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.

Management of small testicular masses: outcomes from a single-centre specialist multidisciplinary team.

OBJECTIVES: To report the management outcomes of men with ≤20-mm small testicular masses (STMs) and to identify clinical and histopathological factors associated with malignancy. PATIENTS AND METHODS: A retrospective analysis of men managed at a single centre between January 2010 and December 2020 with a STM ≤20 mm in size was performed. RESULTS: Overall, 307 men with a median (interquartile range [IQR]) age of 36 (30-44) years were included. Of these, 161 (52.4%), 82 (26.7%), 62 (20.2%) and 2 men (0.7%) underwent surveillance with interval ultrasonography (USS), primary excisional testicular biopsy (TBx) or primary radical orchidectomy (RO), or were discharged, respectively. The median (IQR) surveillance duration was 6 (3-18) months. The majority of men who underwent surveillance had lesions <5 mm (59.0%) and no lesion vascularity (67.1%) on USS. Thirty-three (20.5%) men undergoing surveillance had a TBx based on changes on interval USS or patient choice; seven (21.2%) were found to be malignant. The overall rate of malignancy in the surveillance cohort was 4.3%. The majority of men who underwent primary RO had lesions ≥10 mm (85.5%) and the presence of vascularity (61.7%) on USS. Nineteen men (23.2%) who underwent primary TBx (median lesion size 6 mm) had a malignancy confirmed on biopsy and underwent RO. A total of 88 men (28.7%) underwent RO, and malignancy was confirmed in 73 (83.0%) of them. The overall malignancy rate in the whole STM cohort was 23.8%. Malignant RO specimens had significantly larger lesion sizes (median [IQR] 11 [8-15] mm, vs benign: median [IQR] 8 [5-10] mm; P = 0.04). CONCLUSIONS: Small testicular masses can be stratified and managed based on lesion size and USS features. The overall malignancy rate in men with an STM was 23.8% (4.3% in the surveillance group). Surveillance should be considered in lesions <10 mm in size, with a TBx or frozen-section examination offered prior to RO in order to preserve testicular function.

Outcomes of penile sarcomatoid squamous cell carcinoma from a single tertiary referral centre: a matched cohort study.

OBJECTIVE: To report the oncological survival outcomes of men with penile sarcomatoid squamous cell carcinoma (sSCC). PATIENTS AND METHODS: A retrospective analysis of men with penile sSCC diagnosed between January 2010 and January 2020 in a single centre was conducted. Disease-specific (DSS), recurrence-free (RFS) and metastasis-free (MFS) survival were evaluated. Outcomes were compared with a non-sarcomatoid penile SCC cohort matched to age, type of surgery and tumour stage. Kaplan-Meier plots were used to estimate survival outcomes. RESULTS: In all, 1286 men were diagnosed with penile SCC during the study period and of these 38 (3%) men had sSCC. The median (interquartile range) age and follow-up was 70 (57-81) years and 16 (7-44) months, respectively. Operations performed included: circumcision, one (2.6%); wide local excision, four (10.5%); glansectomy, 11 (29%); partial penectomy, 10 (26%); subtotal/total penectomy, 12 (32%). The Kaplan-Meier estimated 12-, 24- and 36-month DSS was 62% (vs non-sarcomatoid, 67%), 43% (vs non-sarcomatoid, 67%) and 36% (vs non-sarcomatoid, 67%), respectively (P = 0.03). The Kaplan-Meier estimated 12- and 24-month RFS was 47% (vs non-sarcomatoid, 60%) and 28% (vs non-sarcomatoid, 55%), respectively (P = 0.01). The MFS was 52% (vs non-sarcomatoid, 62%) at 12 months and 37% (vs non-sarcomatoid, 57%) at 24 months (P = 0.04). CONCLUSIONS: Sarcomatoid differentiation was associated with a lower DSS, RFS and MFS. Due to the rarity of its incidence and aggressiveness, expert histological review and multidisciplinary management is required in a specialist penile cancer centre.

Outcomes following radical inguinal lymphadenectomy for penile cancer using a fascial-sparing surgical technique.

