Dr. R. Jeffrey Karnes is an Associate Professor and Vice Chair of the Urology Department at the Mayo Clinic in Rochester, Minnesota.
Prostatepedia spoke with him about how imaging impacts salvage focal therapy.
How does newer imaging like gallium-68 PSMA PET/CT impact salvage focal therapy?
Dr. Karnes: PET imaging has been good at detecting metastases, but in terms of imaging the primary tumor, the resolution hasn’t been the best. Now, we and others are moving into a PET/MRI scan.
That is a fusion scan?
Dr. Karnes: A fusion scan with MRI rather than the PET/CT. Obviously, an MRI provides more resolution of the prostate. To me, MRI is obviously the gold standard when it comes to imaging the primary prostate. We’re certainly using the technology. Others are using it. We don’t really know what the exact accuracy is of the MRI/PET fusion scan in those who have had radiation failure.
And, as I mentioned, I don’t think we have really much in the way of a clue regarding the biology of this index lesion in radiation-recurrent cancer in the prostate. I think that in the glands of men who recur after radiation, there is probably higher tumor burden compared to the newly diagnosed patient.
A third problem we have when it comes to focal salvage therapy is that I don’t think we even have a great definition of what constitutes a potential local recurrence after primary radiation. The Phoenix definition used by the American Society for Radiation Oncology is the nadir (or lowest) PSA plus 2. This definition predicts recurrence, but what it really predicts is progression, not necessarily local recurrent disease.
In this country, for many men who fail radiation, the next treatment is hormonal therapy. Hormonal therapy really has only a palliative intent and won’t cure anyone of localized radiation-recurrent disease.
We need to do a better job of appropriately diagnosing radiation failure patients in the first place. What that better job would be, I don’t know. I don’t think routine biopsies, which have been looked at in the past, are the answer. But perhaps imaging sooner rather than waiting for the Phoenix definition makes sense. Maybe, as you mentioned appropriately, with the newer PET/MRI fusion scans, we can image men sooner to try to detect a local recurrent disease earlier.
That being said, I do a lot of salvage radical prostatectomies, almost one a week. This is unpublished, but I have not seen a big stage migration (less extraprostatic extension and/or nodal metastasis) in the last decade. I still see a lot of patients with radiation failure; they come to their salvage prostatectomy with seminal vesicle invasion and nodal disease. Up to a third of patients will have seminal vesicle invasion and I see nodal involvement in up to 20% at salvage surgery.
Why is that relevant to salvage focal therapy?
Dr. Karnes: A lot of the seminal vesicle invasion is not always evident on MRI. And a lot of these patients don’t get routine biopsies of their seminal vesicles. If they undergo a salvage focal therapy, their doctors are obviously going to be missing a significant component of their disease because salvage focal therapy, in my opinion, doesn’t work to ablate the seminal vesicles. Obviously, salvage focal therapy can do a job in the gland itself, but in the appendages, such as seminal vesicles, it is hard to get an appropriate ablation of the entire seminal vesicles because of the risk to adjacent structures— the bladder, the ureters, and so forth.
Another thought I have about salvage focal therapy is when we look at other forms of ablation technologies like cryotherapy or HIFU, we’ve morphed them from whole-gland to focal and now to focal salvage therapies. But I don’t think we even know who the ideal candidate is for whole-gland HIFU or whole-gland cryotherapy let alone the focal form of the therapies in a treatment-naïve patient. Obviously, these are alternatives or options for patients who are newly diagnosed, but more troubling for me is this: I don’t think we know exactly what constitutes a success. How do we monitor whole-gland cryotherapy or whole-gland HIFU? We’ve used PSA failure as a definition, but are we really using the right tool to monitor?