Anticipating and Overcoming Challenges in Implementing Watch-and-Wait for Rectal Cancer

BACKGROUND:

Management of cancer of rectum has undergone dramatic changes in the last two decades. Although both preoperative and postoperative treatments can be effective, neoadjuvant therapy has emerged as standard of care.1 Rectal resection surgery after neoadjuvant treatment has been the mainstay treatment of locally advanced rectal cancer. However, functional outcomes and quality of life after radical resection of the rectum remain suboptimal.2 The excellent oncologic outcomes in patients who achieved pathologic complete response after neoadjuvant treatment questioned the need for radical surgery.3 The watch-and-wait approach (WW) is a noninvasive therapeutic alternative for organ preservation and avoiding operative morbidity.4 In the watch-and-wait (WW) approach, patients with locally advanced rectal cancer who achieve excellent clinical response after neoadjuvant treatment undergo active surveillance rather than rectal cancer surgery.5,6

CASE CAPSULE:

A young 35 year old female, doctor by profession presented with complain of bleeding per rectum since 2 weeks with mild abdominal pain. Her workup profile included a MRI scan of Abdomen and Pelvis showing circumferential wall thickening involving distal rectum and proximal anal canal with transmural extension with maximum wall thickness of 0.9 cm and 4 cm length of involved segment. There were few small sub centimetre enhancing perirectal nodes noted. Her colonoscopy findings included large deep ulcerated growth with irregular mucosal margin in distal most rectum, starting from anorectal junction till 3cm from anal verge involving almost half to 2/3rd of circumference. Biopsy was taken which turned out to be poorly differentiated adenocarcinoma.

Patient being very active with 0 ECOG performance status living an absolutely healthy family life including one boy 10 years old and husband also doctor by profession were very apprehensive and reluctant to go for surgery after the neoadjuvant treatment protocol explained. She also got PET CT scan done which confirmed the same findings  of MRI scan and with no metastases anywhere else in the body.

Repeat consultation with patient and family were quite detailing taking in aspects all possible side effects of neoadjuvant long course radiotherapy (50.4Gy/28#) along with tablet Capecitabine as concurrent chemotherapy followed by reevaluation to decide whether surgery can be omitted as per the response to radiation treatment. Right from the day of starting Radiation therapy, the couple insisted to go for non surgical approach which made the radiation treatment process quite challenging and strict interim analysis to decide if surgery had to be added in case of radiation response not as per watch-and-wait protocol.

Image guided radiation therapy plan was generated with 1.8Gy/# for 5 fractions per week to total of 50.4Gy in 28 fractions over 5.5 weeks along with concurrent oral Capecitabine chemotherapy. The interim scans showed good shrinkage of tumor and acceptable tolerance of radiation and chemotherapy treatment. External beam radiation therapy was concluded in March 2022 and called for follow up after 2 weeks. The sigmoidoscopy and  MRI abdomen and pelvis showed complete regression of tumor which made our decision to go for watch-and-wait protocol more determined. Patient was planned for endorectal brachytherapy boost of 5Gy for 3 fractions. After completion of radiation treatment, patient was kept for strict follow up every quarterly with MRI abdomen and pelvis, sigmoidoscopy and CEA levels.

Patient has completed two years post treatment and now kept for biannual check up. with MRI abdomen and pelvis, sigmoidoscopy and CEA levels.

DISCUSSION:

Chemoradiation is the mainstay of treatment for watch-and-wait protocol in rectal cancer cases.  Rectal surgery is associated with significant morbidity including gastrointestinal, genitourinary, and sexual problems. In addition, patients with very low tumors undergo abdominoperineal resection, which results in permanent colostomy. The excellent oncologic outcomes in patients who achieved pathologic complete response (CR) after neoadjuvant treatment questioned the need for radical resection surgery. Our present case with a very young professionally active lady with pathologic complete response after radiation treatment and till date disease free gives us more hope for pursuing watch-and-wait protocol for selective rectal cancer cases. The WW approach has proven its safety and effectiveness in many studies, including a prospective phase 2 randomized study and a large international database study in patients with rectal cancer with clinical or near complete response after neoadjuvant treatment.7 The WW approach can be a good therapeutic option in patients who do not hope for surgery.8 Since both surgery and the WW approach have their pros and cons, clinicians should carefully evaluate each patient’s goals for treatment and patient’s motivation and strict compliance for regular follow up visits to avoid surgery for maintaining their quality of life or pursue more definite treatment. The optimal intensity of neoadjuvant treatment to maximize tumor response must be determined.9 However with growing evidence the WW approach is a safe and effective option in patients who achieved excellent tumor response after neoadjuvant treatment.

REFERENCES: 

1. Van Gijn W, et al. Preoperative radiotherapy combined with total mesorectal excision for resecteable rectal cancer. 12 year follow up of the multicentre radnomised controlled TME trial. Lancet Oncol 2011;12(6):575-582.

2. Pappou EP, Temple LK, Patil S, et al. Quality of life and function after rectal cancer surgery with and without sphincter preservation. Front Oncol 2022;12:944843.

3. Habr-Gama A, Perez RO, Nadalin W, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg 2004;240:711–8.

4. Appelt AL, Ploen J, Harling H, et al. High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol 2015;16:919–27. 

5. Renehan AG, Malcomson L, Emsley R, et al. Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis. Lancet Oncol 2016;17:174–83. 

6. Dossa F, Chesney TR, Acuna SA, Baxter NN. A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2017;2:501–13.

7. Van der Valk MJ, Hilling DE, Bastiaannet E, et al. Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study. Lancet 2018;391:2537–45.

8. Garcia-Aguilar J, Patil S, Gollub MJ, et al. Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. J Clin Oncol 2022;40:2546–56.

9. Sun Myint A, Smith FM, Gollins S, et al. Dose escalation using contact X-ray brachytherapy after external beam radiotherapy as nonsurgical treatment option for rectal cancer: outcomes from a single-center experience. Int J Radiat Oncol Biol Phys 2018;100:565–73.