Multiple rectal carcinomas successfully treated by intersphincteric resection with neoadjuvant therapy without radiation therapy: A case report

doi:10.21203/rs.3.rs-2189365/v1

Download PDF

Case Report

Multiple rectal carcinomas successfully treated by intersphincteric resection with neoadjuvant therapy without radiation therapy: A case report

https://doi.org/10.21203/rs.3.rs-2189365/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background

In recent years, neoadjuvant chemoradiotherapy (NACRT) followed by total mesorectal resection has been the standard of care to prevent recurrence of locally advanced rectal cancer. However, radiotherapy is associated with several serious side effects in rectal cancer patients, including fecal incontinence, dysuria, sexual, dysfunction, and secondary cancer. Neoadjuvant chemotherapy (NAC) has demonstrated comparable efficacy to NACRT for advanced rectal cancer without these problematic side effects. Here, we present a case of advanced lower rectal cancer with multiple tumors that was successfully treated with NAC and intersphincteric resection.

Case presentation

A 56-year-old man presented with bloody stools and was diagnosed with lower rectal cancer cT3N1aM0 cStage IIIB and rectosigmoid cancer cT4aN1aM0 cStage IIIB following investigations by colonoscopy, whole-body contrast-enhanced computed tomography, and magnetic resonance imaging. Abdominoperineal resection was recommended but the patient refused, and thus NAC was proposed. Genetic testing revealed negativity for RAS and BRAF mutations, and hence five courses of mFOLFOX6 (fluorouracil, levofolinate, and oxaliplatin) and panitumumab regimen were administered. Subsequent imaging revealed a yellow clinical partial response for rectosigmoid cancer and a yellow clinical complete response for lower rectal cancer. Hospital tests showed no abnormal data, and the preoperative diagnosis was lower rectal cancer ycT0N0M0 ycStage 0 and sigmoid rectal cancer ycT2N0M0 ycStage I. Therefore, laparoscopic intersphincteric resection and a diverting stoma were performed at our institution 39 days after NAC was completed. The postoperative period was mostly uneventful apart from suture failure on postoperative day 12, and the patient was discharged on postoperative day 43. No cancer cells or lymph node metastasis were evident in postoperative pathology. Five months after surgery the colostomy was closed, and the patient had good anal function and no fecal incontinence 9 months after surgery. No recurrence had occurred 1 year after surgery.

Conclusions

NAC is efficacious in patients with multiple advanced rectal cancers and negates the requirement for abdominoperineal resection.

advanced rectal cancer

neoadjuvant chemotherapy

intersphincteric resection

In recent years, neoadjuvant chemoradiotherapy (NACRT) followed by total mesorectal excision has been widely accepted to control local recurrence of locally advanced rectal cancer [1, 2]. However, while radiotherapy (RT) improves local control of rectal cancer, some patients suffer from late complications associated with RT, including dysuria, fecal incontinence, sexual dysfunction, and secondary cancer [3–5]. Conversely, there are reports that preoperative chemotherapy for advanced rectal cancer has good results [6, 7].

In this study, we describe a case of preoperative chemotherapy and intersphincteric resection for advanced lower rectal cancer in a patient who was admitted to Kurume University Hospital and resulted in a pathological complete response (pCR).

