Recruitment in this trial was from primary care physicians. Patients were fit men, with no symptoms, aged 50-69. Patients were monitored in prostate check clinics, run mostly by research nurses, providing care and constant support. All men with a rising PSA were invited to the hospital for a prostate biopsy. If prostate cancer was found, the patients were evaluated by clinicians, and men suitable for the trial (localized disease only) were randomized to one of the 3 arms of the trial.
The trial was run in the entire United Kingdom with 228,966 men invited to be tested, 100,444 patients (44%) that actually attended, and 82,429 patients (82%) who ultimately underwent PSA testing. Overall 8,566 had a high PSA (10%), consequently, 7,414 prostate biopsies were performed (87%) with 2,896 prostate cancers diagnosed (39%). Eventually, 1643 patients (61%) were randomly allocated to either AM, surgery, or radiotherapy. The mean age of these 1,643 patients was 62 (50-69), mean PSA was 4.6 (3-20.9) and more than 76% had Gleason 6 and T1c disease.
Approximately 80% of men on AM had no sign of progression. However, more than half of the patients in AM had received radical treatment by 10 years, while 44% of them avoided treatment.
In all three arms the prostate cancer specific death was very low (1%) and the survival rate was 99% with no difference between the 3 arms. 10% of the men died of other causes with no differences between the arms, mostly from cardiovascular or respiratory diseases. When looking at metastasis, radical treatment was shown to reduce metastasis and disease progression by 50%, with surgery and radiotherapy having similar effectiveness.
The ProtecT study also included validated patient reported outcome measures (PROMs) assessed at baseline (before diagnosis), 6 and 12 months after randomization, and annually thereafter. Patients filled questionnaires on urinary symptoms and impact on quality of life, sexual and bowel function symptoms, psychological status, generic health status, and cancer specific quality of life. Fortunately, the compliance rates for filling these questionnaires were very high, with over 85% compliance rate for the entire duration of the trial. Overtime, the study demonstrated similar physical and mental health scores over a 6 year period with similar results among all 3 arms. The incontinence and its impact scores were more significant in the surgery arm, being lower than the other arms in the first 12 months, but then slowly returning to the baseline level with time. When assessing erectile function, there is a clear and significant drop in the surgery and radiotherapy arms in the first 12 months, which slowly return to a higher level with time. Radiotherapy has less of an impact than surgery in the short term, but in the long term the difference is less significant. When looking at bowel function, there is more of an impact in the radiation arm, but the difference is less significant than the difference in erectile dysfunction and incontinence, seen in the surgery arm. No real difference was seen among the 3 arms in the depression and anxiety scores over time.
Dr. Catto continued and stated that this trial is an example of a successful implementation of a surgical randomized prospective trial. Furthermore, it is important to note several additional points, including: that a trial with 3 arms with surveillance is possible, the tremendous advantages of a trial led by nurses providing care and counselling, and the need for optimal trial design, which encourages study entry, compliance and preservation. Despite the high financial burden associated with this trial (mentioning it cost 60 million pounds for the UK government to initiate this trial), this trial was a success.
The ProtecT study has taught us that in PSA screened men the risk of prostate cancer death is low (1% over an average of 10 years), the risk of other cause mortality is higher (10% over an average of 10 years), and both surgery and radiotherapy reduce the risk of cancer progression and spread by around 50%. Additionally, the study demonstrated that remaining on AM avoids treatment side effects, but less than 50% of men who start AM remain on it. Furthermore, men have good physical and mental health throughout the study without any differences between the arms.
Dr. Catto concluded his presentation by stating what ProtecT did no teach us. The study does not tell us whether multiparametric MRI could assist to better risk stratify patients, no data is presented on what happened to patients excluded from the ProtecT trial, what the “real world” outcomes from surveillance are (very different from the ProtecT trial), and lastly, what are the specific outcomes stratified by treatment received.
Speaker: James Catto, United Kingdom
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan, at the 37th Congress of Société Internationale d’Urologie - October 19-22, 2017- Lisbon, Portugal