Evaluation of Outcomes Following Focal Ablative Therapy for Treatment of Localized Clinically Significant Prostate Cancer in Patients >70 Years: A Multi-institute, Multi-energy 15-Year Experience.

PURPOSE: In older patients who do not wish to undergo watchful waiting, focal therapy could be an alternative to the more morbid radical treatment. We evaluated the role of focal therapy in patients 70 years and older as an alternative management modality. MATERIALS AND METHODS: A total of 649 patients across 11 UK sites receiving focal high-intensity focused ultrasound or cryotherapy between June 2006 and July 2020 reported within the UK-based HEAT (HIFU Evaluation and Assessment of Treatment) and ICE (International Cryotherapy Evaluation) registries were evaluated. Primary outcome was failure-free survival, defined by need for more than 1 focal reablation, progression to radical treatment, development of metastases, need for systemic treatment, or prostate cancer-specific death. This was compared to the failure-free survival in patients undergoing radical treatment via a propensity score weighted analysis. RESULTS: Median age was 74 years (IQR: 72, 77) and median follow-up 24 months (IQR: 12, 41). Sixty percent had intermediate-risk disease and 35% high-risk disease. A total of 113 patients (17%) required further treatment. Sixteen had radical treatment and 44 required systemic treatment. Failure-free survival was 82% (95% CI: 76%-87%) at 5 years. Comparing patients who had radical therapy to those who had focal therapy, 5-year failure-free survival was 96% (95% CI: 93%-100%) and 82% (95% CI: 75%-91%) respectively (P < .001). Ninety-three percent of those in the radical treatment arm had received radiotherapy as their primary treatment with its associated use of androgen deprivation therapy, thereby leading to potential overestimation of treatment success in the radical treatment arm, especially given the similar metastases-free and overall survival rates seen. CONCLUSIONS: We propose focal therapy to be an effective management option for the older or comorbid patient who is unsuitable for or not willing to undergo radical treatment.

A Comparison of Prostate Cancer Detection between Visual Estimation (Cognitive Registration) and Image Fusion (Software Registration) Targeted Transperineal Prostate Biopsy.

PURPOSE: We compared clinically significant prostate cancer detection by visual estimation and image fusion targeted transperineal prostate biopsy. MATERIALS AND METHODS: This multicenter study included patients with multiparametric magnetic resonance imaging lesions undergoing visual estimation or image fusion targeted transperineal biopsy (April 2017-March 2020). Propensity score matching was performed using demographics (age and ethnicity), clinical features (prostate specific antigen, prostate volume, prostate specific antigen density and digital rectal examination), multiparametric magnetic resonance imaging variables (number of lesions, PI-RADS® score, index lesion diameter, whether the lesion was diffuse and radiological T stage) and biopsy factors (number of cores, operator experience and anesthetic type). Matched groups were compared overall and by operator grade, PI-RADS score, lesion multiplicity, prostate volume and anesthetic type using targeted-only and targeted plus systematic histology. Multiple clinically significant prostate cancer thresholds were evaluated (primary: Gleason ≥3+4). RESULTS: A total of 1,071 patients with a median age of 67.3 years (IQR 61.3-72.4), median prostate specific antigen of 7.5 ng/ml (IQR 5.3-11.2) and 1,430 total lesions underwent targeted-only biopsies (visual estimation: 372 patients, 494 lesions; image fusion: 699 patients, 936 lesions). A total of 770 patients with a median age of 67.4 years (IQR 61-72.1), median prostate specific antigen of 7.1 ng/ml (IQR 5.2-10.6) and 919 total lesions underwent targeted plus systematic biopsies (visual estimation: 271 patients, 322 lesions; image fusion: 499 patients, 597 lesions). Matched comparisons demonstrated no overall difference in clinically significant prostate cancer detection between visual estimation and image fusion (primary: targeted-only 54% vs 57.4%, p=0.302; targeted plus systematic 51.2% vs 58.2%, p=0.123). Senior urologists had significantly higher detection rates using image fusion (primary: targeted-only 45.4% vs 63.7%, p=0.001; targeted plus systematic 39.4% vs 64.5%, p <0.001). CONCLUSIONS: We found no overall difference in clinically significant prostate cancer detection, although image fusion may be superior in experienced hands.

Factors associated with spontaneous stone passage in a contemporary cohort of patients presenting with acute ureteric colic: results from the Multi-centre cohort study evaluating the role of Inflammatory Markers In patients presenting with acute ureteric Colic (MIMIC) study.