A 59-year-old man with no specific medical history and a family history of rectal cancer (father and son) visited his previous hospital for the presence of bloody stools. The patient was referred to his previous hospital for colonoscopy (CS), which revealed advanced colorectal cancer in the lower rectum and rectosigmoid (Fig. 1). According to LGS findings (Fig. 2), whole-body Ce-CT (Fig. 3), and magnetic resonance imaging (Fig. 4), he was diagnosed with lower rectal cancer cT3N1aM0 cStage IIIB and rectosigmoid cancer cT4aN1aM0 cStage IIIB. The lower edge of the lower rectal cancer was 2 cm from the anal verge. The previous physician recommended abdominoperineal resection, but the patient preferred anal preservation, and thus neoadjuvant therapy was selected. Because he had multiple cancers, neoadjuvant chemoradiotherapy was not indicated, and the decision was made to administer neoadjuvant chemotherapy. Genetic testing of this tumor revealed wild-type RAS and wild-type BRAF V600. The patient subsequently received five courses of chemotherapy consisting of mFOLFOX6 (fluorouracil, levofolinate, and oxaliplatin) and panitumumab regimens. CS (Fig. 5), LGS, and Ce-CT after neoadjuvant chemotherapy showed ycCR for lower rectal cancer and ycPR for rectosigmoid cancer. He was referred to our hospital for intersphincteric resection (ISR). There were no abnormal findings in blood and urine tests (tumor markers were CEA 1.9 ng/ml and CA19-9 < 2 U/ml), electrocardiogram, or respiratory function tests performed at the hospital. The preoperative diagnosis was lower rectal cancer ycT0N0M0 ycStage 0 and sigmoid rectal cancer ycT2N0M0 ycStage I, and the surgical plan was determined. Laparoscopic ISR + diverting stoma was performed 39 days after the last chemotherapy administration. Surgery time was 6 hours 39 minutes and blood loss was 115 ml. No major problems occurred intraoperatively. The postoperative course showed Clavien–Dindo IIIa suture failure on postoperative day 12, but the patient healed conservatively and was discharged on postoperative day 43. Postoperative pathology showed no cancer cells and no lymph node metastasis in either lower rectal or rectosigmoid cancer (Figs. 6 and 7). The colostomy was closed 5 months after surgery, and anorectal function tests 9 months after the initial surgery revealed good anal function (maximal static pressure: 34 mmHg; voluntary contraction pressure: 650 mmHg; functional anal canal length: 43 mm; rectal pressure during defecation: 1.38 mmHg; minimal stool volume: 50 mmHg; tolerable stool volume: 80 mmHg) and no fecal incontinence. One year has passed since the surgery and no recurrence has been observed.

The standard treatment for advanced rectal cancer is TME followed by radiation chemotherapy [1, 2]. Trinani et al. reported that neoadjuvant therapy with mFOLFOX6 and panitumumab in cStage III rectal cancer with wild-type KRAS resulted in a complete response rate of 2.0% and a partial response rate of 86% [7]. Bagaria et al. used bioinformatic analysis to identify a genetic biomarker for resistance to radiation chemotherapy in rectal cancer [8].

The application of molecular targeted agents is expected to improve response rates, but its safety has not been established. Delayed wound healing due to preoperative bevacizumab administration, especially at the anastomotic site, is a serious complication and thus a matter of concern, and in the N-SOG 03 study, the rate of suture failure, a possible side effect of bevacizumab, was extremely high at 27.8% [9]. In a phase II study by the Kyoto University group, FOLFOX plus cetuximab was administered to patients with wild-type KRAS and was reported to be safe, with a PR rate of 80%, an R0 resection rate of 100%, and a postoperative complication rate of 10% [10]. In a phase II study by the Yokohama City University group, six courses of FOLFOX plus panitumumab were administered preoperatively, and the pCR rate was 8.0%, which was lower than expected but still safe [7]. Anti-EGFR antibodies may be an option for RAS wild-type patients. Oshiro et al. reported that neoadjuvant chemotherapy (NAC) with a RAS mutation was associated with a good prognosis in RAS/BRAF wild-type patients regardless of the degree of response to NAC, while non-responders with a RAS/BRAF mutation had a poor prognosis [11]. As personalized therapy progresses, the time will come when treatment for Stage II/III patients will also be determined by genetic mutation status.

In conclusion, we report a case of difficult-to-treat multiple advanced rectal cancer that was administered neoadjuvant chemotherapy, which resulted in successful and complete anorectal-sparing surgery. Although neoadjuvant therapy without radiotherapy is less efficient than neoadjuvant therapy with radiotherapy, it may be an option for patients with multiple rectal cancers, as in this case.

