Prostatic urethral lift for subjects in urinary retention (PULSAR): 12-Month results of a prospective controlled trial compared with real-world outcomes.

Objective: To examine the safety and efficacy of prostatic urethral lift (PUL) in acute urinary retention (AUR) patients within a controlled (PULSAR) and real-world setting (Real-World Retrospective study). Materials and methods: PULSAR was a 12-month prospective study of PUL in AUR patients (n = 51) performed at six centres in the United Kingdom; enrolled BPH patients aged ≥50 years, with prostate volume of ≤100 cc. AUR was defined as being catheter dependent with at least one prior failed trial without catheter (TWOC) while on an alpha-blocker. RWR consisted of 3226 consecutive PUL patients across 22 international sites treated between July 2017 and March 2020; 469 of whom were in urinary retention (RWRr), that is, catheter-dependent at the time of their procedure. Symptom response, uroflow and catheter independence rates were compared between PULSAR and RWRr subjects. A logistical regression model was constructed to evaluate patient baseline and dynamic factors predicting success after the procedure. Results: Seventy-three percent of PULSAR subjects were catheter independent and free from surgical reintervention at 12 months post-PUL. Success was associated with higher voiding efficiency during the perioperative period. Slightly higher catheter-independent rates (80%) were seen in RWRr patients; variables that influenced success included age <70 years, lower baseline prostate-specific antigen (PSA), lower baseline post-void residual (PVR) and shorter pre-procedural catheter duration. Logistic regression of the combined PULSAR and RWRr retention groups revealed that procedural age <70 years and higher bladder voiding efficiency (BVE) were associated with success. Conclusions: Lower baseline PSA and PVR, younger age and shorter pre-procedure catheter durations drove successful outcomes in AUR patients undergoing PUL. Post-PUL voiding efficiencies may help ascertain long-term response to treatment.

Long-term multicentre experience of adjuvant radiotherapy for pN3 squamous cell carcinoma of the penis.

OBJECTIVE: To present the long-term adjuvant radiotherapy outcomes of patients with pN3 squamous cell carcinoma of the penis (SCCp) treated at two UK centres. PATIENTS AND METHODS: We conducted a retrospective audit of all pN3 SCCp patients, deemed suitable for adjuvant therapy by a specialist multidisciplinary team at St George's and Leeds Hospitals, who received adjuvant radiotherapy. Primary outcomes were recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). Secondary outcomes were time to adjuvant treatment, frequency of in-field recurrence, site and side of recurrence, and dose and schedule of radiotherapy. RESULTS: A total of 146 patients were included: 121 completed radiotherapy, 4 did not complete radiotherapy and 21 did not start it. The median (interquartile range [IQR]) age was 59 (54-70)years. The 5-year RFS was 51%, CSS was 51% and OS was 44%. Adjuvant radiotherapy was started at a median (IQR) of 75 (48-106) days. A dose of 45 Gy in 20 fractions was most commonly used. Of the 125 patients who started adjuvant treatment, 55 relapsed. Of these relapses, 30 occurred in an inguinal or pelvic nodal station and 26 of the 30 were in a radiation field. Relapses in 18 of the 55 cases were in visceral sites only and seven were in both nodal (non-irradiated sites) and visceral sites. Doses of <50 Gy were used more commonly before 2013 and higher doses (>50 Gy) were more commonly used after 2013. CONCLUSIONS: Application of a standard radiotherapy protocol within a centralized supra-network setting has achieved survival outcomes that would appear better than those previously documented for either radiotherapy or chemotherapy in a cohort with solely pN3 disease. The addition of adjuvant chemotherapy may improve these outcomes further. These data suggest that adjuvant radiotherapy has a role to play in the management of men with pN3 SCCp.

Recent advances in managing Peyronie's disease.

Treating men with Peyronie's disease remains a challenging problem facing clinicians working across urology and sexual medicine fields. Patients can often be left disappointed by current treatment paradigms, and an overall lack of suitable molecular targets has limited the options for novel, effective medical therapy. Managing men with Peyronie's disease often involves careful counselling alongside multifaceted and possible combination treatments to help improve symptoms whilst ameliorating potential side effects of therapy. We review the latest medical literature and evidence in the contemporary management of Peyronie's disease.

--- ---Recent advances in managing Peyronie's disease.

