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FOCAL THERAPY Comparison of Adverse Events and Quality of Life Between Focal Therapy and Whole-gland Treatment in Prostate Cancer

By: Ruben Olivares, MD, Cleveland Clinic, Ohio; Tarik Benidir, MD, University of Florida, Miami | Posted on: 09 Jun 2023

Prostate cancer affects nearly 1 in 8 men,1 representing the most common noncutaneous malignancy. Fortunately, most diagnoses are identified when the disease is presumed to be organ confined, which opens the discussion on an ever-growing array of treatment options. While a Christmas shopping list of treatment strategies may seem positive for the field of urology, patients are nonexperts, and yet they must face a difficult decision of selecting a treatment course. Should a patient decide to pursue active surveillance for high-volume low-risk or low-volume intermediate-risk disease, they must live with the potential consequence of disease progression and loss of oncologic control. Alternatively, should a patient seek a radical therapy with curative intent, they must accept the short-term sequelae of surgery and the possible long-term sequelae of either surgical- or radiation-induced side effect profiles, both shown to impact overall quality of life.1,2 Decisional conflict and regret are not only a real phenomenon, but also a growing concern for patients with this disease, accentuated by a strong feeling of self-blame on those perceived to have made the wrong treatment choice.3 A recent meta-analysis in nearly 20,000 patients identified how 1/5 patients regretted their treatment choice.4 Regret was not related to patient race, age, or employment status, nor was it related to oncologic factors such as the initial grade group or PSA. The regret was circled around quality-of-life outcomes and intimately associated with complications of select procedures, notably urinary incontinence, urinary symptoms (irritative ± obstructive), bowel function, and sexual function.5 For those undergoing radical therapies, treatment did impact their perceived masculinity especially in the context of lingering side effects. This meta-analysis importantly emphasizes the need to establish thorough discussion with patients regarding not only the side-effect profiles of both active surveillance and radical therapies, but also the existence of decisional regret, which can be mitigated to some extent with patient education.

The recently updated 15-year outcome from the PROTECT trial comparing patient monitoring to radical prostatectomy to radiation treatment is an impactful publication which warrants further discussion. Radical therapies as compared to monitoring did improve both clinical progression-free survival and metastasis-free-survival, but this did not correlate to an increase in overall survival. Granted, radical therapies also reduced the need for androgen deprivation therapy which carries significant side-effect profiles, but on the other hand, 25% of those in the monitoring group never needed further treatment at 15 years and would have been overtreated had they been randomized to the intervention arms.5 Because clinical progression/metastasis does not necessarily coincide with patient symptoms, and because overall survival was not extended, urologists must appreciate how mitigating therapies which negatively impact quality of life are of germane importance when men are initially presented with a prostate cancer diagnosis. Cue in focal therapy.

While prostate cancer is a largely multifocal disease, up to 25% of prostate cancers are truly unifocal.6 Secondly, index lesions, which are often MRI visible, are considered to be the driver of metastasis and have higher genomic risk scores than their MRI-invisible and/or nonindex lesion counterparts.7 As such, focal therapy may cure unifocal patients while mitigating progression risk in a meaningful proportion of multifocal patients. Focal therapy is increasingly recognized as an acceptable treatment option in well-selected men with clinically significant localized prostate cancer, with a strong preference for treating the intermediate-risk population. The adequate medium-term oncologic control in select men8 is further encouraged by its clear advantage over radical therapies in mitigating the functional side effects of whole gland treatment.

While multicenter randomized clinical trials are absolutely needed to cement the value of focal therapy in the armamentarium of practicing urologists, focal therapy has now been studied in over 8 energy sources, mostly at the stage 2 (exploratory phase).9 Furthermore, systematic reviews incorporating over 70 studies in nearly 6,000 men show promising functional results and superior results to radical therapies. When examining some of the most commonly utilized energy sources, high-intensity focused ultrasound with or without preoperative transurethral prostatectomy demonstrated an immediate median 95% pad-free rate, irreversible electroporation and cryoablation had a median 100% pad-free rate after treatment, and photodynamic therapy showed no changes in continence.9 From a sexual function perspective, high-intensity focused ultrasound did garner some increase in erectile dysfunction by 12%-20% and an increased need for phosphodiesterase type 5 inhibitor use from 11%-17%. Similarly, irreversible electroporation had a mild effect on sexual function, but these proportions were significantly better than robot-assisted radical prostatectomy (P < .05).9 When comparing whole gland to focal cryoablation, erectile function was significantly improved with the focal approach (69% to 47% P < .05).9

Although most of these studies are single center and prospective and involve a wide array of focal options, sexual and urinary outcomes are consistently described with superior rates to whole gland approaches.9 With the current growing body of evidence supporting patient-centered quality-of-life measures as holding a meaningful seat at the table of patient care, can focal therapy serve as a middle ground, a compromise, and perhaps a preference in select patients between absolute oncologic control (radical therapies) and absolute functional outcomes (monitoring)? Multicenter randomized clinical trials will determine if, when, and how focal therapy should be practiced in the ever-changing world of localized prostate cancer management.

  1. Lardas M, Liew M, van den Bergh RC, et al. Quality of life outcomes after primary treatment for clinically localised prostate cancer: a systematic review. Eur Urol. 2017;72(6):869-885.
  2. Kesch C, Heidegger I, Kasivisvanathan V, et al. Radical prostatectomy: sequelae in the course of time. Front Surg. 2021;8:684088.
  3. Roese NJ, Summerville A, Fessel F. Regret and behavior: comment on Zeelenberg and Pieters. J Consum Psychol. 2007;17(1):25-28.
  4. Fanshawe JB, Wai-Shun Chan V, Asif A, et al. Decision regret in patients with localised prostate cancer: a systematic review and meta-analysis. Eur Urol Oncol. 2023;S2588-9311(23)00037-8.
  5. 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.
  6. Eggener SE, Scardino PT, Carroll PR, et al. Focal therapy for localized prostate cancer: a critical appraisal of rationale and modalities. J Urol. 2007;178(6):2260-2267.
  7. Purysko AS, Magi-Galluzzi C, Mian OY, et al. Correlation between MRI phenotypes and a genomic classifier of prostate cancer: preliminary findings. Eur Radiol. 2019;29(9):4861-4870.
  8. Reddy D, Peters M, Shah TT, et al. Cancer control outcomes following focal therapy using high-intensity focused ultrasound in 1379 men with nonmetastatic prostate cancer: a multi-institute 15-year experience. Eur Urol. 2022;81(4):407-413.
  9. 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.