Early versus late hormonal therapy: debating the issues

Hormonal therapy for prostate cancer has traditionally been reserved for advanced disease, but current evidence suggests that earlier use can confer a survival advantage. Survival benefit has been observed among patients with TNM stage T3 tumors who were treated with hormonal therapy plus external irradiation. Patients with nodal metastases (D1) who received immediate treatment with hormonal therapy after radical prostatectomy and pelvic lymphadenectomy also survived longer than those who were treated only after disease progression. The patients included in these studies are distinguished from those exhibiting "biochemical" failure (ie, increased levels of prostate-specific antigen, despite local therapy). It is in these patients that the use of hormonal therapy is, at present, controversial. For the purpose of identifying the subgroup of patients who might specifically benefit from early hormonal treatment, various schemas for defining predictors of poor outcome have been developed, including nomograms and artificial neural network programs. As with hormonal therapy, the use of chemotherapy in prostate cancer has been regarded as a palliative option for hormone-refractory disease. However, positive experience with early chemotherapy in other cancers suggests that such strategies might be similarly beneficial in prostate cancer. Limited clinical data show that chemotherapy combined with hormonal therapy can increase the initial response rate and prolong survival in locally advanced disease (T3 or D2), but not in metastatic tumors. An international trial is under way to evaluate the role of adjuvant chemotherapy in patients with localized prostate cancer who are at high risk of relapse after radical prostatectomy. Thus, accumulating evidence provides a rationale for continued investigation into the use of early hormonal therapy in selected patients.