Zagars G K, Pollack A, von Eschenbach A C
Department of Clinical Radiotherapy, University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.
Int J Radiat Oncol Biol Phys. 1995 Aug 30;33(1):23-35. doi: 10.1016/0360-3016(95)00154-Q.
Prostate-specific antigen (PSA) is a powerful pretreatment prognosticator and a sensitive post-treatment outcome measure for clinically localized prostate cancer treated with radiation therapy. Today, the pretreatment serum PSA level appears to supersede both grade and T-stage as a determinant of outcome. This study was undertaken to attempt a reconciliation between the old (pre-PSA) and the new (PSA) data-in particular to address the question of why stage and grade apparently play so little role in this PSA era.
We analyzed the outcome of two cohorts of men with T1-T4, NO, or NX, MO prostate cancer, one group (648 patients) treated and followed in the pre-PSA era (1966-1988), another group (707 patients) treated and followed in the PSA era (1987-1993)--who received definitive radiation as their only initial treatment. The patterns of relapse and prognostic factors for these groups were compared and contrasted using univariate and multivariate techniques.
At a median follow-up of 6.5 years, the relapse patterns in the pre-PSA series were: local in 109 (17%), nodal in 17 (3%), and distant metastatic in 186 (29%). Actuarial local and metastatic rates at 5 years were 13 and 26%, respectively. Local recurrence was only weakly predictable, Gleason grade being the only significant, albeit weak, covariate. Metastatic failure, however, was highly significantly and meaningfully correlated with Gleason grade and T-stage. Because metastasis was the most common adverse end point in this series, overall freedom from progression also correlated with grade and stage. At a median follow-up of 31 months, the patterns of failure in the PSA series were: local in 77 (11%), nodal in 3 (< 1%), and distant metastatic in 24 (3%). Actuarial local and metastatic rates at 5 years were 30 and 6%, respectively. Local recurrence was highly and meaningfully correlated with pretreatment PSA level, which was the only significant determinant of this end point. Metastatic failure was highly correlated with Gleason grade and T-stage, with PSA playing a much lesser, though significant role. The inversion of failure patterns (local vs. distant) between the two series was striking. The high incidence of local failure in the PSA series was almost entirely related to positive prostatic biopsies pursuant to the investigation of the postradiation rising PSA profile. Of the 77 local recurrences, 69 (90%) were identified in this way. Among 99 men with rising PSA values who underwent investigation (CT scans, bone scans, and biopsies), disease was found in 86, and the patterns of disease in these 86 were: local only in 62 (72%), local and metastatic in 7, and metastatic in 17 (20%). The most common event in the PSA series was the rising PSA profile, and this, too, strongly correlated with the pretreatment PSA level.
Based on our earlier finding that the major source of pretreatment serum PSA in patients with clinically localized disease is the primary tumour itself and on the findings in the present report, we conclude that the new major message conveyed by serum PSA relates to the primary tumor and its likely outcome. Gleason grade and T-stage remain major determinants of metastatic relapse. The total and permanent eradication of prostate cancer from the prostate with conventional doses of external beam radiation therapy is harder to achieve than generally appreciated.
前列腺特异性抗原（PSA）是临床上局限性前列腺癌放射治疗的一种强大的治疗前预后指标和敏感的治疗后结果衡量指标。如今，治疗前血清PSA水平似乎已取代分级和T分期，成为预后的决定因素。本研究旨在尝试调和旧的（PSA时代之前）和新的（PSA时代）数据，特别是解决在这个PSA时代分期和分级为何显然作用甚微的问题。
我们分析了两组T1 - T4、NO或NX、M0前列腺癌男性患者的治疗结果，一组（648例患者）在PSA时代之前（1966 - 1988年）接受治疗并随访，另一组（707例患者）在PSA时代（1987 - 1993年）接受治疗并随访，他们均接受根治性放疗作为唯一的初始治疗。使用单因素和多因素技术对这些组的复发模式和预后因素进行了比较和对比。
中位随访6.5年时，PSA时代之前系列的复发模式为：局部复发109例（17%），淋巴结转移17例（3%），远处转移186例（29%）。5年的精算局部复发率和转移率分别为13%和26%。局部复发仅具有微弱的可预测性，Gleason分级是唯一显著的（尽管较弱）协变量。然而，转移失败与Gleason分级和T分期高度显著且密切相关。由于转移是本系列中最常见的不良终点，总体无进展也与分级和分期相关。中位随访31个月时，PSA系列的失败模式为：局部复发77例（11%），淋巴结转移3例（<1%），远处转移24例（3%）。5年的精算局部复发率和转移率分别为30%和6%。局部复发与治疗前PSA水平高度且密切相关，这是该终点的唯一显著决定因素。转移失败与Gleason分级和T分期高度相关，PSA虽有显著作用但作用较小。两个系列之间失败模式（局部与远处）的反转很明显。PSA系列中局部失败的高发生率几乎完全与放疗后PSA水平升高后进行的前列腺活检阳性有关。在77例局部复发中，69例（90%）是通过这种方式发现的。在99例PSA值升高并接受检查（CT扫描、骨扫描和活检）的男性中，86例发现有疾病，这86例疾病的模式为：仅局部病变62例（72%），局部和转移7例，转移17例（20%）。PSA系列中最常见的事件是PSA水平升高，这也与治疗前PSA水平密切相关。
基于我们早期的发现，即临床局限性疾病患者治疗前血清PSA的主要来源是原发性肿瘤本身，以及本报告中的发现，我们得出结论，血清PSA传达的新主要信息与原发性肿瘤及其可能的结果有关。Gleason分级和T分期仍然是转移复发的主要决定因素。用常规剂量的外照射放疗从前列腺中完全和永久根除前列腺癌比一般认为的更难实现。