OBJECTIVES: To assess the relationship of white blood cell count (WBC) and other routinely collected inflammatory and clinical markers including stone size, stone position, and medical expulsive therapy use (MET), with spontaneous stone passage (SSP) in a large contemporary cohort of patients with acute ureteric colic, as there are conflicting data on the role of WBC and other inflammatory markers in SSP in patients with acute ureteric colic. PATIENTS AND METHODS: Multicentre retrospective cohort study coordinated by the British Urology Researchers in Surgical Training (BURST) Research Collaborative at 71 secondary care hospitals across four countries (UK, Republic of Ireland, Australia, and New Zealand). In all, 4170 patients presented with acute ureteric colic and a computed tomography confirmed single ureteric stone. Our primary outcome measure was SSP, as defined by the absence of need for intervention to assist stone passage (SP). Multivariable mixed effects logistic regression was used to explore the relationship between key patient factors and SSP. RESULTS: In all, 2518 patients were discharged with conservative management and had further follow-up with a SSP rate of 74% (n = 1874/2518). Sepsis after discharge with conservative management was reported in 0.6% (n = 16/2518). On multivariable analysis neither WBC, neutrophils count, nor C-reactive protein (CRP) predicted SSP, with an adjusted odds ratio (OR) of 0.97 (95% confidence interval [CI] 0.91-1.04, P = 0.38), 1.06 (95% CI 0.99-1.13, P = 0.1) and 1.00 (95% CI 0.99-1.00, P = 0.17), respectively. MET also did not predict SSP (adjusted OR 1.11, 95% CI 0.76-1.61). However, stone size and stone position were significant predictors. SSP for stones <5 mm was 89% (95% CI 87-90) compared to 49% (95% CI 44-53) for stones ≥5-7 mm, and 29% (95% CI 23-36) for stones >7 mm. For stones in the upper ureter the SSP rate was 52% (95% CI 48-56), middle ureter was 70% (95% CI 64-76), and lower ureter was 83% (95% CI 81-85). CONCLUSION: In contrast to the previously published literature, we found that in patients with acute ureteric colic who are discharged with initial conservative management neither WBC, neutrophil count, nor CRP, helps determine the likelihood of SSP. We also found no overall benefit from the use of MET. Stone size and position are important predictors and our present findings represent the most comprehensive SP rates for each millimetre increase in stone size from a large contemporary cohort adjusting for key potential confounders. We anticipate that these data will aid clinicians managing patients with acute ureteric colic and help guide management decisions and the need for intervention.

Robotic MR-guided high dose rate brachytherapy needle implantation in the prostate (ROBiNSon)-a proof-of-concept study.

Objective.A robotic needle implant device for MR-guided high-dose-rate (HDR) prostate brachytherapy was developed. This study aimed to assess the feasibility and spatial accuracy of HDR brachytherapy using the robotic device, for a single intraprostatic target point.Approach.Five patients were treated from November 2019-June 2022 with the robot. The robot fits a 1.5 T MR scanner and the needle can be shifted and angulated. An intraprocedural MR scan was fused with the diagnostic MR and one preplanned needle position was selected for robotic insertion. The needle entry point and angles were set for a needle tip target point within the intraprostatic target volume. The needle was tapped stepwise towards the target point pneumatically. Final needle position was verified with MR, followed by plan optimization and dose delivery. Any remaining planned needles were inserted manually. Needle tip to geometrical target error (NTG-error) was defined as the deviation of the actual tip position relative to the predefined geometric target point, using MR-coordinates. Needle tip to treatment target error (NTT-error) was defined as the deviation of the actual tip position relative to the treatment target point, using fused MR-images pre- and post-needle implantation taking into account prostate deformation. Difference between NTT-error and NTG-error and fiducial marker shifts indicated prostate movement. For determining prostate deformation, the Jaccard index and prostate volumes were assessed.Main results.The robotic device was able to tap the needle to the planned depth for all patients. Mean robotic procedure duration was 142 min. NTG-error was 3.2 (range 1.1-6.7) mm and NTT-error 4.5 (range 2.6-9.6) mm. Marker displacements were smaller than 3 mm. No treatment-related acute toxicity was reported. Feasibility of needle placement within the prostate was considered adequate.Significance.MR-guided robotic needle insertion is feasible with a mean geometric accuracy of 3.2 mm and <3 mm prostate movement.

