OncologyDiagnostic Evaluation Of PSA Recurrence And Review Of Hormonal Management After Radical Prostatectomy
UroToday.com - At present, no consensus exists on how patients with PSA recurrence after radical prostatectomy (RP) should be treated. Although patients with postoperative PSA recurrence frequently undergo androgen deprivation therapy (ADT) before evidence of metastatic disease, the benefit of this approach is uncertain. As no randomized studies are performed in this clinical setting there is no conclusive evidence that hormone therapy (HT) after RP will prolong survival or reduce morbidity.
Today, three randomized studies have evaluated the effect of adjuvant HT after RP in clinical settings other than PSA recurrence [1-4]. Survival advantage of immediate ADT after RP has only been proven in patients with positive lymph node prostate cancer in a single randomized study [1, 2]. Several retrospective analyses have been performed on the use of immediate and delayed HT in patients with surgically managed lymph node positive prostate cancer. However, to date no recommendations can be made regarding the optimal timing and duration of adjuvant HT after RP. Whether these data of adjuvant HT after RP in other clinical settings are relevant to men with rising postoperative PSA levels is uncertain.
In the meantime we can only rely on the data of 3 retrospective studies including patients with postoperative PSA recurrence who received HT after RP. One study demonstrates that early ADT after PSA recurrence does not affect clinical-metastasis-free survival in the overall cohort of patients but can delay the onset of metastases in high-risk patients with Gleason score > 7 and/or PSADT à‚£ 12 months [5]. A recent study from the Mayo Clinic shows that adjuvant ADT (within 90 days after surgery) after RP results in modest improvements of cancer-specific survival and systemic progression-free survival in a large cohort of high-risk patients. However, the survival advantage is lost when ADT is delivered at the time of PSA recurrence or systemic progression [6]. Another retrospective study demonstrates that even deferred ADT at the time of documented metastases after RP can result in long survival with a median failure time of 168 months from RP to death [7]. We should take into account that these studies are limited by their retrospective design. Moreover, early ADT may unnecessarily expose many patients with prostate cancer to the side effects of therapy.
Evidence from prospective randomized studies is needed before recommending the use of early hormone ADT in patients with PSA recurrence. Other non-traditional hormonal approaches and combinations of HT with radiotherapy and/or chemotherapy are currently under study.
References:
1. Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med 1999; 341(24): 1781-1788.
2. Messing EM, Manola J, Yao J, Kiernan M, Crawford D, Wilding G et al. Immediate versus deferred androgen deprivation treatment in patients with node positive prostate cancer after radical prostatectomy and pelvic lymhadenectomy. Lancet Oncology 2006; 7: 472-479.
3. Wirth MP, Weissbach L, Marx FJ, Heckl W, Jellinghaus W, Riedmiller H et al. Prospective randomized trial comparing flutamide as adjuvant treatment versus observation after radical prostatectomy for locally advanced, lymph node-negative prostate cancer. Eur Urol 2004; 45(3): 267-270; discussion 270.
4. McLeod DG, Iversen P, See WA, Morris T, Armstrong J, Wirth MP. Bicalutamide 150 mg plus standard care vs. standard care alone for early prostate cancer. BJU Int 2006; 97(2): 247-254.
5. Moul JW, Wu H, Sun L, McLeod DG, Amling C, Donahue T et al. Early versus delayed hormonal therapy for prostate specific antigen only recurrence of prostate cancer after radical prostatectomy. J Urol 2004; 171(3): 1141-1147.
6. Siddiqui SA, Boorjian SA, Inman B, Bagniewski S, Bergstralh EJ, Blute ML. Timing of androgen deprivation therapy and its impact on survival after radical prostatectomy: a matched cohort study. J Urol 2008; 179(5): 1830-1837; discussion 1837.
7. Makarov DV, Humphreys EB, Mangold LA, Carducci MA, Partin AW, Eisenberger MA et al. The natural history of men treated with deferred androgen deprivation therapy in whom metastatic prostate cancer developed following radical prostatectomy. J Urol 2008; 179(1): 156-161; discussion 161-152.
Written by H.Van Poppel, MD et al. as part of Beyond the Abstract on UroToday.com
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