Spontaneous regression of extensive colorectal cancer peritoneal metastases: first you see it, then you do not

An 82-year-old female with a background of rheumatoid arthritis receiving methotrexate presented with abdominal pain and weight loss. A computed tomography (CT) scan revealed ascites and omental nodularity (Fig. 1a). Percutaneous omental biopsy showed poorly differentiated adenocarcinoma possibly of gastrointestinal or pancreaticobiliary origin. Immunostaining for DNA mismatch repair proteins (MMR) showed deficiency in MLH-1 and PMS-2 expression. Methotrexate was ceased and 3 months later an updated CT scan was performed in anticipation of commencing palliative chemotherapy. Notwithstanding the patient having received no anti-cancer therapy in the interval from the initial scan, images showed resolution of ascites and only a single residual 9 mm omental nodule (Fig. 1b). Oral capecitabine was commenced 5 days after the CT scan. With the unexpected finding of spontaneous tumour regression capecitabine was abandoned at the next clinic attendance with only a single 14-day course completed. Rectal bleeding prompted repeat CT scan and colonoscopy 13 months after diagnosis. A hepatic flexure tumour was biopsied with histology and MMR status concordant with the initial omental biopsy. Repeat CT scan showed the primary tumour but no evidence of metastatic disease. The patient was offered a laparoscopic right hemicolectomy. At laparoscopy, no peritoneal metastases were seen. Right hemicolectomy revealed a pT3 pN1a adenocarcinoma. The patient remains asymptomatic on no therapy 20 months after diagnosis. Spontaneous regression (SR) of malignant tumours is rare. SR of colorectal cancer (CRC) accounts for less than 2% of all SR cases, with 60 reported cases to date.1, 2 MMR deficiency (dMMR) is identified in ~15% of primary and 5% of metastatic CRC.3 The dMMR subset of CRC is highly responsive to immunotherapy in both primary (response rate up to 100%) and metastatic disease (durable control up to 70%).4, 5 The first case report of CRC SR that reported dMMR status appeared in 2019.6 Karakuchi et al. speculated colonoscopic biopsy incited an immunologic response sufficient to obliterate the dMMR tumour.6 Subsequent case reports of SR of CRC have emphasized dMMR status.7, 8 We speculate discontinuation of methotrexate in the patient led to sufficient immune reconstitution to allow immunologic-mediated regression of widespread metastatic disease. The same mechanism was suspected in a report of regression of multiple hepatic dMMR CRC metastases in an organ transplant recipient discontinuing transplant rejection drugs.9 This case emphasizes the potential importance of immune responsiveness of the dMMR subset of CRC, and to reiterate the words of Sir William Osler ‘[illustrating] the uncertainty of prognosis and the truth of the statement that no condition, however, desperate, is quite hopeless’.10 This case report was conducted following the written consent provided by the patient. The patient's written consent has been provided together with the submission of this manuscript. Patient anonymity has been preserved at all times throughout the writing of this case report. Samuel Pau: Conceptualization; methodology; writing – original draft. Jesse Fischer: Conceptualization; methodology; supervision. Ian Kennedy: Conceptualization; supervision.