Recurrence characteristics after focal salvage HDR brachytherapy in prostate cancer.

BACKGROUND AND PURPOSE: Radiorecurrent prostate cancer is often confined to the prostate, predominantly near the index lesion. The purpose of this study was to look at recurrence characteristics in patients treated with focal salvage high dose-rate (HDR) brachytherapy. MATERIALS AND METHODS: Patients treated with MRI-guided HDR brachytherapy, with a single fraction of 19 Gy from July 2013 to October 2021 as focal salvage treatment, were prospectively included in the current study. Imaging data were collected regarding the occurrence of local, regional and distant recurrences, including location of local recurrences (LR) in relation to the HDR radiotherapy field. RESULTS: One hundred seventy-five patients were included after focal salvage HDR brachytherapy (median follow-up 36 months (IQR 23-50)). Three-years biochemical recurrence-free survival, LR-free survival, in-field LR-free survival, out-of-field LR-free survival, any-recurrence-free survival and ADT-free survival were 43% (95%CI 34%-52%), 51% (41%-61%), 70% (61%-80%), 92% (88%-97%), 42% (32%-52%) and 86% (80%-92%), respectively. Larger GTV-size and shorter PSA doubling time were associated with in-field LR in multivariable analysis. CONCLUSION: After focal salvage HDR brachytherapy with a dose of 1x19 Gy for local prostate cancer recurrence, subsequent recurrences are mostly local and in-field.

Focal therapy versus radical prostatectomy and external beam radiotherapy as primary treatment options for non-metastatic prostate cancer: results of a cost-effectiveness analysis.

AIMS: Focal therapy treats individual areas of tumour in non-metastatic prostate cancer in patients unsuitable for active surveillance. The aim of this work was to evaluate the cost-effectiveness of focal therapy versus prostatectomy and external beam radiotherapy (EBRT). MATERIALS AND METHODS: A Markov cohort health state transition model with four health states (stable disease, local recurrence, metastatic disease and death) was created, evaluating costs and utilities over a 10-year time horizon for patients diagnosed with non-metastatic prostate cancer. National Health Service (NHS) for England perspective was used, based on direct healthcare costs. Clinical transition probabilities were derived from prostate cancer registries in patients undergoing radical prostatectomy, EBRT and focal therapy using cryotherapy (Boston Scientific) or high-intensity focused ultrasound (HIFU) (Sonablate). Propensity score matching was used to ensure that at-risk populations were comparable. Variables included age, prostate-specific antigen (PSA), International Society of Urological Pathology (ISUP) grade group, maximum cancer core length (mm), T-stage and year of treatment. RESULTS: Focal therapy was associated with a lower overall cost and higher quality-adjusted life year (QALY) gains than either prostatectomy or EBRT, dominating both treatment strategies. Positive incremental net monetary benefit (NMB) values confirm focal therapy as cost-effective versus the alternatives at a willingness to pay (WTP) threshold of £30,000/QALY. One-way deterministic sensitivity analyses revealed consistent results. LIMITATIONS: Data used to calculate the transition probabilities were derived from a limited number of hospitals meaning that other potential treatment options were excluded. Limited data were available on later outcomes and none on quality of life data, therefore, literature-based estimates were used. CONCLUSIONS: Cost-effectiveness modelling demonstrates use of focal therapy (cryotherapy or HIFU) is associated with greater QALY gains at a lower overall cost than either radical prostatectomy or EBRT, representing good value for money in the NHS.

Focal therapy can be used for the primary treatment of individual areas of cancer in those patients with prostate cancer whose disease has not spread (localized or non-metastatic prostate cancer) and whose disease is unsuitable for active monitoring. Focal therapy in these patients results in similar control of the cancer to more invasive therapies, such as surgical removal of the prostate and radiotherapy, with the benefit of fewer sexual, urinary and rectal side effects. This work considered whether using focal therapy (either freezing the cancer cells using cryotherapy or using high-intensity focused ultrasound [HIFU] to destroy cancer cells) was good value for money in the National Health Service (NHS) compared with surgery or radiotherapy. An economic model was developed which considered the relative impact of treatment with focal therapies, surgery or radiotherapy within the NHS in England. Previously collected information from people undergoing treatment for their prostate cancer, together with published literature and clinical opinion, was used within the model to predict the treatment pathway, costs incurred and the results of treatment in terms of patient benefits (effectiveness and quality of life). The model showed that focal therapy using either cryotherapy or HIFU was associated with a lower overall cost and higher patient benefit than either surgery or radiotherapy, indicating that focal therapy represents good value for money in the NHS.

