Active Surveillance for Intermediate-Risk PCa May Be Unsafe

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Nearly 1 in 3 patients diagnosed with Gleason 3+4 favorable intermediate-risk prostate cancer had their disease upgraded or upstaged at radical prostatectomy.
Nearly 1 in 3 patients diagnosed with Gleason 3+4 favorable intermediate-risk prostate cancer had their disease upgraded or upstaged at radical prostatectomy.

New study findings raise questions about the safety of managing intermediate-risk prostate cancer (PCa) with active surveillance (AS).

The study found that nearly one third of men diagnosed with Gleason 3+4 favorable intermediate-risk PCa are found to harbor worse disease than their prostate biopsy and clinical examination would suggest, David D. Yang, MD, of Harvard Medical School in Boston, and colleagues reported online ahead of print in European Urology Focus.

Using the National Cancer Database, Dr Yang's team studied 10,089 patients diagnosed during 2010–2012 with Gleason 3+4 tumors, PSA below 10 ng/mL, and cT1c-2a PCa with fewer than 50% positive biopsy cores who underwent radical prostatectomy.

At pathology, 30.3% of patients were upgraded (based on the presence of tertiary Gleason 5 in a Gleason 7 tumor or Gleason 4+3 or above) or upstaged (pT3–4 or N1).

Multivariate logistic regression analysis identified the upper ranges of customary factors as independent predictors of upgrading or upstaging: higher PSA, higher percentage positive biopsy cores, older age, and cT2a versus cT1c. In adjusted analyses, men with a PSA level of 8.1–9.9 ng/mL had a 93% increased risk of upgrading or upstaging compared with those who had a PSA level below 4.0 ng/mL. Compared with men who had fewer than 12.5% positive biopsy cores, those with 37.5% to 49.9% positive cores had a 79% increased risk. Patients aged 67 years or more had a 46% increased risk compared with those aged 55 years or less. Men with cT2a cancer had a 33% increased risk versus those with cT1c cancer. All of these increases were statistically significant.

The investigators determined that the strongest predictors of upgrading and upstaging were PSA and percentage positive biopsy cores. The risk of upgrading or upstaging increased from 21.7% for patients with fewer than 12.5% positive cores and PSA level of 4.0 ng/mL or below to 44.3% for men with 37.5%–49.9% positive cores and a PSA level of 8.1–9.9 ng/mL.

Despite current guidelines advocating AS, the findings indicate that some men with Gleason 3+4 disease should not consider it. Older patients with a combination of high PSA, high percentage positive cores, and cT2a tumors have a nearly 50% risk of more aggressive PCa and would benefit from more aggressive therapy. In contrast, younger patients with low PSA, low percentage of positive cores, and cT1c tumors have about a 20% risk of worse disease. “These patients may be reasonable candidates for AS, assuming close follow-up involves additional PSA measurements, repeat biopsies, and initiation of definitive therapy as appropriate in a timely fashion,” Dr Yang and colleagues stated. “However, additional tools, including multiparametric magnetic resonance imaging (mpMRI) and genomics tests, should be developed and incorporated into clinical practice for ruling out more advanced disease in these patients.”

Black race did not emerge as a predictor of upgrading or upstaging, but the team cautioned that is unclear whether black men can safely have AS.

Study limitations included incomplete key information influencing prognosis, including perineural invasion, percentage of cancer in a core, PSA density, and percentage of Gleason 4 disease.

The new study corroborates the findings of another recently published study by Hiten D. Patel, MD, MPH, and colleagues at Johns Hopkins University in Baltimore. In a retrospective cohort study of men with intermediate-risk PCa who underwent RP, the rate of adverse findings was 24.7% among patients with low-volume intermediate-risk (LVIR) disease compared with 5.8% and 4.7% for those with low-risk (LR) and very-low-risk (VLR) disease, respectively, according to a report in JAMA Oncology. Men with LVIR had a 4.5-fold greater risk of adverse pathologic findings compared with men who had LR disease and 5.1-fold greater risk compared with those who had VLR disease. The authors concluded that no subset of patients with intermediate-risk PCa is likely to benefit from AS.

References

Yang DD, Mahal BA, Muralidhar V, et al. Risk of Upgrading and Upstaging Among 10 000 Patients with Gleason 3 + 4 Favorable Intermediate-risk Prostate Cancer. Eur Uro Focus. doi: 10.1016/j.euf.2017.05.011

Patel HD, Tosoian JJ, Carter HB, Epstein JI. Adverse pathologic findings for men electing immediate radical prostatectomy: Defining a favorable intermediate-risk group. JAMA Oncol 2017; published online ahead of print.

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