In both trial groups mean age of recruited patients was approximately 67, ~30% were of black race and 55% were married. 85% of the men were fully active and 56% had no comorbidities. Their mean PSA was 10.2, approximately 50% had T1c disease, 70% had Gleason 6 disease and ~40% had low D’Amico tumor risk group. Median time of follow-up was 12.7 years (IQR 7.3-15.6), with an all-cause mortality of 64% and prostate cancer mortality of 9.4% (ranging from ~5% in low risk disease patients to ~16% in high risk disease patients).
Over a 20 year follow-up all-cause mortality was similar among both groups. When specifically looking at the low risk patients, surgery did not reduce the all-cause mortality when compared to observation. However, based on local histopathology, in men with intermediate risk disease, surgery reduced mortality when compared to observation with a hazard ratio (HR) of 0.68 (95% CI 0.5-0.92, p=0.01) and absolute risk reduction (ARR) of 14.5% (CI 95% 2.8-25.6). These difference began approximately 2-3 years after surgery and increased throughout the course of the study. In contrast, when basing data on central histopathology, both the relative and absolute risks decreased substantially, and become non-significant. Lastly, when looking at high risk patients, whether based on local or central histopathology, results were not significant and no differences could be demonstrated.
Death from prostate cancer did not differ in a statistical significant way when both groups were compared. When looking specifically at men with low risk disease, death from prostate cancer was rare and no differences could be discerned. In men with intermediate disease based on local histopathology, there was a benefit to surgery with a HR of 0.53 (95% CI 0.25-1.11 p=0.04) with and ARR of 7.3% (CI 95% -0.9-15.7). The difference was more clearly demonstrated after 10-12 years from surgery. However, when using central histopathology in intermediate risk men, the statistical differences disappeared and no difference between the groups was seen.
Surgery reduced the risk of treatment for disease progression by an absolute 26%. Regional and systemic progression was rare and no difference was demonstrated between the groups. In patients who underwent surgery adverse events within 30 days from surgery occurred in ~20% of patients, and death occurred in 0.4% of men. Approximately 20% of men who underwent surgery reported limitation in day to day activity compared to 15% in the observation group. Incontinence occurred in approximately 40% of patients who underwent surgery, compared to 15% in the observation group. Similar with erectile dysfunction, which increased to approximately 80% in the surgery group, compared to 40-50% in the observation group, which gradually increased through time.
Within the first 2 years of the study, bother due to prostate cancer or its related therapy was significantly higher in the surgery group compared to the observation group (25% vs 20%). 20% of the patients in the observation group ultimately underwent radical treatment, usually within 4 years from randomization.
When looking at the cancer specific mortality and treatment benefit in the 3 important trials - SPCG-4 (pre-PSA era), PIVOT (early PSA era) and ProtecT (PSA screened patients), it is clear that PSA screen detected cancers are much higher in ProtecT than in SPCG-4, but that cancer mortality and treatment benefit gradually decrease from SPCG-4 to ProtecT.
Summarizing the results of PIVOT, Dr. Wilt stated that after nearly 20 years, surgery did not significantly reduce all-cause or prostate cancer specific mortality compared with observation, with absolute difference of less than 5%. Furthermore, surgery resulted in adverse effects, but did reduce disease progression and subsequent treatments. Lastly, observation is currently an even higher value option, according to Dr. Wilt, because PSA screening detects more indolent tumors, treatment refinement such as changes in surgical approaches and radiotherapy delivery systems have had little changes in the benefits and harms, but have significantly higher costs. Finally, treatments for advanced disease is beneficial with acceptable harms, making observation a viable option, according to Dr. Wilt’s perspective.
Dr. Wilt concluded his presentation suggesting that physicians should recommend initial observation or PSA based monitoring for patients with low PSA, and low risk prostate cancer, and to men above the age of 65 or younger men with life limiting comorbidities. Additionally, guidelines should encourage greater use of observation, and younger and healthier men with higher risk disease should balance benefits and harms before making treatment decisions.
Speaker: Timothy Wilt, United States
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