Abstract
Background
This study aimed to investigate the prognostic factors and the utility of the neoadjuvant rectal (NAR) score for patients who have locally advanced rectal cancer (LARC) treated with preoperative short-course radiotherapy (SRT) or long-course concurrent chemoradiotherapy (CRT).
Methods
Of 314 consecutive stage 2 or 3 rectal cancer patients enrolled from January 2006 to December 2017, 205 underwent preoperative SRT (2500 cGy/5 fractions), and 109 underwent preoperative CRT (4200–5080 cGy/21–28 fractions) after total mesorectal excision (TME). The study calculated NAR scores using the following equation: [5 pN − 3(cT − pT) + 12]2/9.61.
Results
The multivariate analysis showed that age above 65 years, pT4, pN2, NAR scores higher than 16, and distance from anal verges (< 8 cm) were significant prognostic factors for overall survival (OS), whereas, pN2, NAR scores lower than 16, and distance from anal verges (< 8 cm) were significant prognostic factors for disease-free survival (DFS) and distant metastasis (DM). The patients with an NAR score higher than 16, had a 5-year OS rate of 67.6%, a DFS rate of 56.9%, a locoregional recurrence (LRR) rate of 7.7%, and a DM rate of 35% compared with corresponding rates of 87.6%, 76.7%, 5.4%, and 7.2% for the patients with an NAR score of 16 or lower (p < 0.001 for OS, < 0.001 for DFS, 0.25 for LRR, and < 0.001 for DM).
Conclusions
For patients who undergo SRT or CRT for LARC, a higher NAR score is associated with worse OS and DFS and higher DM rates at 5 years. The NAR score could be used as a short-term surrogate end point after neoadjuvant therapy for LARC.
References
van Gijn W, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet. Oncol 2011;12:575–82.
Sebag-Montefiore D, Stephens RJ, Steele R, et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009;373:811–20.
Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial: long-lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol. 2005;23:5644–50.
Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345:638–46.
Swedish Rectal Cancer T, Cedermark B, Dahlberg M, et al. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997;336:980–7.
Sauer R, Liersch T, Merkel S, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30:1926–33.
Roh MS, Colangelo LH, O’Connell MJ, et al. Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol. 2009;27:5124–30.
Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–40.
NCCN Guideline, Rectal Cancer (2020). Retrieved 1 March 2020 at https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf 3025.
Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006;93:1215–23.
Ngan SY, Burmeister B, Fisher RJ, et al. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012;30:3827–33.
Maas M, Nelemans PJ, Valentini V, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11:835–44.
George TJ Jr, Allegra CJ, Yothers G. Neoadjuvant rectal (NAR) score: a new surrogate endpoint in rectal cancer clinical trials. Curr Colorectal Cancer Rep. 2015;11:275–80.
Valentini V, van Stiphout RG, Lammering G, et al. Nomograms for predicting local recurrence, distant metastases, and overall survival for patients with locally advanced rectal cancer on the basis of European randomized clinical trials. J Clin Oncol. 2011;29:3163–72.
Yothers G GTJ, Petrelli NJ, et al. Neoadjuvant rectal cancer (RC) score predicts survival: potential surrogate endpoint for early phase trials. J Clin Oncol. 2014;32(15(Suppl)):3533.
Yeh CH, Chen MF, Lai CH, Huang WS, Lee SP, Chen WC. Comparison of treatment results between surgery alone, preoperative short-course radiotherapy, or long-course concurrent chemoradiotherapy in locally advanced rectal cancer. Int J Clin Oncol. 2012;17:482–90.
Franke AJ, Parekh H, Starr JS, Tan SA, Iqbal A, George TJ Jr. Total neoadjuvant therapy: a shifting paradigm in locally advanced rectal cancer management. Clin Colorectal Cancer. 2018;17:1–12.
Erlandsson J, Holm T, Pettersson D, et al. Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial. Lancet Oncol. 2017;18:336–46.
Hospers G, Bahadoer RR, Dijkstra EA, et al. Short-course radiotherapy followed by chemotherapy before TME in locally advanced rectal cancer: the randomized RAPIDO trial. (2020) ASCO Virtual Scientific Program. Retrieved 17 July 2020 https://meetinglibrary.asco.org/record/185464/abstract.
