Nick Watkin

EAU Guidelines on Penile Cancer: 2014 Update

CONTEXT Penile cancer has high mortality once metastatic spread has occurred. Local treatment can be mutilating and devastating for the patient. Progress has been made in organ-preserving local treatment, lymph node management, and multimodal treatment of lymphatic metastases, requiring an update of the European Association of Urology guidelines. OBJECTIVE To provide an evidence-based update of treatment recommendations based on the literature published since 2008. EVIDENCE ACQUISITION A PubMed search covering the period from August 2008 to November 2013 was performed, and 352 full-text papers were reviewed. Levels of evidence were assessed and recommendations graded. Because there is a lack of controlled trials or large series, the levels of evidence and grades of recommendation are low compared with those for more common diseases. EVIDENCE SYNTHESIS Penile squamous cell carcinoma occurs in distinct histologic variants, some of which are related to human papilloma virus infection; others are not. Primary local treatment should be organ preserving, if possible. There are no outcome differences between local treatment modes in superficial and T1 disease. Management of inguinal lymph nodes is crucial for prognosis. In impalpable nodes, invasive staging should be done depending on the risk factors of the primary tumour. Lymph node metastases should be treated by surgery and adjuvant chemotherapy in N2/N3 disease. CONCLUSIONS Organ preservation has become the standard approach to low-stage penile cancer, whereas in lymphatic disease, it is recognised that multimodal treatment with radical inguinal node surgery and adjuvant chemotherapy improves outcome. PATIENT SUMMARY Approximately 80% of penile cancer patients of all stages can be cured. With increasing experience in the management of penile cancer, it is recognized that organ-preserving treatment allows for better quality of life and sexual function and should be offered to all patients whenever feasible. Referral to centres with experience is recommended.

Two-Center Evaluation of Dynamic Sentinel Node Biopsy for Squamous Cell Carcinoma of the Penis

PURPOSE Sentinel node biopsy is used to evaluate the nodal status of patients with clinically node-negative penile carcinoma. Its use is not widespread, and the majority of patients with clinically node-negative disease undergo an elective inguinal lymph node dissection. Reservations about the use of sentinel node biopsy include the fact that most current results come from one institution and the supposedly long learning curve associated with the procedure. The purpose of this study was to address these issues by analyzing results from two centers and by evaluating the learning curve. PATIENTS AND METHODS All patients undergoing sentinel node biopsy for penile carcinoma at two centers were included. The sentinel node identification rate, false-negative rate, and morbidity of the procedure were calculated. RESULTS from the first 30 procedures were assessed for a potential learning curve. Results A total of 323 patients with penile squamous cell carcinoma, which included 611 clinically node-negative groins, were scheduled for sentinel node biopsy. A sentinel node was found in 572 of the 592 groins (97%) that proceeded to sentinel node biopsy. In 79 groins, a sentinel node was positive for tumor. Six inguinal node recurrences occurred after a negative sentinel node procedure, all within 15 months after sentinel node biopsy. The combined false-negative rate was 7%. Complications occurred in 4.7% of explored groins. None of the false-negative procedures occurred in the initial 30 procedures. CONCLUSION Sentinel node biopsy is a suitable procedure to stage clinically node-negative penile cancer, and it has a low complication rate. No learning curve was demonstrated in this study.

