PD-1/PD-L1 inhibitors for early and middle stage microsatellite high-instability and stable colorectal cancer: a review.

BACKGROUND: Programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are important immune checkpoint molecules that contribute to tumor immune evasion. However, the main treatment modalities for patients with early and intermediate stage colorectal cancer (CRC) are surgery, and the role of PD-1/PD-L1 inhibitors in these patients is not yet clear. Therefore, this study aims to review the treatment progress of PD-1/PD-L1 inhibitors for early- and intermediate-stage microsatellite high-instability (MSI-H) and stable (MSS) colorectal cancer, in order to provide more options for patients with early- and intermediate-stage colorectal cancer. MATERIALS AND METHODS: A scoping review of clinical trial registries ( Clinicaltrials.gov and EU clinical trial registers) and PubMed/Medline database of trials on PD-1/PD-L1 Inhibitors for early and middle-stage MSI-H and MSS CRC was done up to March 2024. RESULTS: A total of 19 trials related to early to mid-stage MSH-I or MSS CRC were included. Among them, 6 trials are in recruiting status, 3 trials are in active, not recruiting status, 3 trials are completed, 1 trial is terminated, and 1 trial is unknown. Of these, 9 trials involve MSI-H type CRC, and 10 trials involve MSS type CRC. Preclinical phase I/II trials are predominant, with only 3 clinical phase III trials. In trials related to MSI-H type CRC, 4 studies involve PD-1/PD-L1 inhibitors combined with neoadjuvant therapy, and 5 studies involve combination therapy. In trials related to MSS type CRC, 3 studies involve PD-1/PD-L1 inhibitors combined with targeted therapy, 2 studies involve PD-1/PD-L1 inhibitors combined with chemotherapy, 1 study involves PD-1/PD-L1 inhibitor combined immunotherapy, 1 study involves PD-1/PD-L1 inhibitors combined with bacterial therapy, and 3 studies involve PD-1/PD-L1 inhibitors combined with comprehensive therapy. As for primary outcome measures, 4 trials select pathological complete response rates, 3 trials select progression-free survival rate, 3 trials select objective response rate, 3 trials select overall survival rate, 4 trials select disease-free survival rate, 1 trial selects clinical complete response rate, and 1 trial selects percentage of participants with a dose-limiting toxicity. CONCLUSION: For early- and middle-stage MSI-H and MSS CRC, PD-1/PD-L1 inhibitors have shown some therapeutic efficacy, as evidenced by phase I/II studies. However, contemporary trial designs exhibit heterogeneity, with relatively few inclusion criteria, the use of various drug combinations and regimens, and significant variations in reported endpoints. Nevertheless, more double-arm, multicenter, randomized controlled trials are still needed to confirm the efficacy of immunotherapy.

Short-term and long-term efficacy in robot-assisted treatment for mid and low rectal cancer: a systematic review and meta-analysis.

OBJECTIVE: This study aims to conduct a meta-analysis to evaluate the short-term and long-term therapeutic effects of robot-assisted laparoscopic treatment in patients with mid and low rectal cancer. METHODS: A comprehensive search strategy was employed to retrieve relevant literature from PubMed, NCBI, Medline, and Springer databases, spanning the database inception until August 2023. The focus of this systematic review was on controlled studies that compared the treatment outcomes of robot-assisted (Rob) and conventional laparoscopy (Lap) in the context of mid and low rectal cancer. Data extraction and literature review were meticulously conducted by two independent researchers (HMW and RKG). The synthesized data underwent rigorous analysis utilizing RevMan 5.4 software, adhering to established methodological standards in systematic reviews. The primary outcomes encompass perioperative outcomes and oncological outcomes. Secondary outcomes include long-term outcomes. RESULT: A total of 11 studies involving 2239 patients with mid and low rectal cancer were included (3 RCTs and 8 NRCTs); the Rob group consisted of 1111 cases, while the Lap group included 1128 cases. The Rob group exhibited less intraoperative bleeding (MD = -40.01, 95% CI: -57.61 to -22.42, P < 0.00001), a lower conversion rate to open surgery (OR = 0.27, 95% CI: 0.09 to 0.82, P = 0.02), a higher number of harvested lymph nodes (MD = 1.97, 95% CI: 0.77 to 3.18, P = 0.001), and a lower CRM positive rate (OR = 0.46, 95% CI: 0.23 to 0.95, P = 0.04). Additionally, the Rob group had lower postoperative morbidity rate (OR = 0.66, 95% CI: 0.53 to 0.82, P < 0.0001) and a lower occurrence rate of complications with Clavien-Dindo grade ≥ 3 (OR = 0.60, 95% CI: 0.39 to 0.90, P = 0.02). Further subgroup analysis revealed a lower anastomotic leakage rate (OR = 0.66, 95% CI: 0.45 to 0.97, P = 0.04). No significant differences were observed between the two groups in the analysis of operation time (P = 0.42), occurrence rates of protective stoma (P = 0.81), PRM (P = 0.92), and DRM (P = 0.23), time to flatus (P = 0.18), time to liquid diet (P = 0.65), total hospital stay (P = 0.35), 3-year overall survival rate (P = 0.67), and 3-year disease-free survival rate (P = 0.42). CONCLUSION: Robot-assisted laparoscopic treatment for mid and low rectal cancer yields favorable outcomes, demonstrating both efficacy and safety. In comparison to conventional laparoscopy, patients experience reduced intraoperative bleeding and a lower incidence of complications. Notably, the method achieves comparable short-term and long-term treatment results to those of conventional laparoscopic surgery, thus justifying its consideration for widespread clinical application.