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.
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.
For patients with localized (non-metastatic) squamous cell carcinoma of the anal canal, adding systemic chemotherapy before standard chemoradiation does not improve outcomes. Randomized trial data has shown no positive impact from this neoadjuvant approach, reinforcing that concurrent chemoradiation remains the standard of care for curative intent in this setting.
While the POD1UM-303 trial protocol for retifanlimab in anal cancer was one year, clinicians may continue therapy for patients with a partial response. If active, controlled disease remains, the risk of progression upon stopping may outweigh the low toxicity risk from monotherapy, prompting a discussion to continue treatment.
A PD-L1 CPS score of zero should not automatically disqualify patients with metastatic anal cancer from receiving immunotherapy. The clinical distinction between a CPS of zero and one is marginal, and given the therapy's potential for benefit and low toxicity, clinicians should give patients the benefit of the doubt and offer the treatment.
The benefits of HPV vaccination on reducing anal cancer incidence will not be fully realized for over three decades. Because the disease typically affects people in their sixties and seventies, the impact of vaccinating teenagers today will only become apparent when that cohort reaches the peak age of diagnosis, delaying observable population-level effects.