A New Way to Stratify High-Risk PCa Patients

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Data suggest considering the presence of tertiary grade 5 disease, which affects PSA recurrence risk.

BOSTON—Prostate cancer patients with a Gleason score of 9 or 10 have a risk of PSA recurrence following radical prostatectomy or radiation therapy similar to that of men having a Gleason score of 7 with tertiary grade 5 disease, data suggest.

Clinicians should consider the presence of tertiary grade 5 disease when risk-stratifying high-risk prostate cancer patients, according to researchers.

“Historically, tertiary grades have not been incorporated into the Gleason scoring system, but there has been a great deal of interest recently in addressing the prognostic value of tertiary grade 5 disease,” said lead investigator Akash Nanda, MD, PhD, a radiation oncology resident in the Harvard Radiation Oncology Program in Boston. Findings were reported here at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

In 2005, the International Society of Urologic Pathology Consensus Conference proposed that a Gleason score of 3 + 4 with tertiary grade 5 be reclassified as Gleason 8 and a Gleason score of 4 + 3 with tertiary grade 5 be reclassified as Gleason 9.  Furthermore, a recent study showed that men with a Gleason score of 7 with tertiary grade 5 had a similar risk of PSA recurrence as those who had a Gleason score of 8-10 (JAMA. 2007;298:1533). 

“Based on that study, we hypothesized that the tertiary grade 5 component in men with Gleason score 7 disease may be equally important as the primary or secondary grade 5 components in men with Gleason score 9 to 10 disease in predicting PSA recurrence,” Dr. Nanda said.

Dr. Nanda and his colleagues analyzed data from 312 men (median age 68 years) with localized prostate cancer and Gleason score 7 with tertiary grade 5, Gleason 8 without grade 5, or Gleason 9 to 10. All men underwent radical prostatectomy or external beam radiotherapy with or without androgen suppression therapy.

After a median follow-up of 5.7 years, men with a Gleason score of 8 had a lower risk of PSA recurrence than men with a Gleason score of 9 or 10. Men having a Gleason score of 7 with tertiary grade 5 disease had a risk of PSA recurrence similar to that of men with a Gleason score of 9 or 10.

Men with a Gleason score of 9 or 10 and those with a Gleason score of 7 with tertiary grade 5 disease had median PSA recurrence-free survivals of 4.5 and 5.0 years, respectively. Both of these times were less than the 5.4 years for men with a Gleason score of 8.

“That is important because the traditional high-risk category is Gleason 8 to 10,” Dr. Nanda said. “Our results would suggest further stratification into 8 versus 9, 10, and 7 with tertiary grade 5. In other words, sub-stratification based on the presence or absence of any Gleason grade 5 component (primary, secondary, or tertiary). There is a great deal of interest in testing the addition of novel systemic agents to the standard of care in randomized clinical trials for men with high-risk prostate cancer. It would be nice to optimally stratify these patients up front to help better identify those patients who would benefit the most from the addition of systemic therapy to the current standard of care.”

He cautioned that this study is retrospective, so the conclusions can only be viewed as hypothesis-generating and need to be further validated in a prospective setting.
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