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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. Following the eligibility criteria PSA

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

Objectives To assess change in functional outcomes after a second focal high-intensity focused ultrasonography (HIFU) treatment compared with outcomes after one focal HIFU treatment. Patients and methods In this multicentre study (2005-2016), 821 men underwent focal HIFU for localized non-metastatic prostate cancer. The patient-reported outcome measures of International Prostate Symptom Score (IPSS), pad usage and erectile function (EF) score were prospectively collected for up to 3 years. To be included in the study, completion of at least one follow-up questionnaire was required. The primary outcome was comparison of change in functional outcomes between baseline and follow-up after one focal HIFU procedure vs after a second focal HIFU procedure, using IPSS, Expanded Prostate Cancer Index Composite (EPIC) and International Index of Erectile Function (IIEF) questionnaires. Results Of 821 men, 654 underwent one focal HIFU procedure and 167 underwent a second focal HIFU procedure. A total of 355 (54.3%) men undergoing one focal HIFU procedure and 65 (38.9%) with a second focal HIFU procedure returned follow-up questionnaires, respectively. The mean age and prostate-specific antigen level were 66.4 and 65.6 years, and 7.9 and 8.4 ng/mL, respectively. After one focal HIFU treatment, the mean change in IPSS was -0.03 (P = 0.02) and in IIEF (EF score) it was -0.4 (P = 0.02) at 1-2 years, with no subsequent decline. Absolute rates of erectile dysfunction increased from 9.9% to 20.8% (P = 0.08), leak-free continence decreased from 77.9% to 72.8% (P = 0.06) and pad-free continence from 98.6% to 94.8% (P = 0.07) at 1-2 years, respectively. IPSS prior to second focal HIFU treatment compared to baseline IPSS prior to first focal HIFU treatment was lower by -1.3 (P = 0.02), but mean IPSS change was +1.4 at 1-2 years (P = 0.03) and +1.2 at 2-3 years (P = 0.003) after the second focal HIFU treatment. The mean change in EF score after the second focal HIFU treatment was -0.2 at 1-2 years (P = 0.60) and -0.5 at 2-3 years (P = 0.10), with 17.8% and 6.2% of men with new erectile dysfunction. The rate of new pad use was 1.8% at 1-2 years and 2.6% at 2-3 years. Conclusion A second focal HIFU procedure causes minor detrimental effects on urinary function and EF. These data can be used to counsel patients with non-metastatic prostate cancer prior to considering HIFU therapy.

