Bin K. Kroon

Presence of high-risk human papillomavirus DNA in penile carcinoma predicts favorable outcome in survival.

There is evidence that a subset of penile carcinomas is caused by infection with high‐risk human papillomavirus (HPV). However, extensive studies on the possible influence of HPV infection on clinical outcome of penile cancer are lacking. This investigation is aimed to examine the prevalence of high‐risk HPV in a large series of penile squamous‐cell carcinomas (SCCs) and to determine the relationship between HPV and survival. Formalin‐fixed, paraffin‐embedded tumor specimens of 171 patients with penile carcinoma were tested for high‐risk HPV DNA presence by GP5+/6+‐PCR. The clinical course of the patients and the histopathological characteristics of the primary tumors were reviewed. High‐risk HPV DNA was detected in 29% of the tumors, with HPV 16 being the predominant type, accounting for 76% of high‐risk HPV containing SCCs. Disease‐specific 5‐year survival in the high‐risk HPV‐negative group and high‐risk HPV‐positive group was 78% and 93%, respectively (log rank test p = 0.03). In multivariate analysis, the HPV status was an independent predictor for disease‐specific mortality (p = 0.01) with a hazard ratio of 0.14 (95% CI: 0.03–0.63). Our results indicate that the presence of high‐risk HPV (29%) confers a survival advantage in patients with penile carcinoma.

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.

Ultrasonography‐guided fine‐needle aspiration cytology before sentinel node biopsy in patients with penile carcinoma

To assess the accuracy of ultrasonography (US)‐guided fine‐needle aspiration cytology (FNAC) for detecting occult lymph node metastases in patients with squamous cell carcinoma of the penis.

Human papillomavirus prevalence in invasive penile cancer and association with clinical outcome.

PURPOSE The incidence of penile cancer is increasing, and is suggested to be explained by changes in sexual practice and increased exposure of men to sexually transmitted high risk human papillomavirus infection. In penile cancers from a Dutch population treated in 1963 to 2001 we found a high risk human papillomavirus prevalence of about 30%. In this study we assessed the prevalence of high risk human papillomavirus-DNA in a more recent, contemporary penile cancer cohort and its association with patient survival. MATERIALS AND METHODS High risk human papillomavirus-DNA presence was assessed by GP5+6+ polymerase chain reaction in 212 formalin fixed, paraffin embedded invasive penile tumor specimens of patients treated between 2001 and 2009. The 5-year disease specific survival was calculated using the Kaplan-Meier method with the log rank test and Cox regression. RESULTS High risk human papillomavirus-DNA was detected in a subset of penile cancer cases (25%, 95% CI 19-31). HPV16 was the predominant type, representing 79% (42 of 53) of all high risk human papillomavirus infections. The 5-year disease specific survival in the high risk human papillomavirus negative group and the high risk human papillomavirus positive group was 82% and 96%, respectively (log rank test p=0.016). Adjusted for stage, grade, lymphovascular invasion and age, human papillomavirus status was still prognostic for disease specific survival (p=0.030) with a hazard ratio of 0.2 (95% CI 0.1-0.9). CONCLUSIONS High risk human papillomavirus-DNA was observed in a quarter of penile cancer cases. No relevant increase in high risk human papillomavirus prevalence in recent decades was observed. The presence of high risk human papillomavirus-DNA in penile cancer confers a survival advantage.

Probability of Downsizing Primary Tumors of Renal Cell Carcinoma by Targeted Therapies Is Related to Size at Presentation

OBJECTIVE To evaluate the probability of downsizing primary renal tumors by targeted therapy in correlation to size. METHODS A literature search was conducted and our own data were pooled with data of retrospective series and prospective trials in which patients were treated with tyrosine kinase inhibitors (TKIs) and in which tumor sizes before and after treatment were reported. Included were 89 primary clear cell renal tumors, including 34 from our institutes. The longest diameter of the primary tumors before and after treatment was obtained. Primary tumor size at presentation was divided in 4 categories: <5 cm (n=10), 5 to 7 cm (n=21), 7 to 10 cm (n=31), and >10 cm (n=27). Pearson correlation and t test were used for statistical analysis. RESULTS The TKI was sorafenib in 21 tumors and sunitinib in the remaining 68. Smaller tumor size was related to more effective downsizing (P=0.01). Median downsizing was 32% (-46% to 11%) in the first group (<5 cm) and 11% (-55% to 16%) in the second group (5-7 cm); however, 8 of 21 (38%) in this group reduced to a range of 2.3 to 4.7 cm in which ablative techniques are feasible and nephron-sparing surgery may benefit from the reduced size. Median downsizing was 18% (-39% to 2%) in tumors of 7 to 10 cm and 10% (-31% to 0%) in those>10 cm. CONCLUSION The smaller the primary tumor, the greater the likelihood and the more effective the downsizing. A potential benefit of neoadjuvant treatment to downsize the primary tumor for ablative techniques or nephron-sparing surgery may exist, particularly in tumors sized 5 to 7 cm.

Microarray gene‐expression profiling to predict lymph node metastasis in penile carcinoma

To determine the value of gene‐expression profiling as a predictor of the status of the regional nodes in patients with penile carcinoma.

Is There a Role for Neoadjuvant Targeted Therapy to Downsize Primary Tumors for Organ Sparing Strategies in Renal Cell Carcinoma

With an increasing number of small renal masses being diagnosed organ-preserving treatment strategies such as nephron-sparing surgery (NSS) or radiofrequency and cryoablation are gaining importance. There is evidence that preserving renal function reduces the risk of death of any cause, cardiovascular events, and hospitalization. Some patients have unfavourable tumor locations or large tumors unsuitable for NSS or ablation which is a clinical problem especially in those with imperative indications to preserve renal function. These patients may benefit from downsizing primary tumors by targeted therapy. This paper provides an overview of the current evidence, safety, controversies, and ongoing trials.

Prepubic sentinel node location in penile carcinoma.

An unusual sentinel node location in a patient with penile carcinoma is described. The preoperative lymphoscintigram showed a prepubic sentinel node. The node could be harvested during surgery. This case illustrates one of the advantages of lymphatic mapping in penile carcinoma: preoperative lymphoscintigraphy can identify lymph nodes outside the usual nodal basins.

Dynamic Sentinel Lymph Node Biopsy in Penile Carcinoma

Squamous cell carcinoma accounts for more than 95% of malignant penile neoplasms. The pattern of dissemination is predominantly lymphogenic to the inguinal nodes. Treatment of patients with penile carcinoma and proven inguinal metastases is straightforward, and consists of treatment of the primary lesion and regional lymph node dissection. For individuals with impalpable nodes, however, treatment has been a subject of debate for many years. Routine elective inguinal lymph node dissection leads to overtreatment in the majority of patients because of the low incidence of occult lymph node metastases. On the other hand, a wait-and-see policy harbors the risk of patients presenting with metastasis at a stage when cure is no longer possible (1). Unfortunately, primary tumor characteristics are rather unreliable in predicting occult metastases (2),(3). In addition, staging with computerized tomography and magnetic resonance imaging has so far not been shown to improve the accuracy of detecting occult metastases (4). Staging with ultrasound along with fine-needle aspiration biopsy is more accurate, but still has a relatively low sensitivity (5).

Cancer of the Penis and Scrotum

Cancer of the penis is a rare malignancy with incidence rates of 0.3 to 8 per 100,000. High-incidence areas are found in South America, the highest being Brazil (8/100,000). It has a low incidence in countries where circumcision at birth or at a very young age is practiced (e.g. Israel, Middle East) (1,2).