Short-term outcomes of preoperative chemotherapy in patients with upper ampullary rectal cancer

The purpose of the study: to analyze short-term efficacy and tolerability of preoperative chemotherapy in patients with upper ampullary rectal carcinoma. Material and methods. A prospective study conducted at the cancer research institute (tomsk, russia) between 2018 and 2020 included 47 patients with operable cancer of the upper ampullary part of the rectum with mrt3n0m0 (mesorectal fascia involvement (crm+) or low-grade cancer), mrt4аn0m0 and mrt3–4аn1m0. All patients were divided into two groups. Group i comprised 22 patients, who received 3 cycles of chemotherapy with folfox-4 followed by surgery. Group ii consisted of 25 patients, who underwent surgery alone. All patients underwent arterior resection of the rectum. Results. Group i patients completed all three cycles of preoperative chemotherapy. Downstaging after chemotherapy was observed in 16 (72.7 %) patients. No severe side effects of chemotherapy were found. The frequency of radical surgeries (r0) was 100 %. No significant differences in the rate of postoperative complications between the treatment groups were observed (18.2 % and 16 %, respectively, p>0.05). There were no cases of postoperative mortality. Conclusion. Compared with surgery alone, preoperative chemotherapy followed by surgery demonstrates a high short-term efficacy, does not adversely affect the course of the perioperative period.

1. Kaprin A.D., Starinskiy V.V., Shakhzadova A.O. Malignant neoplasms in Russia in 2019 (morbidity and mortality). Moscow, 2020. 250 p. (in Russian).

2. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018; 68(6): 394–424. doi:10.3322/caac.21492.

3. Rasulov A.O., Mamedli Z.Z., Kuz’michev D.V., Khudoerov D.H., Kozlov N.A., Suraeva Yu. E., Balyasnikova S.S. Organ saving treatment of rectal cancer. Pelvic Surgery and Oncology. 2016; 6(4): 13–17. (in Russian). doi: 10.17650/2220-3478-2016-6-4-13-17.

4. McCarthy K., Pearson K., Fulton R., Hewitt J. Pre-operative chemoradiation for non-metastatic locally advanced rectal cancer. Cochrane Database Syst Rev. 2012; 12: CD008368. doi: 10.1002/14651858.CD008368.pub2.

5. Oronsky B., Reid T., Larson C., Knox S.J. Locally advanced rectal cancer: The past, present, and future. Semin Oncol. 2020 Feb; 47(1): 85–92. doi: 10.1053/j.seminoncol.2020.02.001.

6. Afanasyev S.G., Dobrodeyev A.Yu., Avgustinovich A.V., Tarasova A.S., Volkov M.Yu., Urmonov U.B., Dimcha A.A., Startseva J.A., Plakseeva D.A., Usova A.V., Spirina L.V. Organ saving treatment of low rectal cancer. Problems in Oncology. 2019; 65(6): 850–854. (In Russian).

7. Ferrari L., Fichera A. Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer. Gastroenterol Rep. 2015; 3(4): 277–88. doi: 10.1093/gastro/gov039.

8. Rödel C., Graeven U., Fietkau R., Hohenberger W., Hothorn T., Arnold D., Hofheinz R.D., Ghadimi M., Wolff H.A., Lang-Welzenbach M., Raab H.R., Wittekind C., Ströbel P., Staib L., Wilhelm M., Grabenbauer G.G., Hoffmanns H., Lindemann F., Schlenska-Lange A., Folprecht G., Sauer R., Liersch T.; German Rectal Cancer Study. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015; 16(8): 979–989. doi.org/10.1016/S1470-2045(15)00159-X..

9. Lee Y., Hsieh C., Chuang J. Prognostic significance of partial tumor regression after preoperative chemoradiotherapy for rectal cancer: a meta-analysis. Dis Colon Rectum. 2013; 58(9): 1093–101. doi: 10.1097/DCR.0b013e318298e36b

10. Peeters K.C., van de Velde C.J., Leer J.W., Martijn H., Junggeburt J.M., Kranenbarg E.K., Steup W.H., Wiggers T., Rutten H.J., Marijnen C.A. Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients – a Dutch colorectal cancer group study. J. Clin. Oncol. 2005 Sep 1; 23(25): 6199–206. doi: 10.1200/JCO.2005.14.779.

11. Marijnen C., van de Velde C., Putter H., van den Brink M.. Maas C.P., Martijn H., Rutten H.J., Wiggers T., Kranenbarg E.K., Leer J.W., Stiggelbout A.M. Impact of short-term preoperative radiotherapy on healthrelated quality of life and sexual functioning in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol. 2005; 23(9): 1847–58.

