肿瘤抑制基因（TP53、PTEN、RB1）改变对转移性、激素敏感型前列腺癌的影响及治疗结局的差异。
Differential impact of tumor suppressor gene (TP53, PTEN, RB1) alterations and treatment outcomes in metastatic, hormone-sensitive prostate cancer.
机构信息
Division of Hematology and Medical Oncology, Phoenix, AZ, USA.
Department of Quantitative Health Sciences, Scottsdale, AZ, USA.
出版信息
Prostate Cancer Prostatic Dis. 2022 Sep;25(3):479-483. doi: 10.1038/s41391-021-00430-4. Epub 2021 Jul 22.
BACKGROUND
Altered tumor suppressor genes (TSG-alt) in prostate cancer are associated with worse outcomes. The prognostic value of TSG-alt in metastatic, hormone-sensitive prostate cancer (M1-HSPC) is unknown. We evaluated the effects of TSG-alt on outcomes in M1-HSPC and their prognostic impact by first-line treatment.
METHODS
We retrospectively identified patients with M1-HSPC at our institution treated with first-line androgen deprivation therapy plus docetaxel (ADT + D) or abiraterone acetate (ADT + A). TSG-alt was defined as any alteration in one or more TSG. The main outcomes were Kaplan-Meier-estimated progression-free survival (PFS) and overall survival, analyzed with the log-rank test. Clinical characteristics were compared with the χ test and Kruskal-Wallis rank sum test. Cox regression was used for univariate and multivariable analyses.
RESULTS
We identified 97 patients with M1-HSPC: 48 (49%) with ADT + A and 49 (51%) with ADT + D. Of 96 patients with data available, 33 (34%) had 1 TSG-alt, 16 (17%) had 2 TSG-alt, and 2 (2%) had 3 TSG-alt. The most common alterations were in TP53 (36%) and PTEN (31%); 6% had RB1 alterations. Median PFS was 13.1 (95% CI, 10.3-26.0) months for patients with normal TSGs (TSG-normal) vs. 7.8 (95% CI, 5.8-10.5) months for TSG-alt (P = 0.005). Median PFS was lower for patients with TSG-alt vs TSG-normal for those with ADT + A (TSG-alt: 8.0 [95% CI, 5.8-13.8] months vs. TSG-normal: 23.2 [95% CI, 13.1-not estimated] months), but not with ADT + D (TSG-alt: 7.8 [95% CI, 5.7-12.9] months vs. TSG-normal: 9.5 [95% CI, 4.8-24.7] months). On multivariable analysis, only TSG-alt predicted worse PFS (hazard ratio, 2.37; 95% CI, 1.42-3.96; P < 0.001).
CONCLUSIONS
The presence of TSG-alt outperforms clinical criteria for predicting early progression during first-line treatment of M1-HSPC. ADT + A was less effective in patients with than without TSG-alt. Confirmation of these findings may establish the need for inclusion of molecular stratification in treatment algorithms.
背景
前列腺癌中改变的肿瘤抑制基因（TSG-alt）与更差的预后相关。在转移性、激素敏感型前列腺癌（M1-HSPC）中，TSG-alt 的预后价值尚不清楚。我们评估了 TSG-alt 对 M1-HSPC 患者一线治疗结局的影响及其预后影响。
方法
我们回顾性地确定了我院接受一线雄激素剥夺治疗加多西他赛（ADT+D）或醋酸阿比特龙（ADT+A）治疗的 M1-HSPC 患者。TSG-alt 定义为一个或多个 TSG 的任何改变。主要结局是通过对数秩检验分析的 Kaplan-Meier 估计无进展生存期（PFS）和总生存期。采用 χ 检验和 Kruskal-Wallis 秩和检验比较临床特征。采用单因素和多因素分析 Cox 回归。
结果
我们确定了 97 例 M1-HSPC 患者：48 例（49%）接受 ADT+A 治疗，49 例（51%）接受 ADT+D 治疗。在 96 例有数据可查的患者中，33 例（34%）有 1 个 TSG-alt，16 例（17%）有 2 个 TSG-alt，2 例（2%）有 3 个 TSG-alt。最常见的改变是 TP53（36%）和 PTEN（31%）；6%的患者存在 RB1 改变。TSG 正常（TSG-正常）患者的中位 PFS 为 13.1 个月（95%CI，10.3-26.0），而 TSG-alt 患者为 7.8 个月（95%CI，5.8-10.5）（P=0.005）。对于接受 ADT+A 治疗的患者，与 TSG-正常相比，TSG-alt 患者的中位 PFS 更低（TSG-alt：8.0 个月[95%CI，5.8-13.8] vs. TSG-正常：23.2 个月[95%CI，13.1-未估计]），但接受 ADT+D 治疗的患者则不然（TSG-alt：7.8 个月[95%CI，5.7-12.9] vs. TSG-正常：9.5 个月[95%CI，4.8-24.7]）。多因素分析显示，只有 TSG-alt 预测 PFS 更差（危险比，2.37；95%CI，1.42-3.96；P<0.001）。
结论
在 M1-HSPC 患者的一线治疗中，TSG-alt 的存在优于临床标准，可预测早期进展。ADT+A 在 TSG-alt 阳性患者中的疗效不如 TSG-alt 阴性患者。这些发现的证实可能需要将分子分层纳入治疗算法中。
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