Neoadjuvant S-1 and Oxaliplatin Plus Bevacizumab Therapy for High-risk Locally Advanced Rectal Cancer: A Prospective Multicenter Phase II Study

Overview

Journal Ann Gastroenterol Surg

Date 2024 Jan 22

PMID 38250676

Authors

Takuya Miura

Hajime Morohashi

Yoshiyuki Sakamoto

Takuji Kagiya

Tatsuya Hasebe

Yoshihito Nakayama

Hiromasa Fujita

Kenichi Hakamada

Affiliations

Soon will be listed here.

Abstract

Aim: We report the short/mid-term results of surgery for high-risk locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy (NAC, four courses of S-1 + oxaliplatin+ bevacizumab) without radiotherapy with the primary aim of ypT0-2.

Methods: High-risk LARC was defined as cT4b, mesorectal fascia (MRF) ≤1 mm (MRF+), or lateral lymph node metastasis (cLLN+) on high-resolution MRI. The planned 32 cases from April 2018 to December 2021 were all included.

Results: There were 10 patients at cT4b (31.2%), 26 MRF+ (81.3%), and 22 cLLN+ (68.8%). Thirteen (40.6%) underwent NAC after a colostomy for stenosis. NAC was completed in 26 (81.2%) cases. Grade 3 or higher adverse events occurred in six (18.7%). One patient developed progressive disease (3.2%). Eleven were ycT0-3MRF-LLN- (34.3%). Curative-intent surgery was performed on 31, with sphincter-preserving surgery in 20, abdominoperineal resection in nine, total pelvic exenteration in two, and lateral lymph node dissection in 24. Two had R1/2 resection (6.4%). A Grade 3 or higher postoperative complication rate occurred in 3.2%. Pathological complete response and ypT0-2 rates were 12.9% and 45.1%. Three-year disease-free survival rates (3yDFS) for ypT0-2 and ypT ≥3 were 81.2%, 46.6% ( = 0.061), and 3-year local recurrence rates (3yLR) were 0%, 48.8% ( = 0.015). 3yDFS for ycT0-3MRF-LLN- and ycT4/MRF+/LLN+ were 87.5%, 48.0% ( = 0.031) and 3yLR were 0%, 42.8% ( = 0.045).

Conclusion: NAC yielded a clinically significant effect in about half of high-risk LARC patients. If NAC alone is ineffective, radiotherapy should be added, even if extended surgery is intended.

Citing Articles

Neoadjuvant S-1 and oxaliplatin plus bevacizumab therapy for high-risk locally advanced rectal cancer: A prospective multicenter phase II study.

Miura T, Morohashi H, Sakamoto Y, Kagiya T, Hasebe T, Nakayama Y Ann Gastroenterol Surg. 2024; 8(1):71-79.

PMID: 38250676 PMC: 10797815. DOI: 10.1002/ags3.12720.

References

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

Komori K, Fujita S, Mizusawa J, Kanemitsu Y, Ito M, Shiomi A . Predictive factors of pathological lateral pelvic lymph node metastasis in patients without clinical lateral pelvic lymph node metastasis (clinical stage II/III): The analysis of data from the clinical trial (JCOG0212). Eur J Surg Oncol. 2018; 45(3):336-340. DOI: 10.1016/j.ejso.2018.11.016. View

Ogawa S, Hida J, Ike H, Kinugasa T, Ota M, Shinto E . The important risk factor for lateral pelvic lymph node metastasis of lower rectal cancer is node-positive status on magnetic resonance imaging: study of the Lymph Node Committee of Japanese Society for Cancer of the Colon and Rectum. Int J Colorectal Dis. 2016; 31(10):1719-28. DOI: 10.1007/s00384-016-2641-3. View

Akiyoshi T, Watanabe T, Miyata S, Kotake K, Muto T, Sugihara K . Results of a Japanese nationwide multi-institutional study on lateral pelvic lymph node metastasis in low rectal cancer: is it regional or distant disease?. Ann Surg. 2012; 255(6):1129-34. DOI: 10.1097/SLA.0b013e3182565d9d. View

Uehara K, Hiramatsu K, Maeda A, Sakamoto E, Inoue M, Kobayashi S . Neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy for poor-risk rectal cancer: N-SOG 03 Phase II trial. Jpn J Clin Oncol. 2013; 43(10):964-71. DOI: 10.1093/jjco/hyt115. View

