Metastatic BRAF^V600E mutated colorectal cancer is associated with poor overall survival and modest effectiveness to standard therapies. Furthermore, survival is influenced by the microsatellite status. Patients with microsatellite-stable and BRAF^V600E mutated colorectal cancer have the worst prognosis under the wide range of genetic subgroups in colorectal cancer. Herein, we present a patient case of an impressive therapeutic efficacy of dabrafenib, trametinib, and cetuximab as later-line therapy in a 52-year-old woman with advanced BRAF^V600E mutated, microsatellite-stable colon cancer. This patient achieved a complete response after 1 year of triple therapy. Due to skin toxicity grade 3 and recurrent urinary tract infections due to mucosal toxicity, a therapy de-escalation to dabrafenib and trametinib was performed, and the double therapy was administered for further 41 months with ongoing complete response. For 1 year, the patient was off therapy and is still in complete remission.

Purpose: The aim of this retrospective analysis was to determine if the response to preoperative radio(chemo)therapy is predictive for survival among patients with locally advanced rectal cancer and may act as a potential surrogate endpoint for disease free survival and overall survival.Results: Eight hundred seventy-eight patients from five centers were analyzed. There were 304 women and 574 men; the median age was 64.7 years. 77.6% and 22.4% of patients received neoadjuvant radiochemotherapy or short-course radiotherapy, resulting in a pathological complete response in 7.3%. T-downstaging and N-downstaging occurred in 50.5% and 37% of patients after neoadjuvant therapy. In patients with T-downstaging, the 10-year DFS and 10-year OS were 64.8% and 66.8% compared to 37.1% and 45.9% in patients without T-downstaging. N-downstaging resulted in 10-year DFS and 10-year OS in 56.2% and 62.5% compared to 47.3% and 52.3% without N-downstaging. Based on routinely evaluated clinical parameters, an absolute risk prediction calculator was generated for 5-year disease-free survival, and 5-year overall survival.Conclusion: T-downstaging and N-downstaging after neoadjuvant radiochemotherapy or short-course radiotherapy resulted in better DFS and OS compared to patients without response. Based on clinical parameters, 5-year DFS, and 5-year OS can be predicted using a prediction calculator.

Summary The treatment paradigm for locally advanced rectal cancer has changed in recent years. Neoadjuvant radiochemotherapy followed by total mesorectal excision and postoperative chemotherapy has been the standard of care since many years. With this multidisciplinary approach the local recurrence rate is low, but the occurrence of distant metastases and impairments of quality of life due to bowel, bladder, and sexual dysfunction are still unresolved problems. The integration of induction or consolidation chemotherapy into the neoadjuvant setting, a watch-and-wait strategy without surgery for patients with clinical complete response, the integration of immunotherapy into the neoadjuvant setting in microsatellite-instable rectal cancer as well as the selective omission of neoadjuvant radiotherapy now represent different treatment options and enable individualization of therapy for locally advanced rectal cancer. Here, we provide an overview of the latest developments in the treatment of locally advanced rectal cancer and a discussion on which patients need more intensive or less intensive therapy.

Summary: Despite recent advances in therapy, certain subtypes of colorectal cancer, such as those that are microsatellite instability (MSI-high), mismatch repair deficient (dMMR) or tumor mutation burden high (TMB-H), remain a treatment challenge. In recent years, interest in neoadjuvant therapy strategies for localized colorectal cancer has increased—especially treatment with immunotherapies. At ASCO meeting 2024, updated data on 6‑month course of dostarlimab in patients with dMMR locally advanced rectal cancer as well as several trials investigating the use of neoadjuvant immunotherapy monotherapy or immunotherapy combinations in high-risk stage II–III dMMR colon cancer were presented.