Background

Intermediate clinical endpoints (ICEs) prognostic for overall survival (OS) are needed for men receiving postprostatectomy radiation therapy (PORT) to improve clinical trial design.

Objective

To identify a potential ICE for men receiving PORT.

Design, setting, and participants

We performed an institutional review board–approved multi-institutional retrospective study of 566 men consecutively treated with PORT at tertiary care centers from 1986 to 2013. The median follow-up was 8.2 yr.

Outcome measurements and statistical analysis

Biochemical failure (BF), distant metastases (DM), and castrate-resistant prostate cancer (CRPC) were evaluated for correlation with OS and assessed as time-dependent variables in a multivariable Cox proportional hazards model and in landmark analyses at 1, 3, 5, and 7 yr after PORT. Cross-validated concordance (c) indices were used to assess model discrimination.

Results and limitations

OS at 1, 3, 5, and 7 yr after PORT was 98%, 95%, 90%, and 82%, respectively. In a time-varying model controlling for clinical and pathologic variables, BF (hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.45–3.71; p < 0.001), DM (HR 6.52, 95% CI 4.20–10.1; p < 0.001), and CRPC (HR 2.47, 95% CI 1.56–3.92; p < 0.001) were associated with OS. In landmark analyses, 5-yr DM had the highest c index when adjusting for baseline covariates (0.78), with 5-yr DM also providing the greatest increase in discriminatory power over a model only including baseline covariates. These findings require validation in prospective randomized data.

Conclusions

While limited by the retrospective nature of the data, 5-yr DM is associated with lower OS following PORT, outperforming the prognostic capability of BF and CRPC at 1, 3, 5, or 7 yr after treatment. Confirmation of this ICE as a surrogate for OS is needed from randomized trial data so that it can be incorporated into future clinical trial design.

Patient summary

We assessed potential intermediate clinical endpoints prognostic for overall survival in a cohort of men receiving radiotherapy after prostatectomy. We identified the development of metastatic disease within 5 yr after treatment as the strongest predictor of overall survival.

中文翻译：

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前列腺切除术后放疗后的中间终点：5 年远处转移预测总生存期

背景

接受前列腺切除术后放射治疗 (PORT) 的男性需要预测总生存期 (OS) 的中间临床终点 (ICE) 以改进临床试验设计。

客观的

为接受 PORT 的男性确定潜在的 ICE。

设计、设置和参与者

我们对 1986 年至 2013 年在三级护理中心连续接受 PORT 治疗的 566 名男性进行了机构审查委员会批准的多机构回顾性研究。中位随访时间为 8.2 年。

结果测量和统计分析

评估生化失败 (BF)、远处转移 (DM) 和去势抵抗性前列腺癌 (CRPC) 与 OS 的相关性，并在多变量 Cox 比例风险模型和 1、3、 PORT 后 5 年和 7 年。交叉验证的一致性 ( c ) 指数用于评估模型区分。

结果和局限性

PORT 后 1、3、5 和 7 年的 OS 分别为 98%、95%、90% 和 82%。在控制临床和病理变量的时变模型中，BF（风险比 [HR] 2.32，95% 置信区间 [CI] 1.45–3.71；p  < 0.001），DM（HR 6.52，95% CI 4.20–10.1；p  < 0.001) 和 CRPC (HR 2.47, 95% CI 1.56–3.92; p  < 0.001) 与 OS 相关。在里程碑分析中，5 年 DM 在调整基线协变量时具有最高的c指数 (0.78)，与仅包括基线协变量的模型相比，5 年 DM 的判别力也提供了最大的增加。这些发现需要在前瞻性随机数据中进行验证。

结论

虽然受限于数据的回顾性，但 5 年 DM 与 PORT 后 OS 较低相关，在治疗后 1、3、5 或 7 年优于 BF 和 CRPC 的预后能力。需要从随机试验数据中确认该 ICE 作为 OS 的替代物，以便将其纳入未来的临床试验设计。

患者总结

我们评估了前列腺切除术后接受放射治疗的一组男性总体生存期的潜在中间临床终点预后。我们确定治疗后 5 年内发生转移性疾病是总生存期的最强预测因子。