Abstract
Context: Multimodal therapy is the current recommended treatment of choice for rectal cancer. The downsizing effects of the neoadjuvant therapy/tumour regression can be assessed histologically in the resection specimen.
Aims: To assess the prognostic significance of pathological grade of tumour regression in rectal cancer treated with long course neoadjuvant therapy.
Settings and Design: This is a 5 year retrospective study conducted at a tertiary centre in South India.
Methods and Material: 137 patients with rectal adenocarcarcinoma pre-treated by long course neoadjuvant chemoradiation followed by surgery were analysed and categorised based on the Tumour Regression Grade(TRG) into 2 groups- Group 1(Good response, TRG 0,1) and Group 2 (Poor response, TRG 2,3). Other clinical and pathological features like lymphovascular/ perineural invasion, discontinuous extramural tumour deposits, resection margin status and pTNM stage of tumour were also evaluated and all variables along with TRG were correlated with disease progression and 5 year survival.
Statistical analysis used: IBM SPSS version 20.0 software. Categorical variables expressed using frequency and percentage and the continuous variables presented using mean and standard deviation. The chi-square test was used for finding prognostic factors. Univariate analyses of survival were carried out by Kaplan-Meier method and the evaluations of differences were performed with Log Rank test.
Results: Group 1 showed reduced risk for disease progression (p 0.01) and better mean disease free period and overall survival (p 0.017 and p <0.001 respectively). Poor tumour regression was associated with lymphovascular and perineural invasion, regional lymph node metastases (p<0.001), and advanced stage of disease, and predicted an unfavourable outcome with estimated shorter mean time until disease progression.
Conclusions: Assessment of primary tumour regression is an independent prognostic predictor. The addition of lymph node status is recommended in the pathological tumour regression grading system.
Keywords: Tumour Regression Grade; rectal cancer; neoadjuvant chemoradiotherapy; pathological complete response.
References
- Tveit, KM, Guldvog I, Hagen Set al. Randomized controlled trial of postoperative radiotherapy and short-term time-scheduled 5-fluorouracil against surgery alone in the treatment of Dukes B and C rectal cancer: Norwegian Adjuvant Rectal Cancer Project Group. Br J Surg 1997; 84(8):1130-1135.
- Gastrointestinal Tumor Study Group. Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med. 1985 Jun 6;312(23):1465-72.
- Janjan NA, Khoo VS, Abbruzzese J et al.Tumor downstaging and sphincter preservation with preoperative chemora-diation in locally advanced rectal cancer: The M.D. Anderson Cancer Center experience. Int J RadiatOncolBiol Phys 1999; 44:1027-1038.
- Theodoropoulos G, Wise WE, Padmanabhan A et al. T-level downstaging and complete pathologic response after preoperative chemoradiation for advanced rectal cancer result in decreased recurrence and improved disease-free survival. Dis ColonRectum. 2002 Jul;45(7):895-903.
- Rödel C, Martus P, Papadoupolos T, Fuzesi 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.
- Capirci C, Valentini V, Cionini Let al.Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: long–term analysis of 566 ypCR patients. Int J Radiat Oncol Biol Phys2008 ; 72(1): 99–107.
- Maas M, Nelemans 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(9):835–844.
- Kwok H, Bissett IP, Hill GL. Preoperative staging of rectal cancer. Int JColorectal 2000 Feb;15(1):9-20.
- Ryan R, Gibbons D, Hyland JMP et al.Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Histopathology2005;47(2):141-146.
- Protocol for the examination of specimens from patients with primary carcinoma of the colon and rectum 2016. College of American Pathologists, [Revised: January 28, 2016Version: 3.4.0.0]. Available from: www.cap.org/cancerprotocols.
- JS Shin, TG Tut, V Ho et al.Predictive Markers of Radiotherapy-Induced Rectal Cancer Regression. J Clin Pathol 2014; 67(10):859-864.
- Janjan NA, Crane C, Feig BW et al. Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer. Am J Clin Oncol 2001; 24:107–112.