NACRT, neoadjuvant chemoradiotherapy; RT, radiation therapy; pCR, pathological complete response; CS, colonoscopy; LGS, lower gastrointestinal series; Ce-CT, contrast-enhanced computed tomography; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; ycCR, yellow clinical complete response; ycPR, yellow clinical partial response; ISR, intersphincteric resection.

Ethics approval and consent to participate

Ethics approval was obtained from our hospital’s review board (2021-078).

Consent for publication

Written consent for publication of the patient’s details including medical records and images was obtained from the patient.

Availability of data and materials

Data supporting the conclusions of this study are included in this published article.

Competing interests

The authors declare that they have no competing interests.

Funding

Not applicable.

Authors’ contributions

HW and TY designed the report, analyzed the data, and wrote the manuscript. FF MN, TS, and YA collected the patient’s clinical data and coordinated and drafted the manuscript. MN, KF, TS, NY, and KK performed the pathological diagnosis and wrote part of the manuscript. All authors read and approved the final manuscript.

Acknowledgements

The authors thank T Tanabe, R Sakamoto, K Moritani, and S Tsukamoto, all of whom served as staff members at the Department of Colorectal Surgery, Kurume University of Medicine. We also thank H. Nikki March, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345:638–6.
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;24:4620–5.
Birgisson H, Påhlman L, Gunnarsson U, Glimelius B. Adverse effects of preoperative radiation therapy for rectal cancer: long-term follow-up of the Swedish Rectal Cancer Trial. J Clin Oncol. 2005;23:8697–705.
Peeters KC, van de Velde CJ, Leer JW, Martijn H, Junggeburt JM, Kranenbarg EK, et al. 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;23:6199–206.
Wang TH, Liu CJ, Chao TF, Chen TJ, Hu YW. Second primary malignancy risk after radiotherapy in rectal cancer survivors. World J Gastroenterol. 2018;24:4586–95.
Okuyama T, Sameshima S, Takeshita E, Yoshioka R, Yamagata Y, Ono Y, et al. Therapeutic effects of oxaliplatin-based neoadjuvant chemotherapy and chemoradiotherapy in patients with locally advanced rectal cancer: a single-center, retrospective cohort study. World J Surg Oncol. 2018;16:105.
Toritani K, Watanabe J, Suwa Y, Nakagawa K, Suwa H, Ishibe A, et al. A prospective, single-arm, multicenter trial of neoadjuvant chemotherapy with mFOLFOX6 plus panitumumab without radiotherapy for locally advanced rectal cancer. Int J Colorectal Dis. 2020;35:2197–204.
Bagaria J, Kim KO, Bagyinszky E, An SSA, Baek JH. Discriminating potential genetic markers for complete response and non-complete response patients to neoadjuvant chemotherapy with locally advanced rectal cancer. Int J Environ Res Public Health. 2022;19:4008.
Uehara K, Hiramatsu K, Maeda A, Sakamoto E, Inoue M, Kobayashi S, et al. Neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy for poor-risk rectal cancer: N-SOG 03 Phase II trial. Jpn J Clin Oncol. 2013;43:964–71.
Hasegawa S, Goto S, Matsumoto T, Hida K, Kawada K, Matsusue R, et al. A multicenter phase 2 study on the feasibility and efficacy of neoadjuvant chemotherapy without radiotherapy for locally advanced rectal cancer. Ann Surg Oncol. 2017;24:3587–95.
Oshiro T, Uehara K, Aiba T, Mukai T, Ebata T, Nagino M. Impact of RAS/BRAF mutation status in locally advanced rectal cancer treated with preoperative chemotherapy. Int J Clin Oncol. 2018;23:681–8.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Multiple rectal carcinomas successfully treated by intersphincteric resection with neoadjuvant therapy without radiation therapy: A case report

Status:

Version 1

Abstract

Background

Case presentation

Conclusions

Figures

Background

Case Presentation

Discussion And Conclusions

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1