BACKGROUND: Recurrent prostate cancer after radiotherapy occurs in one in five patients. The efficacy of prostate magnetic resonance imaging (MRI) in recurrent cancer has not been established. Furthermore, high-quality data on new minimally invasive salvage focal ablative treatments are needed. OBJECTIVE: To evaluate the role of prostate MRI in detection of prostate cancer recurring after radiotherapy. DESIGN, SETTING, AND PARTICIPANTS: The FORECAST trial was both a paired-cohort diagnostic study evaluating prostate multiparametric MRI (mpMRI) and MRI-targeted biopsies in the detection of recurrent cancer and a cohort study evaluating focal ablation at six UK centres. A total of 181 patients were recruited, with 155 included in the MRI analysis and 93 in the focal ablation analysis. INTERVENTION: Patients underwent choline positron emission tomography/computed tomography and a bone scan, followed by prostate mpMRI and MRI-targeted and transperineal template-mapping (TTPM) biopsies. MRI was reported blind to other tests. Those eligible underwent subsequent focal ablation. An amendment in December 2014 permitted focal ablation in patients with metastases. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcomes were the sensitivity of MRI and MRI-targeted biopsies for cancer detection, and urinary incontinence after focal ablation. A key secondary outcome was progression-free survival (PFS). RESULTS AND LIMITATIONS: Staging whole-body imaging revealed localised cancer in 128 patients (71%), with involvement of pelvic nodes only in 13 (7%) and metastases in 38 (21%). The sensitivity of MRI-targeted biopsy was 92% (95% confidence interval [CI] 83–97%). The specificity and positive and negative predictive values were 75% (95% CI 45–92%), 94% (95% CI 86–98%), and 65% (95% CI 38–86%), respectively. Four cancer (6%) were missed by TTPM biopsy and six (8%) were missed by MRI-targeted biopsy. The overall MRI sensitivity for detection of any cancer was 94% (95% CI 88–98%). The specificity and positive and negative predictive values were 18% (95% CI 7–35%), 80% (95% CI 73–87%), and 46% (95% CI 19–75%), respectively. Among 93 patients undergoing focal ablation, urinary incontinence occurred in 15 (16%) and five (5%) had a grade ≥3 adverse event, with no rectal injuries. Median follow-up was 27 mo (interquartile range 18–36); overall PFS was 66% (interquartile range 54–75%) at 24 mo. CONCLUSIONS: Patients should undergo prostate MRI with both systematic and targeted biopsies to optimise cancer detection. Focal ablation for areas of intraprostatic recurrence preserves continence in the majority, with good early cancer control. PATIENT SUMMARY: We investigated the role of magnetic resonance imaging (MRI) scans of the prostate and MRI-targeted biopsies in outcomes after cancer-targeted high-intensity ultrasound or cryotherapy in patients with recurrent cancer after radiotherapy. Our findings show that these patients should undergo prostate MRI with both systematic and targeted biopsies and then ablative treatment focused on areas of recurrent cancer to preserve their quality of life.

Objective To compare cancer control in anterior compared to posterior prostate cancer lesions treated with a focal HIFU therapy approach. Materials and methods In a prospectively maintained national database, 598 patients underwent focal HIFU (Sonablate®500) (March/2007–November/2016). Follow-up occurred with 3-monthly clinic visits and PSA testing in the first year with PSA, every 6–12 months with mpMRI with biopsy for MRI-suspicion of recurrence. Treatment failure was any secondary treatment (ADT/chemotherapy, cryotherapy, EBRT, RRP, or re-HIFU), tumour recurrence with Gleason ≥ 3 + 4 on prostate biopsy without further treatment or metastases/prostate cancer-related mortality. Cases with anterior cancer were compared to those with posterior disease. Results 267 patients were analysed following eligibility criteria. 45 had an anterior focal-HIFU and 222 had a posterior focal-HIFU. Median age was 64 years and 66 years, respectively, with similar PSA level of 7.5 ng/ml and 6.92 ng/ml. 84% and 82%, respectively, had Gleason 3 + 4, 16% in both groups had Gleason 4 + 3, 0% and 2% had Gleason 4 + 4. Prostate volume was similar (33 ml vs. 36 ml, p = 0.315); median number of positive cores in biopsies was different in anterior and posterior tumours (7 vs. 5, p = 0.009), while medium cancer core length, and maximal cancer percentage of core were comparable. 17/45 (37.8%) anterior focal-HIFU patients compared to 45/222 (20.3%) posterior focal-HIFU patients required further treatment (p = 0.019). Conclusion Treating anterior prostate cancer lesions with focal HIFU may be less effective compared to posterior tumours.

Focal therapy aims to treat areas of cancer to confer oncological control whilst reducing treatment-related functional detriment.To report oncological outcomes and adverse events following focal high-intensity focused ultrasound (HIFU) for treating nonmetastatic prostate cancer.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).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.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-Dindo2 adverse events occurred in 0.5% (7/1379). The median 10-yr follow-up is lacking.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.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.

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.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.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).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.

