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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 4/2016

01-04-2016 | Colorectal Cancer

Predictors of Pathologic Complete Response Following Neoadjuvant Chemoradiotherapy for Rectal Cancer

Authors: Eisar Al-Sukhni, MD, MSc, Kristopher Attwood, PhD, David M. Mattson, MD, Emmanuel Gabriel, MD, PhD, Steven J. Nurkin, MD, MS

Published in: Annals of Surgical Oncology | Issue 4/2016

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Abstract

Background

Some patients with rectal cancer who receive neoadjuvant chemoradiotherapy (nCRT) achieve a pathologic complete response (pCR) and may be eligible for less radical surgery or non-operative management. The aim of this study was to identify variables that predict pCR after nCRT for rectal cancer and to examine the impact of pCR on postoperative complications.

Methods

A retrospective review was performed of the NCDB from 2006 to 2011. Patients with rectal cancer who received nCRT followed by radical resection were included in this study. Multivariable analysis of the association between clinicopathologic characteristics and pCR was performed, and propensity-adjusted analysis was used to identify differences in postoperative morbidity between pCR and non-pCR patients.

Results

A total of 23,747 patients were included in the study. Factors associated with pCR included lower tumor grade, lower clinical T and N stage, higher radiation dose, and delaying surgery by more than 6–8 weeks after the end of radiation, while lack of health insurance was linked with a lower likelihood of pCR. Complete response was not associated with an increased risk of major postoperative complications.

