Precision in Prostate Cancer: Dr. Amir Lebastchi on Tailoring Focal Therapy for Optimal Outcomes

In a recent interview for GU Oncology Now, Advisory Board Editor Akhil Abraham Saji, MD, of Swedish Health Services, spoke with Amir H. Lebastchi, MD, Assistant Professor of Clinical Urology at University of Southern California’s Keck School of Medicine, at the Wester Section American Urological Association Annual Meeting in Kauai, Hawaii.

Dr. Lebastchi is considered one of the foremost experts in the field of focal therapy, publishing extensively on the topic since his residency at the University of Michigan and throughout his fellowship at the National Institutes of Health (NIH).

Together, Dr. Saji and Dr. Lebastchi engage in an in-depth exploration of focal therapy for prostate cancer, covering its historical evolution, current techniques and energy modalities, the critical roles of magnetic resonance imaging (MRI) and biomarkers in patient selection and risk stratification, posttreatment follow-up protocols, management of recurrences, comparisons with alternative treatments such as radical prostatectomy, and a balanced advocacy for integrating focal therapy into clinical practice with careful patient selection.

Dr. Saji: Could you provide a brief overview of the history of focal therapy?

Dr. Lebastchi: Focal therapy has long been a part of oncology, particularly in genitourinary (GU) oncology. We have seen its application in the ablation of renal tumors and prostate cryotherapy, which has been available for many years. In fact, cryotherapy was grandfathered into guidelines as an alternative for patients unsuitable for surgery or radiation. More recently, advancements in technology have expanded the options within focal therapy. These include newer modalities such as high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), TULSA, laser therapy, and several others. While I cannot name them all here, these energy-based technologies are increasingly used to ablate prostate tissue effectively.

Dr. Saji: Could you explain the role of MRI in prostate cancer workups in your practice and how you use it on a day-to-day basis?

Dr. Lebastchi: MRI has been instrumental in making focal therapy a viable option for prostate cancer. It allows us to visualize prostate cancer more clearly, detect it with greater accuracy, and improve risk stratification. By pinpointing exactly where the disease is located, we can target and treat cancer with precision. In my practice, I use MRI before every initial biopsy. It helps me determine where to focus, enabling both targeted and systematic biopsies. We have published on this approach in The New England Journal of Medicine and through the NIH. Performing both biopsy types is essential to assess the disease’s distribution, whether it is confined to the target area or more widespread throughout the prostate. This information is crucial for better risk stratification and selecting appropriate candidates for focal therapy.

Dr. Saji: What is the role of MRI in cases where cancers are not MRI visible?

Dr. Lebastchi: If a cancer is not MRI visible, the role of MRI might initially seem limited. However, imaging often lags behind pathology. In cases of low-risk cancer, I like to monitor patients over time with MRI, as a cancer that is not visible today may become visible and targetable in the future. Imaging follows pathology and biology, so it often takes time for changes to manifest on MRI. Continuously using MRI in these cases helps us track disease progression and ensures timely intervention if needed.

Dr. Saji: Can we briefly discuss the current state of focal therapy for prostate cancer and its place in the guidelines?

Dr. Lebastchi: At present, focal therapy is not fully endorsed by the guidelines. It is an option for patients who are unsuitable for whole-gland treatment options, but it is important to inform patients that focal therapy is still considered investigational. The guidelines are waiting for long-term outcomes data before fully endorsing it. In Europe, focal therapy is recognized as an option as long as it is recorded in registries. Collecting data and understanding how focal therapy works is crucial. While technologies like HIFU and cryotherapy are approved for prostate tissue ablation, they are not yet officially approved for treating prostate cancer specifically.

Dr. Saji: What would be your definition of the ideal focal therapy patient?

Dr. Lebastchi: This is a very common question. The ideal patient is one with intermediate-risk disease, typically Gleason scores of 3+4 or 4+3. I avoid treating patients with low-risk disease or high-risk disease. The cancer should be visible on MRI or PSMA PET scans so it can be effectively monitored over time. It should also be away from critical structures and not exhibit high-risk features such as a cribriform pattern, proximity to the rectum, or extraprostatic extension. For those starting out, it is best to treat intermediate-risk, unifocal disease with clinically significant features—generally Gleason 7 or higher. In my practice, I do not routinely treat Gleason 6 cancers, as they often do not require intervention. The focus should always be on clinically significant cancer that genuinely needs treatment.

Dr. Saji: Do you treat grade group 3 and grade group 2 cancers differently?

Dr. Lebastchi: No, I treat them the same way. In fact, the distinction between grade group 2 and 3 often depends on the pathologist and how rigorously they analyze the tissue. I prefer performing hemi-ablation, treating one side of the prostate while leaving the other untouched. This approach allows me to monitor the treated side and determine whether the therapy was effective if there is a recurrence in the same area. I follow consistent treatment templates for both grade groups.

Dr. Saji: Could you discuss the different energy modalities, including nonthermal techniques like IRE and high-frequency ultrasound? Which do you prefer, and for what cases?

Dr. Lebastchi: I often describe the prostate as divided into the northern and southern hemispheres. The area from 3 o’clock to 9 o’clock represents the southern hemisphere, where the majority of prostate cancers are located. For cancers in this region, I prefer transrectal energy modalities that approach from below, such as high-frequency ultrasound.

For cancers in the northern hemisphere (9 o’clock to 3 o’clock), which are more anterior, I prefer transperineal modalities like cryotherapy and IRE. These modalities provide a more direct route to anterior tumors through the perineal skin. That said, you can treat southern hemisphere cancers with cryotherapy and IRE if necessary. This division is simply my practice preference: posterior cancers are more accessible with transrectal techniques, while anterior cancers are better addressed transperineally due to shorter distances to the tumor.

Dr. Saji: What is the role of biomarkers in your practice? With prostate-specific antigen (PSA) and newer biomarkers like ExosomeDX and Decipher, how do you incorporate them?

Dr. Lebastchi: In my practice, I use biomarkers at various stages, starting with the prebiopsy phase. Tests like Select mdx and MyProstateScore help determine whether a patient needs a biopsy.

After the biopsy, if there is a suspicious target on the MRI but the biopsy results come back negative, I use Confirm mdx. This test analyzes tissue methylation to identify missed cancers, particularly when the results seem inconsistent with imaging findings.

For decision-making, I rely on GPS, Decipher, and occasionally Prolaris. These tests provide valuable insights into the cancer’s aggressiveness, which helps me determine whether a patient is a good candidate for focal therapy. I avoid focal therapy for patients with high-risk scores on these tests. Conversely, for low-risk patients based on pathology, these markers can reveal underlying aggressive disease missed by the biopsy. In such cases, they are essential for better risk stratification and treatment planning.

Dr. Saji: What is your follow-up protocol for patients who undergo focal therapy, whether it is IRE, Cryo, HIFU, or Focal One?

Dr. Lebastchi: A strict surveillance protocol is critical after focal therapy, as it ensures we responsibly monitor patient outcomes. This allows us to identify which patients had successful treatments and which did not. In 2020, I co-authored a Delphi consensus on this topic, which provided expert recommendations for follow-up. The consensus suggests PSA tests every three months during the first year—similar to the protocol after radical prostatectomy—along with imaging between six and 12 months post treatment, followed by a biopsy within that timeframe.

Recently, there has been a trend toward delaying the biopsy, especially for patients who show excellent treatment responses, potentially pushing it out to two years. However, it is essential to place these patients back on an active surveillance protocol after treatment, akin to standard active surveillance protocols that include regular biopsies. If the biopsy results are negative, they continue on a post-ablation surveillance protocol.

Dr. Saji: How do you manage in-field recurrence versus out-of-field recurrence during follow-up?

Dr. Lebastchi: This was addressed in the Delphi consensus as well. The general agreement among experts is that patients with recurrence can often be offered repeat focal therapy, either with the same or a different modality. For instance, if the initial treatment targeted the posterior prostate and the recurrence is in the anterior, you could treat the anterior area separately, perhaps with cryotherapy.

Repeat focal therapy is a viable option, and importantly, it does not “burn any bridges.” Patients can still undergo radical prostatectomy or radiation if needed. These procedures are often less challenging than post-radiation cases because the treatment was focal and localized. I always advise starting on the contralateral side during surgery and then moving to the diseased side, transitioning from the known to the unknown, which simplifies the surgical approach compared to post-radiation cases.

Dr. Saji: What has been your experience with pelvic prostatectomy after focal therapy, compared to the challenges associated with post-radiation prostatectomy?

Dr. Lebastchi: I agree that pelvic prostatectomy after focal therapy is much less complex than after radiation. This is partly because focal therapy is less invasive and localized. In my experience, the challenges arise when the initial focal therapy was too conservative. Some failures occur because we were overly cautious, aiming to preserve the ease of future radical prostatectomy.

The nature of tissue damage also differs significantly between these treatments. Freezing tissue with cryotherapy or ablating with HIFU or IRE does not have the widespread effects of radiation, which impacts the entire pelvis. This distinction makes post-focal therapy prostatectomy more similar to operating on a native prostate than to a post-radiation case.

Dr. Saji: Is there anything else you would like to share about focal therapy and its future direction?

Dr. Lebastchi: I encourage the medical community to expand its perspective and consider incorporating focal therapy into the treatment options for prostate cancer. We use a similar approach in bladder cancer, which is far more lethal. For example, with high-grade T1 bladder cancer, we do not immediately remove the bladder. Instead, we use treatments like bacillus Calmette-Guerin or other localized therapies, even though these have higher failure rates than focal therapy for prostate cancer.

However, while I advocate for a more open-minded approach to focal therapy, I also caution against being overly aggressive. We should not treat all patients indiscriminately. Patient selection is critical to achieving good outcomes, and the approach must remain measured and evidence based. Focal therapy has great potential, but it should be applied thoughtfully.