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Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Rectal Cancer | Research

Exploring treatment outcomes in Stage II-III rectal cancer patients undergoing neoadjuvant therapy at a tertiary care center in Pakistan: a comprehensive analysis of pathological outcomes

Authors: Misbah Younus Soomro, Saqib Raza Khan, Hafiz Muhammad, Sujjawal Ahmad, Nawazish Zehra, Insia Ali, Mirza Rameez Samar, Arif Hameed, Munira Moosajee, Yasmin Abdul Rashid

Published in: BMC Cancer | Issue 1/2024

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Abstract

Background

Rectal cancer treatment has transformed in recent years, with neoadjuvant treatment (NT) and total neoadjuvant treatment (TNT) aiming to enhance pathological responses. This pioneering study in our country delves into rectal cancer management, offering crucial insights by examining pathological outcomes in patients treated with the NT and TNT approach, shaping the evolving landscape.

Methods

In this retrospective-cohort study spanning January 2017 to December 2022 at a tertiary care hospital in Pakistan, ethical approval was obtained to examine outcomes of two treatments. Patients were divided into TNT (chemoradiation and pre-surgery 5 FU-based chemotherapy) and NT (chemoradiation, surgery, and subsequent 5 FU-based chemotherapy). The primary end-point was response rates—no response, pathological complete response (pCR), near complete response (near CR), and partial response (PR). The Chi-Square Test for Independence assessed the association between treatment response and type (TNT or NT). Data analysis used STATA MP 64; significance was set at p < 0.05 for all two-tailed tests.

Results

We analyzed 77 patients, 60 underwent standard neoadjuvant chemoradiation, and 17 followed the total neoadjuvant approach. Predominantly male, most were > 65 with ECOG 0–1. The TNT group showed higher response rates (76% vs 62%, p = 0.039), with 40.38% achieving pCR. In the overall population, pCR and near-CR were similar (27.2% vs 26%), while PR were 14%. Treatment characteristics correlated significantly with chemotherapy type, concurrent chemoradiation, LVI, PNI, and T, N, M staging (p < 0.05). Median overall survival was not reached, and mean survival was 89.1 months (CI: 95.0 to 83.3). Side effects varied, with notable differences in neuropathy, diarrhea, oral mucositis, and thrombocytopenia between NT and TNT groups.