PURPOSE: To describe our surgical technique and report the oncological outcomes and complication rates using a fascial-sparing radical inguinal lymphadenectomy (RILND) technique for penile cancer patients with cN+ disease in the inguinal lymph nodes. METHODS: Over a 10-year period, 660 fascial-sparing RILND procedures were performed in 421 patients across two specialist penile cancer centres. The technique used a subinguinal incision with an ellipse of skin excised over any palpable nodes. Identification and preservation of the Scarpa's and Camper's fascia was the first step. All superficial inguinal nodes were removed en bloc under this fascial layer with preservation of the subcutaneous veins and fascia lata. The saphenous vein was spared where possible. Patient characteristics, oncologic outcomes and perioperative morbidity were retrospectively collected and analysed. Kaplan-Meier curves estimated the cancer-specific survival (CSS) functions after the procedure. RESULTS: Median (interquartile range, IQR) follow-up was 28 (14-90) months. A median (IQR) number of 8.0 (6.5-10.5) nodes were removed per groin. A total of 153 postoperative complications (36.1%) occurred, including 50 conservatively managed wound infections (11.9%), 21 cases of deep wound dehiscence (5.0%), 104 cases of lymphoedema (24.7%), 3 cases of deep vein thrombosis (0.7%), 1 case of pulmonary embolism (0.2%), and 1 case of postoperative sepsis (0.2%). The 3-year CSS was 86% (95%Confidence Interval [95% CI] 77-96), 83% (95% CI 72-92), 58% (95% CI 51-66), respectively, for the pN1, pN2 and pN3 patients (p < 0.001), compared to a 3-year CSS of 87% (95% CI 84-95) for the pN0 patients. CONCLUSION: Fascial-sparing RILND offers excellent oncological outcomes whilst decreasing the morbidity rates. Patients with more advanced nodal involvement had poorer survival rates, emphasizing the need for adjuvant chemo-radiotherapy.

Focal HIFU therapy for anterior compared to posterior prostate cancer lesions.

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.

Prostate Specific Antigen Criteria to Diagnose Failure of Cancer Control following Focal Therapy of Nonmetastatic Prostate Cancer Using High Intensity Focused Ultrasound.

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 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.

Evaluation of functional outcomes after a second focal high-intensity focused ultrasonography (HIFU) procedure in men with primary localized, non-metastatic prostate cancer: results from the HIFU Evaluation and Assessment of Treatment (HEAT) registry.

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.

Factors influencing urinary retention after transperineal template biopsy of the prostate: outcomes from a regional cancer centre.

INTRODUCTION: Multi-parametric MRI (MP-MRI) prior to prostate biopsy is the investigation of choice for an elevated age-related PSA and abnormal digital rectal examination. MP-MRI in combination with transperineal template mapping biopsy has facilitated the development of the concept of targeted biopsies, either cognitively or with software fusion. Urinary retention is a recognised complication of transperineal prostate biopsy, with reported incidence being 1.6-11.4%. We present patient and procedure-related factors, which influence occurrence of urinary retention after transperineal template biopsy. PATIENTS AND METHODS: Retrospective data collection of 243 consecutive cases of transperineal template biopsies performed at a single institution were recorded and analysed. Biopsies were taken using a standard 5-mm template in 4-6 sectors, depending on the prostate volume. RESULTS: 31/243 (12.8%) patients developed urinary retention, defined as patient discomfort and inability to micturate and bladder scan of ≥ 600 ml. Patients in the retention group were significantly older (mean 68.7 vs. 65.8 years, P = 0.034). Prostate volume was significantly greater in comparison with the non-retention group (mean 75.4 vs. 57.2 cc, P = 0.0016). The number of biopsies taken was positively correlated with urinary retention (median 35 vs. 32 biopsies, P = 0.045), and this was independent of prostate size (R2 = 0.2). Presenting PSA, pre-operative flow and histopathological outcome were independent of urinary retention. CONCLUSIONS: Factors resulting in an increased risk of urinary retention are advancing age (> 68.7 years); a larger prostate volume (> 75 cc); greater number of biopsies (> 35); greater severity of lower urinary tract symptoms prior to biopsy and diabetes. Targeted biopsies alone, instead of a full template, may avoid urinary retention in the high-risk groups identified.

