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Published in: International Journal of Colorectal Disease 6/2018

01-06-2018 | Original Article

Do clinical criteria reflect pathologic complete response in rectal cancer following neoadjuvant therapy?

Authors: Aurelie Garant, Livia Florianova, Adrian Gologan, Alan Spatz, Julio Faria, Nancy Morin, Carol-Ann Vasilevsky, Te Vuong

Published in: International Journal of Colorectal Disease | Issue 6/2018

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Abstract

Background

Clinical complete response (cCR) in rectal cancer is being evaluated as a tool to identify patients who would not require surgery in the curative management of rectal cancer. Our study reviews mucosal changes after neoadjuvant therapy for rectal cancer in patients treated at our center.

Methods

Pathology reports were retrieved for patients treated with neoadjuvant chemoradiation therapy (CRT) or high-dose rate brachytherapy (HDRBT). The macroscopic appearance of the specimen was compared with pathologic staging.

Results

This study included 282 patients: 88 patients underwent neoadjuvant CRT and 194 patients underwent HDRBT; all patients underwent total mesorectal excision (TME). There were 160 male and 122 female patients with a median age of 65 years (range 29–87). The median time between neoadjuvant therapy and surgery was 50 and 58 days. Sixty patients (21.2%) were staged as ypT0N0, 21.2% had a pathologic complete response (pCR), and only 3.2% had a cCR. Of the 67 patients with initial involvement of the circumferential radial margin (CRM), 44 converted to pathologic CRM−. Two hundred seventy-three patients (96.8%) had mucosal abnormalities. Of the 222 patients with residual tumor, 70 patients had no macroscopic tumor visualized but an ulcer in its place.

