Neoadjuvant chemoradiation for down staging of locally-advanced rectal cancer, and assessment of clinical response with digital rectal examination, magnetic resonance imaging and colonoscopy
DOI:
https://doi.org/10.18203/2349-2902.isj20243228Keywords:
Locally-advanced rectal cancer, Neoadjuvant chemoradiation, Downstaging, Response assessment, AccuracyAbstract
Background: In this era of total neoadjuvant treatment (TNT) followed by rectal preservation non-operative management (NOM) or wait and watch (WW) approach for non-metastatic locally-advanced rectal cancer (LARC), reliable and reproducible response evaluation to neoadjuvant therapies forms the cornerstone. Through this study, we try to evaluate clinical response of locally-advanced rectal cancer to neoadjuvant chemoradiation (CRT) in terms of downstaging and total mesorectal excision (TME), and the accuracy of digital rectal examination (DRE), magnetic resonance imaging (MRI) and colonoscopy in the assessment of clinical response to neoadjuvant CRT.
Methods: Histologically proven locally advanced rectal adenocarcinoma patients, after pretreatment evaluation, were considered for neoadjuvant chemoradiation, i.e., intensity-modulated radiation therapy (IMRT) with 5-fluorouracil (5-FU) and leucovorin-based concurrent chemotherapy. Patients were evaluated 6-8 weeks after completion of CRT and clinical response assessed by means of DRE, colonoscopy and MRI of pelvis. Following surgery, pathological response was assessed on the final histopathological examination (HPE).
Results: Twenty-two patients were accrued for this protocol, of which, 15 (68.2%) were male and 7 (31.8%) were female. Downstaging and TME was achieved in 90.9% of the patients. The sensitivity of DRE, colonoscopy and MRI to detect a complete response was 66.67% and specificity was 94.74%. There were no severe toxicities or deaths reported.
Conclusions: Neoadjuvant concurrent chemoradiotherapy with bolus 5-FU and leucovorin is an accepted modality of treatment for locoregionally-advanced rectal cancer, which offers higher rates of downstaging and TME. Digital rectal examination, colonoscopy and MRI together can be reliably used to assess response following neoadjuvant CRT.
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References
Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, et al. Global Cancer Observatory: Cancer Today. International Agency for Research on Cancer, Lyon, France. 2024. Available at: https://gco.iarc.who.int/today. Accessed on 15 August 2024.
Kapiteijn E, Marijnen CAM, Nagtegaal ID, Putter H, Steup WH, Wiggers T, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345:638-46.
Minsky BD. Adjuvant therapy for rectal cancer. ASCO Annual Meeting Educational Book. J Clin Oncol. 2002;472-7.
MacFarlane JK, Ryall RD, Heald RJ. Mesorectal excision for rectal cancer. Lancet. 1993;341:457-60.
Heald RJ, Moran BJ, Ryall RD, Sexton R, MacFarlane JK. Rectal cancer: the Basingstoke experience of total mesorectal excision, 1978-1997. Arch Surg. 1998;133:894-9.
Bosset JF, Calais G, Daban A. Does the addition of chemotherapy to radiation increase acute toxicity in patients with rectal cancer: Report of 22921 EORTC phase III trial. J Clin Oncol. 2003;21:294.
Gerard JP, Conroy T, Bonnetain F, Bouche O, Chapet O, Closon-Dejardin MT, et al. Properative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006;24:4620-5.
Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355:1114-23.
Wang XJ, Zheng ZR, Chi P, Lin HM, Lu XR, Huang Y. Effect of interval between neoadjuvant chemoradiotherapy and surgery on oncological outcome for rectal cancer: a systematic review and meta-analysis. Gastroenterol Res Pract. 2016;6756859-63.
Habr-Gama A, Perez RO, Proscurshim I, Campos FG, Nadalin W, Kiss D, et al. Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy. J Gastrointest Surg. 2006;10(10):1319-29.
Habr-Gama A, Perez RO, Wynn G, Marks J, Kessler H, Gama-Rodrigues J. Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: characterization of clinical and endoscopic findings for standardization. Dis Colon Rectum. 2010;53(12):1692-8.
Patel UB, Taylor F, Blomqvist L, George L, Evans H, Tekkis P, et al. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. J Clin Oncol: Off J AM Soc Clin Oncol. 2011;29:3753-60.