Investigating the role of SPECT/CT in dynamic sentinel lymph node biopsy for penile cancers.

PURPOSE: Currently, most centres use 2-D planar lymphoscintigraphy when performing dynamic sentinel lymph node biopsy in penile cancer patients with clinically impalpable inguinal nodes. This study aimed to investigate the role of SPECT/CT following 2-D planar lymphoscintigraphy (dynamic and static) in the detection and localization of sentinel lymph nodes in the groin. METHODS: A qualitative (visual) review was performed on planar followed by SPECT/CT lymphoscintigraphy in 115 consecutive patients (age 28-86 years) who underwent injection of 99mTc-nanocolloid followed by immediate acquisition of dynamic (20 min) and early static scans (5 min) initially and further delayed static (5 min) images at 120 min followed by SPECT/CT imaging. The lymph nodes detected in each groin on planar lymphoscintigraphy and SPECT/CT were compared. RESULTS: A total of 440 and 467 nodes were identified on planar scintigraphy and SPECT/CT, respectively. Overall, SPECT/CT confirmed the findings of planar imaging in 28/115 cases (24%). In the remaining 87 cases (76%), gross discrepancies were observed between planar and SPECT/CT images. SPECT/CT identified 17 instances of skin contamination (16 patients, 13%) and 36 instances of in-transit lymphatic tract activity (24 patients, 20%) that had been interpreted as tracer-avid lymph nodes on planar imaging. In addition, SPECT/CT identified 53 tracer-avid nodes in 48 patients (42%) that were not visualized on planar imaging and led to reclassification of the drainage basins (pelvic/inguinal) of 27 tracer-avid nodes. CONCLUSIONS: The addition of SPECT/CT improved the rate of detection of true tracer-avid lymph nodes and delineated their precise (3-D) anatomic localization in drainage basins.

Management of non-visualization following dynamic sentinel lymph node biopsy for squamous cell carcinoma of the penis.

OBJECTIVES: To review the management and clinical outcomes of uni- or bilateral non-visualization of inguinal lymph nodes during dynamic sentinel lymph node biopsy (DSNB) in patients diagnosed with penile cancer and clinically impalpable inguinal lymph nodes (cN0), and to develop an algorithm for the management of patients in which non-visualization occurs. PATIENTS AND METHODS: This is a retrospective observational study over a period of 4 years, comprising 166 patients with penile squamous cell carcinoma undergoing DSNB and followed up for a minimum of 6 months. All cases diagnosed with uni- or bilateral non-visualization of sentinel nodes in this cohort were identified from a penile cancer database. The management of the inguinal lymph nodes after non-visualization and the oncological outcomes including local and regional recurrence rates were documented. RESULTS: Out of 166 consecutive patients undergoing DSNB, 20 patients (12%) had unilateral non-visualization after injection of intradermal 99m Tc. Of these 20 patients, seven underwent repeat DSNB at a later date, with six having successful visualization. One patient had persistent non-visualization and proceeded to a superficial modified inguinal lymphadenectomy (SML). None of these patients experienced recurrence at follow-up. A further seven patients underwent modified SML with on-table frozen-section analysis of the lymph node packet; none of these patients were found to have micrometastatic disease in the inguinal lymph nodes, although one patient developed metastatic inguinal node disease at a later date. Six patients elected to undergo clinical surveillance and have remained disease-free. CONCLUSION: Patients with impalpable inguinal lymph nodes undergoing DSNB with ≥G2 T1 disease should ideally have bilateral visualization of the sentinel lymph nodes, reflecting the drainage pattern from the primary tumour. In the present series, 12% of patients were found to have unilateral non-visualization after DSNB. Among patients offered a repeat DSNB at a later date, localizing the sentinel node was successful in 86% of cases. Patients with favourable histological characteristics can be placed on clinical surveillance. Those with high-risk disease can be offered a repeat DSNB procedure on the proviso that SML may be carried out if there is repeated non-visualization. Larger cohorts are required to validate this proposed algorithm.

