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.

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.

Therapeutic outcomes and analysis of Doppler findings in 25 patients with non-ischemic priapism.

Non-ischemic priapism (NiP) is painless partial tumescence caused by genital trauma and the formation of intracorporal arterio-venous fistula. This is a retrospective study of 25 men with NiP and reports the long-term erectile function and colour doppler ultrasound (CDUS) findings after treatment for NiP. Unstimulated CDUS was performed at diagnosis, 1 week and at last follow-up after treatment. CDUS traces were analysed: peak systolic velocity (PSV), end diastolic velocity (EDV), resistive index (RI) and mean velocity (MV) were calculated. Erectile function was assessed using the IIEF-EF questionnaire. At the last follow-up (median 24 months), 16 men had normal erectile function (64%): median IIEF-EF score 29 (IQR 28.5-30; σ2 2.78) and nine had erectile dysfunction (36%): median IIEF-EF score 17 (IQR 14-22; σ2 33.6). MV and EDV were statistically higher in those patients with erectile dysfunction at last follow-up compared to patients with normal erectile function: median MV 5.3 cm/s (IQR 2.4-10.5 cm/s; σ2 34) vs 2.95 cm/s (IQR 1.03-3.95; σ2 3.4) p < 0.002 and median EDV 4.0 cm/s (IQR 1.5-8.0; σ2 14.7) vs 0 cm/s (IQR 0-1.75; σ2 2.21) p < 0.004. Erectile dysfunction was observed in 36% of men treated for NiP and was associated with abnormal low resistance resting CDUS waveforms. Further investigation for persistent arteriovenous fistulation should be considered in these patients.

Fournier's gangrene of the penis complicating both COVID-19- and Mpox-related genital ulceration - A case report.

Fournier's gangrene is a rare, rapidly progressive, fulminant form of infective necrotising fasciitis of the genital, perianal and perineal regions. We present a case of Fournier's gangrene of the penis complicating acute genital ulceration and recurrent paraphimosis that was secondary to contemporaneous COVID-19 and Mpox infection in an otherwise healthy 41-year-old man. It is important for clinicians to be aware of Fournier's gangrene, as early detection remains the cornerstone of effective tissue and indeed life conserving management.

Primary penile melanoma and genital lichen sclerosus.

Background: There is a well-established association between squamous cell cancer and genital lichen sclerosus (GLSc). Although there have been several reported cases of vulval melanoma (MM) associated with LSc, particularly in the paediatric population, fewer cases of male genital (M) GLSc and penile (Pe)MM have been published. Objectives: The aim of this study was to explore further the relationship between PeMM and MGLSc by reviewing all the cases managed by our multidisciplinary service over a finite period. Methods: All patients known to our tertiary urology and male genital dermatology service with a diagnosis of PeMM and where histology was available for review were identified over an 11-year period (2011-2022). The histology was reviewed by two independent, mutually 'blinded' histopathologists. Photographs and clinical notes, where available, were retrospectively reviewed by two independent dermatologists for signs or symptoms of LSc. Results: Eleven patients with PeMM were identified for review. Histopathological examination found evidence of LSc in nine patients, and review of clinical photos corroborated the presence of LSc in three. Overall, features of LSc were present in nine out of eleven cases (82%). Conclusion: The presence of LSc in 9 out of 11 cases of PeMM is suggestive of a causative relationship between LSc and PeMM. This may be due to chronic melanocytic distress created by chronic inflammation secondary to LSc.

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.

