Adjuvant chemotherapy improves OS in rectal cancer

Adjuvant chemotherapy appeared associated with improved OS among patients with rectal cancer who achieved pathological complete response after neoadjuvant chemotherapy and resection, according to two studies published in JAMA Oncology.

In separate propensity score matching analyses, Fahima Dossa, MD, general surgery resident at University of Toronto, and colleagues, and Patricio M. Polanco, MD, assistant professor in the department of surgery at UT Southwestern Medical Center, and colleagues, showed adjuvant chemotherapy improved OS among patients with locally advanced disease, particularly those with node-positive disease.

“As techniques to increase the rates of pathological complete response improve, it is becoming increasingly important to determine the optimal treatment paradigm for these patients,” Dossa and colleagues wrote.

Current guidelines indicate preoperative neoadjuvant chemoradiotherapy followed by surgical resection and adjuvant chemotherapy as the standard of care for patients with locally advanced rectal cancer.

Earlier research has shown adjuvant chemotherapy to be effective among patients with rectal cancer who did not receive neoadjuvant chemotherapy, whereas more recent clinical trials suggested no additional survival benefit. Therefore, the role and efficacy of adjuvant chemotherapy for these patients has remained unclear.

Study findings

Dossa and colleagues identified 2,455 patients (59.8% men) with nonmetastatic invasive cancer from the National Cancer Data Base who experienced pathological complete response after neoadjuvant chemotherapy and resection. Researchers used propensity scores to match 667 patients (median age, 57 years) who received adjuvant chemotherapy and 8-week follow-up after resection 1:1 with patients (median age, 61 years) who did not receive adjuvant chemotherapy.

Standardized differences between patients treated with and without adjuvant chemotherapy for all covariates included in the analysis were less than 0.1.

Median follow-up for all patients was 3.1 years (interquartile range [IQR], 1.94-4.4).

Results showed 3-year OS rates of 97.6% among patients who received adjuvant therapy compared with 94% among patients who did not receive adjuvant therapy (HR = 0.44; 95% CI, 0.28-0.7). Five-year OS also appeared higher for the adjuvant therapy group, at 95% compared with 88.2%.

Researchers conducted a sensitivity analysis that included the year of cancer diagnosis. The analysis showed similar results, even with the addition of diagnosis (HR = 0.48; 95% CI, 0.29-0.78).

Subgroup analyses showed a 3-year OS rate of 98.3% for patients with node-positive disease treated with adjuvant chemotherapy compared with 93.1% for those who did not receive adjuvant therapy (HR = 0.24; 95% CI, 0.1-0.58). Researchers did not observe the same benefit for patients with node-negative disease (HR = 0.64; 95% CI, 0.34-1.21).

In a separate study, Polanco and colleagues identified 2,764 patients with stage II or stage III disease from the National Cancer Data Base who experienced pathological complete response after neoadjuvant chemotherapy and resection. Among these, 772 patients received adjuvant chemotherapy, of whom 741 were matched using propensity scores with patients who underwent observation only after neoadjuvant chemotherapy.

The median follow-up was 39 months (IQR, 26-55).

Patients who underwent adjuvant chemotherapy had improved OS compared with the observation group (HR = 0.5; 95% CI, 0.32-0.79).

OS rates appeared higher among patients in the adjuvant chemotherapy group than the observation group at 1 year (99.7% vs. 99.2%), 3 years (97.1% vs. 93.6%) and 5 years (94.7% vs. 88.4%; P = .005).

Subgroup analyses indicated that, overall, patients with stage III and stage IV disease benefitted from adjuvant chemotherapy. Patients with stage III, stage IV or node-positive disease demonstrated the highest benefit (HR = 0.47; 95% CI, 0.25-0.91), although this was not statistically significant among other staging subgroups.

Potential limitations

Both studies retrospectively collected data, which could result in bias.

Also, the results of both studies should be “carefully interpreted,” due to the propensity score methods used, according to George J. Chang, MD, MS, FACS, FASCRS, deputy chair of the department of surgical oncology in the division of surgery, and chief of the section of colon and rectal surgery at The University of Texas MD Anderson Cancer Center.

“[Although] propensity score methods have great utility in observational studies, their underlying limitations for causal inference cannot be overlooked,” Chang wrote in a related editorial. “Although a trial in which patients are [randomly assigned] based on their pathologic stage may yield definitive evidence, large sample size requirements and strong clinician bias may preclude its completion.”

Chang further noted that other treatment measures should be investigated.

“Given the favorable prognosis of [complete response] status following neoadjuvant chemoradiation therapy, the potential harms of adjuvant therapy, including risk for long-term neuropathy, cannot be ignored and alternative strategies for analysis that are less subject to unmeasured confounding should be pursued,” he wrote. – by Melinda Stevens

Disclosure s : The study authors and Chang report no relevant financial disclosures.