Effects of pathological upstaging or upgrading on metastasis and cancer-specific mortality in men with clinical low-risk prostate cancer

Objectives: To determine if the presence of adverse pathological features in patients eligible for active surveillance (AS) are prognostic of poor oncological outcomes, independent of pretreatment risk. Patients and Methods: A retrospective analysis was performed on patients who underwent radical prostatectomy (RP) at two institutions (Cleveland Clinic Foundation and Memorial Sloan Kettering Cancer Center) between 1987 and 2008, and who had subsequent follow-up. Rates of biochemical recurrence, metastasis and death from prostate cancer were compared amongst patients with adverse pathological features (Gleason score ≥7, ≥pT3, or lymph node invasion) based on D'Amico clinical risk (low vs intermediate/high). We also compared survival outcomes between patients with and without pathological upgrading/upstaging amongst D'Amico low-risk patients. Univariate and multivariable Cox regression models were used to assess the association between clinical risk, pathological reclassification, and oncological outcomes. Results: We identified 16 341 patients who underwent RP, of whom 6 371 were clinically low-risk. Adverse outcomes in men with adverse pathological features were significantly lower in those with low clinical risk, with an ~50% and ~70% reduction in the risk of metastasis and death, respectively. Only pathological upgrading/upstaging to Gleason score ≥8, seminal vesicle invasion, and lymph node invasion from clinical low-risk disease, were associated with adverse outcomes. However, these types of reclassification were rare. Conclusion: Clinical low-risk patients with pathological upgrading/upstaging have substantially lower rates of important oncological outcomes compared to those with higher pretreatment risk and not substantially different than low-risk patients without pathological upgrading/upstaging. These results call into question the use of this endpoint to counsel patients about the merits and risks of AS.