Predictors of early relapse in high risk prostate cancer patients treated with neoadjuvant mitoxantrone and docetaxel

Abstract

4640 Background: The addition of chemotherapy (CTX) to primary treatment is being evaluated in clinical trials to improve outcomes in high-risk prostate cancer. Factors that predict relapse after combined treatment with CTX and radical prostatectomy (RP) are not known. Understanding which clinical and pathologic factors affect outcome can facilitate the design of studies of combined modality treatment of high-risk prostate cancer. Methods: Using the Kaplan-Meier method and log-rank test for univariate analyses and Cox’s proportional hazards regression for the multivariate analysis, we examined the relationship between progression-free survival (PFS, defined as time to serum PSA ≥ 0.4 ng/mL) and a series of variables in men with high risk prostate cancer (cT2b or T3a or PSA ≥ 15 ng/mL or Gleason score (GS) ≥ 4+3) who received 4 cycles of docetaxel (35 mg/m2) and mitoxantrone (2–5 mg/m2) weekly for 3 of every 4 weeks prior to RP. Pre-CTX variables were PSA, PSA density (PSAD), age, biopsy GS, and cT stage. Post-treatment variables were: CTX doses delivered, %PSA change, surgical GS, pT stage, pN stage, margin status, Ki-67 index (% Ki-67 staining cells/total cancer cells from a tissue microarray), and presence of intraductal carcinoma (IDC). Results: 48 patients received at least 1 cycle of CTX and were evaluable for efficacy endpoints. Median follow-up is 18.6 months. Estimated PFS at 2 years is 70±14%. In univariate analyses PSA ≥ 15 ng/dL (p=0.02), presence of IDC (p=0.003), and lymph node metastases (+LN) (p<0.001) were associated with shorter PFS. In a multivariate analysis of pre-treatment factors, PSAD (HR 1.25 per 0.1 ng/ml/cc, 95%CI 1.03–1.5, p=0.03) was the only factor significantly associated with shorter PFS. When both pre- and post-treatment factors were included, PSAD (HR 1.3 per 0.1 ng/ml/cc, 95%CI 1.05–1.6, p=0.02) and +LN (HR 27, 95% CI 6–125, p<0.001) were independent predictors of shorter PFS. There was a trend for biopsy GS 8–10 (HR 3.9, 95%CI 0.9–16.9, p=0.068). Conclusions: Our early results show that in high risk prostate cancer treated with neoadjuvant chemotherapy followed by radical prostatectomy, PSAD and persistent nodal disease are significantly associated with early relapse. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, OSI