PURPOSE: We determined whether prostate specific antigen criteria after focal high intensity focused ultrasound to treat prostate cancer could diagnose treatment failure. MATERIALS AND METHODS: A total of 598 patients in a prospectively maintained national database underwent focal high intensity focused ultrasound with a Sonablate® 500 device from March 2007 to November 2016. Followup consisted of 3-month clinic visits and prostate specific antigen testing in year 1 with prostate specific antigen measurement every 6 to 12 months and multiparametric magnetic resonance imaging with biopsy for magnetic resonance imaging suspicious for recurrence. Treatment failure was considered any secondary treatment, tumor recurrence with Gleason 3 + 4 or greater disease on prostate biopsy without further treatment or metastasis and/or prostate cancer related mortality. To diagnose failure we evaluated a series of nadir + x thresholds with x values of 0.1 to 2.0 ng/ml. RESULTS: Median patient age was 65 years (IQR 60-71) and the median Gleason score was 7 (range 6-9). Gleason 3 + 4 or greater disease was present in 80% of cases. Tumors were radiologically staged as T1c-T2c in 522 of the 596 patients (88%) and as and T3a/b in 74 (12.4%). Baseline median prostate specific antigen was 7.80 ng/ml (IQR 5.96-10.45) in failed cases and 6.77 ng/ml (IQR 2.65-9.71) in cases without failure. Optimal performance according to the Youden index to indicate the most appropriate nadir + x at all analyzed time points at 3-month intervals showed that nadir + 1.0 ng/ml would have 27.3% to 100% sensitivity and 39.4% to 85.6% specificity depending on the time of evaluation in the first 3 years. Nadir + 1.5 ng/ml showed 18.2% to 100% sensitivity and 60.6% to 91.8% specificity with nadir + 2.0 ng/ml leading to similar sensitivity and specificity ranges. Nadir + 1.0 ng/ml at 12 months and nadir + 1.5 ng/ml at 24 and 36 months had 100% sensitivity and 96.1% to 100% negative predictive value. CONCLUSIONS: Following focal high intensity focused ultrasound a prostate specific antigen nadir of 1.0 ng/ml at 12 months and 1.5 ng/ml at 24 to 36 months might be used to triage men requiring magnetic resonance imaging and biopsy. These data need prospective validation.

Objectives To evaluate diagnostic accuracy of mpMRI in a non-academic hospital using transperineal template prostate mapping (TPM) biopsy as a reference standard. Secondary objectives included evaluating why mpMRI missed significant cancer. Materials and methods 101 men received pre-biopsy mpMRI and TPM-biopsy over 16 months. Disease status was assigned at hemigland level. Primary histological definition of clinical significance was Gleason grade >/ = 4 + 3 or maximum cancer core length (MCCL) >/ = 6 mm. Positive mpMRI was defined as Prostate Imaging Reporting and Data System (PI-RADS) score >/ = 3. Results Median age 69 (IQR 62–76). Median PSA 7 ng/ml (IQR 4.6–9.8). mpMRI had sensitivity 76.9%, specificity 60.7%, PPV 40.4% and NPV 88.3% at primary definitions. For detecting any Gleason >/ = 7 mpMRI had sensitivity 73.2%, specificity 60.3%, PPV 41.4% and NPV 85.4%. Mean MCCL was lower where significant cancer was missed compared to those correctly identified (5.8 mm versus 7.7 mm respectively, p = 0.035). Conclusion mpMRI performance characteristics were very encouraging when compared to contemporary clinical trials. In a non-academic hospital setting, negative mpMRI was just as good at ruling-out significant disease, though the ability of positive mpMRI to accurately detect significant disease was lower. An mpMRI-guided diagnostic pathway should be accompanied by appropriate mpMRI protocol optimisation, training, and quality control.

Primary testicular tumour is unusual in elderly population. We present a case of 74 year old with adult type granulosa cell tumour, located at the right testis. The patient had right radical inquinal orchiectomy. The tumour composed of a cystic component which had a number of different areas. Many areas showed a granulosa cell morphology with Call-Exner bodies. Our report highlights one more challenging case of testicular tumours in elderly, which are quite problematic in terms of prognosis and management. Long-term follow up is recommended, since metastases of the disease may appear late in the clinical course.