Defining a Patient-Reported Outcome Measure for Urethral Stricture Surgery

BACKGROUND A systematic literature review did not identify a formally validated patient-reported outcome measure (PROM) for urethral stricture surgery. OBJECTIVE Devise a PROM for urethral stricture surgery and evaluate its psychometric properties in a pilot study to determine suitability for wider implementation. DESIGN, SETTING, AND PARTICIPANTS Constructs were identified from existing condition-specific and health-related quality of life (HRQoL) instruments. Men scheduled for urethroplasty were prospectively enrolled at five centres. INTERVENTION Participants self-completed the draft PROM before and 6 mo after surgery. MEASUREMENTS Question sets underwent psychometric assessment targeting criterion and content validity, test-retest reliability, internal consistency, acceptability, and responsiveness. RESULTS AND LIMITATIONS A total of 85 men completed the preoperative PROM, with 49 also completing the postoperative PROM at a median of 146 d; and 31 the preoperative PROM twice at a median interval of 22 d for test-retest analysis. Expert opinion and patient feedback supported content validity. Excellent correlation between voiding symptom scores and maximum flow rate (r = -0.75), supported by parallel improvements in EQ-5D visual analogue and time trade-off scores, established criterion validity. Test-retest intraclass correlation coefficients ranged from 0.83 to 0.91 for the total voiding score and 0.93 for the construct overall; Cronbachs α was 0.80, ranging from 0.76 to 0.80 with any one item deleted. Item-total correlations ranged from 0.44 to 0.63. These values surpassed our predefined thresholds for item inclusion. Significant improvements in condition-specific and HRQoL components following urethroplasty demonstrated responsiveness to change (p < 0.0001). Wider implementation and review of the PROM will be required to establish generalisability across different disease states and for more complex interventions. CONCLUSIONS This pilot study has defined a succinct, practical, and psychometrically robust PROM designed specifically to quantify changes in voiding symptoms and HRQoL following urethral stricture surgery.

Prognostic Factors for Occult Inguinal Lymph Node Involvement in Penile Carcinoma and Assessment of the High-Risk EAU Subgroup: A Two-Institution Analysis of 342 Clinically Node-Negative Patients

BACKGROUND The European Association of Urology (EAU) guidelines advise an elective bilateral lymphadenectomy in clinically node-negative (cN0) patients with high-risk penile carcinoma (≥pT2, G3, or lymphovascular invasion [LVI]). OBJECTIVE Our aim was to assess prognostic factors for occult metastasis and to determine whether current EAU guidelines accurately stratify patients at high risk. DESIGN, SETTING, AND PARTICIPANTS Data of 342 cN0 patients with histologically proven invasive penile squamous cell carcinoma who had undergone the current dynamic sentinel node biopsy (DSNB) protocol were analysed. A complete ipsilateral inguinal lymphadenectomy was only done if the sentinel node was tumour positive. MEASUREMENTS The presence of occult metastasis was established by preoperative ultrasound and tumour-positive fine-needle aspiration cytology, tumour-positive sentinel nodes, and groin metastases during follow-up after a negative DSNB procedure. Median follow-up was 31 mo. RESULTS AND LIMITATIONS Sixty-eight of 342 patients (20%) and 87 of 684 groins (13%) had occult nodal involvement including 6 patients (2%) with a groin metastasis after negative DSNB. Corpus spongiosum invasion, corpus cavernosum invasion, histologic grade, and LVI were each significant prognosticators for occult metastasis on univariate analysis. On multivariate analysis, grade (odds ratio [OR]: 3.3 for intermediate and 4.9 for poor, respectively) and LVI (OR: 2.2) remained predictive factors. In total, 245 patients (72%) were classified high risk according to EAU guidelines. Among them, the incidence of occult metastasis was 23% (57 of 245). A potential limitation of this study is the lack of external review. CONCLUSIONS Histologic grade and LVI are independent prognostic factors for occult metastasis in penile carcinoma. Although both predictors are incorporated into the current EAU guidelines, the stratification of patients needing a lymph node dissection is inaccurate. Approximately 77% of high-risk patients (188 of 245) would have had a negative bilateral inguinal lymphadenectomy. For the time being, DSNB is considered a more suitable staging method than EAU risk stratification for an accurate determination of patients who require lymph node dissection.

Dynamic sentinel lymph node biopsy in patients with invasive squamous cell carcinoma of the penis: a prospective study of the long-term outcome of 500 inguinal basins assessed at a single institution.

