Purpose Clinical features characteristic of small-cell prostate carcinoma (SCPC), (““anaplastic””) often emerge during the progression of prostate cancer. We sought to determine the efficacy of platinum-based chemotherapy in patients meeting at least one of seven prospectively defined “anaplastic” clinical criteria, including exclusive visceral or predominantly lytic bone metastases, bulky tumor masses, low PSA levels relative to tumor burden or short response to androgen deprivation therapy. Experimental Design A 120-patient phase II trial of frontline carboplatin and docetaxel (CD) and second-line etoposide and cisplatin (EP) was designed to provide reliable clinical response estimates under a Bayesian probability model with early stopping rules in place for futility and toxicity. Results Seventy-four of 113 (65.4%) and 24 of 71 (33.8%) were progression free after 4 cycles of CD and EP, respectively. Median overall survival (OS) was 16 months (95% CI, 13.6-19.0 months). Of the 7 “anaplastic” criteria, bulky tumor mass was significantly associated with poor outcome. Lactic acid dehydrogenase (LDH) strongly predicted for OS and rapid progression. Serum carcinoembryonic antigen (CEA) concentration strongly predicted OS but not rapid progression. Neuroendocrine markers did not predict outcome or response to therapy. Conclusion Our findings support the hypothesis that patients with “anaplastic” prostate cancer are a recognizable subset characterized by a high response rate of short duration to platinum-containing chemotherapies, similar to SCPC. Our results suggest that CEA is useful for selecting therapy in men with CRPC and consolidative therapies to bulky high-grade tumor masses should be considered in this patient population.

Urachal carcinomas are usually locally advanced at presentation with a high risk of distant metastases. However, long-term survival following radical resection occurs in a significant fraction of patients (16 of 35 in our series), supporting an attempt at margin-negative, en bloc resection if at all possible. Chemotherapy appropriate for enteric type adenocarcinoma can induce objective responses but meaningful improvement in survival is not yet demonstrated.

The maximum-tolerated dose and recommended phase II dose of bortezomib in this schedule is 1.6 mg/m(2). Biologic activity (inhibition of nuclear factor-kappa B-related markers) and antitumor activity is seen in AIPCa at tolerated doses of bortezomib. This agent should be further explored with chemotherapy agents in advanced prostate cancer.

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