Primary Whole-gland Ablation for the Treatment of Clinically Localized Prostate Cancer: A Focal Therapy Society Best Practice Statement.

CONTEXT: Whole-gland ablation is a feasible and effective minimally invasive treatment for localized prostate cancer (PCa). Previous systematic reviews supported evidence for favorable functional outcomes, but oncological outcomes were inconclusive owing to limited follow-up. OBJECTIVE: To evaluate the real-world data on the mid- to long-term oncological and functional outcomes of whole-gland cryoablation and high-intensity focused ultrasound (HIFU) in patients with clinically localized PCa, and to provide expert recommendations and commentary on these findings. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, Embase, and Cochrane Library publications through February 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. As endpoints, baseline clinical characteristics, and oncological and functional outcomes were assessed. To estimate the pooled prevalence of oncological, functional, and toxicity outcomes, and to quantify and explain the heterogeneity, random-effect meta-analyses and meta-regression analyses were performed. EVIDENCE SYNTHESIS: Twenty-nine studies were identified, including 14 on cryoablation and 15 on HIFU with a median follow-up of 72 mo. Most of the studies were retrospective (n = 23), with IDEAL (idea, development, exploration, assessment, and long-term study) stage 2b (n = 20) being most common. Biochemical recurrence-free survival, cancer-specific survival, overall survival, recurrence-free survival, and metastasis-free survival rates at 10 yr were 58%, 96%, 63%, 71-79%, and 84%, respectively. Erectile function was preserved in 37% of cases, and overall pad-free continence was achieved in 96% of cases, with a 1-yr rate of 97.4-98.8%. The rates of stricture, urinary retention, urinary tract infection, rectourethral fistula, and sepsis were observed to be 11%, 9.5%, 8%, 0.7%, and 0.8%, respectively. CONCLUSIONS: The mid- to long-term real-world data, and the safety profiles of cryoablation and HIFU are sound to support and be offered as primary treatment for appropriate patients with localized PCa. When compared with other existing treatment modalities for PCa, these ablative therapies provide nearly equivalent intermediate- to long-term oncological and toxicity outcomes, as well as excellent pad-free continence rates in the primary setting. This real-world clinical evidence provides long-term oncological and functional outcomes that enhance shared decision-making when balancing risks and expected outcomes that reflect patient preferences and values. PATIENT SUMMARY: Cryoablation and high-intensity focused ultrasound are minimally invasive treatments available to selectively treat localized prostate cancer, considering their nearly comparable intermediate- to long term cancer control and preservation of urinary continence to other radical treatments in the primary setting. However, a well-informed decision should be made based on one's values and preferences.

Focal Cryotherapy for localized prostate cáncer / Crioterapia Focal para el cáncer de próstata localizado

OBJECTIVE: To systematically review the oncological and functional outcomes of contemporary primary prostate focal cryotherapy for localized prostate cancer in the context of current developments in prostate focal therapy. METHODS: We performed a systematic search of the Pubmed, Cochrane and Embase databases to identify studies where primary prostate focal cryotherapy was performed to treat prostate cancer. These included reports on focal/ lesion/ sector ablation, hemi-ablation and partial prostate ablation. We excluded salvage focal therapy studies. Where multiple reports were published over time from a single cohort, the latest one was used. RESULTS: Our search yielded 290 publications, including 17 primary reports on eight single-center cohort studies and one multi-center registry report. Of 1,595 men identified, mean age was 60.5-69.5 years and mean PSA 5.1-7.8 ng/ml. When stratified Arch. Esp. Urol. 2016; 69 (6): 317-326 317 by D'Amico risk criteria, 52% of the aggregate total number of men were low-risk, 38% intermediate-risk and 10% high-risk. Besides 12-core TRUS biopsy, 3 cohorts reported using TTMB and one included mpMRI to select men for focal treatment. Median follow-up ranged from 13-63 months. BPFS ranged from 71-98%. The overall post-treatment positive biopsy rate was 8-25%. Among 5 cohorts with a mandatory 6-12 month posttreatment biopsy, 216 of 272 men (79%) did undergo biopsy, with 47 positive (21.8%). Of these, 15 were infield, 26 outfield, 2 bilateral and 4 undeclared. Ten upgraded to Gleason ≥ 7. Overall, two men had metastatic disease and none died of prostate cancer. Post-treatment continence rates were 96-100% and rates of erectile dysfunction ranged from 0-42%. The rate of post-treatment urinary retention ranged from 0-15%. The rate of recto-urethral fistula was 0-0.1%. CONCLUSION: Focal cryotherapy for localized prostate cancer is a safe and provides good preservation of sexual and urinary function. Accurate cancer localization and risk stratification is key to patient selection. In highly selected patients, focal therapy has good short to medium term oncological efficacy

