Rising serum PSA after treatment for localized prostate cancer: Systemic therapy
- Judd W Moul, MD, FACS
Judd W Moul, MD, FACS
- James H. Semans, MD Professor of Surgery
- Division of Urologic Surgery
- Duke University Medical Center
- Director, Duke Prostate Center
- Duke Cancer Institute
- Mary-Ellen Taplin, MD
Mary-Ellen Taplin, MD
- Associate Professor of Medicine
- Harvard Medical School
- Section Editors
- Nicholas Vogelzang, MD
Nicholas Vogelzang, MD
- Section Editor — Prostate Cancer
- Professor of Medicine
- University of Nevada School of Medicine
- US Oncology Research
- W Robert Lee, MD, MS, MEd
W Robert Lee, MD, MS, MEd
- Section Editor — Prostate Cancer
- Professor of Radiation Oncology
- Duke University Medical Center
- Jerome P Richie, MD, FACS
Jerome P Richie, MD, FACS
- Section Editor — Cancer of the Urethra, Penis, and Ureter; Urologic Surgery; Prostate Cancer
- Elliott Carr Cutler Professor of Surgery
- Harvard Medical School
Prostate-specific antigen (PSA) is a sensitive and specific serum marker for prostate tissue. Serial measurements are routinely obtained to detect early disease recurrence in men who have received definitive treatment for localized disease. (See "Follow-up surveillance during and after treatment for prostate cancer".)
Monitoring PSA after definitive treatment of localized prostate cancer with either radiation therapy (RT) or radical prostatectomy leads to the identification of men with a PSA-only (biochemical) recurrence. In this situation, increases in serum PSA are not accompanied by signs, symptoms, or radiographic evidence of locally recurrent or disseminated disease. (See "Rising serum PSA following local therapy for prostate cancer: Definition, natural history, and risk stratification", section on 'Definition of biochemical progression'.)
For men in whom there is a significant likelihood that disease is confined to the prostatic bed, salvage therapy may result in prolonged disease-free survival [1,2]. (See "Rising serum PSA after radiation therapy for localized prostate cancer: Salvage local therapy" and "Rising or persistently elevated serum PSA following radical prostatectomy for prostate cancer: Management".)
However, systemic treatment may be indicated for some men when clinical and radiographic features suggest that disseminated disease is highly probable, and hence, salvage local therapy is not indicated. In others cases, systemic therapy may be useful in men when comorbidity or advanced age precludes aggressive local salvage therapy.
The role of systemic therapy in men with a PSA recurrence without evidence of disseminated disease will be reviewed here. The management of patients with disseminated prostate cancer is discussed separately. (See "Overview of the treatment of disseminated prostate cancer".)
- Punnen S, Cooperberg MR, D'Amico AV, et al. Management of biochemical recurrence after primary treatment of prostate cancer: a systematic review of the literature. Eur Urol 2013; 64:905.
- Fossati N, Karnes RJ, Cozzarini C, et al. Assessing the Optimal Timing for Early Salvage Radiation Therapy in Patients with Prostate-specific Antigen Rise After Radical Prostatectomy. Eur Urol 2016; 69:728.
- van den Bergh RC, van Casteren NJ, van den Broeck T, et al. Role of Hormonal Treatment in Prostate Cancer Patients with Nonmetastatic Disease Recurrence After Local Curative Treatment: A Systematic Review. Eur Urol 2016; 69:802.
- Loblaw DA, Virgo KS, Nam R, et al. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol 2007; 25:1596.
- Garcia-Albeniz X, Chan JM, Paciorek AT, et al. Immediate versus deferred initiation of androgen deprivation therapy in prostate cancer patients with PSA-only relapse (abstract 5003). 2014 American Society of Clinical Oncology meeting.
- Garcia-Albeniz X, Chan JM, Paciorek A, et al. Immediate versus deferred initiation of androgen deprivation therapy in prostate cancer patients with PSA-only relapse. An observational follow-up study. Eur J Cancer 2015; 51:817.
- Fu AZ, Tsai HT, Haque R, et al. Mortality and Androgen Deprivation Therapy as Salvage Treatment for Biochemical Recurrence after Primary Therapy for Clinically Localized Prostate Cancer. J Urol 2017; 197:1448.
- Han M, Partin AW, Pound CR, et al. Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience. Urol Clin North Am 2001; 28:555.