Value of Targeted Biopsies and Combined PSMA PET/CT and mp-MRI Imaging in Locally Recurrent Prostate Cancer after Primary Radiotherapy.

Radiorecurrent prostate cancer is conventionally confirmed using systematic and/or targeted biopsies. The availability of multiparametric (mp) MRI and prostate specific membrane antigen (PSMA) PET/CT has increased diagnostic accuracy. The objective was to determine the positive predictive value (PPV) of combined mp-MRI and PSMA PET/CT and whether pathology verification with MR-targeted biopsies remains necessary for patients with radiorecurrent prostate cancer. Patients with locally recurrent prostate cancer who were referred for 19 Gy single-dose MRI-guided focal salvage high dose rate (HDR) brachytherapy between 2015 and 2018 were included in the current analysis. Patients were selected if they underwent pre-biopsy mp-MRI and PSMA PET/CT. Based on these images, lesions suspect for isolated tumor recurrence were transperineally biopsied using transrectal ultrasound fused with MRI. A total of 41 patients were identified from the database who underwent cognitive targeted (n = 7) or MRI/PSMA-transrectal ultrasound (TRUS) fused targeted (n = 34) biopsies. A total of 40 (97.6%) patients had positive biopsies for recurrent cancer. Five patients initially had negative biopsies (all MRI/PSMA-TRUS fusion targeted), four of whom recurrence was confirmed after a re-biopsy. One (2.4%) patient refused re-biopsy, leading to a positive predictive value (PPV) for combined imaging of 97.6%. Biopsies can therefore safely be withheld when the results of the combined mp-MRI and PSMA PET/CT are conclusive, avoiding an unnecessary invasive and burdensome procedure.

Cancer Control Outcomes Following Focal Therapy Using High-intensity Focused Ultrasound in 1379 Men with Nonmetastatic Prostate Cancer: A Multi-institute 15-year Experience.

BACKGROUND: Focal therapy aims to treat areas of cancer to confer oncological control whilst reducing treatment-related functional detriment. OBJECTIVE: To report oncological outcomes and adverse events following focal high-intensity focused ultrasound (HIFU) for treating nonmetastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: An analysis of 1379 patients with ≥6 mo of follow-up prospectively recorded in the HIFU Evaluation and Assessment of Treatment (HEAT) registry from 13 UK centres (2005-2020) was conducted. Five or more years of follow-up was available for 325 (24%) patients. Focal HIFU therapy used a transrectal ultrasound-guided device (Sonablate; Sonacare Inc., Charlotte, NC, USA). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Failure-free survival (FFS) was primarily defined as avoidance of no evidence of disease to require salvage whole-gland or systemic treatment, or metastases or prostate cancer-specific mortality. Differences in FFS between D'Amico risk groups were determined using a log-rank analysis. Adverse events were reported using Clavien-Dindo classification. RESULTS AND LIMITATIONS: The median (interquartile range) age was 66 (60-71) yr and prostate-specific antigen was 6.9 (4.9-9.4) ng/ml with D'Amico intermediate risk in 65% (896/1379) and high risk in 28% (386/1379). The overall median follow-up was 32 (17-58) mo; for those with ≥5 yr of follow-up, it was 82 (72-94). A total of 252 patients had repeat focal treatment due to residual or recurrent cancer; overall 92 patients required salvage whole-gland treatment. Kaplan-Meier 7-yr FFS was 69% (64-74%). Seven-year FFS in intermediate- and high-risk cancers was 68% (95% confidence interval [CI] 62-75%) and 65% (95% CI 56-74%; p = 0.3). Clavien-Dindo >2 adverse events occurred in 0.5% (7/1379). The median 10-yr follow-up is lacking. CONCLUSIONS: Focal HIFU in carefully selected patients with clinically significant prostate cancer, with six and three of ten patients having, respectively, intermediate- and high-risk cancer, has good cancer control in the medium term. PATIENT SUMMARY: Focal high-intensity focused ultrasound treatment to areas of prostate with cancer can provide an alternative to treating the whole prostate. This treatment modality has good medium-term cancer control over 7 yr, although 10-yr data are not yet available.

Determining the safety of ultrafocal salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer: A toxicity assessment of 150 patients.

