Second-Look Surgery Plus Intraperitoneal Chemo No Benefit for Colorectal Metastases

By Lisa Rapaport

August 13, 2020

(Reuters Health) - Second-look surgery plus oxaliplatin hyperthermic intraperitoneal chemotherapy (HIPEC) is no better than standard surveillance at prolonging disease-free survival for patients with colorectal peritoneal metastases, a new study suggests.

Researchers examined data on 150 patients with a primary colorectal cancer and localized peritoneal metastases removed during tumor resection, a perforated tumor, or resected ovarian metastases. Randomization was stratified by treatment center, nodal status, and risk factors for metastases.

After six months of adjuvant systemic chemotherapy without signs of cancer recurrence, patients were randomized (1:1) to receive either surveillance under French guidelines or second-look surgery plus HIPEC.

In the treatment arm, surgery consisted of a complete exploration of the abdominal cavity via xyphopubic incision, and resection of all peritoneal implants if resectable; oxaliplatin-HIPEC consisted of oxaliplatin 460 mg/m2 or oxaliplatin 300 mg/m2 plus irinotecan 200 mg/m2, plus intravenous fluorouracil 400 mg/m2, or in cases of neuropathy consisted of mitomycin-HIPEC (mitomycin 35 mg/m2).

Three-year disease-free survival was 53% in the surveillance group compared with 44% in the treatment group (hazard ratio 0.97) after a median follow-up of 50.8 months.

"Therefore, in these patients with a primary colorectal cancer with synchronous and localized peritoneal metastases removed during tumor resection, resected ovarian metastases, and perforated colorectal cancer, appropriate monitoring, taking into account the high risk of peritoneal recurrence, appears to be appropriate, compared to systematic second-look surgery plus oxaliplatin HIPEC," said study leader Dr. Diane Goere of the department of surgical oncology at University Hospital Saint-Louis - APHP and the University of Paris.

There are several possible explanations for the lack of a disease-free survival benefit in the treatment arm, Dr. Goere said by email.

It's possible that there was no benefit from prophylactic oxaliplatin HIPEC in patients without peritoneal metastases at the time of second-look surgery, Dr. Goere said. And, it's also possible that because patients were treated at centers that specialized in peritoneal disease, they received better diagnosis and treatment at an earlier stage in the surveillance arm.

Another possibility is that the patients included in the analysis who had medium risk of recurrent peritoneal disease - a perforated tumor - may have made it look as though there wasn't a benefit in the treatment arm, Dr. Goere said.

"The results of this study may have been different if only patients with synchronous resected peritoneal metastases and ovarian metastases had been included," Dr. Goere said

There were no treatment-related deaths in the study.

A total of 29 patients in the treatment group (41%) had serious adverse events (grade 3-4 complications) including intra-abdominal adverse events such as hemorrhage or digestive leakage in 12 patients (23%) and hematological adverse events in 13 patients (18%).

One limitation of the study is the use of intraperitoneal chemotherapy, the researchers note in Lancet Oncology. Patients might be resistant to oxaliplatin because the majority of them had already received adjuvant systemic chemotherapy that included oxaliplatin, the researchers point out.

The findings suggest there is a risk of peritoneal recurrence which cannot be seen at any modern imaging, said Dr. Brendan Moran of the Royal Prince Alfred Hospital in Sydney, Australia, author of an editorial accompanying the study.

"The good news is that we do not have to do routine second look and we should monitor carefully by imaging, despite its limitations, and be aware that imaging is only an estimate for small areas of disease," Dr. Moran said by email.

SOURCE: and Lancet Oncology, online July 24, 2020.