Peyronie's disease remains an under-reported and debilitating problem which can result in significant physical and psychological symptoms for some men. The classic symptom complex includes penile curvature, penile plaque, and penile pain. Men can also present with erectile dysfunction, penile instability, and penile shortening, alongside feelings of low mood/libido, dysmorphobia, and low self-esteem. This review highlights the current key publications in the medical literature and provides updates on new clinical therapies whilst postulating about potential future treatments on the horizon.

Challenges and controversies in the management of penile cancer.

Penile cancer is a rare disease, accounting for ~1% of all malignancies in men. Poor awareness of the condition among the public and clinicians often causes long delays in diagnosis and treatment, which may result in the development of advanced disease that might require extensive and emasculating surgery. In the UK, the development of supraregional penile cancer centres has pooled resources and expertise, which has led to considerable improvements in our understanding and management of this rare condition over the past decade. However, significant gaps in our knowledge still exist. Several areas of diagnosis and management remain areas of controversy, ranging from preventive strategies and treatment of premalignant disease to the assessment of lymph node involvement and the management of advanced disease.

Male genital premalignant dermatoses.

The spectrum of conditions affecting the penile skin is varied and ranges from simple, benign dermatoses to premalignant and malignant conditions. Recently, improved understanding of the aetiology and natural history of these conditions has shaped new treatment paradigms and a functional knowledge of dermatology, urology and genitourinary medicine is required to successfully diagnose and treat these men. In this article, we explore the common precancerous states that can lead to penile carcinoma and review the recent advances with regards to the molecular basis for these dermatoses and the treatments that may be most effective for these men.

Therapeutic strategies for patients with micropenis or penile dysmorphic disorder.

Micropenis in adults is defined as a stretched length of <7.5 cm. Many aetiologies exist, including congenital and endocrinological causes as well as pathological conditions, such as penile lichen sclerosus, trauma and genital cancer. The resulting reduction in functional penile length can lead to considerable psychosexual morbidity. Furthermore, the subset of patients with micropenis who also suffer from penile dysmorphic disorder require careful and intensive psychological counselling. Corrective surgery for micropenis can be performed in patients with realistic expectations. Total phalloplasty using radial-artery-based forearm skin flaps can offer restoration of normal penile length in selected patients. More-conservative surgical techniques to improve length or girth are limited by minimal enhancement but associated with a significantly lower rate of complications and comorbidity compared to total phalloplasty. Emerging tissue engineering techniques might represent a suitable alternative to penile replacement surgery in the future.

A peculiar case of bilateral, spontaneous thromboses of the pampiniform plexi.

Acute thrombosis of the pampiniform plexus is an uncommon clinical problem which causes a diagnostic conundrum in men presenting urgently to medical personnel. We present an unusual case of a young man who presented with metachronous thromboses of his pampiniform plexi and review the literature to explore potential aetiologies and therapeutic strategies.

DNA replication licensing factors and aneuploidy are linked to tumor cell cycle state and clinical outcome in penile carcinoma.

PURPOSE: The DNA replication licensing machinery is integral to the control of proliferation, differentiation, and maintenance of genomic stability in human cells. We have analyzed replication licensing factors (RLF), together with DNA ploidy status, to investigate their role in progression of penile squamous cell carcinoma and to assess their utility as novel prognostic tools. EXPERIMENTAL DESIGN: In a cohort of 141 patients, we linked protein expression profiles of the standard proliferation marker Ki67 and the RLFs Mcm2 and geminin to clinicopathologic variables, ploidy status, and clinical outcome. RESULTS: Increased Ki67, Mcm2, and geminin levels were each significantly associated with arrested tumor differentiation (P < 0.0001) and aneuploidy (P < or = 0.01). Accelerated cell cycle progression was linked to increasing tumor size, stage, and depth of invasion. Aneuploid tumors significantly correlated with tumor grade (P < 0.0001). Biomarker expression and DNA ploidy status were significant predictors of locoregional disease progression [Mcm2 (P = 0.02), geminin (P = 0.02), Ki67 (P = 0.03), and aneuploidy (P = 0.03)] in univariate analysis. Importantly, aneuploidy was a strong independent prognosticator for overall survival (hazard ratio, 4.19; 95% confidence interval, 1.17-14.95; P = 0.03). Used in conjunction with conventional pathologic information, multiparameter analysis of these variables can stratify patients into low- or high-risk groups for disease progression (Harrell's c-index = 0.88). CONCLUSIONS: Our findings suggest that RLFs and tumor aneuploidy may be used as an adjunct to conventional prognostic indicators, identifying men at high risk of disease progression. Our results also identify the DNA replication initiation pathway as a potentially attractive therapeutic target in penile squamous cell carcinoma.