Feasibility of performing dynamic sentinel lymph node biopsy as a delayed procedure in penile cancer.

INTRODUCTION: Patients diagnosed with penile cancer and clinically impalpable inguinal lymph nodes (cN0), normally undergo dynamic sentinel lymph node biopsy (DSNB) at the same time as the primary penile surgery. The aim of this study is to investigate the diagnostic accuracy and clinical outcomes of performing DSNB in patients who have already undergone surgery for the primary penile cancer. METHODS: Ninety-two patients with unilateral or bilateral impalpable inguinal lymph nodes (LNs) who had already undergone primary resection of the penile tumour (stage ≥ T1G2) were included in this study. All patients underwent a preoperative USS of the groin(s) with fine needle aspiration cytology (FNAC). Provided that the FNAC was clear, DSNB was performed. Radical inguinal lymphadenectomy was performed if the histological analysis of the SLN confirmed the presence of micrometastatic disease. RESULTS: DSNB was undertaken in 165 groins with a nonvisualisation rate of 4.8 % (8/165 groins). The SLN was positive for micrometastatic disease in nine groins (5.5 %) from a total of eight patients (8.7 %). One patient developed regional recurrence in a prepubic LN after excision of bilateral negative SLN (1.1 %). The three-year disease-specific survival for patients with negative and positive SLN was 98.8 and 87.5 %, respectively (p = 0.042). Using DSNB, occult LN metastases in penile cancer can be detected with a sensitivity of 88.9 % and specificity of 100 %. CONCLUSIONS: We have demonstrated that DSNB is feasible as a delayed procedure to localise the SLN. Surgical resection of the primary penile lesion does not appear to change the lymphatic drainage.

Long-term outcomes of penile squamous cell carcinoma in men age ≤50 years old compared with men >50 years old from a single tertiary referral centre: a propensity score matched analysis.

Penile cancer (PeCa) is rare, and the oncological outcomes in younger men are unclear. We aimed to analyse and compare oncological outcomes of men age ≤50 years (y) and >50 years with PeCa. A retrospective analysis of men ≤50 y with penile squamous cell carcinoma managed at a tertiary centre was performed. A propensity score matched cohort of men >50 y was identified for comparison. Matching was according to tumour, nodal stage and the types of primary surgery. Overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and metastasis-free survivals (MFS) were estimated using Kaplan-Meier plots and compared using log-rank tests. Between 2005-2020, 100 men ≤50 y (median (IQR) age, 46 y (40-49)) were identified and matched with 100 men >50 y (median (IQR) age, 65 y (59-73)). 10, 24, 32, 34 men age ≤50 y were diagnosed in 2005-2007, 2008-2012, 2013-2016 and 2017-2020 respectively. Median (IQR) follow-up was 53.5 (18-96) months. OS at 2 years: ≤50 y, 86%>50 y, 80.6%; 5 years: ≤50 y, 78.1%, >50 y, 63.1%; 10 years: ≤50 y, 72.3%, >50 y, 45.6% (p = 0.01). DSS at 2 years: ≤50 y, 87.2%>50 y, 87.8%; 5 years: ≤50 y, 80.9%>50 y, 78.2%; 10 years: ≤50 y, 78%, >50 y, 70.9% (p = 0.74). RFS was 93.1% in the ≤50 y group (vs. >50 y, 96.5%) at 2 year, and 90% (vs. >50 y, 88.5%) at 5 years, p = 0.81. Within the ≤50 y group, 2 years and 5 years MFS was 93% (vs. >50 y, 96.5%), and 89.5% (vs. >50 y, 92.7%) respectively, (p = 0.40). There were no statistical significance in DFS, RFS and MFS in men age ≤50 y and >50 y. PeCa in younger patients is fatal, public awareness and patient education are crucial for early detection and management.

A study protocol for a feasibility randomised controlled trial investigating videoendoscopic radical inguinal lymphadenectomy versus open radical inguinal lymphadenectomy in patients with penile cancer (VELRAD).

