How would you work up a patient with prostate cancer with bone scan suspicious for metastatic disease and a negative PSMA PET/CT?

While some bone metastases are 99mTc-positive and PSMA-negative, this circumstance is quite rare (< 2%). Based on this alone, in cases like this, I typically conclude that the patient is clinically M0. However, I do consider 3 other factors: the prevalence of bone metastases within the patient’s particular risk group, CT imaging appearance and location, and other explanations for false positive findings on a bone scan.

In general, the base rate of metastases is quite low in patients with less th...

The answer all depends on context. Roughly 10% of prostate cancer mets will be negative on PSMA but show up positive on FDG PET. I have seen clinical scenarios where Occam's Razor no longer applies. How positive is the bone scan/was there any equivocation? Consider that they may have other potential primary tumors such as lung and colon. Now that 25%of all solid tumor malignancies diagnosed in North America occur in patients who have a history of other solid tumor malignancies, this should be hi...

Based on clinical suspicion, would do an MRI of the bone in question and consider for bx based on MRI findings.

I like the approach laid out by @Dr. First Last. If both MRI and PSMA are negative, I would probably assume the bone scan lesion was a false positive.

I am also generally in favor of biopsy for solitary bone lesions on imaging. I know we may not be convinced by a negative biopsy, but we would know we had the right answer if the biopsy came back positive. The difference between cM1b and cM0 is obviously important.

I will also note that bone lesions that are sclerotic on CT *before treatment* can ...

I appreciate everyone's response on this question. I think it is important to inform everyone on how the case turned out. A little more information on this case that spurred this question, and to answer Dr. @Dr. First Last's excellent questions. The patient was a newly diagnosed T1c, PSA 15.28, Gleason score 4+3=7. This imaging was a part of an initial staging workup. The abnormal bone scan was performed approximately 3 weeks prior to the normal PSMA Pet/CT.

My initial plan was to obtain an MRI ...

RT for cure.

We need more information here. Is this a newly diagnosed case? If this is the initial diagnosis, what is the PSA and Gleason score? What is the risk stratification? If a bone scan is done, I assume this is at least unfavorable intermediate group? Or, if this is a patient with post-prostatectomy or radiation therapy with failure of PSA to fall to undetectable levels? Or, is this a patient who had undetectable PSA after initial surgical or radiation therapy, and now having biochemical recurrence? ...