After Surgery for Colorectal Cancer, Intensive Monitoring of Little Benefit: PRODIGE 13
Is intensive monitoring of patients after curative colorectal cancer resection warranted? Not necessarily, according to the findings of PRODIGE 13, reported at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.1
“After curative surgery, the addition of CEA [carcinoembryonic antigen] surveillance and/or CT does not provide any benefit in 5-year overall survival,” said Come Lepage, MD, of the CHU Dijon in France. “Our study shows that optimization of diagnostic procedures in terms of overall survival benefits remains to be determined. CEA surveillance is unnecessary, and CT scans should be performed only in cases of suspected recurrence,” Dr. Lepage maintained.
“For colon cancer, preliminary results show that surveillance using CEA with or without CT leads to an increase in curative resections, but this management has no impact on overall survival.”— Come Lepage, MD
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The phase III PRODIGE 13 trial compared the impact of two types of follow-up care on the long-term survival of patients with stage II and III colorectal cancer who had undergone curative resection. Intensive monitoring did not lead to an improvement in survival, although it did enable more curative-intent surgeries for patients who developed second cancers, Dr. Lepage reported.
PRODIGE 13 Details
“The objective of surveillance after surgery for colorectal cancer is to improve survival by detecting recurrences and/or metachronous cancers. We have at our disposal several tools, including physical examination, biology (CEA), imaging (chest x-ray, abdominal ultrasound, CT scans), and colonoscopy. The questions are what evaluations should be performed, and what is the optimal frequency for surveillance for cancer recurrence,” commented Dr. Lepage.
He noted that many societies recommend “intensive follow-up,” yet this is based more on expert opinion than data, and it has not been shown to improve survival. In fact, the latest update by the Cochrane group failed to draw a definite conclusion because of the heterogeneity of studies, “making it impossible to define adequate surveillance,” Dr. Lepage added.
PRODIGE 13, a prospective phase III multicenter trial conducted in France and Belgium, sought to provide more objective data to inform such monitoring. It evaluated 5-year overall survival in 2,009 patients with fully resected stage II or III colorectal cancer. They were randomly assigned to intensive radiologic monitoring (CT scan every 6 months) vs standard monitoring (abdominal ultrasonography every 3 months and thoracic radiography every 6 months) with or without CEA assessments.
There were two randomizations. The first was to CEA testing every 3 months for 2 years, then every 6 months for 3 years, or no CEA monitoring at all. These two arms were then randomly assigned again to either CT scan alternating with abdominal ultrasonography every 3 months for 3 years, then biannually for 2 years, or abdominal ultrasonography every 3 months for 3 years, then biannually for 2 years, plus a biannual chest x-ray every 5 years. The addition of CT scans to abdominal ultrasonography constituted “intensive” imaging.
The result of the randomizations was four categories of patients: intensive imaging (ie, CT plus ultrasonography plus CEA), intensive imaging without CEA, standard imaging plus CEA, and standard imaging without CEA.
No Survival Benefit, More Second Surgeries With Intensive Monitoring
After a median follow-up of 6.5 years, 22% of patients had a recurrence of cancer, and 1.7% of patients had a second colorectal cancer diagnosis. Of these recurrences, 8.4% were localized, 74.7% were metastatic, and 15.7% were both. These recurrences were treated with curative intent in 86.7% of patients with localized disease, in 52.3% with metastatic disease, and in 44.6% with recurrences of both types.
Despite differences in the intensity of monitoring, no differential overall survival benefits seemed to emerge between the arms or according to the type of surveillance (ie, CEA surveillance or not and CT scan surveillance or not). Recurrence-free survival was also similar, and no subgroup differences were observed.
Intensive monitoring did, however, allow for more patients with colon cancer with recurrences to undergo additional surgery, Dr. Lepage reported. The frequency of surgical treatment with curative intent was significantly higher for the group receiving radiographic assessments and CEA testing (59.5%) and those receiving standard imaging plus CEA (66.3%) than those receiving intensive follow-up without CEA testing (50.7%) or standard imaging without CEA assessment (40.9%; P = .0035). The enhanced use of this second surgery, however, did not translate into a difference in survival.
- PRODIGE 13 evaluated the impact of intensive surveillance on patients with stage II or III colorectal cancer after surgery with curative intent.
- No overall survival benefit was found for the use of CEA assessments or CT scans.
- Intensive monitoring did result in more patients undergoing second curative-intent surgery for colon cancer with recurrences; however, this did not improve overall survival.
- The study authors concluded that in this patient population, CEA surveillance is unnecessary, and CT scans are warranted only in cases of suspected recurrence.
“For colon cancer, preliminary results show that surveillance using CEA with or without CT leads to an increase in curative resections, but this management has no impact on overall survival,” Dr. Lepage commented.
According to Dr. Lepage, the guidelines for colorectal cancer surveillance after curative resection should be amended, with the new standard based on symptom assessment and aided by ultrasonography and chest x-ray. Final analysis of the secondary endpoints of this study will be available in 2021. Ancillary studies are underway.
DISCLOSURE: Dr. Lepage has received honoraria from Amgen and Bayer; has served as a consultant or advisor to Advanced Accelerator Applications and Novartis; and has been reimbursed for travel, accommodations, or other expenses by Bayer, Ipsen, Merck Serono, Novartis, and Sanofi/Aventis.
1. Lepage C, Phelip JM, Cany L, et al: Effect of 5 years of imaging and CEA follow-up to detect recurrence of colorectal cancer: PRODIGE 13 a FFCD phase III trial. ESMO Virtual Congress 2020. Abstract 398O. Presented September 19, 2020.
The invited discussant of PRODIGE 13 was Tim Price, MBBS, DHthSc, Professor at the University of Adelaide, Australia, senior consultant medical oncologist, and Director of Medical Oncology and Clinical Cancer Research at the Queen Elizabeth Hospital. As he reminded listeners, the current ASCO...