Corporal Skip Metastases in Penile Squamous Cell Carcinoma: An Unknown and Distinct Pattern of Spread with Poor Prognosis.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is characterised by stepwise lymphatic dissemination. Skip metastases (SkMs) are rare metastases in the corpus cavernosum or spongiosum without continuity to the primary tumour or its resection site. OBJECTIVE: To assess the distinct pattern of spread in SkM+ patients and the effect of SkM on prognosis. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective analysis of patients with SkM+ PSCC at ten high-volume international referral centres between January 2006 and May 2022. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We evaluated histopathological data, primary lymph node (LN) staging, and metastatic spread. We included a cohort of patients matched for pT stage, LN status, and grade who did not have SkM (SkM-) to compare the SkM prognosis and predictive value for cancer-specific mortality (CSM). RESULTS AND LIMITATIONS: Among the 63 SkM+ patients who met our inclusion criteria, the SkM diagnosis was synchronous in 54.0% and metastases were mostly located in the corpus cavernosum. SkM was symptomatic in 14% of cases, was detected on imaging in 32%, and was found incidentally on pathological examination in 27%. Fifty-one patients (81%) presented with positive LNs and 28 (44%) developed distant metastases. Seven patients (11%) presented with or developed distant metastasis without displaying any LN involvement. The 2-yr cancer-specific survival estimates were 36% (95% confidence interval [CI] 25-52%) for SkM+ and 66% (95% CI 55-80%) for matched SkM- patients (p < 0.001). On multivariable Cox regression analysis, SkM presence was an independent predictor for higher CSM (hazard ratio 2.05, 95% CI 1.06-4,12; p = 0.03). CONCLUSIONS: PSCC-related SkM is associated with aggressive disease behaviour and poor survival outcomes. Palpation of the entire penile shaft is essential, and distant staging is recommended in patients suspected of having SkM owing to the tendency for distant metastatic spread. PATIENT SUMMARY: We investigated outcomes for patients with cancer of the penis who had metastases in the tissues responsible for erection. We found that metastases in this location were associated with poor prognosis, even in the absence of more typical spread of cancer via the lymph nodes.

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.

Genital lichen sclerosus and melanoma; a systematic review.

Background: Lichen sclerosus (LSc) is a chronic, inflammatory, destructive skin disease with a predilection for the genitalia (GLSc). An association with vulval (Vu) and penile (Pe) squamous carcinoma (SCC) is now well established but melanoma (MM) has only rarely been reported complicating GLSc. Methods: We have performed a systematic literature review of GLSc in patients with genital melanoma (GMM). Only articles that mentioned both GMM and LSc affecting either the penis or vulva were included. Results: Twelve studies with a total of 20 patients were included. Our review shows that an association of GLSc with GMM has been more frequently reported in women and female children than men viz, 17 cases compared with three. It is notable that five of the cases (27.8%) concerned female children aged under twelve. Discussion: These data suggest a rare association between GLSc and GMM. If proven, there arise intriguing questions about pathogenesis and consequences for counselling of patients and follow-up.

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.

Complications and outcomes following injection of foreign material into the male external genitalia for augmentation: a single-centre experience and systematic review.

Injection of exogenous material into the penis and scrotum has been performed for augmentation purposes. Complications include cosmetic dissatisfaction, penile necrosis and lymphoedema. We report the complications and outcomes from a single centre with an updated systematic review of the literature. A retrospective review of all cases presenting with foreign substance injection into the genitalia, over a 10-year period was performed. Thirty-five patients with a mean (standard deviation (SD); range) age of 36.9 (±9.1; 22-61) years at presentation were included. The mean (SD; range) time between injection and presentation was 7.8 (±5.8; 1 day-20 years) years. The most common injected substance was silicone (n = 16, 45.7%) and liquid paraffin (n = 8, 22.9%). The penile shaft (94.3%) was the most injected site. The most common presentations were cosmetic dissatisfaction (57.1%) and pain and/or swelling (45.7%). Surgery was required in 32 (91.4%) cases. Primary procedures included local excision and primary closure (n = 19, 59.4%), circumcision (n = 5, 15.6%), excision with a split skin graft or a scrotal flap reconstruction (n = 5, 15.6%). Three (8.6%) patients presented with necrosis and required acute debridement. Overall, 18 patients had more than 1 procedure, and 8 patients required 3 or more procedures. A systematic search of the literature identified 887 articles of which 68 studies were included for analysis. The most common substance injected was paraffin (47.7%), followed by silicone (15.8%). The majority of patients (77.9%) presented with pain, swelling or penile deformity. 78.8% of the patients underwent surgical treatment, which included excision and primary closure with or without the use of skin grafts (85.1% of all procedures), the use of flaps (12.3%) and penile amputation (n = 2). Complications of foreign body injection into the male genitalia can be serious resulting in necrosis and autoamputation. Surgical intervention is often required to excise abnormal tissue to manage pain and improve cosmesis.

The British Society for Sexual Medicine Guidelines on Male Adult Testosterone Deficiency, with Statements for Practice.

