Raj Nigam

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.

Epigenetics Markers of Metastasis and HPV-Induced Tumorigenesis in Penile Cancer

Purpose: Penile cancer is a rare malignancy in the developed world with just more than 1,600 new cases diagnosed in the United States per year; however, the incidence is much higher in developing countries. Although HPV is known to contribute to tumorigenesis, little is known about the genetic or epigenetic alterations defining penile cancer. Experimental Design: Using high-density genome-wide methylation arrays, we have identified epigenetic alterations associated with penile cancer. Q-MSP was used to validate lymph node metastasis markers in 50 cases. A total of 446 head and neck squamous cell carcinoma (HNSCC) and cervical squamous cell carcinoma (CESCC) samples were used to validate HPV-associated epigenetic alterations. Results: We defined 6,933 methylation variable positions (MVP) between normal and tumor tissue, which includes 997 hypermethylated differentially methylated regions associated with tumor supressor genes, including CDO1, AR1, and WT1. Analysis of penile cancer tumors identified a 4 gene epi-signature which accurately predicted lymph node metastasis in an independent cohort (AUC of 89%). Finally, we explored the epigenetic alterations associated with penile cancer HPV infection and defined a 30 loci lineage-independent HPV specific epi-signature which predicts HPV status and survival in independent HNSCC, CESC cohorts. Epi-signature–negative patients have a significantly worse overall survival [HNSCC P = 0.00073; 95% confidence interval (CI), 0.021–0.78; CESC P = 0.0094; HR = 3.91, 95% CI = 0.13–0.78], HPV epi-signature is a better predictor of survival than HPV status alone. Conclusions: These data demonstrate for the first time genome-wide epigenetic events involved in an aggressive penile cancer phenotype and define the epigenetic alterations common across multiple HPV-driven malignancies. Clin Cancer Res; 21(5); 1196–206. ©2014 AACR.

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

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.

Epithelioid hemangioma of the penis: case report and review of literature

IntroductionEpithelioid hemangioma is a rare vascular tumor found in the penis. It is essential to avoid misdiagnosis with Peyronies disease and penile cancer, as management differs significantly.Case presentationWe present a case of epithelioid hemangioma of the penis in a 50-year-old Caucasian man. We also review the literature to evaluate the incidence of benign vascular anomalies of the penis and their management.ConclusionsEpithelioid hemangioma of the penis should be considered in the differential diagnosis of patients presenting with painful penile lumps. A thorough histological and immunohistochemical examination is required to make the diagnosis. Optimal management is complete local excision and periodic physical examination for local recurrence.

Glansectomy and Split-thickness Skin Graft for Penile Cancer

BACKGROUND Penile cancer is a rare malignancy that is confined to the glans in up to four out of five cases. Although descriptions of glansectomy exist, there are no contemporary video explanations or large published single centre series. OBJECTIVE To show the efficacy and safety of glansectomy and split-thickness skin graft (STSG) reconstruction. DESIGN, SETTING, AND PARTICIPANTS Data were collected retrospectively for patients identified from surgical theatre diaries between February 2005 and January 2016. 177 patients with histologically proven squamous-cell carcinoma on the glans underwent glansectomy and STSG at a tertiary referral centre in the UK. The median follow-up was 41.4 mo. SURGICAL PROCEDURE The skin is incised at the subcoronal level and deepened onto Bucks fascia. Dissection is performed over or under Bucks fascia, depending on suspicion of invasion or risk of disease. The glans is excised and a neoglans is created using a STSG. MEASUREMENTS Local recurrence, cancer-specific survival, overall survival, and complications. RESULTS AND LIMITATIONS Sixteen out of 172 patients (9.3%) experienced local recurrence during the follow-up period. Eighteen out of 174 (10.7%) patients died of penile cancer, while 29 patients in total died during the follow-up period. Of 145 patients, 9% required operative intervention for complications, including graft loss and meatal stenosis. Limitations include the retrospective data collection and the lack of functional and sexual outcomes. CONCLUSIONS Glansectomy and STSG comprise a safe procedure in terms of oncologic control and complications for patients with penile cancer confined to the glans penis. Further studies are required to assess functional and sexual outcomes in these patients. PATIENT SUMMARY We report on the management of penile cancers confined to the head of the penis using glansectomy and a split-thickness skin graft to recreate the appearance of a glans. This technique is safe and effective, with limited complications.

A Multicentre Study of 5-year Outcomes Following Focal Therapy in Treating Clinically Significant Nonmetastatic Prostate Cancer

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

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

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.