INTRODUCTION AND OBJECTIVES:Focal therapy (FT) has a low side-effect profile but there is uncertainty about its medium-long term cancer control compared to radical approaches. Both focal HIFU and f...

5582 Background: Patients that have previously failed radiotherapy for prostate cancer is usually limited to systemic therapy due to morbidity from salvage prostatectomy. We reviewed the outcomes following focal salvage ablative therapy with HIFU or cryotherapy within the UK’s HEAT and ICE registries. Methods: 356 consecutive patients underwent focal ablative treatment after initial radiation treatment failure (28/1/2004-1/10/2019, 194 (54.5%) underwent HIFU (posterior recurrence) and 162 (45.5%) underwent cryotherapy (mostly anterior or T3b). Primary outcome was failure-free survival (FFS) defined as no systemic therapy, whole-gland treatment, metastases or prostate cancer-specific death. Secondary outcomes were adverse events and overall survival. Results: Median (IQR) age was 69years (65-73) and PSA (IQR) was 4.0ng/ml (1-7-7.2). Overall median (IQR) follow-up was 41.3 months (21.4-58.5). Quadrant ablation was performed in 128 (36.0%), hemi-ablation performed in 64 (18.0%), hockey-stick in 5 (1.4%) and 159 (43.8%) had unknown ablative patterns. Due to histological or MRI proven recurrence/residual disease, 31 (8.7%) underwent further focal salvage re-treatment. FFS (95%CI) at 3 and 6 years were 81% (76-87%) and 75% (68-83%) respectively. Median (IQR) time to failure was 15.5 months (19.7). Overall survival (95%CI) at 3 and 6 years were 97% (95-100%) and 88% (81-96%) respectively. Prostate-specific mortality was 2.8%. Overall 3 (0.8%) patients were managed for fistula formation, 16 (4.5%) were treated for UTIs. Conclusions: Salvage focal ablative therapy for radio-recurrent prostate cancer is safe and provides good short to medium-term oncological control. The FORECAST study is awaited to further determine oncological outcomes in this cohort.

Clinically significant nonmetastatic prostate cancer (PCa) is currently treated using whole-gland therapy. This approach is effective but can have urinary, sexual, and rectal side effects.To report on 5-yr PCa control following focal high-intensity focused ultrasound (HIFU) therapy to treat individual areas of cancer within the prostate.This was a prospective study of 625 consecutive patients with nonmetastatic clinically significant PCa undergoing focal HIFU therapy (Sonablate) in secondary care centres between January 1, 2006 and December 31, 2015. A minimum of 6-mo follow-up was available for599 patients. Intermediate- or high-risk PCa was found in 505 patients (84%).Disease was localised using multiparametric magnetic resonance imaging (mpMRI) combined with targeted and systematic biopsies, or transperineal mapping biopsies. Areas of significant disease were treated. Follow-up included prostate-specific antigen (PSA) measurement, mpMRI, and biopsies.The primary endpoint, failure-free survival (FFS), was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality.The median follow-up was 56 mo (interquartile range [IQR] 35-70). The median age was 65 yr (IQR 61-71) and median preoperative PSA was 7.2 ng/ml (IQR 5.2-10.0). FFS was 99% (95% confidence interval [CI] 98-100%) at 1 yr, 92% (95% CI 90-95%) at 3 yr, and 88% (95% 85-91%) at 5 yr. For the whole patient cohort, metastasis-free, cancer-specific, and overall survival at 5 yr was 98% (95% CI 97-99%), 100%, and 99% (95% CI 97-100%), respectively. Among patients who returned validated questionnaires, 241/247 (98%) achieved complete pad-free urinary continence and none required more than 1 pad/d. Limitations include the lack of long-term follow-up.Focal therapy for select patients with clinically significant nonmetastatic prostate cancer is effective in the medium term and has a low probability of side effects.In this multicentre study of 625 patients undergoing focal therapy using high-intensity focused ultrasound (HIFU), failure-free survival, metastasis-free survival, cancer-specific survival, and overall survival were 88%, 98%, 100%, and 99%, respectively. Urinary incontinence (any pad use) was 2%. Focal HIFU therapy for patients with clinically significant prostate cancer that has not spread has a low probability of side effects and is effective at 5 yr.