12. Stephens R.J., Thompson L.C., Quirke P., Grieve R., Couture J., Griffiths G.O., Sebag-Montefiore D. Impact of short-course preoperative radiotherapy for rectal cancer on patients quality of life: data from the Medical Research Council CR07/National Cancer Institute of Canada Clinical Trials Group C016 randomized clinical trial. J Clin Oncol. 2010 Sep 20; 28 (27): 4233–9. doi: 10.1200/JCO.2009.26.5264

13. Nishizawa Y., Saito N., Fujii S., Ito M., Sugito M., Kobayashi A., Nishizawa Y. Association between anal function and therapeutic effect after preoperative chemoradiotherapy followed by intersphincteric resection. Dig Surg. 2012; 29: 439–445. doi: 10.1159/000345586.

14. Deng Y., Chi P., Lan P., Wang L., Chen W., Cui L., Chen D., Cao J., Wei H., Peng X., Huang Z., Cai G., Zhao R., Huang Z., Xu L., Zhou H., Wei Y., Zhang H., Zheng J., Huang Y., Zhou Z., Cai Y., Kang L., Huang M., Wu X., Peng J., Ren D., Wang J. 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: 3223–3233. doi: 10.1200/JCO.18.02309.

15. Bosset J., Collette L., Calais G., Mineur L., Maingon P., Radosevic-Jelic L., Daban A., Bardet E., Beny A., Ollier J.C. Chemotherapy with preoperative radiotherapy in rectal cancer. EORTC Radiotherapy Group Trial 22921. N Engl J Med. 2006; 14(355): 1114–23. doi: 10.1056/NEJMoa060829.

16. Schrag D., Weiser M.R., Goodman K.A., Gonen M., Hollywood E., Cercek A., Reidy-Lagunes D.L., Gollub M.J., Shia J., Guillem J.G., Temple L.K., Paty P.B., Saltz L.B. Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial. J Clin Oncol. 2014 Feb 20; 32(6): 513–8. doi: 10.1200/JCO.2013.51.7904.

17. Koizumi M., Yamada T., Shinji S., Yokoyama Y., Takahashi G., Iwai T., Takeda K., Hara K., Ohta K., Uchida E., Yoshida H. Feasibility of Neoadjuvant FOLFOX Therapy Without Radiotherapy for Baseline Resectable Rectal Cancer. In Vivo. 2018 Jul-Aug; 32(4): 937–943. doi: 10.21873/invivo.11332.

18. Nishizawa Y., Fujii S., Saito N., Ito M., Nakajima K., Ochiai A., Sugito M., Kobayashi A., Nishizawa Y. Differences in tissue degeneration between preoperative chemotherapy and preoperative chemoradiotherapy for colorectal cancer. Int J Colorectal Dis. 2012; 27(8): 1047–53. doi: 10.1007/s00384-012-1434-6

19. Cercek A., Weiser M.R., Goodman K.A. Complete pathologic response in the primary of rectal or colon cancer treated with FOLFOX without radiation J Clin Oncol. 2010, 28: 15 suppl.: 3649–3649.

20. Sakuyama N., Kojima M., Kawano S., Matsuda Y., Mino-Kenudson M., Ochiai A., Ito M. Area of residual tumor is a robust prognostic marker for patients with rectal cancer undergoing preoperative therapy. Cancer Sci. 2018 Mar; 109(3): 871–878. doi: 10.1111/cas.13521.

21. Usova A.V., Frolova I.G., Afanasyev S.G., Tarasova A.S. Potential role of magnetic resonance imaging in diagnosis and assessment of treatment response in patients with rectal cancer. Siberian Journal of Oncology. 2012; 5: 74–80. (in Russian).

22. Hasegawa J., Nishimura J., Mizushima T., Miyake Y., Kim H.M., Takemoto H., Tamagawa H., Noura S., Fujii M., Fujie Y., Kato T., Miwa H., Takemasa I., Ikeda M., Yamamoto H., Sekimoto M., Nezu R., Doki Y., Mori M. Neoadjuvant capecitabine and oxaliplatin (XELOX) combined with bevacizumab for high-risk localized rectal cancer. Cancer Chemother Pharmacol. 2014 May; 73(5): 1079–87. doi: 10.1007/s00280-014-2417-9.

23. Uehara K., Hiramatsu K., Maeda A. Sakamoto E., Inoue M., Kobayashi S., Tojima Y., Yoshioka Y., Nakayama G., Yatsuya H., Ohmiya N. , Goto H., Nagino M. 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.