Advertisement

Feasibility study of a Response Surveillance Program in locally advanced mid and low rectal cancer to increase organ preservation

Published:August 30, 2022DOI:https://doi.org/10.1016/j.ejso.2022.08.031

      Abstract

      Background

      Assessment of tumor response in rectal cancer after neoadjuvant treatment by MRI (Tumour Regression Grade, TRG 1–5) is well standardized. The overall timing and method of defining complete response (cCR) remain controversial. The aim of this work was to evaluate the feasibility of a defined Response Surveillance Program (RSP) to increase organ preservation for locally advanced rectal cancer after neoadjuvant treatment.

      Methods

      A standardized program of clinical (CR), radiological (RR) and metabolic (MR) assessment of tumor response is defined over a 6 month period from completion of NACRT with formal assessment performed every 2 months (M). Patients with TRG1-3 at M2 and TRG1-2 at M4 continue in the program up to M6 assessment. Patients managed with this protocol from 2016 to 2020 were analyzed. The primary endpoint was rectal preservation rate. Secondary endpoints included disease-free survival and overall survival at 3 years.

      Result

      314 potentially suitable patients were enrolled in the RSP and 50 patients completed the six month program and were successfully enrolled into watch and wait. Fourteen (28%) were T2 tumor stage, 27 (54%) T3 and nine (18%) were T4. During watch and wait, patients with locoregional recurrence (n = 11) were treated with local excision (n = 3), endocavitary radiotherapy (n = 1), TME (n = 5) and APR (n = 2). With a median follow-up of 32 months, the rectal preservation rate was 88%, with a 3-year disease-free survival of 67% and an overall survival of 98%.