BACKGROUND AND PURPOSE: Local re-treatment of radiorecurrent prostate cancer is potentially curative. However, the increased risk of severe toxicity may outweigh the opportunity of cancer control. This study aims to evaluate treatment-related toxicity from ultrafocal salvage high-dose-rate brachytherapy (HDR-BT) and to investigate potential risk factors. MATERIALS AND METHODS: Toxicity data from 150 treated patients (July 2013-November 2019) was collected from a prospective registry. The treatment aim was to deliver a single dose of 19 Gy to the recurrent lesion as identified on multiparametric MRI and PET-CT. Treating physicians graded genitourinary (GU) and gastro-intestinal (GI) toxicity and erectile dysfunction (ED) using the Common Terminology Criteria for Adverse Events (CTCAE) 4.0, at baseline and during follow-up. Domains with substantial (≥10%) new-onset grade ≥ 2 toxicity were further evaluated using mixed effects logistic regression to find potential risk factors. RESULTS: Median follow-up time was 20 months (IQR 12-31). Over time, new-onset grade 2 and 3 toxicity was recorded in 41% and 3% (GU), 5% and 0% (GI) and 22% and 15% (ED). While GI toxicity remained stably low, grade ≥ 2 GU toxicity and ED were seen twice as frequent in the late phase (>3 months after treatment). Significant risk factors for grade ≥ 2 toxicity were baseline GU toxicity (grade ≥ 2), baseline ED (grade ≥ 2), IPSS (cut-off ≥ 14) and urethral dose (D10%, cut-off ≥ 17 Gy). CONCLUSION: Ultrafocal salvage HDR-BT is a safe re-treatment option, especially in patients with a favorable symptom profile at baseline. Adherence to urethral dose constraints is important to avoid GU toxicity.

Long-term outcomes of two ablation techniques for treatment of radio-recurrent prostate cancer.

BACKGROUND: In men with recurrence of prostate cancer post radiation therapy, further treatment remains a challenge. The default salvage option of androgen-deprivation therapy (ADT) has adverse effects. Alternatively, selected men may be offered salvage therapy to the prostate. Herein, we present long-term oncological outcomes of two whole-gland ablation techniques, cryotherapy (sCT) and high-intensity-focused ultrasound (sHIFU). METHODS: Men undergoing sCT (1995-2004) and sHIFU (2006-2018) at Western University were identified. Oncological endpoints included biochemical recurrence (BCR), ADT initiation, metastases, castration resistance (CRPC), and prostate cancer-specific mortality (PCSM). Survival analysis with competing risks of mortality was performed. Multivariable analysis was performed using Fine and Gray regression. RESULTS: A total of 187 men underwent sCT and 113 sHIFU. Mean (SD) age of the entire cohort was 69.9 (5.9 years), median pre-radiation PSA 9.6 ng/ml (IQR 6.1-15.2), and pre-salvage PSA 4.5 ng/ml (IQR 2.8-7.0). Median total follow-up was 116 months (IQR 67.5-173.8). A total of 170 (57.6%) developed BCR, 68 (23.4%) metastases, 143 (49.3%) were started on ADT, 58 (20.1%) developed CRPC, and 162 (56%) patients died of which 59 (36.4%) were of prostate cancer. On multivariable analysis, sHIFU (HR 1.65, 95% CI 1.15-2.36, p = 0.006) and pre-salvage PSA (HR 1.09, 95% CI 1.06-1.13, p < 0.0001) were associated with a higher risk of BCR. Similarly, sHIFU patients had a higher risk of CRPC (HR 2.31, 95% CI 1.23-4.35, p = 0.009). The cumulative incidence (for both treatments) of PCSM was 16.5% (95% CI 12.2-21.4%) at 10 years and 28.4% (95% CI 22.1-34.9%) at 20 years, with no difference between treatment modalities. Pre-salvage PSA was a common predictor for the measured oncological outcomes. CONCLUSIONS: Although sHIFU had higher BCR and CRPC rates, there were no differences in PCSM when compared with sCT. The long-term oncological data on two ablation techniques highlighted that only 50% of patients started ADT after 10-year follow-up.

Development and internal validation of multivariable prediction models for biochemical failure after MRI-guided focal salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer.

