Do you change your monitoring strategy for a high risk prostate cancer after XRT if the initial PSAs have never been very high?

In general, a patient whose volume of cancer is out of proportion to their PSA makes me nervous. So, I'm much more worried about the patient with a PSA of 5 and multiple cores positive for high volumes of Grade Group 4-5 cancer than I am about the patient with a PSA of 5 and a single positive core showing <5% Grade Group 4. For these worrisome patients, I tend to follow them more frequently, usually every 3 months for the first 2 years, then every 6 months to year 5, even if their PSA becomes undetectable, because I worry that they have more aggressive disease. I will check a PSA at each visit. In the extremely worrisome patients, i.e., those with high-volume, high-grade disease who present with low or even normal PSA, I would consider re-i...

It is always a concern when the PSA does not represent the severity of the disease. It probably means more dedifferentiated histology. I am usually concerned with only following the PSA on these patients. Generally, I would get an MRI and a bone scan yearly in addition to their 6-month PSA.

I do not change my surveillance strategy per se other than I check PSA q3-4m until testosterone recovery for all high risk patients other than ECE only risk feature. If PSA becomes detectable, I lower my thresholds for PSMA PET for patients that have a low secretory profile which is almost always grade 5 to 0.2 rather than 0.5 for post-prostatectomy and definitive patients I consider at PSA 1. Also for Grade 5, I test q3m regardless of if the patient is under treatment as otherwise, I wait until 3 mo post RT. Grade 5 is just a different animal than other high grade variants we tend to see.

I know the Harvard group was trying to define a high-risk low secreting subset. I’m not sure where that data stands now, but it might be patients we escalate in the future, novel anti androgens, maybe systemic therapy, etc.