Roy A OJ, Myerson R, Markovina S, DeWees T, Parikh P. Short-term endpoints for neoadjuvant rectal cancer therapy: pathologic complete response or neoadjuvant rectal cancer score? Int J Radiat Oncol Biol Phy. 2016;96(Suppl):E201.
ICH GCP|Clinical Trials Registry (2016). Short-Course Radiation Therapy Followed by Preoperative Chemotherapy and Surgery in High-risk Rectal Cancer (LARCT-US). Retrieved 17 May 2020 at https://ichgcp.net/de/clinical-trials-registry/NCT03729687.
Weiner A MS, Khwaja S, et al.. Neoadjuvant rectal cancer (NAR) score applied to phase 2 trial of short-course radiation (RT) and FOLFOX as preoperative therapy for rectal cancer supports a total neoadjuvant approach. Int J Radiat Oncol Biol Phy. 2014;90(Suppl):S389.
Delitto D, George TJ Jr, Loftus TJ, et al. Prognostic value of clinical vs pathologic stage in rectal cancer patients receiving neoadjuvant therapy. J Natl Cancer Institute. 2018;110:460–6.
Silberfein EJ, Kattepogu KM, Hu CY, et al. Long-term survival and recurrence outcomes following surgery for distal rectal cancer. Ann Surg Oncol. 2010;17:2863–9.
Kusters M, Holman FA, Martijn H, et al. Patterns of local recurrence in locally advanced rectal cancer after intraoperative radiotherapy containing multimodality treatment. Radiother Oncol. 2009;92:221–5.
Chapet O, Romestaing P, Mornex F, et al. Preoperative radiotherapy for rectal adenocarcinoma: which are strong prognostic factors? Int J Radiat Oncol Biol Phys. 2005;61:1371–7.
Sun Y, Zhang Y, Wu X, et al. Prognostic significance of neoadjuvant rectal score in locally advanced rectal cancer after neoadjuvant chemoradiotherapy and construction of a prediction model. J Surg Oncol. 2018;117:737–44.
Rosello S, Frasson M, Garcia-Granero E, et al. Integrating downstaging in the risk assessment of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy: validation of Valentini’s nomograms and the neoadjuvant rectal score. Clin Colorectal Cancer. 2018;17:104–112 e102.
Raissouni S MJ, Gresham G, Kumar A, Goodwin R, Jiang M. External validation of the neoadjuvant rectal (NAR) score and Valentini prediction nomogram (VPN): a multicenter study. J Clin Oncol. 2014;32(15 Suppl):3532.
Hong T SJ, Yothers G, et al. Validation of the NSABP neoadjuvant rectal score (NAR) in a prospective phase II study evaluating an experimental regimen and a standard chemoradiation cohort with molecular genotyping. J Clin Oncol. 2014;32(15 Suppl):3599.
van der Valk MJM, Vuijk FA, Putter H, van de Velde CJH, Beets GL, Hilling DE. Disqualification of neoadjuvant rectal score based on data of 6596 patients from the Netherlands Cancer Registry. Clin Colorectal Cancer. 2019;18:e231–6.
Fokas E, Fietkau R, Hartmann A, et al. Neoadjuvant rectal score as individual-level surrogate for disease-free survival in rectal cancer in the CAO/ARO/AIO-04 randomized phase III trial. Ann Oncol. 2018;29:1521–7.
Sloothaak DA, Geijsen DE, van Leersum NJ, et al. Optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer. Br J Surg. 2013;100:933–9.
Kuan FC, Lai CH, Ku HY, et al. The survival impact of delayed surgery and adjuvant chemotherapy on stage II/III rectal cancer with pathological complete response after neoadjuvant chemoradiation. Int J Cancer. 2017;140:1662–9.
Acknowledgments
This study was supported by a research grant from Chang Gung Memorial Hospital (CGRPG6J0071). The authors thank Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi Branch for providing comments and assistance in data analysis.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Disclosure
There are no conflicts of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Huang, WS., Kuan, FC., Lin, MH. et al. Prognostic Significance of Neoadjuvant Rectal Scores in Preoperative Short-Course Radiotherapy and Long-Course Concurrent Chemoradiotherapy for Patients with Locally Advanced Rectal Cancer. Ann Surg Oncol 27, 4309–4318 (2020). https://doi.org/10.1245/s10434-020-09018-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1245/s10434-020-09018-z