Conclusion

Most patients undergoing neoadjuvant therapy for rectal cancer have residual mucosal abnormalities which preclude to a cCR as per published criteria from Brazil. Further studies are required to optimize clinical evaluation and MRI imaging in selected patients.
Literature
1.
go back to reference Glynne-Jones R, Hughes R (2012) Critical appraisal of the ‘wait and see’ approach in rectal cancer for clinical complete responders after chemoradiation. Br J Surg 99(7):897–909CrossRefPubMed Glynne-Jones R, Hughes R (2012) Critical appraisal of the ‘wait and see’ approach in rectal cancer for clinical complete responders after chemoradiation. Br J Surg 99(7):897–909CrossRefPubMed
2.
go back to reference Habr-Gama A et al (2004) Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg 240(4):711–718PubMedPubMedCentral Habr-Gama A et al (2004) Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg 240(4):711–718PubMedPubMedCentral
3.
go back to reference Maas M, Beets-Tan RGH, Lambregts DMJ, Lammering G, Nelemans PJ, Engelen SME, van Dam RM, Jansen RLH, Sosef M, Leijtens JWA, Hulsewé KWE, Buijsen J, Beets GL (2011) Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol 29(35):4633–4640CrossRefPubMed Maas M, Beets-Tan RGH, Lambregts DMJ, Lammering G, Nelemans PJ, Engelen SME, van Dam RM, Jansen RLH, Sosef M, Leijtens JWA, Hulsewé KWE, Buijsen J, Beets GL (2011) Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol 29(35):4633–4640CrossRefPubMed
4.
go back to reference Smith F, Waldron D, Winter D (2010) Rectum-conserving surgery in the era of chemoradiotherapy. Br J Surg 97(12):1752–1764CrossRefPubMed Smith F, Waldron D, Winter D (2010) Rectum-conserving surgery in the era of chemoradiotherapy. Br J Surg 97(12):1752–1764CrossRefPubMed
5.
go back to reference Smith JD, Ruby JA, Goodman KA, Saltz LB, Guillem JG, Weiser MR, Temple LK, Nash GM, Paty PB (2012) Nonoperative management of rectal cancer with complete clinical response after neoadjuvant therapy. Ann Surg 256(6):965–972CrossRefPubMed Smith JD, Ruby JA, Goodman KA, Saltz LB, Guillem JG, Weiser MR, Temple LK, Nash GM, Paty PB (2012) Nonoperative management of rectal cancer with complete clinical response after neoadjuvant therapy. Ann Surg 256(6):965–972CrossRefPubMed
6.
go back to reference Glynne-Jones R, Hughes R (2016) Complete response after chemoradiotherapy in rectal cancer (watch-and-wait): have we cracked the code? Clin Oncol (R Coll Radiol) 28(2):152–160CrossRef Glynne-Jones R, Hughes R (2016) Complete response after chemoradiotherapy in rectal cancer (watch-and-wait): have we cracked the code? Clin Oncol (R Coll Radiol) 28(2):152–160CrossRef
7.
go back to reference Habr-Gama A, Perez RO, Wynn G, Marks J, Kessler H, Gama-Rodrigues J (2010) Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: characterization of clinical and endoscopic findings for standardization. Dis Colon Rectum 53(12):1692–1698CrossRefPubMed Habr-Gama A, Perez RO, Wynn G, Marks J, Kessler H, Gama-Rodrigues J (2010) Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: characterization of clinical and endoscopic findings for standardization. Dis Colon Rectum 53(12):1692–1698CrossRefPubMed
8.
go back to reference Nahas SC, Rizkallah Nahas CS, Sparapan Marques CF, Ribeiro U Jr, Cotti GC, Imperiale AR, Capareli FC, Chih Chen AT, Hoff PM, Cecconello I (2016) Pathologic complete response in rectal cancer: can we detect it? Lessons learned from a proposed randomized trial of watch-and-wait treatment of rectal cancer. Dis Colon Rectum 59(4):255–263CrossRefPubMed Nahas SC, Rizkallah Nahas CS, Sparapan Marques CF, Ribeiro U Jr, Cotti GC, Imperiale AR, Capareli FC, Chih Chen AT, Hoff PM, Cecconello I (2016) Pathologic complete response in rectal cancer: can we detect it? Lessons learned from a proposed randomized trial of watch-and-wait treatment of rectal cancer. Dis Colon Rectum 59(4):255–263CrossRefPubMed
9.
go back to reference Smith FM, Winter D (2014) Watch and wait for rectal cancer: where are we really at? Color Dis 16(5):332–334CrossRef Smith FM, Winter D (2014) Watch and wait for rectal cancer: where are we really at? Color Dis 16(5):332–334CrossRef
10.
go back to reference Nout RA, Devic S, Niazi T, Wyse J, Boutros M, Pelsser V, Vuong T (2016) CT-based adaptive high-dose-rate endorectal brachytherapy in the preoperative treatment of locally advanced rectal cancer: technical and practical aspects. Brachytherapy 15(4):477–484CrossRefPubMed Nout RA, Devic S, Niazi T, Wyse J, Boutros M, Pelsser V, Vuong T (2016) CT-based adaptive high-dose-rate endorectal brachytherapy in the preoperative treatment of locally advanced rectal cancer: technical and practical aspects. Brachytherapy 15(4):477–484CrossRefPubMed
