Do you offer prostate RT to men with 0-3 bone metastases on conventional imaging when PSMA PET shows a very high number of M1 lesions?

This would be a hard no from my standpoint.

I get the rationale here. STAMPEDE found a survival benefit for prostate-directed RT in men with "low volume" disease, which was defined based on the CHAARTED trial with conventional imaging. Therefore, men with low-volume disease on conventional imaging fit the criteria and should be offered it since we don't know how PET staging affects that.

But for me, this is a classic Will Rogers Phenomenon. PSMA PET is much more sensitive than conventional imaging...

Great question, as we are seeing this clinical scenario more and more in practice. I don't think we have a clear answer on this, and I am curious to know how others would approach this case.

There are a few points I'd like to discuss.

Many of the CHAARTED low-volume patients are expected to have polymetastatic disease on PET (~20% in Barbato et al., PMID 33990403).

I think the metastatic burden, quantified by the volume of the disease and not by the number of metastases would also be informative...

This is definitely a case-by-case decision based on many patient-related factors and the exact degree and location of disease burden (is it high volume because there are 6 lesions and not 5?, bulky pelvic nodes, etc), but often yes based on PEACE-1 showing the reduced risks of GU complications and the delay in castrate-resistance, the latter of which is the biggest turning point in the disease process.

Prostate RT is a very well-tolerated treatment and it’s likely that the benefits have increased...

I believe the PSMA scan is more sensitive than conventional imaging, so I wouldn't treat with the intention that OS will be impacted. PEACE-1 is another trial that looked at this, presented at ASCO 2023.

Summary: Prostate-only RT doesn't appear to impact OS in 'low-volume' patients, though there is minimal added toxicity. However, the addition of prostate radiotherapy is associated with a decreased rate of serious GU events irrespective of metastatic burden.