Neoadjuvant Chemotherapy, Excision, and Observation for Early Rectal Cancer: The Phase II NEO Trial (CCTG CO.28) Primary End Point Results
Hagen F Kennecke, Chris J O'Callaghan, Jonathan M Loree, Hussein Moloo, Rebecca Auer, Derek J Jonker, Manoj Raval, Reilly Musselman, Grace Ma, Antonio Caycedo-Marulanda, Vlad V Simianu, Sunil Patel, Lacey D Pitre, Ramzi Helewa, Vallerie L Gordon, Katerina Neumann, Halla Nimeiri, Max Sherry, Dongsheng Tu, Carl J Brown, Hagen F Kennecke, Chris J O'Callaghan, Jonathan M Loree, Hussein Moloo, Rebecca Auer, Derek J Jonker, Manoj Raval, Reilly Musselman, Grace Ma, Antonio Caycedo-Marulanda, Vlad V Simianu, Sunil Patel, Lacey D Pitre, Ramzi Helewa, Vallerie L Gordon, Katerina Neumann, Halla Nimeiri, Max Sherry, Dongsheng Tu, Carl J Brown
Abstract
Purpose: Organ-sparing therapy for early-stage I/IIA rectal cancer is intended to avoid functional disturbances or a permanent ostomy associated with total mesorectal excision (TME). The objective of this phase II trial was to determine the outcomes and organ-sparing rate of patients with early-stage rectal cancer treated with neoadjuvant chemotherapy followed by transanal excision surgery (TES).
Methods: This phase II trial included patients with clinical T1-T3abN0 low- or mid-rectal adenocarcinoma eligible for endoscopic resection who were treated with 3 months of chemotherapy (modified folinic acid-fluorouracil-oxaliplatin 6 or capecitabine-oxaliplatin). Those with evidence of response proceeded to transanal endoscopic surgery 2-6 weeks later. The primary end point was protocol-specified organ preservation rate, defined as the proportion of patients with tumor downstaging to ypT0/T1N0/X and who avoided radical surgery.
Results: Of 58 patients enrolled, all commenced chemotherapy and 56 proceeded to surgery. A total of 33/58 patients had tumor downstaging to ypT0/1N0/X on the surgery specimen, resulting in an intention-to-treat protocol-specified organ preservation rate of 57% (90% CI, 45 to 68). Of 23 remaining patients recommended for TME surgery on the basis of protocol requirements, 13 declined and elected to proceed directly to observation resulting in 79% (90% CI, 69 to 88) achieving organ preservation. The remaining 10/23 patients proceeded to recommended TME of whom seven had no histopathologic residual disease. The 1-year and 2-year locoregional relapse-free survival was, respectively, 98% (95% CI, 86 to 100) and 90% (95% CI, 58 to 98), and there were no distant recurrences or deaths. Minimal change in quality of life and rectal function scores was observed.
Conclusion: Three months of induction chemotherapy may successfully downstage a significant proportion of patients with early-stage rectal cancer, allowing well-tolerated organ-preserving surgery.
Trial registration: ClinicalTrials.gov NCT03259035.
Conflict of interest statement
Carl J. Brown
Honoraria: Ethicon/Johnson & Johnson
Other Relationship: Medtronic (Inst)
No other potential conflicts of interest were reported.
Figures
References
- Chen TY, Wiltink LM, Nout RA, et al. : Bowel function 14 years after preoperative short- course radiotherapy and total mesorectal excision for rectal cancer: Report of a multicenter randomized trial. Clin Colorectal Cancer 14:106-114, 2015
- Sturiale A, Martellucci J, Zurli L, et al. : Long-term functional follow-up after anterior rectal resection for cancer. Int J Colorectal Dis 32:83-88, 2017
- Benson AB, Venook AP, Al-Hawary MM, et al. : NCCN guidelines insights: Rectal cancer, version 6.2020. J Natl Compr Canc Netw 18:806-815, 2020
- Battersby NJ, Juul T, Christensen P, et al. : Predicting the risk of bowel-related quality-of-life impairment after restorative resection for rectal cancer: A multicenter cross-sectional study. Dis Colon Rectum 59:270-280, 2016
- Ihnát P, Slívová I, Tulinsky L, et al. : Anorectal dysfunction after laparoscopic low anterior rectal resection for rectal cancer with and without radiotherapy (manometry study). J Surg Oncol 117:710-716, 2018
- You YN, Baxter NN, Stewart A, Nelson H: Is the increasing rate of local excision for stage I rectal cancer in the United States justified?: A nationwide cohort study from the National Cancer Database. Ann Surg 245:726-733, 2007
- Stitzenberg KB, Sanoff HK, Penn DC, et al. : Practice patterns and long-term survival for early-stage rectal cancer. J Clin Oncol 31:4276-4282, 2013
- Minsky BD, Rich T, Recht A, et al. : Selection criteria for local excision with or without adjuvant radiation therapy for rectal cancer. Cancer 63:1421-1429, 1989