Testosterone deficiency (TD) is an increasingly common problem with significant health implications, but its diagnosis and management can be challenging. A multi-disciplinary panel from BSSM reviewed the available literature on TD and provide evidence-based statements for clinical practice. Evidence was derived from Medline, EMBASE and Cochrane searches on hypogonadism, testosterone therapy (T Therapy) and cardiovascular safety from May 2017 to September 2022. This revealed 1,714 articles, including 52 clinical trials and 32 placebo-controlled randomised controlled trials. A total of twenty-five statements are provided, relating to five key areas: screening, diagnosis, initiating T Therapy, benefits and risks of T Therapy, and follow-up. Seven statements are supported by level 1 evidence, eight by level 2, five by level 3, and five by level 4. Recent studies have demonstrated that low levels of testosterone in men are associated with increased risk of incident type 2 diabetes mellitus, worse outcomes in chronic kidney disease and COVID 19 infection with increased all-cause mortality, along with significant quality of life implications. These guidelines should help practitioners to effectively diagnose and manage primary and age-related TD.

Opposite changes in the expression of clathrin and caveolin-1 in normal and cancerous human prostate tissue: putative clathrin-mediated recycling of EGFR.

Endocytosis, an important macromolecule uptake process in cells, is known to be dysregulated in cancer. Clathrin and caveolin-1 proteins play a major role in receptor-mediated endocytosis. We have used a quantitative, unbiased and semi-automated method to measure in situ protein expression of clathrin and caveolin-1 in cancerous and paired normal (cancer adjacent, non-cancerous) human prostate tissue. There was a significant (p < 0.0001) increase in the expression of clathrin in prostate cancer samples (N = 29, n = 91) compared to normal tissue (N = 29, n = 67) (N = number of patients, n = number of cores in tissue arrays). Conversely, there was a significant (p < 0.0001) decrease in expression of caveolin-1 in prostate cancer tissue compared to normal prostate tissue. The opposite change in expression of the two proteins was highly correlated to increasing cancer aggressiveness. There was also a concurrent increase in the expression of epidermal growth factor receptor (EGFR), a key receptor in carcinogenesis, with clathrin in prostate cancer tissue, indicating recycling of EGFR through clathrin-mediated endocytosis (CME). These results indicate that in prostate cancer, caveolin-1-mediated endocytosis (CavME) may be acting as a brake and increase in CME may facilitate tumorigenicity and aggressiveness of prostate cancer through recycling of EGFR. Changes in the expression of these proteins can also potentially be used as a biomarker for prostate cancer to aid in diagnosis and prognosis and clinical decision-making.

Videoendoscopic Inguinal Lymphadenectomy Versus Radical Open Dissection (VELRAD) in Patients with Male Genital Cancer: A Clinical Trial Update.

VELRAD is the first multicentre feasibility randomised controlled trial comparing videoendoscopic radical inguinal lymphadenectomy versus open dissection for male genital cancer. We have randomised nine patients so far in our attempt to identify the best approach to inguinal lymph node dissection.

The association between penile cancer and HIV infection: A literature review.

Penile cancer is a rare malignancy which HIV infection appears to increase the risk of. The magnitude of this risk and the pathogenesis remain unclear. A comprehensive review of the literature was undertaken using conventional search strategies. Twenty-four publications were identified by this methodology, of which nine were case reports and 15 were observational studies. These studies were highly heterogeneous, with varying study designs, populations, and objectives. The risk of penile cancer within HIV-positive individuals is significantly greater than in those without HIV (RR = 3 .7 to 5.8, 3 studies; SIR = 3.8 to 11.1, 4 studies). HIV is also shown to influence disease characteristics, with a four-fold increased risk of death from penile cancer. Moreover, progression from intraepithelial neoplasia occurs earlier in HIV, six years sooner than in HIV-negative men. HIV-positive men have a higher prevalence of HPV infection. Ethnicity is also shown to modulate the relationship between HIV and penile carcinoma, with a higher risk of cancer in Hispanic, compared with Caucasian, HIV-positive men. This review has collated data from diverse sources to improve understanding of the relationship between HIV and penile cancer. This relationship has been quantitatively and qualitatively characterised and highlights areas deserving further enquiry.

Insertion of Penile Implants in Patients with Priapism: When Is the Right Time?

Acute ischaemic priapism is a urological emergency that requires prompt intervention. Refractory cases result in the development of fibrosis in the corpus cavernosum, which results in erectile dysfunction. Early insertion of a penile prosthesis in refractory cases allows easier dilatation and maintains the penile length and girth.