11.
12.
go back to reference Vuong T, Devic S, Podgorsak E (2007) High dose rate endorectal brachytherapy as a neoadjuvant treatment for patients with resectable rectal cancer. Clin Oncol 19(9):701–705CrossRef Vuong T, Devic S, Podgorsak E (2007) High dose rate endorectal brachytherapy as a neoadjuvant treatment for patients with resectable rectal cancer. Clin Oncol 19(9):701–705CrossRef
13.
go back to reference Vuong T, Niazi T, Devic S (2015) Role of endoluminal brachytherapy for rectal cancer: current status and challenges. Radiother Oncol 115:S111–S112CrossRef Vuong T, Niazi T, Devic S (2015) Role of endoluminal brachytherapy for rectal cancer: current status and challenges. Radiother Oncol 115:S111–S112CrossRef
14.
go back to reference Smith FM, Chang KH, Sheahan K, Hyland J, O'Connell PR, Winter DC (2012) The surgical significance of residual mucosal abnormalities in rectal cancer following neoadjuvant chemoradiotherapy. Br J Surg 99(7):993–1001CrossRefPubMed Smith FM, Chang KH, Sheahan K, Hyland J, O'Connell PR, Winter DC (2012) The surgical significance of residual mucosal abnormalities in rectal cancer following neoadjuvant chemoradiotherapy. Br J Surg 99(7):993–1001CrossRefPubMed
15.
go back to reference Maas M, Lambregts DMJ, Nelemans PJ, Heijnen LA, Martens MH, Leijtens JWA, Sosef M, Hulsewé KWE, Hoff C, Breukink SO, Stassen L, Beets-Tan RGH, Beets GL (2015) 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 22(12):3873–3880CrossRefPubMedPubMedCentral Maas M, Lambregts DMJ, Nelemans PJ, Heijnen LA, Martens MH, Leijtens JWA, Sosef M, Hulsewé KWE, Hoff C, Breukink SO, Stassen L, Beets-Tan RGH, Beets GL (2015) 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 22(12):3873–3880CrossRefPubMedPubMedCentral
16.
go back to reference Weiser MR, Gollub MJ, Saltz LB (2015) Assessment of clinical complete response after chemoradiation for rectal cancer with digital rectal examination, endoscopy, and MRI. Ann Surg Oncol 22(12):3769–3771CrossRefPubMed Weiser MR, Gollub MJ, Saltz LB (2015) Assessment of clinical complete response after chemoradiation for rectal cancer with digital rectal examination, endoscopy, and MRI. Ann Surg Oncol 22(12):3769–3771CrossRefPubMed
17.
go back to reference Hovdenak N, Fajardo LF, Hauer-Jensen M (2000) Acute radiation proctitis: a sequential clinicopathologic study during pelvic radiotherapy. Int J Radiat Oncol Biol Phys 48(4):1111–1117CrossRefPubMed Hovdenak N, Fajardo LF, Hauer-Jensen M (2000) Acute radiation proctitis: a sequential clinicopathologic study during pelvic radiotherapy. Int J Radiat Oncol Biol Phys 48(4):1111–1117CrossRefPubMed
18.
go back to reference Smith FM, Wiland H, Mace A, Pai RK, Kalady MF (2014) Clinical criteria underestimate complete pathological response in rectal cancer treated with neoadjuvant chemoradiotherapy. Dis Colon Rectum 57(3):311–315CrossRefPubMed Smith FM, Wiland H, Mace A, Pai RK, Kalady MF (2014) Clinical criteria underestimate complete pathological response in rectal cancer treated with neoadjuvant chemoradiotherapy. Dis Colon Rectum 57(3):311–315CrossRefPubMed
19.
go back to reference Petrelli F, Sgroi G, Sarti E, Barni S (2016) Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies. Ann Surg 263(3):458–464CrossRefPubMed Petrelli F, Sgroi G, Sarti E, Barni S (2016) Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies. Ann Surg 263(3):458–464CrossRefPubMed
20.
go back to reference de Campos-Lobato LF, Stocchi L, da Luz Moreira A, Geisler D, Dietz DW, Lavery IC, Fazio VW, Kalady MF (2011) Pathologic complete response after neoadjuvant treatment for rectal cancer decreases distant recurrence and could eradicate local recurrence. Ann Surg Oncol 18(6):1590–1598CrossRefPubMed de Campos-Lobato LF, Stocchi L, da Luz Moreira A, Geisler D, Dietz DW, Lavery IC, Fazio VW, Kalady MF (2011) Pathologic complete response after neoadjuvant treatment for rectal cancer decreases distant recurrence and could eradicate local recurrence. Ann Surg Oncol 18(6):1590–1598CrossRefPubMed
21.
go back to reference Tulchinsky H, Shmueli E, Figer A, Klausner JM, Rabau M (2008) An interval >7 weeks between neoadjuvant therapy and surgery improves pathologic complete response and disease-free survival in patients with locally advanced rectal cancer. Ann Surg Oncol 15(10):2661–2667CrossRefPubMed Tulchinsky H, Shmueli E, Figer A, Klausner JM, Rabau M (2008) An interval >7 weeks between neoadjuvant therapy and surgery improves pathologic complete response and disease-free survival in patients with locally advanced rectal cancer. Ann Surg Oncol 15(10):2661–2667CrossRefPubMed
22.
