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Clinical Research

Very-high-risk localized prostate cancer: definition and outcomes

Prostate Cancer and Prostatic Diseases volume 17, pages 57–63 (2014)Cite this article

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Abstract

Background:

Outcomes in men with National Comprehensive Cancer Network (NCCN) high-risk prostate cancer (PCa) can vary substantially—some will have excellent cancer-specific survival, whereas others will experience early metastasis even after aggressive local treatments. Current nomograms, which yield continuous risk probabilities, do not separate high-risk PCa into distinct sub-strata. Here, we derive a binary definition of very-high-risk (VHR) localized PCa to aid in risk stratification at diagnosis and selection of therapy.

Methods:

We queried the Johns Hopkins radical prostatectomy database to identify 753 men with NCCN high-risk localized PCa (Gleason sum 8–10, PSA >20 ng ml−1, or clinical stage ⩾T3). Twenty-eight alternate permutations of adverse grade, stage and cancer volume were compared by their hazard ratios for metastasis and cancer-specific mortality. VHR criteria with top-ranking hazard ratios were further evaluated by multivariable analyses and inclusion of a clinically meaningful proportion of the high-risk cohort.

Results:

The VHR cohort was best defined by primary pattern 5 present on biopsy, or ⩾5 cores with Gleason sum 8–10, or multiple NCCN high-risk features. These criteria encompassed 15.1% of the NCCN high-risk cohort. Compared with other high-risk men, VHR men were at significantly higher risk for metastasis (hazard ratio 2.75) and cancer-specific mortality (hazard ratio 3.44) (P<0.001 for both). Among high-risk men, VHR men also had significantly worse 10-year metastasis-free survival (37% vs 78%) and cancer-specific survival (62% vs 90%).

Conclusions:

Men who meet VHR criteria form a subgroup within the current NCCN high-risk classification who have particularly poor oncological outcomes. Use of these characteristics to distinguish VHR localized PCa may help in counseling and selection optimal candidates for multimodal treatments or clinical trials.

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Acknowledgements

NIH Training Grant T32DK007552 (DS), Howard Hughes Clinician-Scientist Early Careers Award (EMS), AUA/Astellas Rising Star Award (EMS) and Johns Hopkins Clinician Scientist Award (AER)

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Author notes

  1. E M Schaeffer and A E Ross: These authors contributed equally to this work.

Authors and Affiliations

  1. Brady Institute of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    D Sundi, V M Wang, P M Pierorazio, M Han, T J Bivalacqua, M W Ball, A W Partin, E M Schaeffer & A E Ross

  2. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA

    E S Antonarakis

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  1. D Sundi
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  2. V M Wang
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Correspondence to E M Schaeffer.

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Supplementary Information accompanies the paper on the Prostate Cancer and Prostatic Diseases website

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Sundi, D., Wang, V., Pierorazio, P. et al. Very-high-risk localized prostate cancer: definition and outcomes. Prostate Cancer Prostatic Dis 17, 57–63 (2014). https://doi.org/10.1038/pcan.2013.46

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