Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
University of Michigan, Michigan Union, Michigan.
Int J Radiat Oncol Biol Phys. 2014 Aug 1;89(5):1038-1046. doi: 10.1016/j.ijrobp.2014.04.052. Epub 2014 Jul 8.
To test the hypothesis that a genomic classifier (GC) would predict biochemical failure (BF) and distant metastasis (DM) in men receiving radiation therapy (RT) after radical prostatectomy (RP).
Among patients who underwent post-RP RT, 139 were identified for pT3 or positive margin, who did not receive neoadjuvant hormones and had paraffin-embedded specimens. Ribonucleic acid was extracted from the highest Gleason grade focus and applied to a high-density-oligonucleotide microarray. Receiver operating characteristic, calibration, cumulative incidence, and Cox regression analyses were performed to assess GC performance for predicting BF and DM after post-RP RT in comparison with clinical nomograms.
The area under the receiver operating characteristic curve of the Stephenson model was 0.70 for both BF and DM, with addition of GC significantly improving area under the receiver operating characteristic curve to 0.78 and 0.80, respectively. Stratified by GC risk groups, 8-year cumulative incidence was 21%, 48%, and 81% for BF (P<.0001) and for DM was 0, 12%, and 17% (P=.032) for low, intermediate, and high GC, respectively. In multivariable analysis, patients with high GC had a hazard ratio of 8.1 and 14.3 for BF and DM. In patients with intermediate or high GC, those irradiated with undetectable prostate-specific antigen (PSA ≤0.2 ng/mL) had median BF survival of >8 years, compared with <4 years for patients with detectable PSA (>0.2 ng/mL) before initiation of RT. At 8 years, the DM cumulative incidence for patients with high GC and RT with undetectable PSA was 3%, compared with 23% with detectable PSA (P=.03). No outcome differences were observed for low GC between the treatment groups.
The GC predicted BF and metastasis after post-RP irradiation. Patients with lower GC risk may benefit from delayed RT, as opposed to those with higher GC; however, this needs prospective validation. Genomic-based models may be useful for improved decision-making for treatment of high-risk prostate cancer.
验证基因组分类器（GC）是否能预测接受根治性前列腺切除术（RP）后放射治疗（RT）的患者发生生化失败（BF）和远处转移（DM）的假说。
在接受 RP 后 RT 的患者中，确定了 139 名患有 pT3 或阳性切缘、未接受新辅助激素治疗且有石蜡包埋标本的患者。从最高的格里森分级焦点提取核糖核酸，并应用于高密度寡核苷酸微阵列。为了评估 GC 在预测 RP 后 RT 后 BF 和 DM 的性能，与临床列线图相比，进行了接收者操作特征曲线、校准、累积发生率和 Cox 回归分析。
斯蒂芬森模型的接收者操作特征曲线下面积（AUC）分别为 0.70，加入 GC 后，AUC 分别显著提高至 0.78 和 0.80。按 GC 风险组分层，8 年累积发生率分别为 BF 的 21%、48%和 81%（P<.0001），DM 的 0、12%和 17%（P=.032），低、中、高 GC 组分别为 0、12%和 17%。多变量分析显示，GC 高的患者 BF 和 DM 的风险比分别为 8.1 和 14.3。在中高危 GC 患者中，与 RT 开始前 PSA 可检测（>0.2ng/ml）的患者相比，PSA 不可检测（≤0.2ng/ml）的患者 BF 中位生存时间>8 年。8 年时，GC 高且 PSA 不可检测的患者 DM 累积发生率为 3%，而 PSA 可检测的患者为 23%（P=.03）。低 GC 在两组治疗之间无生存差异。
GC 预测 RP 后照射的 BF 和转移。GC 风险较低的患者可能受益于延迟 RT，而不是 GC 较高的患者；然而，这需要前瞻性验证。基于基因组的模型可能有助于改善高危前列腺癌治疗的决策。