Conclusions

Several clinical, pathologic, and treatment variables can help to predict which patients are most likely to have pCR after nCRT for rectal cancer. Awareness of these variables can be valuable in counseling patients regarding prognosis and treatment options.
Literature
1.
Maas M, Melemans 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.CrossRefPubMed
2.
Zorcolo L, Rosman AS, Restivo A, et al. Complete pathologic response after combined modality treatment for rectal cancer and long-term survival: a meta-analysis. Ann Surg Oncol. 2012;19:2822–32.CrossRefPubMed
3.
Yang TJ, Goodman KA. Predicting complete response: is there a role for non-operative management of rectal cancer? J Gastrointest Oncol. 2015;6:241–6.PubMedPubMedCentral
4.
Glynne-Jones R, Hughes R. Critical appraisal of the “wait and see” approach in rectal cancer for clinical complete responders after chemoradiation. Br J Surg. 2012;99:897–909.CrossRefPubMed
5.
Sabbaga J, Braghiroli MI, Hoff PM. Is surgery always necessary in rectal cancer? Oncology (Williston Park) 2014;28:607–11.
6.
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;53:1692–8.CrossRefPubMed
7.
Habr-Gama A, Perez RO, Nadalin W, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004;240:711–7.PubMedPubMedCentral
8.
Maas M, Beets-Tan RG, Lambregts DM, et al. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011;29:4633–40.CrossRefPubMed
9.
Smith JD, Ruby JA, Goodman KA, et al. Nonoperative management of rectal cancer with complete clinical response after neoadjuvant therapy. Ann Surg. 2012;256:965–72.CrossRefPubMed
10.
Dalton RSJ, Velineni R, Osborne ME, et al. A single-centre experience of chemoradiotherapy for rectal cancer: is there potential for nonoperative management? Colorectal Dis. 2012;14:567–71.CrossRefPubMed
11.
Smith RK, Fry RD, Mahmoud NN, Carter Paulson E. Surveillance after neoadjuvant therapy in advanced rectal cancer with complete clinical response can have comparable outcomes to total mesorectal excision. Int J Colorectal Dis. 2015;30:769–74.CrossRefPubMed
12.
Hiotis SP, Weber SM, Cohen AM, et al. Assessing the predictive value of clinical complete response to neoadjuvant therapy for rectal cancer: an analysis of 488 patients. J Am Coll Surg. 2002;194:131–5.CrossRefPubMed
13.
Zmora O, Dasilva GM, Gurland B, et al. Does rectal wall tumor eradication with preoperative chemoradiation permit a change in the operative strategy? Dis Colon Rectum. 2004;47:1607–12.CrossRefPubMed
14.
Stipa F, Zernecke A, Moore HG, et al. Residual mesorectal lymph node involvement following neoadjuvant combined-modality therapy: rationale for radical resection? Ann Surg Oncol. 2004;11:187–91.CrossRefPubMed
15.
Pucciarelli S, Capirci C, Emanuele U, et al. Relationship between pathologic T-stage and nodal metastasis after preoperative chemoradiotherapy for locally advanced rectal cancer. Ann Surg Oncol. 2005;12:111–6.CrossRefPubMed
16.
Yeo SG, Kim DY, Kim TH, et al. Pathologic complete response of primary tumor following preoperative chemoradiotherapy for locally advanced rectal cancer: long-term outcomes and prognostic significance of pathologic nodal status. Ann Surg. 2010;252:998–1004.CrossRefPubMed
17.
Yoon SM, Kim DY, Kim TH, et al. Clinical parameters predicting pathologic tumor response after preoperative chemoradiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys. 2007;69:1167–72.CrossRefPubMed
18.
Das P, Skibber JM, Rodriguez-Bigas MA, et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer. 2007;109:1750–5.CrossRefPubMed
19.
Tulchinsky H, Shmueli E, Figer A, Klausner JM, Rabau M. 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. 2008;15:2661–7.CrossRefPubMed
20.
Kalady MF, de Campos-Lobato LF, Stocchi L, et al. Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann Surg. 2009;250:582–9.PubMed
21.
Lee JH, Kim SH, Kim JG, Cho HM, Shim BY. Preoperative chemoradiotherapy (CRT) followed by laparoscopic surgery for rectal cancer: predictors of the tumor response and the long-term oncologic outcomes. Int J Radiat Oncol Biol Phys. 2011;81:431–8.CrossRefPubMed
22.
Park CH, Kim HV, Cho YB, et al. Predicting tumor response after preoperative chemoradiation using clinic parameters in rectal cancer. World J Gastroenterol. 2011;17:5310–6.CrossRefPubMedPubMedCentral
23.
Wolthuis AM, Penninckx F, Haustermans K, et al. Impact of interval between neoadjuvant chemoradiotherapy and TME for locally advanced rectal cancer on pathologic response and oncologic outcome. Ann Surg Oncol 2012;19:2833–41.CrossRefPubMed
24.
Choi CH, Kim WD, Lee SJ, Park WY. Clinical predictive factors of pathologic tumor response after preoperative chemoradiotherapy in rectal cancer. Radiat Oncol J. 2012;30:99–107.CrossRefPubMedPubMedCentral
25.
Arbea L, Martinez-Monge R, Diaz-Gonzalez JA, et al. Four-week neoadjuvant intensity-modulated radiation therapy with concurrent capecitabine and oxaliplatin in locally advanced rectal cancer patients: a validation phase II trial. Int J Radiat Oncol Biol Phys. 2012;83:587–93.CrossRefPubMed
26.
Wallin U, Rothenberger D, Lowry A, Luepker R, Mellgren A. CEA: a predictor for pathologic complete response after neoadjuvant therapy for rectal cancer. Dis Colon Rectum. 2013;56:859–68.CrossRefPubMed
27.
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.CrossRefPubMed
28.
Huh JW, Kim HR, Kim YJ. Clinical prediction of pathological complete response after preoperative chemoradiotherapy for rectal cancer. Dis Colon Rectum. 2013;56:698–703.CrossRefPubMed
29.
Yang KL, Yang SH, Liang WY, et al. Carcinoembryonic antigen (CEA) level, CEA ratio, and treatment outcome of rectal cancer patients receiving pre-operative chemoradiation and surgery. Radiat Oncol. 2013;8:43.CrossRefPubMedPubMedCentral
30.
Russo AL, Ryan DP, Borger DR, et al. Mutational and clinical predictors of pathologic complete response in the treatment of locally advanced rectal cancer. J Gastrointest Cancer. 2014;45:34–9.CrossRefPubMedPubMedCentral
31.
Garland ML, Vather R, Bunkley N, Pearse M, Bissett IP. Clinical tumor size and nodal status predict pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer. Int J Colorectal Dis. 2014;29:301–7.CrossRefPubMed
