JU INSIGHT: Cell Cycle Progression Score, but Not Phosphatase and Tensin Homolog Loss, Is an Independent Prognostic Factor for Metastasis in Intermediate- and High-risk Prostate Cancer in Men Treated With and Without Salvage Radiotherapy

By: Bruce J. Trock, PhD; Yuezhou Jing, MS; Brent Mabey, MSc; Zaina Sangale, MD; Lauren Lenz, MS; Nora Haney, MD; Igor Vidal, MD; Stephanie A. Glavaris, BS; Gunes Guner, MD; Onur Ertunc, MD; Ibrahim Kulac, MD; Javier A. Baena Del Valle, MD; Tracy Jones, MD; Misop Han, MD; Alan W. Partin, MD, PhD; Todd Cohen, MD; Steven Stone, PhD; Angelo M. De Marzo, MD, PhD | Posted on: 01 Dec 2022

Trock BJ, Jing Y, Mabey B, et al. Cell cycle progression score, but not phosphatase and tensin homolog loss, is an independent prognostic factor for metastasis in intermediate- and high-risk prostate cancer in men treated with and without salvage radiotherapy. J Urol. 2022;208(6):1182-1193.

Study Need and Importance

In the past 2 decades a major change in treatment of intermediate- and high-risk prostate cancer has been the increased use of radical prostatectomy and concomitant decrease in definitive radiotherapy. Outcomes for these men are variable, and clinical variables alone are not sufficient to predict which men will be cured and which will ultimately progress to metastatic disease and death. The Prolaris cell cycle progression (CCP) genomic classifier and the phosphatase and tensin homolog (PTEN) tumor suppressor gene may improve clinical decision making in these patients, but haven’t been directly compared in a contemporary cohort of exclusively intermediate- and high-risk men. Accordingly, we performed the first study to compare associations of CCP and PTEN with metastasis-free survival in a recent cohort of intermediate- and high-risk men overall, and in such men treated with salvage radiotherapy.

What We Found

We found that in 209 intermediate/high-risk men overall, and 172 such men treated with salvage radiotherapy, CCP was independently associated with metastasis-free survival after adjustment for Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S): hazard ratio (95% confidence interval)=3.11 (1.70-5.69) and 1.85 (1.19-2.85), respectively. Adding CCP to CAPRA-S increased the concordance index from 0.861 to 0.899 (overall), and 0.745 to 0.819 (salvage radiotherapy cohort). Although statistically significant in univariate analyses, PTEN was no longer significant after adjustment for CCP or CAPRA-S (see Table). Within National Comprehensive Cancer Network risk categories, after adjusting for CAPRA-S CCP was significant for unfavorable intermediate- and high-risk men, but not favorable intermediate risk.

Limitations

Study limitations include the retrospective sample from a single center of excellence, which may not be representative of all men with intermediate/high-risk prostate cancer. The number of metastatic events was modest, particularly in the salvage radiotherapy cohort. Finally, analysis within National Comprehensive Cancer Network risk categories was an unplanned exploratory analysis.

Interpretation for Patient Care

Although it requires validation in a larger series, the study suggests that CCP may inform decision making in men with unfavorable intermediate- and high-risk disease.

Table. Multivariable Proportional Hazards Regression Analyses of Metastasis-free Survival in a Case Cohort of Intermediate- and High-risk Men (n = 209)

Model	HR (95% CI)
Model 1 CCP (per unit) CAPRA-S (per unit)	3.11 (1.70, 5.69) 1.91 (1.59, 2.30)
Model 2 CCP (per unit) PTEN (loss vs intact)^a	3.36 (1.64, 6.91) 1.82 (0.52, 6.47)
Model 3 PTEN (loss vs intact)^a CAPRA-S (per unit)	2.08 (0.78, 5.57) 1.96 (1.67, 2.30)
Model 4 CCP (per unit) CAPRA-S (per unit) PTEN (loss vs intact)^a	2.71 (1.44, 5.12) 1.90 (1.60, 2.26) 1.82 (0.65, 5.13)
Abbreviations: CAPRA-S, Cancer of the Prostate Risk Assessment Post-Surgical; CCP, cell cycle progression; CI, confidence interval; HR, hazard ratio; PTEN, phosphatase and tensin homolog. ^aN = 195 for analyses of PTEN.