillance; all others underwent TME. Secondary endpoints included 1-year disease-free survival (DFS), overall survival (OS), and R0 surgical resection rate. Results: Twelve patients of a planned 40 were enrolled with a median follow-up duration of 4.1 years. The study was closed early after results of the OPRA trial suggested a benefit of sequencing radiation prior to chemotherapy when seeking organ preservation. Four of the twelve patients (33%, 95% CI = (9.9%, 65.1%)) achieved cCR or nCR after TnT and underwent NOM; one patient had local regrowth 5.5 months after the completion of TnT and underwent TME. All four were free of disease at time of analysis. The 1-year DFS was 100%. The median OS was not reached. All surgical resections were R0 with no local recurrence after TME. Conclusions: This paper suggests that TnT with FOLFOX followed by SCRT is a safe and effective approach for treating locally advanced rectal cancer. This approach can be considered in select patients. The 33% of patients offered NOM is lower than the published 74% in OPRA, however, suggesting that chemotherapy followed by SCRT may not be the most optimal approach if organ preservation is the primary treatment aim.