Colon cancer survival with neoadjuvant chemo vs upfront surgery a toss-up

In the treatment of patients with colon cancer, neoadjuvant chemotherapy does not appear to yield better survival benefit than standard upfront surgery, according to the results of the phase III NeoCol trial presented at ASCO 2023.

The primary endpoint of disease-free survival (DFS) at 2 years was similar among patients who underwent upfront surgery and those who received neoadjuvant chemotherapy (p=0.95), as was the secondary endpoint of overall survival (OS; p=0.95). [ASCO 2023, abstract LBA3503]

“However, neoadjuvant chemotherapy seemed to have more favourable outcomes in terms of chemotherapy cycles, postoperative complications, and downstaging,” reported Dr Lars Henrik Jensen of the Danish Colorectal Cancer Center South and the University Hospital of Southern Denmark, Vejle, Denmark.

The analysis included 246 patients (median age 66 years, 44 percent women) with advanced colon cancer. Most patients (91 percent) had a performance status (PS) score of 0. Close to three-fourths of tumours (73 percent) were classified as T3, with a median outgrowth of 11 mm, while 26 percent were classified as T4 on the baseline CT scan. There were no significant differences in baseline characteristics.

Of the patients, 122 were randomly assigned to the standard arm and 126 in the neoadjuvant arm. Patients in standard arm underwent surgery, whereas those in the neoadjuvant arm received either 3 cycles of CAPOX (oxaliplatin, capecitabine every 3 weeks) or 4 cycles of FOLFOX (oxaliplatin, fluorouracil every 2 weeks) before surgery.

“Adjuvant chemotherapy was based on the postoperative pathology examination … and was not mandatory. It was only offered [in the presence of] postoperative risk factors. Furthermore, any neoadjuvant chemotherapy was subtracted from the number of planned adjuvant cycles,” Jensen pointed out. “This is an important chemotherapy de-escalation feature of the trial.”

Merits of neoadjuvant chemo

Nearly all patients (99 percent) underwent surgery a median of 7 days from randomization in the standard arm and 74 days in the neoadjuvant arm. There were more laparoscopic procedures and a little more right-sided cancers in the standard arm than in the neoadjuvant arm.

“Considering surgical complication, surgery proved to be a safe procedure after neoadjuvant chemotherapy. Absolute numbers are small, but, relatively, the risk of ileus or anastomotic leakage favoured neoadjuvant chemotherapy,” Jensen said.

Meanwhile, the neoadjuvant arm received fewer chemotherapy cycles than the standard group (3 vs 4). There were slightly more postoperative complications in the standard group regarding ileus, anastomotic leakage, and length of stay.

Postoperative pathology examination data revealed tumour downsizing after neoadjuvant chemotherapy, with 3 percent complete responses in T0 category and a total of 10 percent in T2 category. Furthermore, many patients had no lymph node spread, which is an indicator of downstaging, Jensen noted.

In light of the present data, Jensen said: “Neoadjuvant chemotherapy is a widely accepted approach in numerous cancers, with potential benefits such as eliminating micrometastases, reducing tumour size, giving time for improving the patient's conditions before anesthesia and surgery—the so-called prehabilitation.

“Furthermore, if risk factors are eliminated and the tumour is downstaged, postoperative adjuvant chemotherapy may not be necessary at all,” he continued.

The study was limited by the use of preoperative CT scan—which may not be ideal to identify high risk patients, that is patients who are eligible for adjuvant chemotherapy—and the missed opportunity to include patient-reported quality of life, according to Jensen.

“And finally, at the time of study design, mismatch repair and circulating tumour DNA were not established biomarkers in this setting, and they were not included prospectively,” he added.