go back to reference Lambregts DM et al (2011) Long-term follow-up features on rectal MRI during a wait-and-see approach after a clinical complete response in patients with rectal cancer treated with chemoradiotherapy. Dis Colon Rectum 54(12):1521–1528CrossRefPubMed Lambregts DM et al (2011) Long-term follow-up features on rectal MRI during a wait-and-see approach after a clinical complete response in patients with rectal cancer treated with chemoradiotherapy. Dis Colon Rectum 54(12):1521–1528CrossRefPubMed
23.
go back to reference Beets GL, Figueiredo NL, Habr-Gama A, van de Velde CJH (2015) A new paradigm for rectal cancer: organ preservation: introducing the International Watch & Wait Database (IWWD). Eur J Surg Oncol 41(12):1562–1564CrossRefPubMed Beets GL, Figueiredo NL, Habr-Gama A, van de Velde CJH (2015) A new paradigm for rectal cancer: organ preservation: introducing the International Watch & Wait Database (IWWD). Eur J Surg Oncol 41(12):1562–1564CrossRefPubMed
24.
go back to reference Smith JJ et al (2015) Organ preservation in rectal adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management. BMC Cancer 15:767CrossRefPubMedPubMedCentral Smith JJ et al (2015) Organ preservation in rectal adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management. BMC Cancer 15:767CrossRefPubMedPubMedCentral
25.
go back to reference Appelt AL, Pløen J, Harling H, Jensen FS, Jensen LH, Jørgensen JCR, Lindebjerg J, Rafaelsen SR, Jakobsen A (2015) High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol 16(8):919–927CrossRefPubMed Appelt AL, Pløen J, Harling H, Jensen FS, Jensen LH, Jørgensen JCR, Lindebjerg J, Rafaelsen SR, Jakobsen A (2015) High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol 16(8):919–927CrossRefPubMed
26.
go back to reference Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, Kumar AS, Oommen S, Coutsoftides T, Hunt SR, Stamos MJ, Ternent CA, Herzig DO, Fichera A, Polite BN, Dietz DW, Patil S, Avila K, Timing of Rectal Cancer Response to Chemoradiation Consortium (2015) Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol 16(8):957–966CrossRefPubMedPubMedCentral Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, Kumar AS, Oommen S, Coutsoftides T, Hunt SR, Stamos MJ, Ternent CA, Herzig DO, Fichera A, Polite BN, Dietz DW, Patil S, Avila K, Timing of Rectal Cancer Response to Chemoradiation Consortium (2015) Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol 16(8):957–966CrossRefPubMedPubMedCentral
27.
go back to reference Smith JJ, Chow OS, Eaton A, Widmar M, Nash GM, Temple LKF, Guillem JG, Weiser MR, Goodman KA, Cercek A, Saltz L, Gollub MJ, Gonen M, Garcia-Aguilar J, Paty P (2015) Organ preservation in patients with rectal cancer with clinical complete response after neoadjuvant therapy. Am Soc Clin Oncol 33:509CrossRef Smith JJ, Chow OS, Eaton A, Widmar M, Nash GM, Temple LKF, Guillem JG, Weiser MR, Goodman KA, Cercek A, Saltz L, Gollub MJ, Gonen M, Garcia-Aguilar J, Paty P (2015) Organ preservation in patients with rectal cancer with clinical complete response after neoadjuvant therapy. Am Soc Clin Oncol 33:509CrossRef
28.
go back to reference Renehan AG, Malcomson L, Emsley R, Gollins S, Maw A, Myint AS, Rooney PS, Susnerwala S, Blower A, Saunders MP, Wilson MS, Scott N, O'Dwyer ST (2016) Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis. Lancet Oncol 17(2):174–183CrossRefPubMed Renehan AG, Malcomson L, Emsley R, Gollins S, Maw A, Myint AS, Rooney PS, Susnerwala S, Blower A, Saunders MP, Wilson MS, Scott N, O'Dwyer ST (2016) Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis. Lancet Oncol 17(2):174–183CrossRefPubMed
29.
go back to reference Dossa F, Chesney TR, Acuna SA, Baxter NN (2017) A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2(7):501–513CrossRefPubMed Dossa F, Chesney TR, Acuna SA, Baxter NN (2017) A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2(7):501–513CrossRefPubMed
30.
go back to reference Nelson H, Machairas N, Grothey A (2017) Evidence in favor of standard surgical treatment for rectal cancer. JAMA Oncol 3(7):885–886CrossRefPubMed Nelson H, Machairas N, Grothey A (2017) Evidence in favor of standard surgical treatment for rectal cancer. JAMA Oncol 3(7):885–886CrossRefPubMed
Metadata
Title
Do clinical criteria reflect pathologic complete response in rectal cancer following neoadjuvant therapy?
Authors
Aurelie Garant
Livia Florianova
Adrian Gologan
Alan Spatz
Julio Faria
Nancy Morin
Carol-Ann Vasilevsky
Te Vuong
Publication date
01-06-2018
Publisher
Springer Berlin Heidelberg
Published in
International Journal of Colorectal Disease / Issue 6/2018
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-018-3033-7

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