BACKGROUND AND PURPOSE: Magnetic resonance-guided focal salvage high-dose-rate brachytherapy (FS-HDR-BT) for radiorecurrent prostate cancer (PCa) shows low toxicity rates. However, biochemical failure (BF) after treatment occurs frequently. We developed two prediction models for BF (Phoenix definition) with the aim of enhancing patient counselling before FS-HDR-BT and during follow-up. MATERIALS AND METHODS: A prospective cohort of 150 radiorecurrent PCa patients treated with FS-HDR-BT between 2013 and 2020 was used for model development and internal validation. Multivariable Cox Proportional Hazards regression was applied. For model 1, only pre-salvage variables were included as candidate predictors. For model 2, additional (post-)salvage characteristics were tested. After calibration, nomograms and webtools were constructed. Finally, three risk groups were identified. RESULTS: Sixty-one patients (41%) experienced BF. At baseline (model 1), age, gross tumour volume, pre-salvage PSA, and pre-salvage PSA doubling time (PSADT) were predictive of BF. During follow-up (model 2), age, pre-salvage PSA and PSADT, seminal vesicle involvement, post-salvage time to PSA nadir, and percentage PSA reduction were predictive of BF. The adjusted C-statistics were 0.73 (95% CI: 0.66-0.81) and 0.84 (95% CI: 0.78-0.90), respectively, with acceptable calibration. Estimated 2-year biochemical disease-free survival for the low-, intermediate-, and high-risk groups were 84%, 70%, and 31% (model 1), and 100%, 71%, and 5% (model 2). CONCLUSION: Two models are provided for prediction of BF in patients with radiorecurrent PCa treated with FS-HDR-BT. Based on pre- and post-salvage characteristics, we are able to identify patients with a high risk of BF. These findings can aid patient counselling for FS-HDR-BT.

Conventional radical versus focal treatment for localised prostate cancer: a propensity score weighted comparison of 6-year tumour control.

BACKGROUND: For localised prostate cancer, focal therapy offers an organ-sparing alternative to radical treatments (radiotherapy or prostatectomy). Currently, there is no randomised comparative effectiveness data evaluating cancer control of both strategies. METHODS: Following the eligibility criteria PSA < 20 ng/mL, Gleason score ≤ 7 and T-stage ≤ T2c, we included 830 radical (440 radiotherapy, 390 prostatectomy) and 530 focal therapy (cryotherapy, high-intensity focused ultrasound or high-dose-rate brachytherapy) patients treated between 2005 and 2018 from multicentre registries in the Netherlands and the UK. A propensity score weighted (PSW) analysis was performed to compare failure-free survival (FFS), with failure defined as salvage treatment, metastatic disease, systemic treatment (androgen deprivation therapy or chemotherapy), or progression to watchful waiting. The secondary outcome was overall survival (OS). Median (IQR) follow-up in each cohort was 55 (28-83) and 62 (42-83) months, respectively. RESULTS: At baseline, radical patients had higher PSA (10.3 versus 7.9) and higher-grade disease (31% ISUP 3 versus 11%) compared to focal patients. After PSW, all covariates were balanced (SMD < 0.1). 6-year weighted FFS was higher after radical therapy (80.3%, 95% CI 73.9-87.3) than after focal therapy (72.8%, 95% CI 66.8-79.8) although not statistically significant (p = 0.1). 6-year weighted OS was significantly lower after radical therapy (93.4%, 95% CI 90.1-95.2 versus 97.5%, 95% CI 94-99.9; p = 0.02). When compared in a three-way analysis, focal and LRP patients had a higher risk of treatment failure than EBRT patients (p < 0.001), but EBRT patients had a higher risk of mortality than focal patients (p = 0.008). CONCLUSIONS: Within the limitations of a cohort-based analysis in which residual confounders are likely to exist, we found no clinically relevant difference in cancer control conferred by focal therapy compared to radical therapy at 6 years.

Focal therapy compared to radical prostatectomy for non-metastatic prostate cancer: a propensity score-matched study.

INTRODUCTION: Focal therapy (FT) ablates areas of prostate cancer rather than treating the whole gland. We compared oncological outcomes of FT to radical prostatectomy (RP). METHODS: Using prospective multicentre databases of 761 FT and 572 RP cases (November/2005-September/2018), patients with PSA < 20 ng/ml, Gleason

Health-related quality of life after ultrafocal salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer: reporting the patient's perspective.

