Abstract
Purpose
Pathologic complete response (pCR) to neoadjuvant treatment for rectal cancer has been associated with improved local control, reduced distant disease and a survival advantage when compared with non-complete responders. Approximately 10–25 % of patients undergoing neoadjuvant chemoradiotherapy for rectal cancer achieve pCR; however, predictors for its occurrence are inadequately defined. This study aimed to identify clinical and tumour factors that predict pCR in patients receiving neoadjuvant chemoradiotherapy for rectal cancer.
Methods
Consecutive rectal cancer patients diagnosed and treated in the Auckland region between 1 January 2002 and 1 February 2013 were retrospectively identified. Cases were stratified by the occurrence of pCR or non-pCR. Predictive capacity of several patient, tumour and treatment-related variables were then assessed by univariate and regression analyses.
Results
Two hundred ninety-seven patients received neoadjuvant chemoradiotherapy, of whom 34 (11.4 %) achieved pCR. There were no significant differences in age, gender, ethnicity, BMI, pretreatment clinical T or N stage, tumour distance from the anal verge, tumour differentiation, chemoradiotherapy regimen and time interval to surgery between the pCR and non-pCR groups. Univariate analysis identified pretreatment serum CEA levels, a reduction in pre- to post-treatment serum CEA and smaller tumours as significant correlates of pCR. Logistic regression analysis found smaller tumour size and pretreatment clinical N stage as independent clinical predictors for achieving pCR.
Conclusions
Smaller tumour size and pretreatment clinical N stage were independent clinical predictors for achieving pCR. Prospective analysis is recommended for more rigorous risk factor assessment.
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References
Ministry of Health (2012) Cancer: new registrations and deaths 2009. Ministry of Health, Wellington
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90
Bosset J-F, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A et al (2005) Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results—EORTC 22921. J Clin Oncol 23:5620–5627
Bosset J-F, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L et al (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355:1114–1123
Gérard J-P, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin M-T et al (2006) Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol 24:4620–4625
Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740
Aklilu M, Eng C (2011) The current landscape of locally advanced rectal cancer. Nat Rev Clin Oncol 8:649–659
Sanghera P, Wong DWY, McConkey CC, Geh JI, Hartley A (2008) Chemoradiotherapy for rectal cancer: an updated analysis of factors affecting pathological response. Clin Oncol 20:176–183
Martin ST, Heneghan HM, Winter DC (2012) Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer. Br J Surg 99:918–928
Habr-Gama A, Perez RO, Juliao GPS, Proscurshim I, Gama-Rodrigues J (2011) Nonoperative approaches to rectal cancer: a critical evaluation. Semin Radiat Oncol 21:234–239
MacGregor TP, Maughan TS, Sharma RA (2012) Pathological grading of regression following neoadjuvant chemoradiation therapy: the clinical need is now. J Clin Pathol 65:867–871
Das P, Skibber JM, Rodriguez-Bigas MA, Feig BW, Change GJ, Wolff RA et al (2007) Predictors of tumour response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer 109:1750–1755
Kalady MF, Felipe de Campos-Lobato L, Stocchi L, Geisler DP, Dietz D, Lavery IC et al (2009) Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann Surg 250:582–589
Park CH, Kim HC, Cho YB, Yun SH, Lee WY, Park YS et al (2011) Predicting tumor response after preoperative chemoradiation using clinical parameters in rectal cancer. World J Gastroenterol 17:5310–5316
Rodel C, Martus P, Papadoupolos T, Fuzesi L, Klimpfinger M, Fietkau R et al (2005) Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 23:8688–8696
Chan A, Wong A, Jenken D, Heine J, Buie D, Johnson D (2005) Posttreatment TNM staging is a prognostic indicator of survival and recurrence in tethered or fixed rectal carcinoma after preoperative chemotherapy and radiotherapy. Int J Radiat Oncol Biol Phys 61:665–677
Rodel C, Hofheinz R, Liersch T (2012) Rectal cancer: state of the art in 2012. Curr Opin Oncol 24:441–447
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 15:2661–2667
Stein DE, Mahmoud NN, Anne PR, Rose DG, Isenberg GA, Goldstein SD et al (2003) Longer time interval between completion of neoadjuvant chemoradiation and surgical resection does not improve downstaging of rectal carcinoma. Dis Colon Rectum 46:448–453
Lim S-B, Choi SH, Jeong S-Y, Kim DY, Jung KH, Hong YS et al (2008) Optimal surgery time after preoperative chemoradiotherapy for locally advanced rectal cancers. Ann Surg 248:243–251
Garcia-Aguilar J, Smith DD, Avila K, Bergsland EK, Chu P, Krieg RM (2011) Optimal timing of surgery after chemoradiation for advanced rectal cancer: preliminary results of a multi-center, non- randomized phase II prospective trial. Ann Surg 254:97–102
Song S, Hong JC, McDonnell SE, Koong AC, Minsky BD, Chang DT et al (2012) Combined modality therapy for rectal cancer: the relative value of posttreatment versus pretreatment CEA as a prognostic marker for disease recurrence. Ann Surg Oncol 19:2471–2476
Jang NY, Kang S-B, Kim D-W, Kim JH, Lee K-W, Kim IA et al (2011) The role of carcinoembryonic antigen after neoadjuvant chemoradiotherapy in patients with rectal cancer. Dis Colon Rectum 54:245–252
Kirat HT, Ozturk E, Lavery IC, Kiran RP (2012) The predictive value of preoperative carcinoembryonic antigen level in the prognosis of colon cancer. Am J Surg 204:447–452
Klessen C, Rogalla P, Taupitz M (2007) Local staging of rectal cancer: the current role of MRI. Eur Radiol 17:370–389
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 53:1692–1698
Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, Silva e Sousa AH Jr et al (2004) Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy. Ann Surg 240:711–718
Hughes R, Harrison M, Glynne-Jones R (2010) Could a wait and see policy be justified in T3/4 rectal cancers after chemo-radiotherapy? Acta Oncol 49:378–381
Acknowledgments
Mikaela Garland and Noah Bunkley are summer students funded by the University of Auckland. The authors would like to thank Avinesh Pillai (Department of Statistics, University of Auckland) for consulting as a specialist biostatistician.
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The authors have no potential conflicts of interest to declare.
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Garland, M.L., Vather, R., Bunkley, N. et al. Clinical tumour size and nodal status predict pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer. Int J Colorectal Dis 29, 301–307 (2014). https://doi.org/10.1007/s00384-013-1821-7
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DOI: https://doi.org/10.1007/s00384-013-1821-7