Effects of Initial Gleason Grade on Outcomes during Active Surveillance for Prostate Cancer

Whether men with Gleason 3+4 prostate cancer are appropriate active surveillance (AS) candidates remains a matter of debate.

to evaluate the effects of initial Gleason grade 3+3 or 3+4 on clinical outcomes during AS.

We retrospectively reviewed outcomes for men on AS between 1990 and 2016 with Gleason 3+3 or 3+4 who had two or more biopsies.

We evaluated associations of diagnostic grade with reclassification (upgrade ≥ 3+4), treatment, metastasis, adverse surgical pathology, and biochemical recurrence (BCR) after deferred radical prostatectomy (RP), with a sensitivity analysis for the amount of pattern 4 disease.

Of 1243 men, 1119 (90%) had Gleason 3+3 and 124 (10%) 3+4 on initial biopsy. The 5-yr unadjusted reclassification-free survival was 49% regardless of grade, while patients with Gleason 3+4 had lower treatment-free survival (49% vs 64%; p<0.01). On multivariate Cox analysis, grade was associated with lower risk of reclassification (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.46-0.95) and higher risk of treatment (HR 1.37, 95% CI 1.01-1.85). After RP, patients starting with Gleason 3+4 had lower unadjusted 2-yr BCR-free survival (69% vs 93%; p=0.01) and a higher risk of recurrence (HR 3.67, 95% CI 1.30-10.36). Grade was not associated with metastasis (<1% at 5 yr) or adverse pathology. In sensitivity analyses, a single high-grade core was associated with lower risk of reclassification and multiple high-grade cores were associated with a higher risk of treatment. The number of high-grade cores was not independently associated with BCR. Limitations include selection bias, a limited number of intermediate-risk patients, and length of follow-up.

Gleason 3+4 at diagnosis was associated with risk of reclassification, treatment, and BCR. The number of high-grade cores may help in stratifying men with Gleason 3+4 disease.

Some men with Gleason 3+4 prostate cancer may be appropriate surveillance candidates, but longer follow-up and evaluation of more patients are necessary.