Prognostic and Predictive Molecular Subtypes of Prostate Cancer Identified

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Members of the oncology community have long complained that prostate cancer lags behind breast cancer regarding biomarkers for prognosis and treatment, but the good news is that this gap is narrowing. In the largest study of its kind to date, presented at the 58th Annual Meeting of the American Society for Radiation Oncology (ASTRO),1 three different and distinct molecular subtypes of prostate cancer have been identified and validated: subtypes A, B, and C.

Moreover, these subtypes both provide prognostic information about patients’ cancers and have the potential to be used to predict treatment response. One important finding of the study, for example, is that subtype A patients, who have the best prognosis, do not respond as well to radiation as patients in subtypes B and C. This means that strong consideration should be given to offer patients in subtypes B and C to have postoperative radiotherapy.

This work needs to be validated further. The next step is to incorporate genomic testing for the three subtypes upfront in clinical trials to stratify patients. Results of these trials will inform clinical practice as to which patients will benefit from specific therapies.

These molecular subtypes will help us personalize care for each prostate cancer patient, by helping to inform us of their risk of recurrence and their potential benefit from radiation therapy.
— Daniel Spratt, MD

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“Current risk assessment for prostate cancer relies on imperfect tools, such as the digital rectal exam, biopsy, and prostate-specific antigen (PSA). These tools do not give us information about disease biology, accurate risk of recurrence, or whether a patient will benefit from a specific therapy,” said lead author Daniel Spratt, MD, Chief of the Genitourinary Radiotherapy Program at the University of Michigan and Director of the University of Michigan Spine Oncology Program, Ann Arbor.

Three Subtypes

The study included tissue samples from 9 large cohorts of newly diagnosed patients—7 from institutions (1,626 samples), 1 from The Cancer Genome Atlas (TCGA, 497 samples), and 1 from industry (Affymetrix, 2,113 samples).

“This is the largest genomic analysis of men with prostate cancer,” Dr. Spratt stated.

The genomic data from 4,236 tissue samples of men with newly diagnosed localized prostate cancer treated with radical prostatectomy were fed into a system that identified the 100 most common genes. Based on the level of gene expression (increased vs decreased), three clusters of subtypes were identified: subtypes A, B, and C.

Prostate Cancer Subtypes

  • The largest study of genomics to date in prostate cancer has identified and validated three intrinsic subtypes: A, B, and C.
  • These subtypes have been retrospectively and prospectively validated in large numbers of tissue samples from newly diagnosed patients treated with radical prostatectomy.
  • Subtype A has the best prognosis, whereas subtypes B and C have a twofold greater response to radiation than subtype A, suggesting that subtype A patients may not need radiotherapy.
  • With further study and stratification of study patients by genomic subtype, these data could identify which patients need specific treatment.

These subtypes were validated retrospectively in the seven institutional cohorts. Then they were validated prospectively in the other two cohorts, as described above.

“The three clusters were highly reproducible across all cohorts,” he said. “For clinicians, it is important to know what these subtypes mean for patients. Subtype A had the most favorable prognosis.”

The three subtypes had different rates of distant metastasis–free survival at 10 years: subtype A, 73.6%; subtype B, 64.4%; and subtype C, 57.1%. In a multifactorial analysis incorporating other prognostic factors, subtype A was an independent predictor of prognosis.

Response to Radiation

Next, Dr. Spratt and colleagues analyzed the response to postoperative radiation in all three subgroups and found that subtypes B and C had a twofold improved response compared with subtype A.

“This may be one of the first biomarkers to tell us which men will benefit from postoperative radiation,” he stated. “These molecular subtypes will help us personalize care for prostate cancer patients, by helping to inform us of their risk of recurrence and their potential benefit from radiation therapy.”

During the question and answer session at a press conference following his presentation, Dr. Spratt explained that there are already genomic analytics that doctors can order in this disease setting, and we are working with industry to make these subtypes available in these reports, Dr. Spratt said. ■

Disclosure: Dr. Spratt has received a research grant from the Prostate Cancer Foundation.


1. Spratt DE, Zhao SG, Chang SL, et al: Identification and validation of intrinsic subtypes of prostate cancer. 2016 ASTRO Annual Meeting. Abstract 6. Presented September 25, 2016.

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