BACKGROUND: Penile cancer is a rare male genital malignancy. Surgical excision of the primary tumour is followed by radical inguinal lymphadenectomy if there is metastatic disease detected by biopsy, fine needle aspiration cytology (FNAC) or following sentinel lymph node biopsy in patients with impalpable disease. However, radical inguinal lymphadenectomy is associated with a high morbidity rate, and there is increasing usage of a videoendoscopic approach as an alternative. METHODS: A pragmatic, UK-wide multicentre feasibility randomised controlled trial (RCT), comparing videoendoscopic radical inguinal lymphadenectomy versus open radical inguinal lymphadenectomy. Patients will be identified and recruited from supraregional multi-disciplinary team meetings (sMDT) and must be aged 18 or over requiring inguinal lymphadenectomy, with no contraindications to surgical intervention for their cancer. Participants will be followed up for 6 months following randomisation. The primary outcome is the ability to recruit patients for randomisation across all selected sites and the rate of loss to follow-up. Other outcomes include acceptability of the trial and intervention to patients and healthcare professionals assessed by qualitative research and obtaining resource utilisation information for health economic analysis. DISCUSSION: There are currently no other published RCTs comparing videoendoscopic versus open radical inguinal lymphadenectomy. Ongoing study is required to determine whether randomising patients to either procedure is feasible and acceptable to patients. The results of this study may determine the design of a subsequent trial. TRIAL REGISTRATION: Clinicaltrials.gov PRS registry, registration number NCT05592639. Date of registration: 13th October 2022, retrospectively registered.

Genital lichen sclerosus/balanitis xerotica obliterans in men with penile carcinoma: a critical analysis.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The European Association of Urology guidelines identify lichen sclerosus (LS) as a strong risk factor for penile squamous cell carcinoma (pSCC). However, this statement is based on the findings of case-control studies (Level of Evidence 2a) and a direct causal relationship between LS/balanitis xerotica obliterans (BXO) and pSCC remains to be established. Firm guidelines with respect to the appropriate follow-up policy for LS/BXO are lacking, whereas the impact of synchronous LS/BXO on the prognosis of pSCC remains to be determined. The presence of histologically-confirmed synchronous LS/BXO in patients diagnosed with pSCC is relatively high, although it is not associated with an increased risk of adverse histopathological features. LS/BXO can develop in extragenital skin grafts used for reconstruction after organ-sparing surgery for pSCC. OBJECTIVES: To determine the rate of lichen sclerosus/balanitis xerotica obliterans (LS/BXO) in patients with penile squamous cell carcinoma (pSCC) and establish whether the presence of LS/BXO is associated with adverse histopathological features of pSCC. To report the phenomenon of LS involving non-genital skin grafts in patients who underwent organ-sparing surgery and split-skin graft (SSG) reconstruction PATIENTS AND METHODS: Between January 2002 and January 2010, 223 men underwent surgical treatment for pSCC. A group of 52 patients with histologically-confirmed synchronous LS was identified (group A; overall rate of LS/BXO = 23.3%) and compared with a group of patients without synchronous LS (group B; n = 171; 76.7%). A subgroup of patients who underwent surgical excision and SSG reconstruction was also identified The histology reports of graft biopsies obtained during follow-up were reviewed and the rate of LS involving the graft was also recorded. RESULTS: Mean (range) age at diagnosis was 60.9 (34-81) years and 60.7 (28-89) years for groups A and B, respectively (P = 0.958). The mean (range) duration of follow-up was 38.3 (4-92) months for group A and 45.5 (4-107) months for group B (P = 0.162) No statistically significant differences were noted between groups A and B in terms of tumour grade (P = 0.091), stage (P = 0.697), presence of lymphovascular invasion (P = 0.333), histological subtype (P = 0.107), associated carcinoma in situ (P = 0.246) or nodal status at initial diagnosis (P = 0.555). In the subgroup of 188 patients who underwent SSG reconstruction, 41 (21.8%) patients had histologically-confirmed synchronous LS; in this subgroup, 26 (13.8%) patients underwent graft biopsy during follow-up. Genital LS involving the graft was identified in seven specimens, although none of these seven cases had associated recurrent pSCC. CONCLUSIONS: The presence of histologically-confirmed synchronous LS in patients with pSCC is relatively high but is not associated with increased rates of adverse histopathological features, including carcinoma in situ. LS can develop in extragenital skin grafts, although its association with the long-term risk for recurrent pSCC is not apparent in the present study.

