Poor compliance with adjuvant chemotherapy use associated with poorer survival in patients with rectal cancer: An NCDB analysis

Abstract

BACKGROUND: National Comprehensive Cancer Network treatment guidelines for patients with locally advanced rectal cancer include neoadjuvant chemoradiation followed by total mesorectal excision and adjuvant chemotherapy. The objective of the current study was to examine the rate of adjuvant chemotherapy and associated survival in patients with stage II/III rectal cancer. METHODS: The 2006 to 2011 National Cancer Data Base was queried for patients with AJCC clinical stage II/III rectal cancer who underwent neoadjuvant chemoradiation and surgical resection. A mixed effects multivariable logistic regression identified factors associated with the receipt of adjuvant chemotherapy. A mixed effects Cox proportional hazards model was used to estimate the adjusted effect of receiving adjuvant therapy on 5-year overall survival (OS). RESULTS: A total of 14,742 patients were included; 68% of the cohort did not receive adjuvant chemotherapy. When controlled for clinical stage of disease, patients who were aged >70 years, had a higher comorbidity score, and had a pathologic complete response had lower odds of receiving adjuvant therapy. There was a 22-fold difference in the risk-adjusted rate of adjuvant therapy use among hospitals (3.1%-67.7%). Adjuvant therapy was associated with increased 5-year OS when controlled for patient factors, stage of disease, and pathologic response (hazard ratio, 0.65; 95% confidence interval, 0.59-0.71). The greatest survival benefit was noted among patients who achieved a pathologic complete response (hazard ratio, 0.40; 95% confidence interval, 0.23-0.67). CONCLUSIONS: There is poor compliance to National Comprehensive Cancer Network guidelines for adjuvant chemotherapy in patients with locally advanced rectal cancer after neoadjuvant chemoradiation and surgery. Adjuvant therapy appears to be independently associated with improved OS regardless of stage of disease, pathologic response, and patient factors. The greatest survival benefit was observed in patients who were complete responders. Age and comorbidities were found to be significantly associated with nonreceipt of adjuvant therapy. Improved rehabilitation and physical conditioning may improve the odds of patients receiving adjuvant therapy. Cancer 2017;123:52-61.

Omission of Adjuvant Chemotherapy in Rectal Cancer Patients with Pathologic Complete Response: a National Analysis

“…The authors also showed that patients with pCR benefitted from adjuvant therapy, perhaps even more than patients without pCR. 10 Our study, distinct from prior literature, spans a more contemporary time period, captures a more diverse picture of current management, and is the first to identify a trend to forgo adjuvant chemotherapy in patients with pCR.…”

“…Two retrospective studies utilizing the National Cancer Database (NCDB), from 2006 to 2011, demonstrated a survival benefit with adjuvant chemotherapy in the setting of pCR. 9,10 Given these discrepant findings, we used a contemporary cohort of the NCDB to evaluate outcomes in patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiation followed by oncologic resection with a pCR. We hypothesized that there would be poor national compliance with the use of adjuvant chemotherapy in this subset of patients.…”

Total Neoadjuvant Therapy: A Shifting Paradigm in Locally Advanced Rectal Cancer Management

“…The effect of delayed adjuvant CTX was described in a meta-analysis, reporting after a 4-week postoperative interval, each additional 4-week delay in CTX administration resulted in a 14% increase in mortality. 51 A recent population-based analysis by Xu et al 52 examined NCCN guideline adherence and associated survival for adjuvant CTX after NA-CRT and TME. Overall, adjuvant CTX was independently associated with improved OS across all pathologic stages, with the greatest survival benefit noted among patients who achieved a pCR (HR 0.40; 95% CI, 0.23-0.67).…”

“…The authors identified older age (> 70 years) and comorbidities to be significantly associated with nonreceipt of adjuvant therapy, suggesting improved rehabilitation and physical conditioning may improve compliance. 52 Indeed, current national practice guidelines continue to recommend a 4-month CTX course either before or after surgical resection for all patients, independent of those receiving NA-CTX, 3,53 although the established benefit of these recommendations is limited by the data, as previously discussed. Optimal CTX sequencing remains an area of active scientific discovery, but currently there is insufficient evidence to conclude that there is no absolute benefit for systemic CTX in the stage II and III rectal cancer patient population.…”

Investigation of the effect of adjuvant chemotherapy in stage II colorectal cancers

“…Regardless of the present statistics, the mortality rate caused by the colorectal cancers has decreased over the past three decades, which was probably due to faster diagnosis, proper screening and use of better treatment methods [3]. With regard to the nonspecific nature of most of the clinical symptoms such as abdominal pain, bowel habits changes, melena, hematochezia, unjustifiable fatigue and anemia, reducing the morbidity and mortality rates is currently achieved using screening methods such as colonoscopy, double-contrast barium enema, sigmoidoscopy, fecal occult blood testing and virtual colonoscopy, which is the best and golden standard colonoscopy [4]. Choosing the treatment method is based on staging of the disease and surgery is the…”