BACKGROUND Dynamic sentinel node biopsy (DSNB) in combination with ultrasound scan (USS) has been the technique of choice at our centre since 2004 for the assessment of nonpalpable inguinal lymph nodes (cN0) in patients with squamous cell carcinoma of the penis (SCCp). Sensitivity and false-negative rates may vary depending on whether results are reported per patient or per node basin, and with or without USS. OBJECTIVE To determine the long-term outcome of patients undergoing DSNB and USS-guided fine-needle aspiration cytology (FNAC) in our cohort of newly diagnosed cN0 SCCp patients, as well as to analyse any variation in sensitivity of the procedure. DESIGN, SETTING, AND PARTICIPANTS A series of consecutive patients with newly diagnosed SCCp, over a 6-yr period (2004-2010), were analysed prospectively with a minimum follow-up period of 21 mo. All patients had definitive histology of ≥ T1G2 and nonpalpable nodes in one or both inguinal basins. Patients with persistent or untreated local disease were excluded from the study. INTERVENTION All eligible patients had DSNB and USS with or without FNAC of cN0 groins. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was no nodal disease recurrence on follow-up. The secondary end point was complications after DSNB. Sensitivity of the procedure was calculated per node basin, per patient, with DSNB alone, and with USS with DSNB combined. RESULTS AND LIMITATIONS Five hundred inguinal basins in 264 patients underwent USS with or without FNAC and DSNB. Seventy-three positive inguinal basins (14.6%) in 59 patients (22.3%) were identified. Four inguinal basins in four patients were confirmed false negative at 5, 8, 12, and 18 mo. Two inguinal basins had positive USS and FNAC and negative DSNB results. Sensitivity of DSNB with USS, with and without FNAC, per inguinal basin was 95% and per patient was 94%. Sensitivity of DSNB alone per inguinal basin and per patient was 92% and 91%, respectively. The DSNB morbidity rate was 7.6%. CONCLUSIONS DSNB in combination with USS has excellent performance characteristics to stage patients with cN0 SCCp, with a 5% false-negative rate per node basin and a 6% false-negative rate per patient.

Increasing prostate biopsy cores based on volume vs the sextant biopsy: a prospective randomized controlled clinical study on cancer detection rates and morbidity

To determine if a volume‐adjusted increase in the number of biopsy cores could detect more prostate cancers than the standard sextant biopsy alone, without increasing morbidity, and to determine its applicability in Malaysian patients, as a standard sextant biopsy misses 20–25% of prostate malignancies.

SIU/ICUD consultation on urethral strictures: Anterior urethra - Primary anastomosis

The management of primary and recurrent bulbar urethral stricture disease has been a source of controversy with the choice being between endoscopic urethrotomy and open urethroplasty. Further debate exists with regard to the choice of urethroplasty--either excision and primary anastomosis (EPA) or augmentation with a graft or flap. Using PubMed, a 35-year literature search was conducted (1975-2010) for peer-reviewed articles on bulbar strictures treated using EPA. Exclusions included articles with <10 patients, duplications, reviews, or in which the cohort was mixed and the data could not be separately analyzed. Seventeen articles fulfilled the criteria with a total of 1234 patients. Overall success was 93.8%. Reported complications were <5%, and there was no evidence of persistent loss of sexual function. The authors conclude that EPA is associated with a high success rate with low complication rate. Our recommendation is that it should be performed in patients with short isolated bulbar strictures, when expected success rates of other procedures are <90%.

Penile cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

H. Van Poppel1, N. A. Watkin2, S. Osanto3, L. Moonen4, A. Horwich5 & V. Kataja6, on behalf of the ESMO Guidelines Working Group* Department of Urology, University Hospital, KU Leuven, Leuven, Belgium; Department of Urology, St. George’s Hospital, London, UK; Department of Oncology, Leiden University Medical Centre, Leiden; Department of Radiation Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Institute of Cancer Research and Royal Marsden Hospital, Sutton, UK; Cancer Centre, Kuopio University Hospital, Kuopio, Finland

Nicorandil-induced penile ulcerations: a case series.

Study Type – Harm (case series)
Level of Evidence 4

New Developments in the Treatment of Localized Penile Cancer

OBJECTIVES To analyze the current trends in local therapy approaches in patients with penile carcinoma. METHODS The relevant published data since 2000 were reviewed; important series published before 2000 were also included. The reports were classified according to the level of evidence. Review studies and others indirectly related to the topic were also included but not classified. RESULTS New information has suggested that surgical margins of only a few millimeters might be adequate for most localized tumors. A trend toward the use of more conservative therapies instead of amputative surgery has been observed, especially in developed countries. Although the local recurrence rate has been greater after conservative therapies than after amputative surgery, this increased rate does not seemed to have had a negative effect on cancer-specific survival. The quality of life has been superior after conservative procedures with preservation of the penis that seems to give the best results with regard to sexual function. Reconstructive surgery can be performed in selected patients after amputative surgery. CONCLUSIONS Although the level of evidence is low, conservative therapies can be recommended for selected patients with penile carcinoma. Despite the trend for conservative approaches, these patients need psychological support.