A new analysis of three large U.S. cancer databases indicates that a previous influential study that found no benefit to prostate surgery in the early stages of cancer does not reflect real-world patients.
Contrary to what the study suggested, men with localized prostate cancer might benefit from prostate surgery, or prostatectomy. A definitive study is now needed to show the relative benefits of intervention versus observation, researchers say.
The findings, by researchers at the Henry Ford Hospital in Detroit, were recently presented at the European Association of Urology congress (EAU) after publication as a letter, titled “Re: Follow-up of Prostatectomy Versus Observation for Early Prostate Cancer,” in the journal European Urology.
Researchers’ analysis show that the PIVOT study (NCT00007644), the results of which were published in 2017 in the The New England Journal of Medicine, selected a group of patients that may have biased their conclusions.
“It was clear from the first PIVOT analysis in 2012, that surgery (radical prostatectomy) had an advantage over waiting in patients with a poor prognosis. Now this evaluation of the dataset used in PIVOT suggests that the balance needs to change even in early-stage prostate cancer patients. This raises significant questions over just how relevant PIVOT is to real prostate cancer patients, and we need to seriously re-evaluate the PIVOT study, before taking implementation any further,” Hein Van Poppel, MD, a professor at UZ Leuven in Belgium and the EAU adjunct secretary-general, said in a press release.
PIVOT was a long-term follow-up on low-, intermediary- and high-risk prostate cancer patients lasting nearly 20 years. It randomly assigned 731 men with localized prostate cancer either to radical prostatectomy or observation and followed them for a median time of 12.7 years.
The study reported no survival benefit for patients undergoing surgery (mortality due to any cause of 61.3%) compared with those in the observation group (66.8%). Deaths attributed to prostate cancer or treatment were also not significantly different between both groups.
Side effects, however, were higher in those who underwent prostate surgery, including urinary incontinence and erectile dysfunction, which, together with the mortality data, suggested there was no benefit for low-risk patients in having the procedure.
“The direct clinical implication of the PIVOT study is that we should abandon surgery in virtually all prostate cancer patients, and limit our management to observation. However, in most experts’ opinion, this would result in a significant increase in the number of men with metastatic prostate cancer, and in those who will succumb to the disease,” Firas Abdollah, MD, lead author of the letter, said at the EAU congress.
“The PIVOT study has been instrumental in shaping health policy and public discourse about treatment of [prostate cancer] in the USA,” the team wrote in their letter.
Given the major implications of the study, the team set out to evaluate if the patients used in PIVOT represented the real-world population of prostate cancer patients.
They compared the characteristics of the patients enrolled in PIVOT with three large U.S. databases for prostate cancer patients: 60,089 men from the Surveillance, Epidemiology, and End Results (SEER) (2000 to 2004); 63,303 men from the National Cancer Database (NCDB) (2004 to 2005); and 2,847 men from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (1993 to 2001).
They found that men in the PIVOT trial were older than the broader population with a mean age of 67 at diagnosis, compared with 65.8 (PLCO), 61.3 (SEER) and 60.2 (NCDB).
Most of the men (94-96.4%) in the PLCO and NCDB databases had no other diseases, compared with only 56% for men in PIVOT.
Overall mortality in the PIVOT study was much higher, in 64% of patients (over a median follow-up of 12.7 years), than in the other databases where it was between 8% and 23% (over a median follow-up of 12.3 years).
“These findings across multiple large data sets consistently demonstrate that men within PIVOT were older and sicker than their counterparts across the USA,” the team wrote.
Researchers also suggest that treatment approaches in PIVOT may not reflect current clinical practices, referring to the reported progression rates of about 40% with surgery and 68% with observation as much higher than those reflected in current literature.
“Our work shows that the PIVOT trial used a sample of patients who were not representative of the real population affected by prostate cancer,” Abdollah said.
“We don’t have the data to say what comparing like for like would give us, although I think everyone would be surprised if it didn’t tip the survival data more towards surgical intervention. What this really means is that we need to wait until a definitive study can show the relative benefits of intervention versus observation,” he said.
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