Skip Primary Resection for Asymptomatic CRC With Unresectable Metastases?

Patients with colorectal cancer (CRC) who had unresectable metastases and an asymptomatic primary tumor had higher short-term mortality rates if they underwent primary tumor resection followed by systemic treatment compared with patients who received systemic treatment only, a phase III randomized trial found.

The 60-day mortality rate was 11% in the resection arm versus 3% in the systemic treatment arm (P=0.03), reported Miriam Koopman, MD, PhD, of University Medical Center Utrecht in The Netherlands, and colleagues.

In a per-protocol analysis, 60-day mortality was 10% vs 2%, respectively (P=0.048), they noted in JAMA Surgery.

Based on the results of this study, as well as results from a Japanese study, primary tumor resection “can no longer be considered the standard of care in the setting of unresectable metastases,” wrote Yuman Fong, MD, of the City of Hope Medical Center in Duarte, California, in an accompanying commentary.

In addition, patients with elevated serum levels of lactate dehydrogenase (LDH), aspartate aminotransferase, alanine aminotransferase, and/or neutrophils who were randomized to resection had a higher risk of postoperative mortality than patients without these features:

• Of 58 patients with elevated LDH levels, 10 died (17%)
• Of 15 patients with elevated neutrophil levels, four died (27%)
• Of 41 patients with elevated aspartate aminotransferase levels, nine died (22%)
• Of 23 patients with elevated alanine aminotransferase levels, seven died (30%)

Koopman and colleagues also observed that 60-day mortality was higher if patients had multiple abnormal biochemical features that presented simultaneously before surgery. For example, of 39 patients in the resection arm who had two or three abnormal characteristics, five died within 60 days. None of the 44 patients with one characteristic or no unfavorable characteristics died within 60 days.

“Caution should be exercised while considering primary tumor resection in patients” with these elevated levels, the authors wrote.

These results suggest that stenting might be considered rather than resection in patients with transaminitis, leukocytosis, and primary tumors with obstructive symptoms, observed Fong.

The international CAIRO4 study included 196 patients (median age 65, 57% men) with histologically confirmed CRC with unresectable metastases and no severe signs or symptoms of the primary tumor who were randomized 1:1 to systemic treatment with bevacizumab (Avastin) or primary tumor resection followed by bevacizumab.

Grade 3 or 4 adverse events were reported in 23% of patients in the resection arm, most commonly infections (6%), pain (4%), and wound infections (3%), and 30% of patients in the systemic treatment arm, most commonly diarrhea (9%) and pain (8%).

The authors acknowledged that the study had several limitations. For example, “not all patients underwent their allocated treatment, although the difference in 60-day mortality was also observed in the per-protocol analysis,” they wrote. In addition, there were more men in the resection arm than the systemic treatment arm, and prior research has shown that men have a slightly worse prognosis than women.

“These data support systemic therapy with oxaliplatin-based chemotherapy as standard for asymptomatic CRCs in the setting of nonresectable metastases and encourage re-evaluation of patients after 2 to 4 chemotherapy cycles to determine if the metastatic disease has been converted to resectable,” Fong concluded. “Less surgery up front may result in more effective surgery later with a possible curative outcome.”