Patient Selection Key for Focal Therapy in Intermediate Prostate Cancer

Ruben Olivares, MD

Focal therapy has emerged as a potential treatment option for patients with intermediate prostate cancer; however, as long-term data continue to emerge for the newer modality, patient selection and multidisciplinary decision-making remain key for deciding when to utilize this modality, according to Ruben Olivares, MD.

“We have to be very strict in the patient selection [for focal therapy]. That means that we have to put together MRI and pathology, then have a discussion in a collaborative way with radiation oncologists, medical oncologists, and pathologists to try to find the right candidates for this alternative treatment,” Olivares said in an interview with OncLive^®. Olivares is a urology specialist with the Cleveland Clinic in Ohio.

In the interview, Olivares discussed the fundamental differences between focal therapy and conventional localized radiation therapy; underscored the employment of sophisticated guidance techniques and meticulous energy mapping to pinpoint specific regions within the prostate gland for focal therapy; and highlighted ongoing research evaluating this modality.

OncLive: When looking at various types of focal therapy for patients with prostate cancer, what data inform their benefit-risk profiles?

Olivares: For patients with intermediate prostate cancer, we are [currently] living [through] a revolution. We are able to see and detect the area of concern for prostate cancer that, in the future, could drive metastatic spread or mortality. Different sources of energy are able to [be utilized as focal therapy]. There are many sources of energy, but most of the time, this is thermal energy, such as high [intensity focused ultrasound] and cryotherapy that is able to boil or freeze the prostate [cancer] tissue; or interstitial energy, such as irreversible electroporation [IRE], that is able to deliver an electrical current, killing the area of the prostate where the prostate cancer is [localized].

What distinguishes focal therapy from localized radiation therapy in prostate cancer?

The main difference between localized radiation and focal treatment is that we use different guidance. We use fusion capabilities [to give us] precise anatomic guidance where we deliver that [focal therapy]. Secondly, we are able to outline the extension of the energy, [meaning] we can put probes or needles, and using software, we can clearly map the outside layer of where the energy is going to reach.

Which patients are the optimal candidates for focal therapy?

The [ideal] candidates for focal treatment are patients with intermediate prostate cancer, [which] means that a biopsy [shows Gleason] pattern 4. They must have a clear, visible image on the MRI that matches with the biopsy location. Patients need unilateral cancer, where the location from the biopsy should match the location from the MRI.

Patients must understand some uncertainties of the follow-up [data regarding focal therapy]. For example, for radical prostatectomy or irradiation, we have 30 or 40 years of follow-up. Focal treatment is a new alternative for [patients with] intermediate prostate cancer. For now, we have 15 years of follow-up [data] that looks promising; however, it's not the 30 or 40 years [of follow-up], where we know what's going to happen with standard of care.

Digging a little bit more into the data for focal therapy, what does promising mean in this context?

The data clearly show that the functional aspect after focal treatment is wonderful. The risks of having erectile dysfunction or urinary incontinence after focal treatment—despite the energy [used with this modality]—are extremely low. With prostate cancer and follow-up for the oncological outcomes, we need overall survival [(OS) data].

The problem with prostate cancer is that it is a very slow disease. Therefore, to get OS [data for focal therapy], we're going to need 30 to 40 years [of follow-up]. [Data] we are using now [for focal therapy] include failure-free survival [FFS]. We are using metastasis-free survival [(MFS) regarding] the necessity of radical treatment during follow-up. [By saying] ‘promising,’ I'm referring to FFS for now, which looks promising.

Is FFS currently a widely accepted end point?

I would say yes. There is a good correlation with FFS and MFS with OS. We have examples from other tumors in our body that seem [to have] a very slow growing process. We could use MFS and FFS as a surrogate of OS.

Focal therapy was initially considered as an alternative to active surveillance for patients with low-risk disease, and we're now observing its utilization in those with intermediate-risk disease. Do you anticipate its potential escalation to higher-risk populations in the future?

After many clinical trials, we now have a better understanding of the natural history of prostate cancer. What we were doing 10 to 15 years ago to treat a patient with low-grade prostate cancer is not the standard of care anymore. Focal treatment is not going to replace active surveillance; focal treatment is going to enable active surveillance. If we are able to destroy the more aggressive tumor within the prostate gland, we can offer active surveillance to the rest of the prostate.

Are there any forthcoming or scheduled research endeavors in this field that you're eager to see?

Currently, there are almost 10 clinical trials that [are in] different phases, from enrollment to currently running, that are going to give us good information to compare focal treatment with radical options, such as radical prostatectomy or irradiation.

Secondly, I'm interested to see how we can manage the microenvironment inside the prostate. In the future, we are going to see a role for other treatment alongside focal treatment, [such as] focal treatment plus immunotherapy. This is probably not [going to be] systemic therapy, because focal treatment is a patient-driven option, we are probably not going to offer systemic therapy. However, locally, we are going to be able to boost the immune response to tackle the microenvironment inside the prostate as we are using focal treatment.

Three years ago, Cleveland Clinic [established] a focal therapy tumor board. It is a weekly meeting with all the colleagues who are involved in cancer treatment. [This tumor board allows for] better stratification [and finding] good candidates for focal treatment, and it's the backbone [for driving the focal therapy approach].

Considering the importance of early referral for the use of CAR T-cell therapy for patients with hematologic malignancies, when it comes to focal therapy for prostate cancer, what advice would you offer to community oncologists regarding the potential referral of these patients to your care?

In the community setting, they're doing a wonderful job. Prostate-specific antigen screening saves lives, especially in the African American patient population and others. Early referral to the urologist who is going to perform the MRI or biopsy, as needed, is the first step. If we are able to catch [prostate cancer] in the early stage, we are probably going to be able to offer less radical options with less functional impact for our patients. Early referral is the right way to go.

Reference

Olivares R. Evolving role of focal therapy for localized prostate cancer. Presented at: 17th Annual Interdisciplinary Prostate Cancer Congress and Other Genitourinary Malignancies; March 8-9, 2024; New York, NY.