In prostate cancer, the selection of further treatment depends on many factors, including prior treatment, site of recurrence, coexistent illnesses, and individual patient considerations. Definitive radiation therapy can be given to patients who fail only locally following prostatectomy.[1-4] 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 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 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 irradiation 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 II trials of new chemotherapeutic or biologic agents.[8]

Even among patients with metastatic "hormone-refractory prostate cancer," there is some heterogeneity 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) prior response to hormone therapy.[9] 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.[10] 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.[11] Data on whether PSA changes while on chemotherapy are predictive of survival are conflicting.[10,12]

Patients treated with either luteinizing hormone agonists or estrogens as primary therapy are generally maintained with castrate levels of testosterone. One study from the Eastern Cooperative Oncology Group showed that a superior survival resulted when patients were maintained on primary androgen deprivation.[13] However, another study from the Southwest Oncology Group did not show an advantage to continued androgen blockade.[14]

Painful bone metastases can be a major problem in prostate cancer. Many strategies have been studied for palliation, including pain medication, radiation, corticosteroids, bone-seeking radionuclides, gallium nitrate, and bisphosphonates.[15] External-beam radiation therapy for palliation of bone pain can be very useful. Also, the use of radioisotopes, such as strontium-89, has been shown to be effective as palliative treatment of some patients with osteoblastic metastases. When this isotope is given alone, it has been reported to decrease bone pain in 80% of patients treated,[16] and is similar to responses with local or hemibody radiation.[17] When used as an adjunct to external-beam radiation therapy, strontium-89 was shown to slow disease progression and to reduce analgesic requirements, compared to external-beam radiation therapy alone.[18]

Because chemotherapy has limited value in the treatment of patients with refractory disease following hormonal therapy, clinical trials are appropriate. These include trials of new chemotherapeutic or biologic agents.[8,19] Clinical trials exploring the value of chemotherapy for hormone-refractory patients are ongoing.[20-22] Low-dose prednisone may palliate symptoms in some patients treated.[23] A randomized trial showed improved pain control in hormone-resistant patients treated with mitoxantrone plus prednisone compared with those treated with prednisone alone.[24] However, there were no statistically significant differences in overall survival, well-being, or measured global quality of life between the 2 treatments.

References:

1. Lange PH, Reddy PK, Medini E, et al.: Radiation therapy as adjuvant treatment after radical prostatectomy. Journal of the National Cancer Institute Monographs 7: 141-149, 1988.
2. Ray GR, Bagshaw MA, Freiha F: External beam radiation salvage for residual or recurrent local tumor following radical prostatectomy. Journal of Urology 132(5): 926-930, 1984.
3. Carter GE, Lieskovsky G, Skinner DG, et al.: Results of local and/or systemic adjuvant therapy in the management of pathological stage C or D1 prostate cancer following radical prostatectomy. Journal of Urology 142(5): 1266-1271, 1989.
4. Freeman JA, Lieskovsky G, Cook DW, et al.: Radical retropubic prostatectomy and postoperative adjuvant radiation for pathological stage C (PCN0) prostate cancer from 1976 to 1989: intermediate findings. Journal of Urology 149(5): 1029-1034, 1993.
5. Moul JW, Paulson DF: The role of radical surgery in the management of radiation recurrent and large volume prostate cancer. Cancer 68(6): 1265-1271, 1991.
6. Schellhammer PF, Kuban DA, El-Mahdi AM: Treatment of clinical local failure after radiation therapy for prostate carcinoma. Journal of Urology 150(6): 1851-1855, 1993.
7. Bales GT, Williams MJ, Sinner M, et al.: Short-term outcomes after cryosurgical ablation of the prostate in men with recurrent prostate carcinoma following radiation therapy. Urology 46(5): 676-680, 1995.
8. Myers C, Cooper M, Stein C, et al.: Suramin: a novel growth factor antagonist with activity in hormone-refractory metastatic prostate cancer. Journal of Clinical Oncology 10(6): 881-889, 1992.
9. Fossa SD, Dearnaley DP, Law M, et al.: Prognostic factors in hormone-resistant progressing cancer of the prostate. Annals of Oncology 3(5): 361-366, 1992.
10. Kelly WK, Scher HI, Mazumdar M, et al.: Prostate-specific antigen as a measure of disease outcome in metastatic hormone-refractory prostate cancer. Journal of Clinical Oncology 11(4): 607-615, 1993.
11. Small EJ, Vogelzang NJ: Second-line hormonal therapy for advanced prostate cancer: a shifting paradigm. Journal of Clinical Oncology 15(1): 382-388, 1997.
12. Sridhara R, Eisenberger MA, Sinibaldi VJ, et al.: Evaluation of prostate-specific antigen as a surrogate marker for response of hormone-refractory prostate cancer to suramin therapy. Journal of Clinical Oncology 13(12): 2944-2953, 1995.
13. Taylor CD, Elson P, Trump DL: Importance of continued testicular suppression in hormone-refractory prostate cancer. Journal of Clinical Oncology 11(11): 2167-2172, 1993.
14. Hussain M, Wolf M, Marshall E, et al.: Effects of continued androgen-deprivation therapy and other prognostic factors on response and survival in phase II chemotherapy trials for hormone-refractory prostate cancer: a Southwest Oncology Group report. Journal of Clinical Oncology 12(9): 1868-1875, 1994.
15. Scher HI, Chung LW: Bone metastases: improving the therapeutic index. Seminars in Oncology 21(5): 630-656, 1994.
16. Robinson RG: Strontium-89: precursor targeted therapy for pain relief of blastic metastatic disease. Cancer 72(11, Suppl): 3433-3435, 1993.
17. Bolger JJ, Dearnaley DP, Kirk D, et al.: Strontium-89 (Metastron) versus external beam radiotherapy in patients with painful bone metastases secondary to prostatic cancer: preliminary report of a multicenter trial. Seminars in Oncology 20(3, Suppl 2): 32-33, 1993.
18. Porter AT, McEwan AJ, Powe JE, et al.: Results of a randomized Phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer. International Journal of Radiation Oncology, Biology, Physics 25(5): 805-813, 1993.
19. Debruyne FJ, Murray R, Fradet Y, et al.: Liarozole: a novel treatment approach for advanced prostate cancer: results of a large randomized trial versus cyproterone acetate. Urology 52(1): 72-81, 1998.
20. Eisenberger MA: Chemotherapy for prostate carcinoma. Journal of the National Cancer Institute Monographs 7: 151-163, 1988.
21. Pienta KJ, Redman B, Hussain M, et al.: Phase II evaluation of oral estramustine and oral etoposide in hormone-refractory adenocarcinoma of the prostate. Journal of Clinical Oncology 12(10): 2005-2012, 1994.
22. Hudes GR, Greenberg R, Krigel RL, et al.: Phase II study of estramustine and vinblastine, two microtubule inhibitors, in hormone-refractory prostate cancer. Journal of Clinical Oncology 10(11): 1754-1761, 1992.
23. Tannock I, Gospodarowicz M, Meakin W, et al.: Treatment of metastatic prostatic cancer with low-dose prednisone: evaluation of pain and quality of life as pragmatic indices of response. Journal of Clinical Oncology 7(5): 590-597, 1989.
24. Tannock IF, Osoba D, Stockler MR, et al.: Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. Journal of Clinical Oncology 14(6): 1756-1764, 1996.

Back to Content Page                                    <<  Back