Primary squamous cell carcinoma of the scrotum: Outcomes from a specialist center.

BACKGROUND: Squamous cell carcinoma (SCC) of the scrotum is a rare and aggressive cancer. There are no established guidelines on the management of scrotal SCC. OBJECTIVE: To analyze the clinical management and outcomes of scrotal SCC. PATIENTS AND METHODS: A retrospective analysis of patients diagnosed with primary scrotal SCC over a 10-year period was performed. The type of surgery, tumor stage and histological subtypes, recurrence rate and metastases, cancer-specific mortality (CSM), and other-cause mortality (OCM) were analyzed. RESULTS: Between 2012 and 2022, a total of 10 men were identified with primary scrotal SCC. The median (interquartile, IQR) age was 65.5 (55-77) years. Wide local excision was performed in 9 patients and 1 patient underwent a total scrotectomy. The pathological T-stage was: pT1, n = 3; pT2, n = 1; pT3, n = 5 (50%); pT4, n = 1. Four patients had pathologically positive inguinal lymph nodes and 2 had distant metastatic disease at presentation. At a median (IQR) follow-up of 10.5 (4-31) months 5 patients died, of which 3 died from scrotal SCC. CONCLUSION: Scrotal SCC is extremely rare in the UK with only 10 primary cases identified in our center over the past 10 years. Surgical resection of the tumor and appropriate inguinal node staging are required due to a high proportion of cases which metastasize to the inguinal lymph nodes. PATIENT SUMMARY: Scrotal cancer is rare. 10 cases were diagnosed over 10 years at a single center. Around half had disease spread to the groin nodes or distant organs at presentation. Surgical resection was required in all patients. At the time of analysis, half of the patients are alive. Due to the rarity and aggressiveness of the cancer, management should be carried out within a specialist center.

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.

Conservative surgery for squamous cell carcinoma of the penis: resection margins and long-term oncological control.

PURPOSE: We assessed the oncological outcome of penile conserving surgery and identified parameters predicting local recurrence, including resection margins. MATERIALS AND METHODS: A total of 179 patients with invasive penile cancer treated with organ sparing surgery at a tertiary center between 2002 and 2010 fulfilled our study criteria. Demographic, histopathological, management and followup data were recorded in a prospective database. Local, regional and distant recurrence rates, time to recurrence and survival rates were calculated. Survival analysis was performed by the Kaplan-Meier method. Multivariate analysis was used to identify predictors of local recurrence. RESULTS: Mean followup was 42.8 months (range 4 to 107). Local, regional and distant metastatic recurrence developed in 16 (8.9%), 19 (10.6%) and 9 patients (5.0%) at a mean of 26.1, 26.8 and 11.7 months, respectively. The 5-year disease specific survival rate after recurrence was 54.7% (95% CI 46.1-63.3). For patients with isolated local recurrence the 5-year disease specific survival rate was 91.7% compared to 38.4% for those with regional recurrence. The overall 5-year local recurrence-free rate was 86.3% (95% CI 82.6-90.4). Tumor grade (p = 0.003), stage (p = 0.021) and lymphovascular invasion (p = 0.014) were identified as predictors of local recurrence on multivariate analysis. CONCLUSIONS: Penile conserving surgery is oncologically safe and a surgical excision margin of less than 5 mm is adequate. Higher local recurrence rates are associated with lymphovascular invasion, and higher tumor stage and grade. Local recurrence has no negative impact on long-term survival.

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.

Primary Squamous Cell Carcinoma of the Male Proximal Urethra: Outcomes from a Single Centre.

