Extent and predictors of grade upgrading and downgrading in an Australian cohort according to the new prostate cancer grade groupings.

Object: To determine the extent and impact of upgrading and downgrading among men who underwent radical prostatectomy (RP) according to new grade groupings and to identify predictors of upgrading from biopsy grade Group I and II, and downgrading to grade Group I, in a community setting.

Methods: Study participants included 2279 men with non-metastatic prostate cancer diagnosed 2006-2015 who underwent prostatectomy, from the multi-institutional South Australia Prostate Cancer Clinical Outcomes Collaborative registry. Extent of up- or down-grading was assessed by comparing biopsy and prostatectomy grade groupings. Risk of biochemical recurrence (BCR) with upgrading was assessed using multivariable competing risk regression. Binomial logistic regression was used to identify pre-treatment predictors of upgrading from grade Groups I and II, and risk group reclassification among men with low risk disease.

Results: Upgrading occurred in 35% of cases, while downgrading occurred in 13% of cases. Sixty percent with grade Group I disease were upgraded following prostatectomy. Upgrading from grade Group I was associated with greater risk of BCR compared with concordant grading (Hazard ratio: 3.1, 95% confidence interval: 1.7-6.0). Older age, higher prostate-specific antigen levels (PSA), fewer biopsy cores, higher number of positive cores and more recent diagnosis predicted upgrading from grade Group I, while higher PSA and clinical stage predicted upgrading from grade Group II. No clinical risk factors for reclassification were identified.

Conclusion: Biopsy sampling errors may play an important role in upgrading from grade Group I. Improved clinical assessment of grade is needed to encourage greater uptake of active surveillance.