- Janjan NA, Khoo VS, Abbruzzese J et al. Tumor downstaging and sphincter preservation with preoperative chemorad-iation in locally advanced rectal cancer: the M.D. Anderson Cancer center experience. Int J Radiat Oncol Biol Phys 1999; 44:1027–1038
- Mohiuddin M, Regine WF, John WJ et al. Preoperative chemoradiation in fixed distal rectal cancer: Dose time factors for pathological complete response. Int J Radiat Oncol Biol Phys 2000; 46(4):883-888
- Francois Y, Nemoz CJ, Baulieux J et al.Influence of the interval between preoperative radiation therapy and surgery on downstaging and the rate of sphincter-sparing surgery for rectal cancer: The Lyon R90-01 randomized trial. J Clin Oncol 1999; 17(8):2396-2402.
16. Shin J-S, Jalaludin B, Solomon M, et al.Histopathological regression grading versus staging of rectal cancer following radiotherapy. Pathology 2011; 43:24–30.
17. Meguerditchian AN, Bairati I, Legacé R et al. Prognostic significance of lymphovascular invasion in surgically cured rectal carcinoma. The Am J Surg 2005; 189(6):707 - 713
- Bouzourene H, Bosman FT, Seelentag W et al. Importance of tumor regression assessment in predicting the outcome in patients with locally advanced rectal carcinoma who are treated with preoperative radiotherapy. Cancer 2002; 94(4):1121–1130.
- Vecchio FM, Valentini V, Minsky BD et al.The relationship of pathologic tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer. Int J Radiat Oncol Biol Phys 2005; 62(3):752–760.
- Rödel C, Martus P, Papadoupolos T et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 2005; 23(34):8688–8696.
- Ruo L, Tickoo S, Klimstra DS et al. Long-term prognostic significance of extent of rectal cancer response to preoperative radiation and chemotherapy. Ann Surg 2002; 236(1):75–81.
- Read TE, Andujar JE, Caushaj PF et al.Neoadjuvant therapy for rectal cancer: histologic response of the primary tumorpredicts nodal status. Dis Colon Rectum 2004; 47(6):825–831.
- Willett CG, Warland G, Coen J et al. Rectal cancer: the influence of tumor proliferation on response to preoperative irradiation. Int J Radiat Oncol Biol Phys 2005; 32(1):57–61.
- Janjan NA, Abbruzzese J, Pazdur R et al. Prognostic implications of response to preoperative infusional chemoradiation in locally advanced rectal cancer. Radiother Oncol 1999; 51:153–160.
- Dworak O, Keilholz L, Hoffmann A.Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis1997; 12(1):19–23
- Rödel C, Martus P, Papadoupolos T, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol2005; 23(34):8688–8696.
- Wheeler JM, Dodds E, Warren BF, et al.Preoperative chemoradiotherapy and total mesorectal excision surgery for locally advanced rectal cancer: Correlation with rectal cancer regression grade. Dis Colon Rectum 2004 47(12): 2025-31
- Maas M, Nelemans PJ, Valentini V, Das P 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 Oncol11 2010; (9):835-44.
- Lindebjerg, J., Spindler, K.-L. G. et al.The prognostic value of lymph node metastases and tumour regression grade in rectal cancer patients treated with long-course preoperative chemoradiotherapy. Colorectal Disease 2009; 11: 264–269
- Kim SJ, Chang HJ, Kim DY et al.What is the ideal Tumour Regression Grading System in Rectal Cancer Patients after Preoperative Chemoradiotherapy?.Cancer Res Treat. 2016 Jul; 48(3): 998–1009.
- Martin ST, Heneghan HM, Winter DC. Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer. Br J Surg 2012; 99(7):918–28.
Corresponding Author
Dr Roopa Rachel Paulose
Associate Professor of Pathology, Amrita Institute of Medical Sciences and Research Centre (Amrita Vishwa Vidyapeetham), Ponnekkara P.O Kochi, Kerala 682041, India
Email: This email address is being protected from spambots. You need JavaScript enabled to view it., Phone:0091(0)484-6681234, Fax: 0091(0)484-2802020
DOI: https://dx.doi.org/10.18535/jmscr/v6i6.185
