The NCI 9673 trial demonstrated that adding the CTLA-4 inhibitor ipilimumab to the PD-1 inhibitor nivolumab did not improve response rate, PFS, or overall survival in patients with previously treated anal cancer. This finding discourages this combination approach, avoiding unnecessary toxicity.

Data from the Podium-303 trial's crossover arm suggests that waiting to use a PD-1 inhibitor after progression on chemotherapy is less effective than using it concurrently from the start. This supports the synergistic effect of chemo-immunotherapy and favors the concurrent approach as the standard of care.

Contrary to the typical prognosis for metastatic cancers, a subset of patients with metastatic squamous cell carcinoma of the anal canal can be cured. This potential, especially in cases with limited disease burden like lymph node-only metastases, calls for an aggressive, multidisciplinary treatment approach rather than a purely palliative one.

With 72% response rates to neoadjuvant immunotherapy, surgeons are shifting from immediate, aggressive surgery to a "wait-and-see" approach. Shrinking the tumor first can turn a morbid, disfiguring operation into a much simpler procedure, fundamentally changing the initial surgical evaluation for cutaneous squamous cell carcinoma (CSCC).

The practice-changing DYNAMIC trial showed that a ctDNA-guided strategy for stage II colorectal cancer reduces adjuvant chemotherapy use by 50%. Despite this significant de-escalation of treatment, patient outcomes and survival rates were identical to the standard-of-care approach.

Local recurrence of anal cancer in the pelvis post-chemoradiation is a major quality of life issue. These recurrences are often advanced, destructive, and difficult to resect or re-irradiate, leading to significant palliative problems such as severe pain, edema, and radiculopathy that are challenging to manage.

The INTERACT trial showed carboplatin/paclitaxel had similar response rates and PFS to cisplatin/5-FU. It became the standard of care primarily due to its significantly better side effect profile, with lower rates of bone marrow suppression, fatigue, and GI toxicity.

A meta-analysis of over 3,000 patients shows that neoadjuvant chemotherapy for MSS colon cancer provides a 5% improvement in survival. This benefit is clinically meaningful and equivalent in magnitude to the landmark addition of oxaliplatin to 5-FU in the original MOSAIC trial.

Observational data from the BESPOKE study showed that the survival benefit from adjuvant chemotherapy was only seen in patients who tested positive for ctDNA post-surgery. In contrast, ctDNA-negative patients had overlapping survival curves whether they received chemotherapy or not, questioning its utility for that group.