PURPOSE: For patients with a localized prostate cancer recurrence after radiotherapy, focal salvage treatment offers a less toxic alternative to whole-gland treatments, with the potential of preserving health-related quality of life (HR-QoL). With a focus on the patient's perspective of treatment, this study aims to describe HR-QoL after ultrafocal salvage high-dose-rate brachytherapy (HDR-BT), and to explore predictive factors affecting HR-QoL. MATERIAL AND METHODS: We included 100 patients treated with ultrafocal salvage HDR-BT. Prostate cancer-related HR-QoL was assessed by the EORTC QLQ-PR25 questionnaire. Domains were urinary symptoms, bowel symptoms and sexual activity/functioning. For each domain, a mixed effects model was made to estimate HR-QoL trends over time. For domains showing clinically relevant change (≥10 points difference), the mixed effects model was used to explore potential predictors (age, baseline HR-QoL score, T-stage, tumor location, CTV size, dose to organs at risk and history of ADT). RESULTS: Median follow-up was 20 months (IQR 13-30). Mean questionnaire response rate was 86% (range 72-100%). Median baseline scores were 12 (urinary), 0 (bowel) and 67/50 (sexual activity/functioning). Urinary symptoms and sexual functioning showed clinically relevant deterioration over time (maximum difference of 11 and 12 points, respectively). Worse baseline score and higher administered dose to the urethra (≥16 Gy) were predictive of increased urinary symptoms (p < 0.01 and p = 0.03). Better baseline score was predictive of better sexual functioning (p < 0.01). CONCLUSION: Ultrafocal salvage HDR-BT has negligible impact on bowel symptoms but does affect urinary symptoms and sexual functioning. Lower impact is predicted for patients with favorable urinary and sexual function at baseline. Urethral dose constraints should be closely monitored.

MRI-Guided Ultrafocal Salvage High-Dose-Rate Brachytherapy for Localized Radiorecurrent Prostate Cancer: Updated Results of 50 Patients.

PURPOSE: Most patients with local prostate cancer recurrence after radiation therapy undergo palliative androgen deprivation therapy because whole-gland salvage treatments have a high risk of severe toxicity. Focal treatment reduces this risk while offering a second opportunity for cure. We report updated outcomes of ultrafocal salvage high-dose-rate brachytherapy (HDR-BT). METHODS AND MATERIALS: Prospectively collected data from the first 50 treated patients were analyzed. Disease status was assessed by 3T multiparametric magnetic resonance imaging (MRI), 18F-Choline or 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography, and systematic or tumor-targeted biopsies. Ultrafocal salvage HDR-BT (1 × 19 Gy) was performed by implanting the clinical target volume (CTV: gross tumor volume + 5 mm margin) under fused transrectal ultrasound/MRI guidance. Follow-up included toxicity grading (using Common Terminology Criteria for Adverse Events 4.0), quality of life assessment, and prostate-specific antigen (PSA) testing. RESULTS: Median follow-up was 31 months. Median CTV D95% was 18.8 Gy. We observed 2% grade 3 genitourinary toxicity, no grade 3 gastrointestinal toxicity, and 22% newly developed grade 3 erectile dysfunction. Five of 13 patients (38%) with self-reported pretreatment potency (International Index of Erectile Function >17) remained potent. Clinically relevant quality of life deterioration was reported for only 6 of 31 items and was not statistically significant. Biochemical failure (nadir + 2) occurred in 26 patients. Among intraprostatic recurrences, 73% were in field. After 2.5 years, biochemical disease-free survival was 51% (95% confidence interval, 37%-69%), metastases-free survival was 75% (64%-89%), androgen deprivation therapy-free survival was 90% (82%-99%), and overall survival was 98% (94%-100%). Presalvage PSA, CTV size, and stage ≥T3 were significantly associated with biochemical failure. Higher-risk patients (stage ≥T3, PSA ≥10, or PSA double time ≤9 months) had 25% biochemical disease-free survival at 2.5 years versus 71% for lower-risk patients. CONCLUSIONS: At this early stage, MRI-guided ultrafocal HDR-BT seems to be a safe salvage treatment option, with acceptable biochemical control in a well-selected group of patients and potential for effectively postponing androgen deprivation therapy.

MRI-Guided Ultrafocal HDR Brachytherapy for Localized Prostate Cancer: Median 4-Year Results of a feasibility study.

