Researchers have independently validated a proposed new grade-group system for predicting prostate cancer (PCa) outcomes, according to a new report published online ahead of print in BJU International.

The system, which was first proposed in 2013, classifies PCa patients into 5 groups based on the current application of the Gleason score, which has been modified several times since its inception. Patients at lowest risk for adverse outcomes are placed into group 1 (Gleason score 6 or less), and those at highest risk are placed in group 5 (Gleason score 9–10). An important feature of the new system is the distinction made between Gleason 3+4 and 4+3 tumors. Patients with the 3+4 pattern are placed in group 2, whereas those with 4+3 pattern are placed in the higher-risk group 3.

In a study of 694 men who underwent radical prostatectomy (RP), Daniel E. Spratt, MD, and colleagues at the University of Michigan in Ann Arbor demonstrated a step-wise, increased risk of biochemical recurrence (BCR) in these groupings based on both biopsy and RP grade.

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“This new system may allow for improved prognostication, and these results support their clinical implementation,” the authors concluded.

For the study, Dr. Spratt’s group placed patients into groups 1–5 according to Gleason grades (6 or less, 3+4=7, 4+3=7, 4+4=8, and 9–10). The researchers performed separate analyses using biopsy grade and RP grade for group assignment. The primary outcome was biochemical recurrence-free survival (bRFS). The study population had a median follow-up of 52.7 months.

The 5-year actuarial bRFS rates for biopsy-grade groups 1–5 were 94.2%, 89.2%, 73.1%, 63.1%, and 54.7%, respectively. The 5-year actuarial bRFS rates based on RP grade groups were 96.1%, 93%, 74%, 64.4%, and 49.9% for grade groups 1–5, respectively.

In adjusted analyses, compared with patients in biopsy grade group 1, those in grade groups 2, 3, 4, and 5 were at 1.98, 4.20, 5.57, and 9.23 times higher risk of BCR. Compared with patients in RP group 1, those in RP grade groups 2, 3, 4, and 5 were at 2.0, 5.2, 5.9, and 10.4 times increased risk, respectively.

The 5-grade-group system had a higher prognostic discrimination than the widely used 3-tier system (Gleason 6 vs. 7 vs. 8–10), according to the investigators.

The new grading system has been endorsed by the International Society of Urological Pathology and accepted by the World Health Organization. “Our present study provides an independent external validation of this new grading schema from a distinct surgical cohort.”

The original Gleason score, which was introduced in the 1960s, used PCa-related death as an outcome, whereas the new system uses BCR.

In an interview earlier this year with Renal & Urology News, Jonathan I. Epstein, MD, who initially proposed the 5-grade system in 2013 based on a study performed at Johns Hopkins University in Baltimore, said the new system distills pathologic findings into the key differences in prognosis “that can be intuitive to both patients and clinicians.”

An important feature of the new system is the placement of Gleason score 6 cancers into grade group 1. Dr. Epstein pointed out that patients with Gleason score 6 disease often believe their prognosis is worse than it is because Gleason score 6 is half way along the Gleason scoring scale of 2 to 10, when, in fact, a Gleason score 6 tumor is the lowest-grade cancer currently assigned with an excellent prognosis.

“The study by Spratt et al. is one of a growing number of studies that validate the new grading system and helps to support its routine adoption, initially to be used in concert with the Gleason grading system,” Dr. Epstein said in a recent e-mail.

In addition, he noted that a large multinational study of more than 20,000 men he led also supports the concept of the 5 grade-group system. The study was published this year in European Urology.

A weakness of the study by Dr. Spratt and colleagues, which they acknowledged, was that some patients were graded prior to 2005, when grading was different from what is currently recommended, Dr. Epstein said. Even in the pre-2005 cohort, however, the 5 grade groups were distinct in their discrimination of the risk of biochemical recurrence, although the post-2005 graded specimens showed better discrimination.

“Another weakness of the Spratt study, as well as our initial study proposing the new grading system and our subsequent validation study, was that the outcome was BCR, and not death due to prostate cancer,” Dr. Epstein said.

More recently, a report published online ahead of print in the British Journal of Cancer by Daniel M. Berney, MD, and colleagues, documented that the new 5 grade-group system correlates with PCa-specific mortality in a cohort of men treated conservatively.