Three months of induction chemotherapy resulted in successful downstaging for certain patients with early-stage rectal cancer, enabling them to undergo organ-sparing therapy, according to a phase II trial.

In 33 of 58 patients, induction with modified folinic acid, fluorouracil, oxaliplatin 6 (FOLFOX6) or capecitabine-oxaliplatin (CAPOX), followed by transanal excision surgery, resulted in downstaging to ypT0/1N0/X tumors, reported Hagen F. Kennecke, MD, MHA, of Providence Cancer Institute in Portland, Oregon, and colleagues.

The protocol-specific organ preservation rate was 57% (90% CI 45-68). In addition, this rate was similar among T stage subgroups at 63% in the cT1 group (n=8), 54% in the T2 group (n=37), and 62% in the T3ab group (n=13), they stated in the Journal of Clinical Oncology.

Of 23 remaining patients recommended for total mesorectal excision (TME) surgery on the basis of protocol requirements, 13 declined the surgery and proceeded to observation. This resulted in a total of 46 patients, or 79%, achieving organ preservation (90% CI 69-88), defined as the proportion of patients with tumor ypT0/T1goodN0 and who avoided radical surgery.

Kennecke and colleagues noted that this Canadian Cancer Trials Group CO.28 NEO study was done at cancer centers that specialize in rectal cancer diagnosis, therapy, and transanal surgery, and that the concentration of rectal cancer surgeries at high-volume centers has been associated with superior organ-sparing therapy outcomes.

Still, they stressed that as far as they know, “this is the first published study to describe organ-sparing outcomes of patients with stage I and early-stage II rectal cancer treated with induction chemotherapy and transanal surgical excision. The approach offers a much-desired organ-sparing option and warrants further investigation.”

The researchers explained that the current standard therapy for patients with histologically high-risk cT1 and cT2N0 rectal tumors is resection with TME combined with preoperative chemoradiation for patients with T3 or N1 tumors.

“Although locoregional relapse rates with modern neoadjuvant therapy are low and survival is excellent, TME results in issues with bowel function, incontinence, and sexual function,” they said. Thus, the idea behind organ-sparing therapy, such as the neoadjuvant chemotherapy with excision for early-stage I/IIA rectal cancer, is intended to avoid the adverse effects associated with TME.

Among the 13 patients who declined recommended TME, 85% had ypT2N0 tumors and one patient developed a locoregional relapse during the follow-up period that was successfully resected with a TME. Among the 10 patients who proceeded to recommended TME surgery, just two had pathologically N1 tumors.

The 1-year locoregional relapse-free survival rate was 98% (95% CI 86-100) and the 2-year locoregional relapse-free survival rate was 90% (95% CI 58-98), respectively. There were no distant recurrences or deaths.

The authors also investigated rectal function and quality-of-life outcomes and found that there was little change in these scores from baseline.

The trial took place at seven centers in Canada and the U.S. All patients (median age 67 years, 71% male, 83% white) had low- or mid-rectal tumors clinical T1-T3abN0 low- or mid-rectal adenocarcinoma diagnosed by proctoscopy. They were deemed eligible for endoscopic resection by the study surgeon. All patients required pelvic MRI, and CT of the chest, abdomen, and pelvis.

Patients had to have a pretreatment ECOG performance score of 0 or 1 and adequate hematologic and organ function, while exclusion criteria included a history of external-beam pelvic radiation, prior therapy for rectal cancer, or metastatic disease.

Patients received six cycles of modified FOLFOX6 or four cycles of CAPOX, depending on investigator discretion. Pelvic MRI and proctoscopy were performed 2 to 3 weeks after the last dose of chemotherapy and patients who had tumors with protocol-defined evidence of response proceeded to transanal excision surgery. Those with progression or no response to chemotherapy were referred to TME and preoperative pelvic radiation if the MRI revealed cT3ab, cN+, or involved or threatened circumferential radial margin.

The researchers noted that in 2014, the American College of Surgeons launched the National Accreditation Program for Rectal Cancer, which enabled “patients to benefit from novel approaches such as NEO.”

Please enable JavaScript to view the

comments powered by Disqus.