Are finasteride-related penile curvature/Peyronie's disease Adverse Event Reports worthy of further clinical investigation? Disproportionality analysis based on both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) pharmacovigilance databases.

A limited number of studies have described patients on finasteride showing findings which were consistent with Peyronie's disease (PD). We aimed to detect a pharmacovigilance signal of possible association between finasteride and PD-related clinical features. The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was queried to identify the ten drugs which were associated the most with the adverse drug reactions (ADRs) recorded as "penile curvature" and/or "Peyronie's disease". A similar analysis, including the same drugs, was carried out for the EMA (European Medicines Agency) EudraVigilance (EV) database. Descriptive data have been analyzed, and Proportional Reporting Ratios (PRRs) have been computed against the other nine drugs of the database. Overall, 860 reports of "penile curvature" and/or "Peyronie's disease", were identified in the FAERS database, 214 of which (24.9%) were associated with finasteride. Most reports (56.9%) were submitted by healthcare professionals. Where a treatment-indication was stated, the vast majority of reports (176/210; 83.8%) were associated with androgenetic alopecia. The outcome of most ADRs was "serious" (82.2%), with 96 ADRs resulting in levels of permanent disability. For 97/214 individual cases, penile curvature/PD reports were not part of a syndromic cluster suggestive of post-finasteride syndrome (PFS). The PRR resulted 6.6 (95% CI: 5.6-7.8) and 11.8 (95% CI: 9.08-15.33), respectively, in the FAERS and in the EV databases. Notwithstanding the related limitations and biasing factors of pharmacovigilance studies based on spontaneous reporting, the PRR values here identified should be interpreted as strong signals of disproportionality. These findings, per se, are however not useful to confirm any causal association. Clinical studies are needed to investigate on the possible role for finasteride in causing PD-related clinical features, an hypothesis which remains highly speculative due to the very questionable quality of present data.

Treatment of Persistent or Recurrent Varicoceles: A Systematic Review.

CONTEXT: The outcomes and morbidity following treatment for persistent or varicocele recurrence remain controversial. OBJECTIVE: To conduct a systematic review relating to the outcomes following treatment (any surgical or radiological) for varicocele persistence/recurrence. EVIDENCE ACQUISITION: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Prospective and retrospective observational or interventional studies were included until March 2022. Outcomes were pregnancy rate, improvements in semen parameters after treatment compared with those at baseline, pain control, complication rates, and repeat treatment approach. Men of any age with any-grade persistent/recurrent varicoceles were included. EVIDENCE SYNTHESIS: Of 913 articles identified, 18 with 1073 patients were eligible for inclusion. The mean time between the first and repeat treatment ranged between 5.3 and 73.3 months. The indication for repeat treatment was infertility in eight and pain control in six out of 18 studies, whereas four did not provide details for the indication. Of the patients with recurrent/persistent varicoceles initially treated using a radiological intervention, 83.8% underwent another radiological procedure, whereas 16.2% underwent a surgical procedure. Of those initially treated with a surgical procedure, 77.8% underwent a further surgical procedure, whereas 22.2% underwent a radiological procedure. The rate of success of repeat treatment was 60-100%. The reported complications were as follows: hydrocele (up to 16%), testicular atrophy (up to 2%), scrotal hematoma (up to 1.6%), wound infection (up to 6.6%), chronic pain (up to 2.9%), injury to other organs (up to 10%), and thrombophlebitis (up to 5.8%). The rate of symptom resolution was >90% for pain control. Pregnancy rates were 17-58% at 12-month follow-up. Semen parameters improved after repeat treatment compared with that at baseline in 87.5% of studies. The main limitations are the high risk of bias according to the Newcastle and Ottawa Scale, heterogeneity of the included studies, and small simple size. CONCLUSIONS: Treating any grade of persistent/recurrent varicoceles has a good rate of success, pregnancy, and pain control, but there is still a risk of complications. Repeat treatment with the same interventional modality is feasible. The level of evidence is overall low. PATIENT SUMMARY: In this systematic review on persistent or recurrent varicoceles, we showed that repeat treatment with radiological or surgical procedures was feasible, with good success, pregnancy, and pain control rates at follow-up. However, repeat treatment was associated with a higher risk of complications than reported in the published literature relating to patients having their first intervention.