- Brodsky JT, Richard GK, Cohen AM, Minsky BD: Variables correlated with the risk of lymph node metastasis in early rectal cancer. Cancer 69:322-326, 1992
- Salinas HM, Dursun A, Klos CL, et al. : Determining the need for radical surgery in patients with T1 rectal cancer. Arch Surg 146:540-543, 2011
- Lezoche E, Baldarelli M, Lezoche G, et al. : Randomized clinical trial of endoluminal locoregional resection versus laparoscopic total mesorectal excision for T2 rectal cancer after neoadjuvant therapy. Br J Surg 99:1211-1218, 2012
- Garcia-Aguilar J, Shi Q, Thomas CR, Jr, et al. : A phase II trial of neoadjuvant chemoradiation and local excision for T2N0 rectal cancer: Preliminary results of the ACOSOG Z6041 trial. Ann Surg Oncol 19:384-391, 2012
- Verseveld M, de Graaf EJ, Verhoef C, et al. : Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery (CARTS study). Br J Surg 102:853-860, 2015
- Stijns RCH, de Graaf EJR, Punt CJA, et al. : Long-term oncological and functional outcomes of chemoradiotherapy followed by organ-sparing transanal endoscopic microsurgery for distal rectal cancer: The CARTS study. JAMA Surg 154:47-54, 2019
- Rullier E, Vendrely V, Asselineau J, et al. : Organ preservation with chemoradiotherapy plus local excision for rectal cancer: 5-year results of the GRECCAR 2 randomised trial. Lancet Gastroenterol Hepatol 5:465-474, 2020
- Marks JH, Valsdottir EB, DeNittis A, et al. : Transanal endoscopic microsurgery for the treatment of rectal cancer: Comparison of wound complication rates with and without neoadjuvant radiation therapy. Surg Endosc 23:1081-1087, 2009
- Hupkens B, Lambregts D, Van der Sande M, et al. : 2001 Anorectal function after watch and wait-policy in rectal cancer patients. Eur J Cancer 51:S327, 2015
- Bosset JF, Collette L, Calais G, et al. : Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355:1114-1123, 2006. [Erratum: N Engl J Med 357:728, 2007]
- Monson JR, Weiser MR, Buie WD, et al. : Practice parameters for the management of rectal cancer (revised). Dis Colon Rectum 56:535-550, 2013
- Stevenson AR, Solomon MJ, Lumley JW, et al. : Effect of laparoscopic-assisted resection vs open resection on pathological outcomes in rectal cancer: The ALaCaRT randomized clinical trial. JAMA 314:1356-1363, 2015
- Bonjer HJ, Deijen CL, Abis GA, et al. : A randomized trial of laparoscopic versus open surgery for rectal cancer. N Engl J Med 372:1324-1332, 2015
- Fleshman J, Branda M, Sargent DJ, et al. : Effect of laparoscopic-assisted resection vs open resection of stage II or III rectal cancer on pathologic outcomes: The ACOSOG Z6051 randomized clinical trial. JAMA 314:1346-1355, 2015
- Rockwood TH, Church JM, Fleshman JW, et al. : Fecal incontinence quality of life scale: Quality of life instrument for patients with fecal incontinence. Dis Colon Rectum 43:9-17, 2000
- Juul T, Ahlberg M, Biondo S, et al. : International validation of the low anterior resection syndrome score. Ann Surg 259:728-734, 2014
- Marabelle A, Le DT, Ascierto PA, et al. : Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: Results from the phase II KEYNOTE-158 study. J Clin Oncol 38:1-10, 2020
- Marabelle A, Fakih M, Lopez J, et al. : Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: Prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol 21:1353-1365, 2020
- : NEO: Neoadjuvant Chemotherapy, Excision and Observation for Early Rectal Cancer. Bethesda, MD, National Library of Medicine (US), 2000.
- Smith JJ, Strombom P, Chow OS, et al. : Assessment of a watch-and-wait strategy for rectal cancer in patients with a complete response after neoadjuvant therapy. JAMA Oncol 5:e185896, 2019
- Jones HJS, Al-Najami I, Baatrup G, Cunningham C: Local excision after (near) complete response of rectal cancer to neoadjuvant radiation: Does it add value? Int J Colorectal Dis 36:1017-1022, 2021
- Allaix ME, Arezzo A, Morino M: Transanal endoscopic microsurgery for rectal cancer: T1 and beyond? An evidence-based review. Surg Endosc 30:4841-4852, 2016
- Cancer Genome Atlas Network : Comprehensive molecular characterization of human colon and rectal cancer. Nature 487:330-337, 2012
- Xu Z, Aquina CT, Justiniano CF, et al. : Centralizing rectal cancer surgery: What is the impact of travel on patients? Dis Colon Rectum 63:319-325, 2020
- Brady JT, Xu Z, Scarberry KB, et al. : Evaluating the current status of rectal cancer care in the US: Where we stand at the start of the commission on cancer's National Accreditation Program for Rectal Cancer. J Am Coll Surg 226:881-890, 2018. [Erratum: J Am Coll Surg 227:484-487, 2018]
Source: PubMed