The ProtecT trial: analysis of the patient cohort, baseline risk stratification and disease progression

OBJECTIVES: The ProtecT (Prostate testing for cancer and Treatment) trial randomised 1,643 men with localised prostate cancer (PCa) to active monitoring, radical prostatectomy or radical radiotherapy. At 10-year median follow-up there were no differences in mortality between groups, but men receiving radical treatment had their disease progression reduced by half. We tested the hypothesis that the baseline clinico-pathological features of men who progressed (n=198) were different from those with stable disease (n=1,409).

PATIENTS AND METHODS: We stratified the participants' cohort at baseline according to risk of progression using clinical disease stage, pathological grade and PSA, using Cox proportional hazard models.

RESULTS: The findings demonstrated that 34% (n=505) of men had intermediate or high-risk disease, and 66% (n=973) had low-risk PCa. Of 198 men who progressed, 101 (51%) had baseline International Society of Urological Pathology (ISUP) Grade Group 1, 59 (30%) Grade Group 2, and 38 (19%) Grade Group 3 PCa, compared with 79%, 17% and 5% respectively for 1,409 men without progression (p<0.001). In men with progression, 38% and 62% had baseline low- and intermediate / high-risk disease, compared with 69% and 31% for men with stable disease (p<0.001). Treatment received, age (65-69 versus 50-64 years), PSA, Grade Group, clinical stage, risk group, number of positive cores, tumour length and peri-neural invasion were associated with time to progression (p≤0.005). Men progressing after surgery (n=19) were more likely to have a higher Grade Group and pathological stage at surgery, larger tumours, lymph node involvement and positive margins.

CONCLUSIONS: We demonstrate that one-third of the ProtecT cohort consists of intermediate / high risk disease, and the outcomes data at an average of 10-years follow-up are generalisable beyond men with low-risk PCa.