Molecular and genetic pathways in penile cancer.

Penile cancer is a rare malignancy affecting more than 400 men per year in the UK. Studies on the aetiopathogenesis of this cancer have focused on its association with the human papilloma virus; however, there have also been several studies on the genetic and molecular changes that occur. Human papilloma virus has shown differential levels of prevalence in association with different types of penile cancer. The virus seems to act as a trigger for this disease via its oncogenes. We review this process, and assess the independent genetic events that occur in penile cancer. Knowledge of this cancer is progressing slowly and could be furthered by multicentre cooperation and the formation of national tumour banks, which will aid the development of novel therapeutic agents to reduce the morbidity and mortality of penile cancer.

Frenular grafting: an alternative to circumcision in men with a combination of tight frenulum and phimosis.

INTRODUCTION: Men suffering from frenular scarring and stricturing with associated phimosis are traditionally treated with circumcision. In men wishing to retain their foreskin, the treatment options are limited by this dual pathology. Frenuloplasty alone is contraindicated in this clinical setting. AIM: To demonstrate the utility of frenular grafting in patients with a tight frenulum and concomitant phimosis who wish to retain their foreskin. METHODS: Six men were included in the study. Presenting symptoms included bleeding (N = 2) and pain/phimosis (N = 6). Median age is 27 years (25-34 years). All men were healthy and sexually active. We describe a refined technique involving the excision of scarred and redundant frenular tissue and the insertion of a skin graft to the area. MAIN OUTCOME MEASURES: All patients were assessed for graft viability, functional/symptom improvement, time to penetrative intercourse, and overall satisfaction. RESULTS: All men received an interposition skin graft with 100% viability, with no revision surgery required. Postoperatively, all men were sexually active and able to retract their foreskin. CONCLUSIONS: Cosmetic outcomes are encouraging and painless sexual intercourse is attainable in this difficult group of patients.

Vertical rectus abdominis flap reconstruction in patients with advanced penile squamous cell carcinoma.

OBJECTIVES: To evaluate the role of radical surgical debridement and excision with a vertical rectus abdominis myocutaneous (VRAM) flap reconstruction in patients with advanced penile cancer and subcutaneous metastatic disease, as the quality of life in such patients is extremely poor, multimodal treatments often fail and the outlook for the patient is limited with the development of uncontrollable disease. PATIENTS AND METHODS: Four patients with advanced penile cancer presenting with fungating, cutaneous tumour deposits received palliative surgical resections for abdominal and inguinal disease. A VRAM flap was used in all cases to achieve tissue coverage. RESULTS: All grafts were viable and the mean inpatient stay was 14 days. There were no immediate complications after surgery; patient satisfaction and symptom relief was excellent. CONCLUSIONS: Aggressive palliative resection with a VRAM can dramatically improve the patients' quality of life in advanced penile cancer, permitting disease control with satisfactory cosmesis. However, a multidisciplinary approach involving both the urological reconstructive and plastic surgeon is essential.

The role of magnetic resonance imaging in the local staging of penile cancer.

OBJECTIVES: To assess the accuracy of magnetic resonance imaging (MRI) as a local staging technique in penile cancer and its role in selecting patients for conservative surgical management. METHODS: Fifty-five men diagnosed with invasive penile carcinoma on biopsy were locally staged with the use of MRI. Prostaglandin E1 (alprostadil) was injected into the corpora to induce an artificial erection. Radiologic staging was compared against final histopathologic stage of the tumour. Sensitivity, specificity, and kappa agreement values were calculated for each tumour stage. Additionally, corpora cavernosa involvement was reviewed in 20 consecutive cases and suitability for conservative surgery assessed. RESULTS: A good correlation between radiologic and histologic staging was achieved with an overall kappa value of 0.75 (p<0.001). Stage-specific sensitivities and specificities were calculated: T1 (85%; 83%), T2 (75%; 89%), and T3 (88%; 98%). MRI accurately predicted corpora cavernosa invasion in all cases of pathologically proven disease. These patients were selected to undergo partial penectomy. There were no complications using this imaging technique. CONCLUSIONS: This study demonstrates that penile MRI is highly accurate in the local staging of penile cancer. Associated improvements in surgical planning allow the provision of conservative surgical treatments over more radical procedures.

