The ProtecT trial: analysis of the patient cohort, baseline risk stratification and disease progression.
Bryant RJ., Oxley J., Young GJ., Lane JA., Metcalfe C., Davis M., Turner EL., Martin RM., Goepel JR., Varma M., Griffiths DF., Grigor K., Mayer N., Warren AY., Bhattarai S., Dormer J., Mason M., Staffurth J., Walsh E., Rosario DJ., F Catto JW., Neal DE., Donovan JL., Hamdy FC., ProtecT Study Group None., Bollina P., Doble A., Doherty A., Gillatt D., Gnanapragasam V., Hughes O., Kockelbergh R., Kynaston H., Paul A., Paez E., Rowe E.
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.