PTEN Mutations Associated with Increased Recurrence and Decreased Survival in Patients with Prostate Cancer Spinal Metastasis

Abstract

Introduction: Prostate cancer with spinal metastases (PCSM) is associated with high morbidity and mortality. The impact of biomarkers on the prognosis of spinal metastases, however, remains unclear.

Objective: This study explored associations between potential biomarkers, treatment modalities, survival, and neurological outcomes in PCSM patients.

Methods: We conducted a retrospective analysis of 68 patients as part of a neurosurgical cohort with PCSM at a comprehensive cancer center from 2013 to 2023, examining the influence of potential biomarkers, treatment modalities, and demographics on prognosis. The primary outcomes were the identification of biomarkers, overall survival (OS) in years, survival after spinal metastasis in years, spinal metastasis recurrence, and postoperative neurological outcomes via Frankel scores.

Results: All the patients (n = 68) had adenocarcinoma, and the median age was 69 years. The mortality rate was 66% with a median OS of 6 years. Seventy-two biomarkers were identified. An accelerated failure time model (AFT) showed that radiotherapy to the prostate increased the OS (TR = 1.805, p = 0.001), while smoking status (TR = 0.625, p < 0.001) and PTEN gene mutations (TR = 0.504, p = 0.006) were associated with decreased OS. Kaplan-Meier analysis associated PTEN mutations with reduced median OS using the Gehan-Breslow-Wilcoxon test (3.50 vs. 9.49 years; p = 0.001). PTEN mutations were trending towards but were not significant for decreased survival following spinal metastases (2.04 vs. 3.15 years; p = 0.08). Both PTEN (p = 0.02) and Tumor Protein 53 (TP53, p = 0.01) mutations were associated with increased spinal metastasis recurrence when analyzed using Fisher's exact test. No differences were observed in the median OS or survival after spinal metastases among patients with or without androgen receptor splice variant-7 (AR-V7), prostate-specific membrane antigen (PSMA), TP53, or other analyzed biomarkers. Similarly, neither age, receipt of chemotherapy, nor radiotherapy to the spine correlated with OS. Only chemotherapy was associated with a decreased postoperative Frankel Score (p = 0.002).

Conclusions: PTEN mutations and smoking status were associated with decreased OS in patients with PCSM. Both PTEN and TP53 mutations were associated with increased spinal metastasis recurrence. Receipt of radiotherapy to the prostate was correlated with prolonged survival, whereas receipt of radiotherapy to the spine was not. Chemotherapy was associated with decreased postoperative neurological outcomes.

Keywords: genetic biomarkers; malignancy; metastasis; mortality; motor; prostate cancer; sensory; spine.

Figure 1

(A) Biomarker frequency among all patients in the study population. (B) Frequency of therapeutic agents administered to patients in the study population.

Figure 2

Kaplan–Meier overall survival and survival after spinal metastasis curves for patients with metastatic prostate cancer to the spine. Only PTEN was associated with decreased OS. (A) OS by PTEN status, (B) OS by AR-V7 status, (C) OS by PSMA status, (D) OS by TP53 status, (E) Survival time after spinal metastasis by PTEN status, (F) Survival time after spinal metastasis by AR-V7 status, (G) Survival time after spinal metastasis by PSMA status, (H) Survival time after spinal metastasis by TP53 status.