How would you manage a patient with new FDG avid retroperitoneal lymph nodes after completing definitive chemoradiation for stage III anal canal cancer?

I agree with @Dr. First Last. PA nodes are not really systemic disease if you consider the disease biology. They are regional nodes. There is 100% RR and >90% LC with chemoradiation with very low risk.

I would encourage a thorough assessment of extent of current disease. If disease is controlled within the pelvis and the patient experienced progression out of the prior field, then salvage chemoradiation does offer curative potential. MultiD discussion is key for cases like this. @Dr. First Last, t...

Holliday et al., PMID 29907489.

Largest series showing long term DFS and OS with definitive chemo RT for RP nodes at presentation.

I would biopsy these nodes. If positive, I would manage with immunotherapy (preferred, see here for supportive trial information https://ascopubs.org/doi/10.1200/JCO.2020.38.4_suppl.1 ) or carboplatin/Taxol (Rao et al., PMID 32530769). Radiation and surgical oncology teams should also be consulted f...