BACKGROUND: Primary squamous cell carcinoma (SCC) of the male proximal urethra is an aggressive and rare urogenital malignancy. OBJECTIVE: To review the surgical management and outcomes for male proximal urethral SCCs within a single centre and to suggest an algorithm for the surgical management of these rare tumours. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective study of patients undergoing surgery for male proximal urethral SCC within a single tertiary academic centre managing rare genital tumours. Ten patients with a histological diagnosis of proximal urethral SCC were identified from an institutional database over a period of 10 yr with a median follow-up of 22.5 mo (standard deviation±25.77 mo). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Pathological staging, surgical treatment, and neoadjuvant and adjuvant treatment were recorded. Complications according to the Clavien-Dindo classification and overall survival rates were recorded. Kaplan-Meier curves were used for overall survival. RESULTS AND LIMITATIONS: A total of 10 patients were identified of whom eight underwent panurethrectomy and radical prostatectomy. Radical inguinal lymphadenectomy was performed in five patients, which confirmed bilateral metastatic disease. Perioperative complications were reported in six patients (Clavien I and II). Within 6 mo of surgery, 90% of patients developed distant metastatic disease. Nine patients died of urethra cancer during the follow-up. One patient is still on follow-up. The median overall follow-up was 13.92 mo (range: 5-91 mo). At 5 yr, cancer-specific/overall survival was 10%. A limitation of this study is the retrospective design, which is unavoidable for such a rare disease. CONCLUSIONS: Radical surgery allows local disease control, but despite neo/adjuvant treatment, proximal urethral SCC is associated with poor survival outcomes and progression to distant metastatic disease within 6 mo. PATIENT SUMMARY: Proximal urethral squamous cell carcinoma is a rare cancer in men which is often detected late. Patients often present with problems such as voiding, urethral bleeding, or a palpable mass. Aggressive surgery allows local control, but despite this the overall survival is poor. Adjuvant and neoadjuvant radiochemotherapy can improve survival. Multicentric randomised trials are needed to identify the correct treatment modality.

Assessment of Return to Baseline Urinary and Sexual Function Following Primary Focal Cryotherapy for Nonmetastatic Prostate Cancer.

BACKGROUND: The oncological outcomes in men with clinically significant prostate cancer following focal cryotherapy are promising, although functional outcomes are under-reported. OBJECTIVE: To determine the impact of focal cryotherapy on urinary and sexual function, specifically assessing return to baseline function. DESIGN, SETTING, AND PARTICIPANTS: Between October 2013 and November 2016, 58 of 122 men who underwent focal cryotherapy for predominantly anterior clinically significant localised prostate cancer within a prospective registry returned patient-reported outcome measure questionnaires, which included International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-15) questionnaires. INTERVENTION: Standard cryotherapy procedure using either the SeedNet or the Visual-ICE cryotherapy system. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome was return to baseline function of IPSS score and IIEF erectile function (EF) subdomain. Cumulative incidence and Cox-regression analyses were performed. RESULTS AND LIMITATIONS: Probability of returning to baseline IPSS function was 78% at 12 mo and 87% at both 18 and 24 mo, with recovery seen up to 18 mo. For IIEF (EF domain), the probability of returning to baseline function was 85% at 12 mo and 89% at both 18 and 24 mo, with recovery seen up to 18 mo. Only the preoperative IIEF-EF score was associated with a poor outcome (hazard ratio 0.96, 95% confidence interval 0.93-0.999, p = 0.04). The main limitation was that only half of the patients returned their questionnaires. CONCLUSIONS: In men undergoing primary focal cryotherapy, there is a high degree of preservation of urinary and erectile function with return to baseline function occurring from 3 mo and continuing up to 18 mo after focal cryotherapy. PATIENT SUMMARY: In men who underwent focal cryotherapy for prostate cancer, approximately nine in 10 returned to their baseline urinary and sexual function. Keeping in mind that level 1 evidence and long-term data are still needed, in men who wish to preserve urinary and sexual function, focal cryotherapy may be considered an alternative treatment option to radical therapy.