OBJETIVO: Revisión sistemática de los resultados oncológicos y funcionales de la crioterapia focal primaria de la próstata contemporánea en el contexto de los desarrollos actuales en terapia focal prostática. MÉTODOS: Realizamos una búsqueda sistemática de las bases de datos PubMed, Cochrane y Embase para identificar estudios donde se realizara crioterapia focal primaria prostática para el tratamiento del cáncer de próstata. Éstos incluían comunicaciones de ablación focal/lesional/sectorial, hemiablación y ablación prostática parcial. Excluimos los estudios de terapia focal de salvamento. En los casos en que había múltiples artículos de una única cohorte publicados en el tiempo se utilizó el último. RESULTADOS: Nuestra búsqueda obtuvo 290 publicaciones, incluyendo 17 comunicaciones primarias de ocho estudios de cohortes de un único centro y una comunicación de un registro multicéntrico. De 1595 hombres identificados, la edad media era 60,5-69,5años y el PSA medio 5,1-7,8 ng/ml. Estratificando por los criterios de riesgo de D`Amico, el 52% del numero total agregado de hombres eran de bajo riesgo, el 38% de riesgo intermedio y el 10% de alto riesgo. Aparte de la biopsia transrectal de 12 muestras, 3 cohortes comunicaban la utilización de la biopsia por mapeo transperineal con plantilla y una incluía la RMN multiparamétrica para seleccionar casos para terapia focal. La mediana de seguimiento tenía un rango entre 13-63 meses. La supervivencia libre de progresión bioquímica estaba en un rango del 71 al 98%. La tasa global de biopsia positiva después de tratamiento era del 8-25%. Entre 5 cohortes con una biopsia obligatoria a los 6-12 meses post-tratamiento, 216 de 272 hombres (79%) fueron sometidos a biopsia, con 47 biopsias positivas (21,8%). De éstos, 15 estaban dentro del campo, 26 fuera, 2 bilaterales y 4 no declaradas. 10 casos ascendieron a Gleason≥7. Globalmente, dos hombres tuvieron enfermedad metastática y ninguno murió del cáncer de próstata. Las tasas de continencia post-tratamiento fueron del 96-100% y las de disfunción eréctil en el rango entre 0-42%. Las tasa de retención urinaria post tratamiento estaban en el rango entre 0-15%. La tasa de fístula recto-uretral fue de 0-0,1%. CONCLUSIÓN: La crioterapia focal para el cáncer de próstata localizado es segura y ofrece una buena preservación de las funciones urinaria y sexual. La localización precisa del cáncer y la estratificación por riesgos son esenciales para la selección del paciente. En pacientes altamente seleccionados la terapia focal tiene una buena eficacia oncológica a corto y medio plazo

Multi-institutional external validation of urinary TWIST1 and NID2 methylation as a diagnostic test for bladder cancer.

OBJECTIVES: We previously reported a clinical trial in which we were unable to replicate the excellent diagnostic metrics produced in the developmental study of the TWIST1 and NID2 gene methylation assay. In this expanded trial with subjects enrolled from another institution, we reexamine the diagnostic capabilities of the test to externally validate our previous study. MATERIALS AND METHODS: TWIST1 and NID2 gene methylation was assessed in DNA isolated from the urine of subjects at risk of bladder cancer undergoing cystoscopy for hematuria or bladder cancer surveillance. The diagnostic gold standard was cystoscopy. Two thresholds of TWIST1 and NID2 gene methylation were used for determining test result positivity, those published by Renard et al. and Abern et al. The sensitivity, specificity, positive and negative predictive values, diagnostic likelihood ratios, and receiver operating characteristic curves were calculated for each gene, as well as their combination. In all, 3 methods were used to combine TWIST1 and NID2 into a single composite test: (1) believe-the-positive decision rule-if either gene is methylated the test result is positive, which maximizes test sensitivity; (2) believe-the-negative decision rule-if either gene is not methylated the test result is negative, which maximizes test specificity; and (3) a likelihood-based logistic regression model approach that balances sensitivity and specificity. Clinical utility was determined using a decision curve analysis. RESULTS: A total of 209 subjects were evaluated: 40% for hematuria and 60% for bladder cancer surveillance. Approximately 75% were male, most of the prior cancers being low-grade Ta. Using cystoscopy as the gold standard, areas under the curve were 0.67 for TWIST1, 0.64 for NID2, and 0.66 for combined TWIST1 and NID2. Decision rule results revealed optimization of sensitivity at 67% using Renard thresholds and specificity using the Abern thresholds at 69%. We found improved sensitivity (78%) in current smokers. Decision curve analyses revealed that the methylation assay provided only a modest benefit even at high probabilities of missed cancer. CONCLUSION: A urine DNA test measuring TWIST1 and NID2 methylation was externally examined with a larger cohort and its results continue to be poor. These 2 biomarkers are unlikely to replace cystoscopy, but they may be worthy of study in active smokers.