Surgery May Not Be Needed With Locally Advanced Rectal Cancer

Pam Harrison

November 02, 2020

A short course of radiation therapy followed by neoadjuvant chemotherapy resulted in a clinical complete response (CR) in almost half of 90 patients with locally advanced rectal cancer, allowing the majority of responders to skip surgical resection, a retrospective study indicates.

Specifically, at a median follow-up of 16.6 months for living patients, the initial clinical CR was 48% overall.

"While we do not have enough follow-up yet to know the late side-effect profile of this regimen, our preliminary results are promising," Re-I. Chin, MD, Washington University School of Medicine, St. Louis, Missouri, told Medscape Medical News in an email.

The study was presented at the virtual 2020 meeting of the American Society of Radiation Oncology (ASTRO).

"Certainly longer follow-up will be needed in this study but none of the observed patients to date has experienced an unsalvageable failure," said meeting discussant Amol Narang, MD, of Johns Hopkins University, Baltimore, Maryland.

He reminded conference attendees that despite good evidence supporting equivalency in oncologic outcomes between short-course radiation and long-course chemoradiation, the former is "highly underutilized in the US" with a mere 1% usage rate between 2004 and 2014.

The current study's short-course treatment approach was compared in this setting to long-course chemoradiation and adjuvant chemotherapy in the  RAPIDO trial reported at the 2020 annual meeting of the American Society of Clinical Oncology (ASCO), Narang pointed out.

Short-course patients had a higher rate of pathological complete response (pCR) and a lower rate of treatment failure compared with patients who received long course chemoradiation and adjuvant chemotherapy; both patient groups underwent total mesorectal excision — which is different from the current analysis. The RAPIDO investigators concluded that the approach featuring the short-course "can be considered as a new standard of care."

Narang said the data collectively "begs the question as to whether the superiority of long course chemoradiation should really have to be demonstrated to justify its use."

But Chin highlighted toxicity issues. "Historically, there have been concerns regarding toxicity with short-course radiation therapy since it requires larger doses of radiation given over a shorter period of time," Chin explained. "But [the short course] is particularly convenient for patients since it saves them more than a month of daily trips to the radiation oncology department."

Seven Local Failures

The single-center study involved patients with newly diagnosed, nonmetastatic rectal adenocarcinoma treated with short course radiation therapy followed by chemotherapy in 2018 and 2019. Nearly all (96%) had locally advanced disease, with either a T3/T4 tumor or node-positive disease.  Median tumor size was 4.6 cm.

"Many of the patients in the study had low lying tumors," Chin reported, with a median distance from the anal verge of 7 cm.

Radiation therapy was delivered in 25 Gy given in five fractions over 5 consecutive days, with the option to boost the dose to 30 Gy or 35 Gy in five fractions if extra-mesorectal lymph nodes were involved. Conventional 3D or intensity-modulated radiation was used and all patients completed treatment.

The median interval between diagnosis of rectal cancer and initiation of radiation therapy was 1.4 months while the median interval between completion of radiation to initiation of chemotherapy was 2.7 weeks.

The most common chemotherapy regimen was FOLFOX consisting of leucovorin, fluorouracil (5-FU) and oxaliplatin or modified FOLFOX. For patients who received six or more cycles of chemotherapy, the median time spent in treatment was 3.9 months.

For those who completed at least six cycles of chemotherapy, the overall clinical CR was 51% and for patients with locally advanced disease, the clinical CR was 49%. Five of the 43 patients who achieved an initial clinical CR still underwent surgical resection because of patient or physician preference. Among this small group of patients, 4 out of the 5 achieved a pCR and the remaining patient achieved a pathological partial response (pPR).

A total of 42 patients (47% of the group) achieved a partial response following the radiation plus chemotherapy paradigm and one patient had progressive disease; all underwent surgical resection. One patient did not complete chemotherapy and did not get surgery and subsequently died.

This left 38 patients to be managed nonoperatively. In this nonoperative cohort, 79% of patients continued to have a clinical CR rate at the end of follow-up. Of the 7 patients with local failure, 6 were salvaged by surgery, one was salvaged by chemotherapy and all 7 treatment failures had no evidence of disease at last follow-up.

Of the small group of 5 patients who achieved an initial clinical CR following short-course radiation therapy and neoadjuvant chemotherapy, there were no further events in this group, whereas for patients who achieved only an initial partial response or who had progressive disease, 72% remained event-free.

Approximately half of those who achieved a clinical CR to the treatment regimen had no late gastrointestinal toxicities and no grade 3 or 4 toxicities were observed. "Surgical resection of tumors — even without a permanent stoma — can result in significantly decreased bowel function so our goal is to treat patients without surgery and maintain good bowel function," Chin noted.

"For rectal cancer, both short-course radiation therapy and nonoperative management are emerging treatment paradigms that may be more cost-effective and convenient compared to long-course chemoradiation followed by surgery, [especially since] the COVID-19 pandemic...has spurred changes in clinical practices in radiation oncology," she said.

Chin has disclosed no relevant financial relationships. Narang reports receiving research support from Boston Scientific.

American Society of Radiation Oncology 2020 Annual Meeting: Abstract 96. Presented October 26, 2020.

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