Clinical Case Summary

An 80-year-old woman with a history of right ovarian cancer, treated with total hysterectomy and bilateral salpingo-oophorectomy followed by adjuvant radiotherapy in 1984, presented with tenesmus and rectal bleeding. She had long-standing radiation-induced enteritis. Colonoscopy revealed a 50mm ulcerated neoplasm in the distal rectum. Histopathological analysis confirmed a low-grade rectal adenocarcinoma with loss of nuclear expression of the mismatch repair proteins MSH2 and MSH6. Staging with thoracoabdominal CT and pelvic MRI showed a distal rectal adenocarcinoma invading the vagina and levator ani muscle (cT4), cN0, with a suspicious left inguinal lymph node (possible cM1). Given her prior exposure to pelvic radiotherapy and the presence of chronic radiation-induced injury, a multidisciplinary team, after discussion with the patient and her family, decided to initiate off-label neoadjuvant treatment with dostarlimab for six months, completing a total of eight cycles. Six weeks after completion of immunotherapy, flexible sigmoidoscopy demonstrated a clinical near-complete response (near-cCR) and pelvic MRI showed radiologic complete response (rCR), with no evidence of residual tumor or lymphadenopathy. A new flexible sigmoidoscopy is scheduled in four weeks. If cCR is confirmed, the patient will enter a Watch and Wait surveillance program. Traditionally, rectal cancer treatment has relied on a combination of chemoradiotherapy and surgery, resulting in pathologic complete response in up to 25% of patients, but frequently associated with complications and treatment-related toxicity. Recent studies have demonstrated promising results with immune checkpoint inhibitors, particularly dostarlimab as single agent, an antiprogrammed cell death protein 1 monoclonal antibody. In recent studies so far, this agent was remarkably effective in mismatch repair–deficient, locally advanced rectal cancer, showing high rates of cCR and prolonged overall survival.

References

Andrea Cercek et al, A Phase Two, Single-Arm, Open-Label Study With Dostarlimab Monotherapy in Participants With Untreated Stage II/III dMMR/MSI-H Locally Advanced Rectal Cancer (AZUR-1), Clinical Colorectal Cancer

A. Cercek, M. Lumish, J. Sinopoli, J. Weiss, J. Shia, M. Lamendola-Essel, I.H. El Dika, N. Segal, M. Shcherba, R. Sugarman, Z. Stadler, R. Yaeger, J.J. Smith, B. Rousseau, G. Argiles, M. Patel, A. Desai, L.B. Saltz, M. Widmar, K. Iyer, J. Zhang, N. Gianino, C. Crane, P.B. Romesser, E.P. Pappou, P. Paty, J. Garcia-Aguilar, M. Gonen, M. Gollub, M.R. Weiser, K.A. Schalper, L.A. Diaz Jr. PD-1 BLockade in Mismatch Repair-deficient, Locally Advanced Rectal Cancer