Conclusion

Our study adds to evidence favoring neoadjuvant approaches in managing rectal cancer in pakistan. Demonstrating a favorable pcr rate, ongoing research with extended follow-up is essential, given the dynamic landscape of rectal cancer treatment for improved patient outcomes.
Literature
1.
go back to reference Ikram A, Pervez S, Khadim MT, Sohaib M, Uddin H, Badar F, et al. National Cancer Registry of Pakistan: First Comprehensive Report of Cancer Statistics 2015–2019. J Coll Physicians Surg Pak. 2023;33(6):625–32.PubMed Ikram A, Pervez S, Khadim MT, Sohaib M, Uddin H, Badar F, et al. National Cancer Registry of Pakistan: First Comprehensive Report of Cancer Statistics 2015–2019. J Coll Physicians Surg Pak. 2023;33(6):625–32.PubMed
2.
go back to reference Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–49.CrossRefPubMed Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–49.CrossRefPubMed
3.
go back to reference Akbar A, Bhatti AB, Niazi SK, Syed AA, Khattak S, Raza SH, et al. Impact of Time Interval Between Chemoradiation and Surgery on Pathological Complete Response and Survival in Rectal Cancer. Asian Pac J Cancer Prev. 2016;17(1):89–93.CrossRefPubMed Akbar A, Bhatti AB, Niazi SK, Syed AA, Khattak S, Raza SH, et al. Impact of Time Interval Between Chemoradiation and Surgery on Pathological Complete Response and Survival in Rectal Cancer. Asian Pac J Cancer Prev. 2016;17(1):89–93.CrossRefPubMed
4.
go back to reference Mansha MA, Waheed A, Sadaf T, Rashid A, Irfan N, Chaudry SJ. Neoadjuvant Capecitabine and Oxaliplatin Before Concurrent Capecitabine and Radiation in Locally Advanced Rectal Cancers: Experience of a Cancer Hospital in Pakistan. JCO Global Oncology. 2021;7:790–6.CrossRefPubMed Mansha MA, Waheed A, Sadaf T, Rashid A, Irfan N, Chaudry SJ. Neoadjuvant Capecitabine and Oxaliplatin Before Concurrent Capecitabine and Radiation in Locally Advanced Rectal Cancers: Experience of a Cancer Hospital in Pakistan. JCO Global Oncology. 2021;7:790–6.CrossRefPubMed
5.
go back to reference Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, et al. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomized, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012;13(6):579–88.CrossRefPubMed Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, et al. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomized, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012;13(6):579–88.CrossRefPubMed
6.
go back to reference Wang Y, Shen L, Wan J, Zhang H, Wu R, Wang J, et al. Neoadjuvant chemoradiotherapy combined with immunotherapy for locally advanced rectal cancer: a new era for anal preservation. Front Immunol. 2022;13:1067036.CrossRefPubMedPubMedCentral Wang Y, Shen L, Wan J, Zhang H, Wu R, Wang J, et al. Neoadjuvant chemoradiotherapy combined with immunotherapy for locally advanced rectal cancer: a new era for anal preservation. Front Immunol. 2022;13:1067036.CrossRefPubMedPubMedCentral
7.
go back to reference Mohiuddin M, Regine WF, John WJ, Hagihara PF, McGrath PC, Kenady DE, 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):883–8.CrossRefPubMed Mohiuddin M, Regine WF, John WJ, Hagihara PF, McGrath PC, Kenady DE, 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):883–8.CrossRefPubMed
9.
go back to reference Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114–23.CrossRefPubMed Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114–23.CrossRefPubMed
10.
go back to reference Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3–4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006;24(28):4620–5.CrossRefPubMed Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3–4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006;24(28):4620–5.CrossRefPubMed
11.
go back to reference Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30(16):1926–33.CrossRefPubMed Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30(16):1926–33.CrossRefPubMed
12.
go back to reference Wang XJ, Zheng ZR, Chi P, Lin HM, Lu XR, Huang Y. Effect of Interval between Neoadjuvant Chemoradiotherapy and Surgery on Oncological Outcome for Rectal Cancer: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract. 2016;2016:6756859.CrossRefPubMedPubMedCentral Wang XJ, Zheng ZR, Chi P, Lin HM, Lu XR, Huang Y. Effect of Interval between Neoadjuvant Chemoradiotherapy and Surgery on Oncological Outcome for Rectal Cancer: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract. 2016;2016:6756859.CrossRefPubMedPubMedCentral
13.
go back to reference Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, 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):835–44.CrossRefPubMed Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, 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):835–44.CrossRefPubMed
14.