      Conclusion

      This study validates the feasibility of the practical implementation of a Response Surveillance Program to increase organ preservation rates without compromising oncological outcomes in rectal cancer.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Surgical Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Conroy T.
        • Bosset J.-F.
        • Etienne P.-L.
        • Rio E.
        • Francois E.
        • Mesgouez-Nebout N.
        • et al.
        Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial.
        Lancet Oncol. 2021; 22: 702-715
        • Rullier E.
        • Rouanet P.
        • Tuech J.-J.
        • Valverde A.
        • Lelong B.
        • Rivoire M.
        • et al.
        Organ preservation for rectal cancer (GRECCAR 2): a prospective, randomised, open-label, multicentre, phase 3 trial.
        Lancet. 2017; 390: 469-479
        • Martin S.T.
        • Heneghan H.M.
        • Winter D.C.
        Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer.
        Br J Surg. 2012; 99: 918-928
        • Garcia-Aguilar J.
        • Renfro L.A.
        • Chow O.S.
        • Shi Q.
        • Carrero X.W.
        • Lynn P.B.
        • et al.
        Organ preservation for clinical T2N0 distal rectal cancer using neoadjuvant chemoradiotherapy and local excision (ACOSOG Z6041): results of an open-label, single-arm, multi-institutional, phase 2 trial.
        Lancet Oncol. 2015; 16: 1537-1546
        • Habr-Gama A.
        • São Julião G.P.
        • Fernandez L.M.
        • Vailati B.B.
        • Andrade A.
        • Araújo S.E.
        • et al.
        Achieving a complete clinical response after neoadjuvant chemoradiation that does not require surgical resection: it may take longer than you think.
        Dis Colon Rectum. 2019; 62: 802-808
        • Maas M.
        • Beets-Tan R.G.H.
        • Lambregts D.M.J.
        • Lammering G.
        • Nelemans P.J.
        • Engelen S.M.E.
        • et al.
        Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer.
        J Clin Oncol. 2011; 29: 4633-4640
        • Battersby N.J.
        • Dattani M.
        • Rao S.
        • Cunningham D.
        • Tait D.
        • Adams R.
        • et al.
        A rectal cancer feasibility study with an embedded phase III trial design assessing magnetic resonance tumour regression grade (mrTRG) as a novel biomarker to stratify management by good and poor response to chemoradiotherapy (TRIGGER): study protocol for a randomised controlled trial.
        Trials. 2017; 18: 394
        • Fokas E.
        • Appelt A.
        • Glynne-Jones R.
        • Beets G.
        • Perez R.
        • Garcia-Aguilar J.
        • et al.
        International consensus recommendations on key outcome measures for organ preservation after (chemo)radiotherapy in patients with rectal cancer.
        Nat Rev Clin Oncol. 2021; 18: 805-816
        • James R.D.
        • Glynne-Jones R.
        • Meadows H.M.
        • Cunningham D.
        • Sun Myint A.
        • Saunders M.P.
        • et al.
        Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2×2 factorial trial.
        Lancet Oncol. 2013; 14: 516-524
        • Patel U.B.
        • Taylor F.
        • Blomqvist L.
        • George C.
        • 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. 2011; 29: 3753-3760
        • Patel U.B.
        • Brown G.
        • Rutten H.
        • West N.
        • Sebag-Montefiore D.
        • Glynne-Jones R.
        • et al.
        Comparison of magnetic resonance imaging and histopathological response to chemoradiotherapy in locally advanced rectal cancer.
        Ann Surg Oncol. 2012; 19: 2842-2852
        • Rouanet P.
        • Bertrand M.M.
        • Jarlier M.
        • Mourregot A.
        • Traore D.
        • Taoum C.
        • et al.
        Robotic versus laparoscopic total mesorectal excision for sphincter-saving surgery: results of a single-center series of 400 consecutive patients and perspectives.
        Ann Surg Oncol. 2018; 25: 3572-3579
        • Dames N.B.
        • Squire S.E.
        • Devlin A.B.
        • Fish R.
        • Bisset C.N.
        • Tozer P.
        • et al.
        Let’s talk about sex”: a patient-led survey on sexual function after colorectal and pelvic floor surgery.
        Colorectal Dis. 2021; 23: 1524-1551
        • Shiraishi T.
        • Ito M.
        • Sasaki T.
        • Nishizawa Y.
        • Tsukada Y.
        • Ikeda K.
        Association between urinary function and resected pattern of the autonomic nerve system after transanal total mesorectal excision for rectal cancer.
        Colorectal Dis. 2021; 23: 405-414
        • Lemini R.
        • Jabbal I.S.
        • Stanek K.
        • Borkar S.R.
        • Spaulding A.C.
        • Kelley S.R.
        • et al.
        Permanent stoma: a quality outcome in treatment of rectal cancer and its impact on length of stay.
        BMC Surg. 2021; 21: 163
        • Habr-Gama A.
        • Perez R.O.
        • Nadalin W.
        • Sabbaga J
        • Ribeiro Jr U
        • Silva e Sousa Jr A.H.
        • et al.
        Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results.
        Ann Surg. 2004; 240 (; discussion 717-718): 711-717
        • Martens M.H.
        • Maas M.
        • Heijnen L.A.
        • Lambregts D.M.J.
        • Leijtens J.W.A.
        • Stassen L.P.S.
        • et al.
        Long-term outcome of an organ preservation program after neoadjuvant treatment for rectal cancer.
        J Natl Cancer Inst. 2016; 108: djw171
        • Rombouts A.J.M.
        • Al-Najami I.
        • Abbott N.L.
        • Appelt A.
        • Baatrup G.
        • Bach S.
        • et al.
        Can we Save the rectum by watchful waiting or TransAnal microsurgery following (chemo) Radiotherapy versus Total mesorectal excision for early REctal Cancer (STAR-TREC study)?: protocol for a multicentre, randomised feasibility study.
        BMJ Open. 2017; 7e019474
        • Guillem J.G.
        • Chessin D.B.
        • Shia J.
        • Moore H.G.
        • Mazumdar M.
        • Bernard B.
        • et al.
        Clinical examination following preoperative chemoradiation for rectal cancer is not a reliable surrogate end point.
        J Clin Oncol. 2005; 23: 3475-3479
        • Barbaro B.
        • Fiorucci C.
        • Tebala C.
        • Valentini V.
        • Gambacorta M.A.
        • Vecchio F.M.
        • et al.
        Locally advanced rectal cancer: MR imaging in prediction of response after preoperative chemotherapy and radiation therapy.
        Radiology. 2009; 250: 730-739
        • Rödel C.
        • Martus P.
        • Papadoupolos T.
        • Füzesi L.
        • Klimpfinger M.
        • Fietkau R.
        • et al.
        Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer.
        J Clin Oncol. 2005; 23: 8688-8696
        • Siddiqui M.R.S.
        • Bhoday J.
        • Battersby N.J.
        • Chand M.
        • West N.P.
        • Abulafi A.M.
        • et al.
        Defining response to radiotherapy in rectal cancer using magnetic resonance imaging and histopathological scales.
        World J Gastroenterol. 2016; 22: 8414-8434
        • Joye I.
        • Deroose C.M.
        • Vandecaveye V.
        • Haustermans K.
        The role of diffusion-weighted MRI and (18)F-FDG PET/CT in the prediction of pathologic complete response after radiochemotherapy for rectal cancer: a systematic review.
        Radiother Oncol. 2014; 113: 158-165
        • Denecke T.
        • Rau B.
        • Hoffmann K.-T.
        • Hildebrandt B.
        • Ruf J.
        • Gutberlet M.
        • et al.
        Comparison of CT, MRI and FDG-PET in response prediction of patients with locally advanced rectal cancer after multimodal preoperative therapy: is there a benefit in using functional imaging?.
        Eur Radiol. 2005; 15: 1658-1666
        • Hupkens B.J.P.
        • Maas M.
        • Martens M.H.
        • van der Sande M.E.
        • Lambregts D.M.J.
        • Breukink S.O.
        • et al.
        Organ preservation in rectal cancer after chemoradiation: should we extend the observation period in patients with a clinical near-complete response?.
        Ann Surg Oncol. 2018; 25: 197-203
        • van der Valk M.J.M.
        • Hilling D.E.
        • Bastiaannet E.
        • Meershoek-Klein Kranenbarg E.
        • Beets G.L.
        • Figueiredo N.L.
        • et al.
        Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study.
        Lancet. 2018; 391: 2537-2545
        • Bahadoer R.R.
        • Dijkstra E.A.
        • van Etten B.
        • Marijnen C.A.M.
        • Putter H.
        • Meershoek-Klein Kranenbarg E.
        • et al.
        Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial.
        Lancet Oncol. 2021; 22: 29-42
        • Garcia-Aguilar J.
        • Patil S.
        • Kim J.K.
        • Yuval J.B.
        • Thompson H.
        • Verheij F.
        • et al.
        Preliminary results of the organ preservation of rectal adenocarcinoma (OPRA) trial.
        J Clin Oncology. 2020; 38 (–4008): 4008