Gerard JP, Chamorey E, Gourgou-Bourgade S, Benezery K, deLaroche G, Mahe MA, et al. Clinical complete response (cCR) after neoadjuvant chemoradiotherapy and conservative treatment in rectal cancer. Findings from the ACCORD 12/PRODIGE 2 randomized trial. Radiother Oncol: J Europ Soc Therap Radiol Oncol. 2015;115:246-52.
Yeom SS, Lee SY, Kim CH, Kim YJ, Nam TK, Kim HR. Non-operative treatment outcome for rectal cancer patient with clinical complete response after neoadjuvant chemoradiotherapy. Asian J Surg. 2019;42:823-31.
Rodel C, Grabenbauer GG, Papadopoulos T, Hohenberger W, Schmoll HJ, Sauer R. Phase I/II trial of capecitabine, oxliplatin, and radiation for rectal cancer. J Clin Oncol. 2003;21(16):3098-104.
Osti MF, Valeriani M, Masoni L, Tombolini V, Enrici RM. Neoadjuvant chemoradiation for locally advanced carcinoma of the rectum. Tumori J. 2004;90(3):303-9.
Garcia-Aguilar J, Patil S, Gollub M, Kim J, Yuval J, Thompson H, et al. Organ preservation in patients with rectal adenocarcinoma treatment with total neoadjuvant therapy. J Clin Oncol. 2022;40:2546-56.
Roxburgh CS. Organ preservation in rectal cancer: Towards the normal rather than the exception. Br J Surg. 2021;108:745-7.
Guillem JG, Chessin DB, Shia J, Moore HG, Mazumdar M, Bernard B, et al. Clinical examination following preoperative chemoradiation: Diagnostic accuracy and prognostic value. J Cancer Res Clin Oncol. 2014;140:1221-7.
Kahn H, Alexander A, Rakinic J, Nagle D, Fry R. Preoperative staging of irradiated rectal cancers using digital rectal examination, computed tomography, endorectal ultrasound, and magnetic resonance imaging does not accurately predict T0,N0 pathology. Dis Colon Rectum. 1997;40:140-4.
Stefanou AJ, Dessureault S, Sanchex J, Felder S. Clinical tools for rectal cancer response assessment following neoadjuvant treatment in the era of organ preservation. Cancers. 2023;15:5335.
Chen J, Wu Z, Zhang X, Liu Z, Shan F. Optimized tools and timing of response reassessment after neoadjuvant chemoradiation in rectal cancer. Int J Colorectal Dis. 2022;37:2321-33.
Ogura A, Chino A, Konishi T, Akiyoshi T, Kishihara T, Tamegai Y, et al. Endoscopic evaluation of clinical response after preoperative chemoradiotherapy for lower rectal cancer: the significance of endoscopic complete response. Int J Colorectal Dis. 2015;30:367-73.
Schnall MD, Furth EE, Rosato EF, Kressel HY. Rectal tumor stage: correlation of endorectal MR imaging and pathologic findings. Radiology. 1994;190(3):709-14.
Tatli S, Mortele KJ, Breen EL, Bleday R, Silverman SG. Local staging of rectal cancer using combined pelvic phased-array and endorectal coil MRI. J Mag Reson Imag. 2006;23(4):534-40.
Ko HM, Choi YH, Lee JE, Lee KH, Kim JY, Kim JS. Combination assessment of clinical complete response of patients with rectal cancer following chemoradiotherapy with endoscopy and magnetic resonance imaging. Ann Coloproctol. 2019;35(4):202-8.
Maas M, Lambregts DMJ, Nelemans PJ, Heijen LA, Martens MH, Leijtens JWA, et al. Assessment of clinical complete response after chemoradiation for rectal cancer with digital rectal examination, endoscopy, and MRI: Selection for organ-saving treatment. Ann Surg Oncol. 2015;22:3873-80.
Janjan NA, Khoo VS, Abbruzzese J, Wolff R, Rich TA, et al. Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M.D, Anderson Cancer Centre experience. Int J Rad Oncol Biol Phys. 1999;44(5);1027-38.
Kim J, Kim J, Cho M, Song K, Yoon W. Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. Int J Rad Oncol Biol Phys. 2002;54(2):403-8.