- Pound CR, Partin AW, Eisenberger MA, et al. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999; 281:1591.
- Duchesne GM, Woo HH, Bassett JK, et al. Timing of androgen-deprivation therapy in patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial. Lancet Oncol 2016; 17:727.
- Crook JM, O'Callaghan CJ, Duncan G, et al. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med 2012; 367:895.
- Nakabayashi M, Xie W, Buckle G, et al. Long-term follow-up of a phase II trial of chemotherapy plus hormone therapy for biochemical relapse after definitive local therapy for prostate cancer. Urology 2013; 81:611.
- James ND, Sydes MR, Clarke NW, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 2016; 387:1163.
- Oh WK, Manola J, Bittmann L, et al. Finasteride and flutamide therapy in patients with advanced prostate cancer: response to subsequent castration and long-term follow-up. Urology 2003; 62:99.
- Kunath F, Grobe HR, Rücker G, et al. Non-steroidal antiandrogen monotherapy compared with luteinising hormone-releasing hormone agonists or surgical castration monotherapy for advanced prostate cancer. Cochrane Database Syst Rev 2014; :CD009266.
- Tombal B, Borre M, Rathenborg P, et al. Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results. Eur Urol 2015; 68:787.
- Seidenfeld J, Samson DJ, Hasselblad V, et al. Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Ann Intern Med 2000; 132:566.
- Schröder F, Bangma C, Angulo JC, et al. Dutasteride treatment over 2 years delays prostate-specific antigen progression in patients with biochemical failure after radical therapy for prostate cancer: results from the randomised, placebo-controlled Avodart After Radical Therapy for Prostate Cancer Study (ARTS). Eur Urol 2013; 63:779.
- Picus J, Halabi S, Hussain M. Long term efficacy of peripheral androgen blockade on prostate cancer: results of CALGB 9782. J Clin Oncol 2006; 24:234s.
- Barqawi AB, Moul JW, Ziada A, et al. Combination of low-dose flutamide and finasteride for PSA-only recurrent prostate cancer after primary therapy. Urology 2003; 62:872.
- Brufsky A, Fontaine-Rothe P, Berlane K, et al. Finasteride and flutamide as potency-sparing androgen-ablative therapy for advanced adenocarcinoma of the prostate. Urology 1997; 49:913.
- Tay MH, Kaufman DS, Regan MM, et al. Finasteride and bicalutamide as primary hormonal therapy in patients with advanced adenocarcinoma of the prostate. Ann Oncol 2004; 15:974.
- Monk JP, Halabi S, Picus J, et al. Efficacy of peripheral androgen blockade in prostate cancer patients with biochemical failure after definitive local therapy: results of Cancer and Leukemia Group B (CALGB) 9782. Cancer 2012; 118:4139.
- Bañez LL, Blake GW, McLeod DG, et al. Combined low-dose flutamide plus finasteride vs low-dose flutamide monotherapy for recurrent prostate cancer: a comparative analysis of two phase II trials with a long-term follow-up. BJU Int 2009; 104:310.
- Smith MR, Manola J, Kaufman DS, et al. Rosiglitazone versus placebo for men with prostate carcinoma and a rising serum prostate-specific antigen level after radical prostatectomy and/or radiation therapy. Cancer 2004; 101:1569.
- Smith MR, Manola J, Kaufman DS, et al. Celecoxib versus placebo for men with prostate cancer and a rising serum prostate-specific antigen after radical prostatectomy and/or radiation therapy. J Clin Oncol 2006; 24:2723.
- Paller CJ, Ye X, Wozniak PJ, et al. A randomized phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer. Prostate Cancer Prostatic Dis 2013; 16:50.
- Paller CJ, Rudek MA, Zhou XC, et al. A phase I study of muscadine grape skin extract in men with biochemically recurrent prostate cancer: Safety, tolerability, and dose determination. Prostate 2015; 75:1518.
- GENERAL APPROACH
- ANDROGEN DEPRIVATION THERAPY
- When to initiate ADT-based therapy
- Monotherapy versus combined androgen blockade
- Continuous versus intermittent androgen deprivation
- - Approach
- - Role
- ADT PLUS CHEMOTHERAPY
- NONCASTRATING HORMONAL THERAPY
- Antiandrogen monotherapy
- 5-alpha reductase inhibitors
- OTHER APPROACHES
- SURVEILLANCE DURING TREATMENT
- SUMMARY AND RECOMMENDATIONS