ntensive surveillance with carcinoembryonic antigen (CEA) testing and CT scans after colorectal cancer resection did not improve recurrence-free or overall survival when compared with standard abdominal ultrasound and chest x-ray monitoring in a phase 3 trial of almost 2,000 patients.
However, among patients with colon cancer recurrence, those randomized to intensive surveillance more often had a second surgery with curative intent. Even so, there was no overall survival benefit versus standard surveillance in this group.
In short, "none of the follow-up modalities resulted in a difference," said investigator Come Lepage, MD, PhD, of Centre Hospitalier Universitaire de Dijon (France).
Lepage presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
Lepage said the study's results suggest guidelines that include CT and CEA monitoring should be amended, and the standard surveillance methods should be ultrasound and chest x-ray. LePage called CEA surveillance "useless" and said CT scans should be performed only in cases of suspected recurrence.
However, study discussant Tim Price, MBBS, DHSc, of the University of Adelaide, noted that both the intensive and standard arms in this study had abdominal imaging every 3 months, be it ultrasound or CT, so even in the standard arms, surveillance "was still fairly aggressive."
Because of that, the study does not "suggest we should decrease our intensity," Price said.
He added that the study's major finding was that more intensive surveillance led to higher rates of secondary surgery with curative intent, probably because recurrences were caught earlier than they would have been with standard surveillance, when curative surgery was still possible.
Patients in the study were treated during 2009-2015, and that might have also made a difference. "We need to remember that, in 2020, care is very different," Price said. This includes increased surgical interventions and options for oligometastatic disease, plus systemic therapies such as pembrolizumab. With modern treatments, detecting recurrences earlier "may well have an impact on survival."
Perhaps patients would live longer with "earlier diagnosis in today's setting with more active agents and more aggressive surgery and radiotherapy [e.g., stereotactic ablative radiation therapy]," Price said in an interview.
Study Details
The trial, dubbed PRODIGE 13, was done to bring clarity to the surveillance issue. Intensive follow-up after curative surgery for colorectal cancer, including CT and CEA monitoring, is recommended by various scientific societies, but it's based mainly on expert opinion. Results of the few clinical trials on the issue have been controversial, Lepage explained.
PRODIGE 13 included 1,995 subjects with colorectal cancer. About half of patients had stage II disease, and the other half had stage III. Most patients were 75 years or younger at baseline, and there were more men in the study than women. All patients underwent resection with curative intent and had no evidence of residual disease 3 months after surgery. Some patients received adjuvant chemotherapy.
Patients were first randomized to no CEA monitoring or CEA monitoring every 3 months for the first 2 years, then every 6 months for an additional 3 years. Members in both groups were then randomized a second time to either intensive or standard radiologic surveillance.
Surveillance in the standard arm consisted of an abdominal ultrasound every 3 months for the first 3 years, then biannually for an additional 2 years, plus chest x-rays every 6 months for 5 years. Intensive surveillance consisted of CT imaging, including thoracic imaging, alternating with abdominal ultrasound, every 3 months, then biannually for another 2 years.
At baseline, the surveillance groups were well balanced with regard to demographics, primary tumor location, and other factors, but stage III disease was more prevalent among patients randomized to standard radiologic monitoring without CEA.
Results
The median follow up was 6.5 years. There were no significant differences between the surveillance groups with regard to 5-year overall survival (P = .340) or recurrence-free survival (P = .473).
There were no significant differences in recurrence-free or overall survival when patients were stratified by age, sex, stage, CEA at a cut point of 5 mcg/L, and primary tumor characteristics including location, perineural invasion, and occlusion/perforation.
There were 356 recurrences in patients initially treated for colon cancer. CEA surveillance with or without CT scan was associated with an increased incidence of secondary resection with curative intent. The rate of secondary resection was 66.3% in the standard imaging with CEA arm, 59.5% in the CT plus CEA arm, 50.7% with CT imaging but no CEA, and 40.9% with standard imaging and no CEA (P = .0035).
The rates were similar among the 83 patients with recurrence after initial treatment for rectal cancer, but the between-arm differences were not significant. The rate of secondary resection with curative intent was 57.9% in the standard imaging with CEA arm, 47.8% in the CT plus CEA arm, 55% with CT imaging but no CEA, and 42.9% with standard imaging and no CEA.
The research is ongoing, and the team expects to report on secondary outcomes and ancillary studies of circulating tumor DNA, among other things, in 2021.
The study is being funded by the Federation Francophone de Cancerologie Digestive. Lepage disclosed ties with Novartis, Amgen, Bayer, Servier, and AAA. Price disclosed institutional research funding from Amgen and being an uncompensated adviser to Pierre-Fabre and Merck.
SOURCE: Lepage C et al. ESMO 2020, Abstract 398O.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου