FOCAL THERAPY Use of Focal Therapy in Appropriate Candidates Discontinuing Active Surveillance: A Paradigm Shift
By: Wei Phin Tan, MD, NYU Langone Health, New York City; Osamu Ukimura, MD, PhD, Kyoto Prefectural University of Medicine, Japan; Peter Carroll, MD, MPH, University of California, San Francisco | Posted on: 09 Jun 2023
Prostate cancer is the second most common cancer in men globally, and its management remains a significant challenge. While localized low-grade prostate cancer has a long natural course and limited metastatic potential, treatment options can have severe consequences for the patient’s quality of life. The PROTECT trial, which consisted of 77.2% of men with grade group 1 prostate cancer, revealed that the overall survival was similar between men undergoing prostatectomy, radiotherapy, and active surveillance (AS) at 15 years.1 Among those in the prostatectomy group, urinary leakage requiring pads occurred in 18% to 24% of patients over 7 to 12 years, compared with 9% to 11% in the active monitoring group and 3% to 8% in the radiotherapy group.2 Fecal leakage (more than once per week) increased gradually in the radiotherapy group to affect twice as many participants in the radiotherapy group (12%) compared with 6% in the prostatectomy and active monitoring groups by year 12.2 This suggests that prostate cancer may be overtreated, and the resulting consequences can be quite significant to a patient’s quality of life.
Focal therapy (FT) or partial gland ablation entails applying some form of energy to the area of the prostate that contains clinically significant cancer, with the goal of achieving less morbidity yet similar cancer control compared to whole-gland approaches. The emerging field of FT technologies includes high-intensity focused ultrasound, laser ablation, photodynamic therapy, irreversible electroporation, steam ablation, and cryoablation.
Recently, a Delphi consensus from a multidisciplinary, multi-institutional, international prostate cancer expert panel was conducted to determine if there is a role for FT in patients discontinuing AS for prostate cancer.3 The participants were sent the questionnaire electronically in 3 consecutive rounds. At each subsequent round, the aggregate results of the prior round were presented anonymously, and the participants were allowed to modify their responses. Feedback and comments provided by experts were utilized to adjust/refine existing questions or explore controversial topics in greater depth. Achieving consensus was defined by having ≥80% agreement for each question. The panel concluded that there is a role for FT in select men who are discontinuing AS. The panel agreed that FT is less invasive, has greater likelihood of preserving erectile function, has greater likelihood to preserve urinary continence, and is associated with earlier recovery posttreatment.
Although the ideal patient who is a candidate for FT is of much debate, most experts believe that men in good health with unilaterally localized prostate cancer, an MRI visible lesion (T2), grade group 2 or 3 prostate cancer, and PSA <15 are good candidates for FT. Further, in a large cohort of patients on AS for prostate cancer enrolled at the University of California San Francisco, serial biopsy findings in men with early-stage cancer on AS show that dominant tumor location remained relatively stable indicating that 70% of patients on AS who progressed remained favorable for focal or hemigland ablation.4 Workup prior to FT should abide by the standard of care, including contemporary imaging, most commonly prostate-specific membrane antigen positron emission tomography.5
FT has shown promising results in terms of cancer control and preservation of quality of life. Even though data are scarce, cryoablation is thought to have the best oncologic control among the energy modalities for FT. The downside to cryoablation is that it can be difficult to control the spread of the ice ball, potentially resulting in higher rates of erectile dysfunction compared to other energy modalities. FT utilizing cryoablation has a failure-free survival (defined as clinically significant prostate cancer on follow-up biopsy, receiving whole-gland therapy, evidence of metastasis, or death from prostate cancer) of between 53% and 90.5% at 3 to 5 years.6 Contemporary series have shown that major complication rates from FT are extremely low, and rectal urethral fistula occurs in less than 1% of patients.7 Other ablation techniques show favorable outcomes as well.
As the field of FT continues to advance, it will be critical to establish standard criteria for patient selection, define optimal techniques and approaches, and develop consistent protocols for monitoring and follow-up. Through these efforts, FT is likely to become an increasingly valuable option for the management of localized prostate cancer, potentially avoiding unnecessary morbidity and improving patient outcomes.
In conclusion, FT offers a promising alternative for the management of localized prostate cancer in carefully selected patients, particularly in men who are discontinuing AS. However, it should not be used in lieu of AS in men who are good candidates for it, based on a thorough initial evaluation. Patients with clinically insignificant cancer should undergo AS, while those with clinically significant cancer who are suitable candidates should be considered for FT. Therefore, it is important to recognize that AS and FT are intended for different groups of patients.
- Hamdy FC, Donovan JL, Lane JA, et al. Fifteen-year outcomes after monitoring, surgery, or radiotherapy for prostate cancer. N Engl J Med. 2023;10.1056/NEJMoa2214122.
- Donovan JL, Hamdy FC, Lane JA, et al. Patient-reported outcomes 12 years after localized prostate cancer treatment. NEJM Evidence. 2023;2(4):EVIDoa2300018.
- Tan WP, Rastinehad AR, Klotz L, et al. Utilization of focal therapy for patients discontinuing active surveillance of prostate cancer: recommendations of an international Delphi consensus. Urol Oncol. 2021;39:781.e717-781.e724.
- Fasulo V, Cowan JE, Maggi M, et al. Characteristics of cancer progression on serial biopsy in men on active surveillance for early-stage prostate cancer: implications for focal therapy. Eur Urol Oncol. 2022;5(1):61-69.
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Prostate Cancer Version 1.2023. 2022. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf.
- Tan WP, Wysock JS, Lepor H. Partial gland cryoablation for prostate cancer—where are we?. Urology. 2023;20:127-128.
- Hopstaken JS, Bomers JGR, Sedelaar MJP, Valerio M, Fütterer JJ, Rovers MM. An updated systematic review on focal therapy in localized prostate cancer: what has changed over the past 5 years?. Eur Urol. 2022;81(1):5-33.