How would you treat a p16+ small cell neuroendocine tumor of the anal canal with or without metastatic inguinal lymph node metastasis?

Interesting case. Small cell cancers are generally considered radiosensitive, but so is anal squamous cell carcinoma. I personally would do the same RT field and dose. The real conundrum for me is the concurrent chemotherapy regimen - do you keep 5FU/MMC or do you use cisplatin/etoposide? I think a lot of med oncs would do cis/etop because of the small cell histology.

I think the p16 is a bit of a red herring here. Is there squamous cell cancer anywhere in the specimen?

I'd be interested to hear what others think.

I agree. The extremely high DM risk should drive management. Extrapulmonary small cell neuroendocrine cancers all behave like the pulmonary ones. Although it is a rare histology and there is no definitive data, initial cis/etoposide followed by concurrent cis/etoposide IMRT with standard anal cancer dosing should be the preferred approach.