Comparison of pathological complete response rates after neoadjuvant short-course radiotherapy or chemoradiation followed by delayed surgery in locally advanced rectal cancer

Introduction: Patients with locally advanced rectal cancer (LARC) who are unfit for chemoradiation (CRT), are often offered short-course radiotherapy followed by delayed surgery (SCRT-delay). This entails a lower radiation dose, no chemotherapy and a shorter treatment period. This may lower their chances for complete tumor response and, as such, organ-sparing approaches. The purpose of this study was to compare the pathological complete response (pCR) rates between neoadjuvant CRT and SCRT-delay in patients with LARC in a nationwide database from the Netherlands. Methods: In the population based Netherlands Cancer Registry, clinical stage III rectal cancer patients, diagnosed between 2008 and 2014, who underwent CRT or SCTR-delay were selected. pCR (ypT0N0), near pCR (ypT0-1N0), and tumor and nodal downstaging were compared between the treatment groups using multivariable logistic regression analysis. Results: 386 patients underwent SCRT-delay and 3659 patients underwent CRT. The pCR-rate in the SCRT-delay group was significantly lower compared to the CRT-group (6.4% vs. 16.2%, p < 0.001). After adjustment for clinical tumor stage, clinical nodal stage and time interval to surgery, SCRT-delay patients were significantly less likely to reach pCR (adjusted odds ratio 0.3, 95%CI 0.2–0.5). Also, near-pCR (ypT0–1N0) as well as tumor and nodal downstaging was observed less often in the SCRT-delay group. Conclusion: Compared to patients treated with neoadjuvant CRT, those receiving SCRT and delayed surgery are less likely to develop pCR. Novel neoadjuvant treatment strategies for patients not fit enough for CRT are needed to increase their eligibility for organ-sparing treatments