go back to reference Fernandez-Martos C, Garcia-Albeniz X, Pericay C, Maurel J, Aparicio J, Montagut C, et al. Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trial†. Ann Oncol. 2015;26(8):1722–8.CrossRefPubMed Fernandez-Martos C, Garcia-Albeniz X, Pericay C, Maurel J, Aparicio J, Montagut C, et al. Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trial†. Ann Oncol. 2015;26(8):1722–8.CrossRefPubMed
15.
go back to reference Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM-K, 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 randomized, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):29–42.CrossRefPubMed Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM-K, 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 randomized, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):29–42.CrossRefPubMed
16.
go back to reference Garcia-Aguilar J, Patil S, Gollub MJ, Kim JK, Yuval JB, Thompson HM, et al. Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. J Clin Oncol. 2022;40(23):2546–56.CrossRefPubMedPubMedCentral Garcia-Aguilar J, Patil S, Gollub MJ, Kim JK, Yuval JB, Thompson HM, et al. Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. J Clin Oncol. 2022;40(23):2546–56.CrossRefPubMedPubMedCentral
17.
go back to reference Ryan R, Gibbons D, Hyland JM, Treanor D, White A, Mulcahy HE, O’Donoghue DP, Moriarty M, Fennelly D, Sheahan K. Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Histopathology. 2005;47(2):141–6.CrossRefPubMed Ryan R, Gibbons D, Hyland JM, Treanor D, White A, Mulcahy HE, O’Donoghue DP, Moriarty M, Fennelly D, Sheahan K. Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Histopathology. 2005;47(2):141–6.CrossRefPubMed
18.
go back to reference Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, El Dika IH, Segal N, Shcherba M, Sugarman R, Stadler Z. PD-1 blockade in mismatch repair–deficient, locally advanced rectal cancer. N Engl J Med. 2022;386(25):2363–76.CrossRefPubMedPubMedCentral Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, El Dika IH, Segal N, Shcherba M, Sugarman R, Stadler Z. PD-1 blockade in mismatch repair–deficient, locally advanced rectal cancer. N Engl J Med. 2022;386(25):2363–76.CrossRefPubMedPubMedCentral
19.
go back to reference Patel S, Kazi M, Desouza AL, Sukumar V, Gori J, Bal M, Saklani A. Outcomes of rectal cancer patients with a positive pathological circumferential resection margin. Langenbecks Arch Surg. 2022;1:1–9. Patel S, Kazi M, Desouza AL, Sukumar V, Gori J, Bal M, Saklani A. Outcomes of rectal cancer patients with a positive pathological circumferential resection margin. Langenbecks Arch Surg. 2022;1:1–9.
20.
go back to reference Chen T, Wang M, Cheng X, Wang Y, Jiang Y, Fang X, Xiao H. The complementary role of lymphovascular invasion and perineural invasion in the TNM staging process of rectal cancer. Medicine. 2022;101(39):e30687.CrossRefPubMedPubMedCentral Chen T, Wang M, Cheng X, Wang Y, Jiang Y, Fang X, Xiao H. The complementary role of lymphovascular invasion and perineural invasion in the TNM staging process of rectal cancer. Medicine. 2022;101(39):e30687.CrossRefPubMedPubMedCentral
21.
go back to reference Jin J, Tang Y, Hu C, Jiang LM, Jiang J, Li N, Liu WY, Chen SL, Li S, Lu NN, Cai Y. Multicenter, randomized, phase III trial of short-term radiotherapy plus chemotherapy versus long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR). J Clin Oncol. 2022;40(15):1681.CrossRefPubMedPubMedCentral Jin J, Tang Y, Hu C, Jiang LM, Jiang J, Li N, Liu WY, Chen SL, Li S, Lu NN, Cai Y. Multicenter, randomized, phase III trial of short-term radiotherapy plus chemotherapy versus long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR). J Clin Oncol. 2022;40(15):1681.CrossRefPubMedPubMedCentral
22.
go back to reference Adam IJ, Mohamdee MO, Martin IG, Scott N, Finan PJ, Johnston D, et al. Role of circumferential margin involvement in the local recurrence of rectal cancer. Lancet. 1994;344(8924):707–11.CrossRefPubMed Adam IJ, Mohamdee MO, Martin IG, Scott N, Finan PJ, Johnston D, et al. Role of circumferential margin involvement in the local recurrence of rectal cancer. Lancet. 1994;344(8924):707–11.CrossRefPubMed
23.
go back to reference Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006;93(10):1215–23.CrossRefPubMed Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006;93(10):1215–23.CrossRefPubMed
Metadata
Title
Exploring treatment outcomes in Stage II-III rectal cancer patients undergoing neoadjuvant therapy at a tertiary care center in Pakistan: a comprehensive analysis of pathological outcomes
Authors
Misbah Younus Soomro
Saqib Raza Khan
Hafiz Muhammad
Sujjawal Ahmad
Nawazish Zehra
Insia Ali
Mirza Rameez Samar
Arif Hameed
Munira Moosajee
Yasmin Abdul Rashid
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-12241-6

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