Zietman A L, Dallow K C, McManus P A, Heney N M, Shipley W U
Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston 02114, USA.
Urology. 1996 Feb;47(2):236-9. doi: 10.1016/S0090-4295(99)80423-3.
The most relevant endpoint in comparing the efficacy of curative therapies for prostate cancer is cancer-specific death. Prospective trials need to mature for a least a decade to yield meaningful cancer death data due to the long natural history of the disease amd the use of salvage androgen suppression. This delay may be long enough that the tested treatments are outdated by the time of reporting; thus, there is a need for reliable early surrogate endpoints for cancer survival.
This report evaluates 202 patients entered into a single institution prospective randomized study for T3-4 prostate cancer. Patients were accrued between 1982 and 1992 and received radical irradiation to either a standard dose of 67.2 Gy or a higher dose of 75.6 Gy. Median follow-up was 5.4 years. A total 76 men have received androgen suppression or orchiectomy for salvage following relapse. Of this group, 35 experienced a second relapse heralded by a rise in the serum prostate-specific antigen (PSA).
The median survival from the time of second biochemical relapse (defined as a progression with a rise in serum PSA more than 10% above the nadir after androgen suppression) was 27 months. Kaplan-Meier analysis projected a 0% survival for this group at 4 years. All those dying after second biochemical failure died of the prostate cancer.
Second PSA failure (or PSA progression on hormonal therapy) has potential as a surrogate for impending cancer death and its use as an endpoint in prospective studies could allow earlier reporting by 2 to 4 years.
比较前列腺癌根治性疗法疗效时，最相关的终点指标是癌症特异性死亡。由于前列腺癌自然病程较长且采用挽救性雄激素抑制治疗，前瞻性试验至少需要10年才能得出有意义的癌症死亡数据。这种延迟可能足够长，以至于在报告结果时所测试的治疗方法已过时；因此，需要可靠的早期替代终点指标来评估癌症生存率。
本报告评估了202例进入单机构前瞻性随机研究的T3-4期前列腺癌患者。患者于1982年至1992年入组，接受标准剂量67.2 Gy或更高剂量75.6 Gy的根治性放疗。中位随访时间为5.4年。共有76名男性在复发后接受了雄激素抑制或睾丸切除术进行挽救治疗。在这组患者中，35例出现了第二次复发，表现为血清前列腺特异性抗原（PSA）升高。
第二次生化复发（定义为雄激素抑制后血清PSA升高超过最低点10%以上的进展）后的中位生存期为27个月。Kaplan-Meier分析预测该组4年生存率为0%。所有在第二次生化失败后死亡的患者均死于前列腺癌。
第二次PSA失败（或激素治疗期间PSA进展）有可能作为即将发生癌症死亡的替代指标，将其用作前瞻性研究的终点指标可使报告时间提前2至4年。