Diagnosis and management of symptomatic seminal vesicle calculi

Abstract Objective: The aim of this study was to review the management of patients with symptomatic seminal vesicle calculi, from presentation and diagnosis to postoperative outcomes. Materials and methods: A systematic review of the English literature in MEDLINE and Embase was performed, based on the following model: patients with a diagnosis of seminal vesicle calculi; all interventions considered with or without control groups with single and comparator interventions; outcomes considered were incidence, presentation, diagnostic methods and treatment. A narrative synthesis of the data was performed according to PRISMA 2009 guidelines. The study protocol was registered on PROSPERO (CRD42016032971). Results: In total, 213 cases of seminal vesicle calculi from 37 studies were identified between 1928 and 2016. Published articles included cohort studies (16), case–control studies (two) and case reports (19). The most likely aetiology was stasis of ejaculate secondary to impaired drainage of secretions from the seminal vesicles. Transrectal ultrasound remains the primary investigation for haematospermia and painful ejaculation; however, magnetic resonance imaging seems to play an increasingly important role, especially when considering surgery. Transurethral seminal vesiculoscopy and lithotripsy is the ideal procedure for small calculi but requires surgical expertise. For larger calculi a transperitoneal laparoscopic approach is safe in the hands of experienced laparoscopic surgeons. Conclusions: Modern imaging techniques and cross-sectional imaging are leading to an increased number of diagnosed cases of seminal vesicle calculi. Optimal treatment depends on the stone size and burden, and centralization of services will assist in the development of specialized centres.

MP30-10 HIFU DOSE ESCALATION LEADS TO FEWER RECURRENCES IN FOLLOWING FOCAL HIFU IN PROSTATE CANCER

CONCLUSION HIFU dose escalation leads to fewer recurrences in following focal HIFU in prostate cancer P. M. Huber 1,4,6, N. Afzal 8, M. Arya 4,6,7, S. Boxler 1, S. Charman 3, A. Cornaby 3, T. Dudderidge 9, M. Emberton 3,4, S. Guillaumier 3,4, R. J. Hindley 10, L. Leemann 2, H. Lewi 11, N. McCartan 3,4, C. M. Moore 3,4, R. Nigam 12, C. Ogden 13, R. Persad 14, K. Shah 3, G. N. Thalmann 1, J. Virdi 7, M. Winkler 6, H. U. Ahmed 3,5,6 1. Department of Urology, University Hospital Inselspital Berne, CH; 2. Department of Political Science, University of Zurich, CH; 3. Division of Surgery and Interventional Sciences, University College London, London, UK; 4. Department of Urology, UCLH NHS Foundation Trust, London, UK; 5. Division of Surgery, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK; 6. Imperial Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK; 7. Department of Urology, The Princess Alexandra Hospital NHS Trust, Harlow, UK; 8. Department of Urology, Dorset County Hospital NHS Trust, Dorset, UK; 9. Department of Urology, University Hospital Southampton NHS Trust, Southampton, UK; 10. Department of Urology, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, UK; 11. Springfield Hospital, Chelmsford, Essex, UK; 12. Department of Urology, Royal County Surrey Hospital NHS Trust, Surrey, UK; 13. Department of Academic Urology, The Royal Marsden Hospital NHS Foundation Trust, London, UK; 14. Department of Urology, Southmead Hospital, North Bristol NHS Trust, Bristol, UK

2013 CT UROGRAPHY FOR HAEMATURIA: INCIDENTAL DETECTION OF EXTRAURINARY TUMOURS

INTRODUCTION AND OBJECTIVES: Ultrasound of the renal tract is commonly used as a first line imaging investigation for patients with haematuria. With the development of rapid multi-slice Computed Tomography (CT), this modality is now replacing ultrasound in several centres as the initial investigation of haematuria. One argument for CT as a sole primary radiological investigation is that it allows for the incidental diagnosis of clinically significant non urological pathology and malignancies. The purpose of this study was to describe the incidence and types of non-urological tumours found on CT imaging in a prospective cohort of patients attending the haematuria clinic. METHODS: A new protocol for investigating haematuria was implemented at our institution in 2009 with the aim of reducing referral to treatment time. The new Haematuria Pathway replaced intravenous urography and ultrasound with a multi-slice CT urogram on the same day as a flexible cystoscopy in a one-stop service. The results of CT imaging were recorded prospectively and all suspicious tumours, urological and non-urological, were noted. The non-urological tumours confirmed histopathologically were recorded and categorised as: gynaecological, colorectal, hepatopancreatobiliary, adrenal and lower respiratory. RESULTS: 1608 patients with a median age of 66 years (range 27 to 89) were investigated for haematuria from January 2009 to September 2012. Male to female patient ratio was 2:1. 31% of patients had microscopic and 69% macroscopic haematuria. 346 patients (21.5%) were identified with urological tumours. 4.7% were found to have upper tract tumours and 16.8% had bladder tumours. 46 patients (2.9%) were found to have non-urological tumours: gynaecological (0.7%), colorectal (1.3%), hepatopancreatobiliary (0.4%), adrenal (0.3%) and respiratory (0.2%). CONCLUSIONS: The incidence of non-urological tumours found on CT imaging to investigate haematuria was 2.9%. This rate is higher than previously reported. Although there are other advantages for the use of CT as the primary imaging modality for haematuria, this large prospective study reports a relatively limited use as an indirect screener for non-urological malignancies.