Flexible cystoscopy is commonly performed under local anaesthesia. Instillation of lignocaine gel is commonly associated with urethral discomfort, which in some cases results in fierce opposition to further flexible cystoscopy under local anaesthesia. Although studies have demonstrated that the temperature of lignocaine can influence the level of discomfort experienced, to date no study has investigated the influence of the rate of lignocaine delivery on perceived discomfort. We therefore performed a prospective, randomised study to investigate this in patients undergoing flexible cystoscopy. One hundred consenting men were randomised to receive 11 ml of 2% lignocaine hydrochloride gel over either 2 or 10 s. The groups were well matched for age. After instillation of the gel, the patients were immediately asked to score their discomfort using a visual analogue scale. The discomfort experienced by patients that received the gel over 10 s was significantly (p < 0.05; Student’s t test) less than those that received it over 2 s. This was irrelevant of the age of the patient and the number of previous cystoscopies performed. We have demonstrated that slow administration results in decreased discomfort. This may, in turn, reduce the need to resort to general anaesthesia, which is associated with increased morbidity and cost.

Anejaculation may occur as a result of neurological disease, iatrogenic injury or be drug induced. We report a case of a 66 year old man who presented with anejaculation following an emergency abdominal aortic aneurysm repair. Due to an elevated prostate specific antigen (PSA) level, the patient underwent a prostate biopsy and was diagnosed with a prostate adenocarcinoma. This was effectively managed using active surveillance, a treatment modality that aims to select only those patients with significant cancer for radical treatment. Despite the possible cause of anejaculation to be iatrogenic, the reader should be aware that prostate cancer may co-exist in, or cause any disorder of the lower urinary tract.

Objective To compare cancer control rates of standard compared to dose escalation focal high-intensity focused ultrasound (HIFU) of prostate cancer. Materials and methods A prospectively maintained HIFU (Sonablate® 500) database identified 598 patients were identified who underwent focal HIFU (Sonablate® 500) (March/2007-November/2016). Follow-up occurred with 3-monthly clinic visits and PSA testing in the first year. Thereafter, PSA was measured 6-monthly. mpMRI with biopsy was used for MRI-suspicion of recurrence. Treatments were delivered in a quadrant or hemiablation fashion depending on the gland volume as well as tumour volume and location. Prior to mid-2015, standard focal-HIFU was used (two HIFU blocks); after this date some urologists conducted dose escalation focal-HIFU (3 overlapping HIFU blocks). Propensity matching was used to ensure two matched groups leading to 162 cases for this analysis. Treatment failure was defined by any secondary treatment (systemic therapy, cryotherapy, radiotherapy, prostatectomy, or further HIFU), metastasis from prostate cancer without further treatment, tumour recurrence with Gleason score >/=7 (>/=3+4) on prostate biopsy without further treatment, or prostate cancer-related mortality. Complications and side-effects were also compared. Results Median age was 64.5 years (IQR 60-73.5) in the standard focal-HIFU group and 64.5 years (IQR 60-69) in the dose-escalation group. Median prostate volume was 37ml (IQR 17-103) in standard group and 47.5ml (IQR 19-121) in the dose-escalation group. As tumour volume on mpMRI and Gleason score were major matching criteria these were identical with 0.43ml (IQR 0.05-2.5) and Gleason 3+3=6 in 1/32 (3%), 3+4=7 in 27/32 (84%), and 4+3=7 in 4/32 (13%). Recurrence in treated areas were found in 10/32 (31%) when standard treatment zones were applied, and in 6/32 (19%) of dose-escalation focal-HIFU (p=0.007). Conclusion This exploratory study shows that dose escalation focal-HIFU may achieve higher rates of disease control compared to standard focal-HIFU. Further prospective comparative studies are needed.