Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

In prostate cancer, the selection of further treatment depends on many factors, including previous treatment, site of recurrence, coexistent illnesses, and individual patient considerations. Definitive radiation therapy can be given to patients who fail only locally following prostatectomy.[1,2,3,4] An occasional patient can be salvaged with prostatectomy after a local recurrence following definitive radiation therapy;[5] however, only about 10% of patients treated initially with radiation therapy will have local relapse only. In these patients, prolonged disease control is often possible with hormonal therapy, with median cancer-specific survival of 6 years after local failure.[6] Cryosurgical ablation of recurrence following radiation therapy is associated frequently with elevated prostate-specific antigen (PSA) and a high complication rate. This technique is still undergoing clinical evaluation.[7] Most relapsing patients who initially received locoregional therapy with surgery or radiation therapy will fail with disseminated disease and are managed with hormonal therapy. The management of these patients with stage IV disease is discussed in the preceding section. Palliative radiation therapy for bone pain can be very useful. Because of the poor prognosis in prostate cancer patients with relapsing or progressive disease after hormonal therapy, clinical trials are appropriate. These include phase I and phase II trials of new chemotherapeutic or biologic agents.

Even among patients with metastatic hormone-refractory prostate cancer, some heterogeneity is found in prognosis and in retained hormone sensitivity. In such patients who have symptomatic bone disease, several factors are associated with worsened prognosis: poor performance status, elevated alkaline phosphatase, abnormal serum creatinine, and short (<1 year) previous response to hormone therapy.[8] The absolute level of PSA at the initiation of therapy in relapsed or hormone-refractory patients has not been shown to be of prognostic significance.[9] Some patients whose disease has progressed on combined androgen blockade can respond to a variety of second-line hormonal therapies. Aminoglutethimide, hydrocortisone, flutamide withdrawal, progesterone, ketoconazole, and combinations of these therapies have produced PSA responses in 14% to 60% of patients treated and have also produced clinical responses of 0% to 25% when assessed. The duration of these PSA responses has been in the range of 2 to 4 months.[10] Survival rates are similar whether ketoconazole plus hydrocortisone is initiated at the same time as anti-androgen (e.g., flutamide, bicalutamide, or nilutamide) withdrawal or when PSA has risen after an initial trial of anti-androgen withdrawal as seen in the CALGB-9583 trial, for example.[11][Level of evidence: 1iiA] Data on whether PSA changes while on chemotherapy are predictive of survival are conflicting.[9,12]