PURPOSE: For the treatment of localized prostate cancer, focal therapy has the potential to cure with fewer side effects than traditional whole-gland treatments. We report an update on toxicity, quality of life (QoL), and tumor control in our magnetic resonance imaging (MRI)-guided ultrafocal high-dose-rate brachytherapy cohort. METHODS AND MATERIALS: Disease status was evaluated by systematic biopsies and 3T multiparametric MRI. The brachytherapy implant procedure under fused transrectal ultrasound/MRI guidance was followed by a 1.5 T MRI for contour adjustments and catheter position verification. A single dose of 19 Gy was delivered to the tumor with a margin of 5 mm. Genitourinary (GU) toxicity, gastrointestinal (GI) toxicity, and erectile dysfunction (ED) were graded with the Common Terminology Criteria for Adverse Events version 4.0. QoL was measured with RAND-36, European Organisation for Research and Treatment of Cancer QLQ-C30 and PR25. International Prostate Symptom Scores and International Index of Erectile Function scores were obtained. Prostate-specific antigen level was monitored, with biochemical recurrence defined as nadir + 2 ng/mL (Phoenix). RESULTS: Thirty patients with National Comprehensive Cancer Network low- (13%) to intermediate-risk (87%) prostate cancer were treated between May 2013 and April 2016. Median follow-up was 4 years. Median age was 71 years (interquartile range, 68-73) and median initial prostate-specific antigen level was 7.3 ng/mL (5.2-8.1). Maximum Gleason score was 4 + 3 = 7 (in 2 patients). All tumors were radiologic (MRI) stage T2. No grade >2 GU or >1 GI toxicity occurred. International Prostate Symptom Scores only deteriorated temporarily. Mild pretreatment ED deteriorated to moderate/severe ED in 50% of patients. Long-term clinically relevant QoL deterioration was seen in sexual activity and tiredness, whereas emotional and cognitive functioning improved. At 4 years, biochemical disease-free survival was 70% (95% confidence interval, 52%-93%), metastases-free survival was 93% (85%-100%), and overall survival was 100%. Of intraprostatic recurrences, 7 of 9 were out of field. CONCLUSIONS: Ultrafocal high-dose-rate brachytherapy conveys minimal GU or GI toxicity and has a marginal effect on QoL. An early decline in erectile function was seen. Tumor control outcomes are poor (biochemical disease-free survival of 70% [52%-93%] at 4 years), most likely as a result of poor patient selection.

Focal Salvage Treatment of Radiorecurrent Prostate Cancer: A Narrative Review of Current Strategies and Future Perspectives.

Over the last decades, primary prostate cancer radiotherapy saw improving developments, such as more conformal dose administration and hypofractionated treatment regimens. Still, prostate cancer recurrences after whole-gland radiotherapy remain common, especially in patients with intermediate- to high-risk disease. The vast majority of these patients are treated palliatively with androgen deprivation therapy (ADT), which exposes them to harmful side-effects and is only effective for a limited amount of time. For patients with a localized recurrent tumor and no signs of metastatic disease, local treatment with curative intent seems more rational. However, whole-gland salvage treatments such as salvage radiotherapy or salvage prostatectomy are associated with significant toxicity and are, therefore, uncommonly performed. Treatments that are solely aimed at the recurrent tumor itself, thereby better sparing the surrounding organs at risk, potentially provide a safer salvage treatment option in terms of toxicity. To achieve such tumor-targeted treatment, imaging developments have made it possible to better exclude metastatic disease and accurately discriminate the tumor. Currently, focal salvage treatment is being performed with different modalities, including brachytherapy, cryotherapy, high-intensity focused ultrasound (HIFU), and stereotactic body radiation therapy (SBRT). Oncologic outcomes seem comparable to whole-gland salvage series, but with much lower toxicity rates. In terms of oncologic control, these results will improve further with better understanding of patient selection. Other developments, such as high-field diagnostic MRI and live adaptive MRI-guided radiotherapy, will further improve precision of the treatment.

Re-salvage MRI-guided Focal High-dose-rate Brachytherapy for Locally Recurrent Prostate Cancer.

Prostate cancer recurrences are common, even with twenty-first-century primary prostate cancer treatment modalities. The most common salvage treatment is (delayed) hormonal therapy, which is often associated with serious side-effects. Due to the risk of significant toxicity, whole-gland targeted salvage treatments remain unpopular. Consequently, developments in focal therapies have arisen. Magnetic resonance imaging (MRI)-guided focal salvage high-dose-rate brachytherapy (HDR-BT) is a novel treatment aiming for minimal toxicity in recurrent prostate cancer patients. Repeating focal treatment could, therefore, be possible in case of post-salvage recurrence. We report the case of a 77-year-old man who underwent repeat focal HDR-BT.