A prospective study of 100 cases of penile cancer managed according to European Association of Urology guidelines.

OBJECTIVE: To prospectively assess the outcome of patients treated according to the European Association of Urology (EAU) guidelines on the management of penile cancer, a system originally based on retrospective series. PATIENTS AND METHODS: Between 2002 and 2005, 100 consecutive patients (median age 62 years) with penile cancer were treated at one institution; all were categorized and treated according to EAU guidelines. Data were analysed using the z-test, with significance defined as P < 0.05. RESULTS: Survival curves were limited to those with >12 months of follow-up (mean 29); the survival of the whole group was 92%. Of men with palpable nodes, 72% had lymph node involvement, whereas 18% of those with impalpable nodes who had lymphadenectomy according to the guidelines had lymph node disease. The grade of the primary tumour was more predictive than T stage for lymph node involvement and survival. The 3-year disease-specific survival for N0, N1 and N2 disease was 100%, 100% and 73%, respectively, and survival at 12 months for N3 disease was 67%. The median survival for those with metastases was 3 months. CONCLUSION: The overall survival of men with penile cancer is high, with a clear benefit for early lymphadenectomy in men with positive nodal disease. However, the current EAU guidelines are limited in predicting those patients with micrometastatic disease, with the result that 82% of patients undergo unnecessary prophylactic lymphadenectomy. There is a need to identify more accurate molecular markers for predicting lymph node disease, or the role of novel staging techniques must be assessed.

Penile suspensory ligament division for penile augmentation: indications and results.

OBJECTIVE: This study assessed the management of patients requesting penile length enhancement by division of the penile suspensory ligament. METHODS: From September 1998 to January 2005, 42 patients with a variety of etiologies were included; all underwent division of the penile suspensory ligament. The outcome was assessed objectively based on increase in flaccid stretched penile length (SPL) and subjectively using the rates of patient satisfaction. RESULTS: The mean increase in SPL was 1.3+/-0.9 cm (range, -1 to +3 cm), with the addition of a silicone spacer placed between the pubis and penis giving a better outcome (p<0.05). The overall patient satisfaction rate was 35% but lower in the group with penile dysmorphic disorder at 27%. CONCLUSION: Division of the penile suspensory ligament or other augmentation techniques may increase penile length but usually not to a degree that satisfies the patient. Men with penile dysmorphic disorder often have unrealistic expectations regarding the outcome of surgical intervention and should be encouraged to seek psychological help primarily, with surgery reserved as the last resort.

What surgical resection margins are required to achieve oncological control in men with primary penile cancer?

OBJECTIVE: To evaluate the surgical excision margin required for local oncological control in primary penile cancers, as patients with penile cancer who undergo radical amputation suffer marked psychological, functional and cosmetic sequelae, and although organ-sparing surgery has improved the quality of life of these men, the optimum surgical excision margin to achieve oncological control is unknown. PATIENTS AND METHODS: In all, 51 patients (mean age 61 years) diagnosed with squamous cell carcinoma of the penis between May 2000 and December 2004 were selected for treatment with conservative surgical techniques. All patients were staged before surgery using magnetic resonance imaging. Histopathological features of the tumours, including type, grade, stage and distance from the surgical excision margin, were evaluated. All patients were followed in the outpatient department according to European Association of Urology guidelines. RESULTS: The median (range) follow-up of the men was 26 (2-55) months. Patients were treated by wide localized excision (nine), glans excision (26) and partial penectomy (16). The histopathological review included the analysis of 102 surgical margins (deep and skin) with 49 (48%) measured within 10 mm of the tumour edge and 92 (90%) within a <20-mm resection margin. Three patients (6%) had tumour involvement at the surgical margin and had further surgery. During follow-up two patients (4%) developed local tumour recurrence and were treated successfully with partial penectomy. CONCLUSION: A traditional 2-cm excision margin is unnecessary for treating squamous cell carcinoma of the penis. Conservative techniques, involving excision margins of only a few millimetres, appear to offer excellent oncological control.