32.
Zeng WG, Zhou ZX, Liang JW, et al. Impact of interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer on surgical and oncologic outcome. J Surg Oncol. 2014;110:463–7.CrossRefPubMed
33.
Zhu J, Liu F, Gu W, et al. Concomitant boost IMRT-based neoadjuvant chemoradiotherapy for clinical stage II/III rectal adenocarcinoma: results of a phase II study. Radiat Oncol. 2014;9:70.CrossRefPubMedPubMedCentral
34.
Burbach JP, den Harder AM, Intven M, van Vulpen M, Verkooijen HM, Reerink O. Impact of radiotherapy boost on pathological complete response in patient with locally advanced rectal cancer: a systematic review and meta-analysis. Radiother Oncol. 2014;113:1–9.CrossRefPubMed
35.
Kleiman A, Al-Khamis A, Farsi A, et al. Normalization of CEA levels post-neoadjuvant therapy is a strong predictor of pathologic complete response in rectal cancer. J Gastrointest Surg. 2015;19:1106–12.CrossRefPubMed
36.
Elmessiry MM, Abouelnagah GM, Elzeiny MM, et al. Predictors of tumor response to neoadjuvant chemoradiation in locally advanced rectal cancer Egyptian patients. Arch Clin Exp Surg. 2015;4:21–8.
37.
Park YA, Sohn SK, Seong J, et al. Serum CEA as a predictor for the response to preoperative chemoradiation in rectal cancer. J Surg Oncol. 2006;93:145–50.CrossRefPubMed
38.
Kim IY, You SH, Kim YW. Neutrophil-lymphocyte ratio predicts pathologic tumor response and survival after preoperative chemoradiation for rectal cancer. BMC Surg. 2014;14:94.CrossRefPubMedPubMedCentral
39.
Monson JR, Weiser MR, Buie WD, et al. Standards Practice Task Force of the American Society of Colon and Rectal Surgeons. Practice parameters for the management of rectal cancer (revised). Dis Colon Rectum. 2013;56:535–50.CrossRefPubMed
40.
Evans J, Tait D, Swift I, et al. Timing of surgery following preoperative therapy in rectal cancer: the need for a prospective randomized trial? Dis Colon Rectum. 2011;54:1251–9.CrossRefPubMed
41.
Petrelli F, Sgroi G, Sarti E, Barni S. Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies. Ann Surg. 2013. doi:10.​1097/​SLA.​0000000000000368​.
42.
Probst CP, Becerra AZ, Aquina CT, et al. Extended intervals after neoadjuvant therapy in locally advanced rectal cancer: the key to improved tumor response and potential organ preservation. J Am Coll Surg. 2015;221:430–40.
43.
Deng Y, Chi, P, Lan P, et al. A multi-center randomized controlled trial of mFOLFOX6 with or without radiation in neoadjuvant treatment of local advanced rectal cancer (FOWARC study): preliminary results [abstract no. 3500]. J Clin Oncol. 2015;33(15 Suppl).
44.
Chan AK, Wong AO, Langevin J, et al. Preoperative chemotherapy and pelvic radiation for tethered or fixed rectal cancer: a phase II dose escalation study. Int J Radiat Oncol Biol Phys. 2000;48:843–56.CrossRefPubMed
45.
Overgaard M, Overgaard J, Sell A. Dose-resposne relationship for radiation therapy of recurrent, residual, and primarily inoperable colorectal cancer. Radiother Oncol. 1984;217–25.
46.
Wiltshire KL, Ward IG, Swallow C, et al. Preoperative radiation with concurrent chemotherapy for resectable rectal cancer: effect of dose escalation on pathologic complete response, local recurrence-free survival, disease-free survival, and overall survival. Int J Radiat Oncol Biol Phys. 2006;64:709–16.CrossRefPubMed
47.
48.
Parekh A, Truong MT, Pashtan I, et al. Acute gastrointestinal toxicity and tumor response with preoperative intensity modulated radiation therapy for rectal cancer. Gastrointest Cancer Res. 2013;6:137–43.PubMedPubMedCentral
49.
Jabbour SK, Patel S, Herman JM, et al. Intensity-modulated radiation therapy for rectal carcinoma can reduce treatment breaks and emergency department visits. Int J Surg Oncol. 2012;2012:891067.PubMedPubMedCentral
50.
Samuelian JM, Callister MD, Ashman JB, Young-Fadok TM, Borad MJ, Gunderson LL. Reduced acute bowel toxicity in patients treated with intensity-modulated radiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys. 2012;82:1981–7.CrossRefPubMed
51.
Rosenberg AR, Kroon L, Chen L, Li CI, Jones B. Insurance status and risk of cancer mortality among adolescents and young adults. Cancer. 2015;121:1279–86.CrossRefPubMed
52.
53.
Ayanian JZ, Kohler BA, Abe T, Epstein AM. The relation between health insurance coverage and clinical outcomes among women with breast cancer. N Engl J Med. 1993;329:326–31.CrossRefPubMed
54.
Robbins AS, Payluck AL, Fedewa SA, Chen AY, Ward EM. Insurance status, comorbidity level, and survival among colorectal cancer patients age 18 to 64 years in the National Cancer Data Base from 2003 to 2005. J Clin Oncol. 2009;27:3627–33.CrossRefPubMed
55.
Horisberger K, Hofheinz RD, Palma P, et al. Tumor response to neoadjuvant chemoradiation in rectal cancer: predictor for surgical morbidity? Int J Colorectal Dis. 2008;23:257–64.CrossRefPubMed
56.
Stelzmueller I, Zitt M, Aigner F, et al. Postoperative morbidity following chemoradiation for locally advanced low rectal cancer. J Gastrointest Surg. 2009;13:657–67.CrossRefPubMed
57.
Maggiori L, Bretagnol F, Aslam MI, et al. Does pathologic response of rectal cancer influence postoperative morbidity after neoadjuvant radiochemotherapy and total mesorectal excision? Surgery. 2014;155:468–75.CrossRefPubMed
58.
Duldulao MP, Lee W, Le M, et al. Surgical complication and pathologic complete response after neoadjuvant chemoradiation in locally advanced rectal cancer. Am Surg. 2011;77:1281–5.PubMed
59.
Berkel AE, Woutersen DP, van der Palen J, Klaase JM. Prognostic factors for postoperative morbidity and tumor response after neoadjuvant chemoradiation followed by resection for rectal cancer. J Gastrointest Surg. 2014;18:1648–57.CrossRefPubMed
Metadata
Title
Predictors of Pathologic Complete Response Following Neoadjuvant Chemoradiotherapy for Rectal Cancer
Authors
Eisar Al-Sukhni, MD, MSc
Kristopher Attwood, PhD
David M. Mattson, MD
Emmanuel Gabriel, MD, PhD
Steven J. Nurkin, MD, MS
Publication date
01-04-2016
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 4/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-5017-y

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