Patients with newly diagnosed, unfavorable, intermediate-risk prostate cancer often represent a grey zone of clinical decision making. Two patients could share the same characteristics — for instance, their tumors have a Gleason score of 4+3 with otherwise favorable features — but these individuals could have very different disease courses even if they receive the same treatment. Some clinicians see a need for tools that can better stratify this patient population to identify those who might benefit from aggressive therapy.

A study in Urology suggested that the Oncotype DX Genomic Prostate Score® (GPS) assay — which is currently indicated for guiding treatment decisions in low-risk and favorable intermediate-risk disease at the time of diagnosis — could also help predict long-term clinical outcomes in men with unfavorable intermediate-risk disease.1 Along with a patient’s prostate-specific antigen (PSA) level at diagnosis, as well as the grade and stage of the cancer, the authors suggested the assay could help inform clinicians and patients’ treatment planning. 

“If you were below [a GPS score of] 40, your cancer was going to behave more like lower-risk disease, whereas if you had a score above 40, it was going to behave more like high-risk disease, where it’s clear that we need to treat more aggressively,” said Jennifer Cullen, PhD, MPH, associate professor and associate director of cancer population sciences at the Case Comprehensive Cancer Center in Cleveland, Ohio, and lead author of the study.

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The GPS assay ascertains the expression levels of 17 genes — 12 are cancer-related, and 5 are controls — in mRNA extracted from tumor biopsies, and produces a score from 0 to 100 to indicate the aggressiveness of the tumor. According to current National Comprehensive Cancer Network (NCCN) and American Society for Clinical Oncology (ASCO) guidelines, the test may be offered to patients who have been newly diagnosed with low-risk or favorable intermediate-risk disease, and could help a physician determine if active surveillance or a more aggressive therapy would be the best clinical course for a patient.2,3

The new research aimed to understand whether the GPS assay could also be useful in men diagnosed with unfavorable intermediate-risk disease. In these patients, the decision whether more aggressive treatment is warranted is a more complicated one.

Dr Cullen and colleagues undertook a statistical analysis of GPS data collected from 2 previously studied cohorts of men with intermediate-risk disease who had been treated with radical prostatectomy.4,5 One cohort included patients treated at 2 US military medical centers. This was more diverse than the second cohort, which comprised a number of patients treated within the Kaiser Permanente Northern California system. Otherwise, the 2 cohorts were similar save for small differences, Dr Cullen explained. Taken together, there were 175 individuals with unfavorable, intermediate-risk disease.

The authors found that when GPS scores were assessed as dichotomous values (either above or below 40), they could be used as predictors of the time to biochemical recurrence of disease (BCR), development of distant metastases (DM), and prostate-specific death (PCD) after surgery.

For instance, men with GPS scores lower than 40 had BCR rates similar to patients with favorable, intermediate-risk disease, and their 10-year risk of BCR was around 12%. However, patients with GPS scores higher than 40 had BCR rates similar to those with high-risk prostate cancer, with most projected to experience BCR within 10 years.

Overall, the wide range of GPS scores documented across the 175 patients suggested that the unfavorable, intermediate-risk group is not a homogenous one, the authors noted. 

“It was a welcome finding to see that the GPS could be useful in this additional subset of men,” Dr Cullen noted, adding that the findings support the current ASCO recommendations that say the assay may be considered in select patients with unfavorable, intermediate-risk disease. However, “we definitely need additional studies,” she added. 

“There are a number of genomic and/or transcriptomic tools that are emerging for use and helping us more intelligently guide efforts to intensify treatment or potentially to de-escalate treatment in particular patients so that we’re not treating everybody with a kitchen-sink approach . . . This study adds to that literature,” noted Amar U. Kishan, MD, vice chair of clinical and translational research of the department of radiation oncology at the David Geffen School of Medicine at the University of California, Los Angeles, who wasn’t involved in the new research.

One limitation of the study, however, is that all patients were treated with surgery, “so seeing how this extrapolates to patients [who] are treated with radiation, with or without hormone therapy, is unclear because that’s a different mechanism of treating cancer,” he noted. In addition, as acknowledged by the authors, the patients were not initially classified as having favorable or unfavorable intermediate-risk disease, as they were treated at a time when that stratification scheme did not yet exist. Perhaps the patients would have been treated differently today based on those classifications, Dr Kishan suggested. 

In addition, although 1 of the cohorts included a relatively high proportion of patients who self-reported as African American (19%), the tool has not yet been shown to perform comparably in other ethnic and racial cohorts, Dr Cullen said.

Another recent study in the Journal of Clinical Oncology suggested that the GPS assay was not predictive in a different subset of patients who were on active surveillance and who ultimately underwent surgery.6 “I think that study needs to be replicated in other cohorts,” Dr Cullen said.

She hopes the findings could help push the tool into clinical practice to help guide treatment decisions for patients with unfavorable, intermediate-risk disease, she said. “This would build out yet another risk stratum [in which] we could say the GPS is useful for this patient subset as well.”

Disclosure: This study was funded by Genomic Health Inc., an Exact Sciences Corporation, which developed the Genomic Prostate Score assay. In addition, some of the investigators disclosed various financial ties to the pharmaceutical industry in this study. For a full list of disclosures, please refer to the original paper.


  1. Cullen J, Kuo H, Shan J et al. The 17-gene Genomic Prostate Score test as a predictor of outcomes in men with unfavorable intermediate risk prostate cancer [published online ahead of print June 7, 2020]. Urology. doi:10.1016/j.urology.2020.05.045
  2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Prostate Cancer, Version 2.2020—May 21, 2020. Accessed July 13, 2020.
  3. Eggener SE, Rumble RB, Armstrong AJ, et al. Molecular biomarkers in localized prostate cancer: ASCO Guideline. J Clin Oncol. 2019;38(13):1474-1494.
  4. Cullen J, Rosner IL, Brand TC, et al. A biopsy-based 17-gene Genomic Prostate Score predicts recurrence after radical prostatectomy and adverse surgical pathology in a racially diverse population of men with clinically low- and intermediate-risk prostate cancer. Eur Urol. 2015:68(1):123-131.
  5. Van Den Eeden SK, Lu R, Zhang N et al. A biopsy-based 17-gene Genomic Prostate Score as a predictor of metastases and prostate cancer death in surgically treated men with clinically localized disease. Eur Urol. 2018:73(1):129-138.
  6. Lin DW, Zheng Y, McKenney JK et al. 17-gene Genomic Prostate Score test results in the Canary Prostate Active Surveillance Study (PASS) cohort. J Clin Oncol. 2020:38(14):1549-1557.

This article originally appeared on Cancer Therapy Advisor