ASCO GU 2018: Evaluation of a Predefined as Threshold in a Large Cohort of Men with Localized Prostate Cancer

San Francisco, CA (UroToday.com) Recently, a clinical cell−cycle risk (CCR) score has been developed to include both molecular [cell cycle progression (CCP) RNA signature] and clinical [Cancer of the Prostate Risk Assessment (CAPRA)] features.1 Previous validations have demonstrated that this combined CCR score provides improved prognostic information relative to molecular or clinical features alone - in a cohort of men with NCCN-defined low-risk PCa, the CCP score improved clinical risk stratification of men who were at increased risk of BCR.2 As such, a CCR threshold score may help identify men with low−risk disease who may be candidates for active surveillance (AS). A CCR score threshold of 0.8 has been previously validated in a cohort of conservatively managed men - men with a CCR score equal to the threshold had an estimated 10−year disease−specific mortality risk of 3.3%, while men with scores below the threshold had a 2.7% risk.

In this study, the authors externally validate the CCR score using their retrospective institutional data of 767 men with localized prostate adenocarcinoma who were treated between 2006 and 2011; median clinical follow−up time of 5.6 years measured from date of diagnosis.

Of these men, 217 men had CCR scores ≤ 0.8, thereby meeting criteria for low-risk disease and AS candidacy. However, it should be noted that in this institution, during that time period, AS was the not the treatment modality of choice – hence, 125 were treated by radical prostatectomy, 61 with radiation, 2 with radiation with hormones, 2 with hormones only, and 19 with watchful waiting. Treatment for eight men was unknown.

Of these men, only one patient (0.5%) with a CCR score below the 0.8 AS threshold progressed to metastatic disease; he had been initially treated with radiation. As such, due to lack of RP pathology, it is possible he had higher risk disease missed on biopsy.

7-year MFS, BCR-free survival, and cancer-specific mortality is significantly lower in men with CCR score < 0.8, even within AUA low, intermediate and high risk populations. There no deaths in men with CCR < 0.8.

However, based on these findings, the authors state that the AS cutoff for the CCR score helps identify men with low risk of metastatic spread. It should be noted, though, that as many of these men were treated, this is a hard conclusion to make – treatment naturally modifies their expected clinical course.

Speaker: Daniel Canter

Co-authors: Julia E. Reid, Maria Latsis, Margaret Variano, Shams Halat, Kristen E. Gurtner, Michael K. Brawer, Steven Stone, Stephen Bardot

Institution(s): Multi-institutional

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA

References:
1. Cuzick J, Stone S, Fisher G, et al. Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort. Br J Cancer. 2015 Jul 28;113(3):382-9. doi: 10.1038/bjc.2015.223. Epub 2015 Jun 23.
2. Tosoian JJ, Chappidi MR, Bishoff JT, et al. Prognostic utility of biopsy-derived cell cycle progression score in patients with National Comprehensive Cancer Network low-risk prostate cancer undergoing radical prostatectomy: implications for treatment guidance. BJU Int. 2017 Dec;120(6):808-814. doi: 10.1111/bju.13911. Epub 2017 Jun 11.

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