Chemotherapy and local excision led to organ preservation in over half of early-stage rectal cancer patients in a small study, but follow-up was only a median of 15.4 months.
Even so, “we believe that subsequent trials ... are warranted,” said lead investigator Hagen F. Kennecke, MD, medical director of GI oncology at Providence Cancer Institute, Portland, Ore., who presented the findings at the American Society of Clinical Oncology annual meeting.
“The results are quite promising,” said study discussant Karyn Stitzenberg, MD, a surgical oncologist at the University of North Carolina, Chapel Hill.
“The reported organ preservation rates of 57% to 79% compare favorably with the rates previously demonstrated in studies of neoadjuvant chemoradiation followed by local excision,” but longer-term follow up is needed “to know the true organ preservation rate,” she said.
Organ preservation – sparing the rectum during treatment – is a hot topic in rectal cancer. Total mesorectal excision (TME) is still the go-to option, but it’s fraught with bad GI, urinary, sexual, and other complications for patients. “Consequently, the concept of organ preservation ... is very appealing,” Dr. Stitzenberg explained.
The chemoradiation/local excision approach she referenced is gaining traction as an alternative, but the radiation component is itself associated with substantial short- and long-term problems, including sphincter dysfunction and wound healing complications.
The goal of Dr. Kennecke’s study, dubbed NEO [Neoadjuvant, Excision, Observation], was to see if the radiation could be left out altogether.
Recruited at eight centers in Canada and one in the United States, the 58 subjects had clinical stage T1-T3 A/B node-negative tumors with no pathologic high-risk features.
They received neoadjuvant FOLFOX (six cycles in 32 patients, 91% completion rate) or CAPOX (four cycles in 26 patients, 89% completion); 56 of the 58 subjects then went on to transanal endoscopic tumor excision; one of the other two patients wasn’t eligible because of tumor progression and the other one declined.
The 33 patients who were stage T0/T1N0 after treatment were spared organ removal and underwent observation every 3-6 months. TME was recommended for the 23 others who were stage 2 or higher or had nodal metastases following chemotherapy and excision.
The numbers translated to a per-protocol organ preservation rate of 57% over a median follow-up of 15.4 months; when the 13 patients who declined TME were added, the rate climbed to 79%.
Although “organ preservation in rectal cancer is becoming an increasingly promising and realistic option for a subset of patients,” Dr. Stitzenberg said, there are more reasons to be cautious beyond the short follow-up.
“The standard of care treatment for these patients would have been proctectomy ... Most would not have [had] systemic chemotherapy. As a result, the added morbidity of FOLFOX or CAPOX needs to be considered.” The study reported that there were no unexpected toxicities, but “what were the expected toxicities? How many patients experienced grade 3 to 5 complications?” she wondered.
Also, how realistic is it to expect patients to report for surveillance every few months outside of a trial? And how can they best be watched to make sure recurrence is caught “while salvage TME is still feasible? There are many longer-term follow-up questions that remain to be answered,” Dr. Stitzenberg said.
Even with short follow-up, there were two locoregional recurrences across the cohort (3.5%), both treated by TME to R0/1 resection. There were no distant relapses.
Subjects were a median of 67 years old, and over two-thirds were men. The majority had stage 2 disease at baseline. Tumors were well to moderately differentiated nonmucinous rectal adenocarcinomas with a median height of 6 cm.
The work was funded by the Canadian Cancer Trials Group. Dr. Kennecke disclosed relationships with Advanced Accelerator Applications, Ipsen, and Taiho Pharmaceutical. Dr. Stitzenberg had no relevant disclosures.