european urology supplements 8 (2009) 448–452

available at www.sciencedirect.com journal homepage: www.europeanurology.com

Role of Chemotherapy in Nonmetastatic Hormone-Refractory Prostate Cancer Joaquim Bellmunt * Department of Medical Oncology, University Hospital del Mar-IMIM, Solid Tumor Oncology (GU & GI), Passeig Maritim, 25–29, 08003-Barcelona, Spain

Article info

Abstract

Keywords: Nonmetastatic hormonerefractory prostate cancer Docetaxel PSA DT PSA progression only

Context: Docetaxel chemotherapy has become the standard first-line treatment for metastatic hormone-refractory prostate cancer (HRPC). Nowadays, one of the goals of research is to determine optimal management strategies for different patient populations with prostate cancer. Objective: Because the utility of docetaxel in patients with nonmetastatic HRPC has not yet been evaluated, one of the most challenging questions is to define the role of chemotherapy in nonmetastatic HRPC. Evidence acquisition: In a recently published subset analysis of TAX-327, a multivariate prognostic model incorporating prostate-specific antigen (PSA) kinetics has been developed to predict survival at 1, 2, and 5 yr in men with metastatic HRPC treated with chemotherapy. This novel model includes PSA doubling time (PSA DT), baseline pain, baseline PSA level, age, type of progression at baseline (measurable disease or bone scan compared with PSA only), presence of liver metastases, and the number of metastatic disease sites. Evidence synthesis: The authors found a statistically significantly better overall survival in patients with PSA 114 ng/ml and PSA DT >55 d. Patients with a PSA DT of 55 d. Patients with a PSA DT 45 d and no pain had an overall median survival of 32.4 mo, whereas patients with severe pain and PSA DT 25% over baseline or nadir with an absolute increase of at least 2–5 ng/ml, was a strong predictor of survival regardless of whether or not the patients achieved a PSA nadir. The authors also recommended PSA progression as a suitable end point in phase 2 studies. Consequently, it now seems clear that in hormone-resistant prostate cancer, evaluation of PSA kinetics is mandatory, especially in selected circumstances in which chemotherapy has no clear indication, including asymptomatic patients and patients who have PSA progression only. Evaluation of PSA kinetics can help us to inform the patient and his family about prognosis and about the potential benefits of the early indication of chemotherapy. It could be hypothesized that docetaxel-based chemotherapy could have a role in those patients with nonmetastatic HRPC who have a very short PSA doubling time.

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european urology supplements 8 (2009) 448–452

Conclusions

Based on recent data, we now have robust evidence supporting the use of chemotherapy in men with HRPC, although there is less evidence on when it should be started. Even though some cases of nonmetastatic HRPC with slow PSA asymptomatic progression should be considered for second-line hormonal manipulations, presently, men with metastatic HRPC should be treated with docetaxel every 3 wk in all symptomatic cases and in all cases with bone-scan progression. In nonmetastatic HRPC, chemotherapy could be indicated based on PSA level and PSA DT considerations.

Conflicts of interest The author has been a consultant and advisor during the past 2 yr for Sanofi-Aventis and Novartis regarding the subject matter under consideration in this paper.

Funding support None.

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