How would you approach de novo metastatic castrate sensitive prostate cancer with extensive locoregional spread causing rectal compression, retroperitoneal lymphadenopathy, and PSA >3000 but no visceral or bone metastases?  

It sounds like from the question that the patient has T4 disease invading the rectum. This makes the patient ineligible for surgical resection with curative intent. He might still be a candidate for curative intent radiation therapy/ADT +/- abiraterone per STAMPEDE. His highly elevated PSA is very w...

RP lymphadenopathy would suggest metastatic disease and possibly there is more disease than visible on conventional imaging. I would suggest PSMA PET and start the patient on ADT+ARPI; based on the response in 3-6 months, he may benefit from local regional radiotherapy.

I also agree with the idea of ADT+-ARPI first, followed by consideration of prostate-directed RT. But there is a major issue. The largest third-party prior authorization company is very specific in that if you treat with ADT first, they are no longer eligible for prostate RT. I have lost this fight...

Great answers and agree with ADT+ARSI.  One thing that's not clear to me from the stem, but can come up with bulky T4 tumors is whether or not a diverting colostomy makes sense. Depending on the scenario, it can be very helpful prior to palliative or semi-definitive RT. Otherwise, I like the 3...