Ogura A, Akiyoshi T, Nagasaki T, Konishi T, Fujimoto Y, Nagayama S . Feasibility of Laparoscopic Total Mesorectal Excision with Extended Lateral Pelvic Lymph Node Dissection for Advanced Lower Rectal Cancer after Preoperative Chemoradiotherapy. World J Surg. 2016; 41(3):868-875. DOI: 10.1007/s00268-016-3762-0. View

Glynne-Jones R, Counsell N, Quirke P, Mortensen N, Maraveyas A, Meadows H . Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control. Ann Oncol. 2014; 25(7):1356-1362. DOI: 10.1093/annonc/mdu147. View

Bahadoer R, Dijkstra E, van Etten B, Marijnen C, Putter H, Meershoek-Klein Kranenbarg E . 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 randomised, open-label, phase 3.... Lancet Oncol. 2020; 22(1):29-42. DOI: 10.1016/S1470-2045(20)30555-6. View

Fernandez-Martos C, Garcia-Albeniz X, Pericay C, Maurel J, Aparicio J, Montagut C . 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. DOI: 10.1093/annonc/mdv223. View

10.

Hong Y, Park Y, Lim H, Lee J, Kim T, Kim K . S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for first-line treatment of patients with metastatic colorectal cancer: a randomised, non-inferiority phase 3 trial. Lancet Oncol. 2012; 13(11):1125-32. DOI: 10.1016/S1470-2045(12)70363-7. View

11.

Patel U, Blomqvist L, Taylor F, George C, Guthrie A, Bees N . MRI after treatment of locally advanced rectal cancer: how to report tumor response--the MERCURY experience. AJR Am J Roentgenol. 2012; 199(4):W486-95. DOI: 10.2214/AJR.11.8210. View

12.

Kim M, Chang G, Lim H, Song M, Park S, Sohn D . Oncological Impact of Lateral Lymph Node Dissection After Preoperative Chemoradiotherapy in Patients with Rectal Cancer. Ann Surg Oncol. 2020; 27(9):3525-3533. DOI: 10.1245/s10434-020-08481-y. View

13.

Takemasa I, Hamabe A, Miyo M, Akizuki E, Okuya K . Essential updates 2020/2021: Advancing precision medicine for comprehensive rectal cancer treatment. Ann Gastroenterol Surg. 2023; 7(2):198-215. PMC: 10043777. DOI: 10.1002/ags3.12646. View

14.

Oki E, Murata A, Yoshida K, Maeda K, Ikejiri K, Munemoto Y . A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC). Ann Oncol. 2016; 27(7):1266-72. PMC: 4922318. DOI: 10.1093/annonc/mdw162. View

15.

Miura T, Morohashi H, Sakamoto Y, Kagiya T, Hasebe T, Nakayama Y . Neoadjuvant S-1 and oxaliplatin plus bevacizumab therapy for high-risk locally advanced rectal cancer: A prospective multicenter phase II study. Ann Gastroenterol Surg. 2024; 8(1):71-79. PMC: 10797815. DOI: 10.1002/ags3.12720. View

16.

Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L . Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial. J Clin Oncol. 2019; 37(34):3223-3233. PMC: 6881102. DOI: 10.1200/JCO.18.02309. View

17.

Brown G, Daniels I, Richardson C, Revell P, Peppercorn D, Bourne M . Techniques and trouble-shooting in high spatial resolution thin slice MRI for rectal cancer. Br J Radiol. 2005; 78(927):245-51. DOI: 10.1259/bjr/33540239. View

18.

Fokas E, Allgauer M, Polat B, Klautke G, Grabenbauer G, Fietkau R . Randomized Phase II Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: CAO/ARO/AIO-12. J Clin Oncol. 2019; 37(34):3212-3222. DOI: 10.1200/JCO.19.00308. View

19.

Hashiguchi Y, Muro K, Saito Y, Ito Y, Ajioka Y, Hamaguchi T . Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol. 2019; 25(1):1-42. PMC: 6946738. DOI: 10.1007/s10147-019-01485-z. View

20.

Smith J, Nash G, Weiser M, Temple L, Guillem J, Paty P . Multivisceral resections for rectal cancer. Br J Surg. 2012; 99(8):1137-43. DOI: 10.1002/bjs.8820. View