A Prospective Multicenter Comparison Study of Risk-adapted Ultrasound-directed and Magnetic Resonance Imaging-directed Diagnostic Pathways for Suspected Prostate Cancer in Biopsy-naïve Men.

BACKGROUND: European Association of Urology guidelines recommend a risk-adjusted biopsy strategy for early detection of prostate cancer in biopsy-naïve men. It remains unclear which strategy is most effective. Therefore, we evaluated two risk assessment pathways commonly used in clinical practice. OBJECTIVE: To compare the diagnostic performance of a risk-based ultrasound (US)-directed pathway (Rotterdam Prostate Cancer Risk Calculator [RPCRC] #3; US volume assessment) and a magnetic resonance imaging (MRI)-directed pathway. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective multicenter study (MR-PROPER) with 1:1 allocation among 21 centers (US arm in 11 centers, MRI arm in ten). Biopsy-naïve men with suspicion of prostate cancer (age ≥50 yr, prostate-specific antigen 3.0-50 ng/ml, ± abnormal digital rectal examination) were included. INTERVENTION: Biopsy-naïve men with elevated risk of prostate cancer, determined using RPCRC#3 in the US arm and Prostate Imaging Reporting and Data System scores of 3-5 in the MRI arm, underwent systematic biopsies (US arm) or targeted biopsies (MRI arm). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the proportion of men with grade group (GG) ≥2 cancer. Secondary outcomes were the proportions of biopsies avoided and GG 1 cancers detected. Categorical (nonparametric) data were assessed using the Mann-Whitney U test and χ2 tests. RESULTS AND LIMITATIONS: A total of 1965 men were included in the intention-to-treat population (US arm n = 950, MRI arm n = 1015). The US and MRI pathways detected GG ≥2 cancers equally well (235/950, 25% vs 239/1015, 24%; difference 1.2%, 95% confidence interval [CI] -2.6% to 5.0%; p = 0.5). The US pathway detected more GG 1 cancers than the MRI pathway (121/950, 13% vs 84/1015, 8.3%; difference 4.5%, 95% CI 1.8-7.2%; p < 0.01). The US pathway avoided fewer biopsies than the MRI pathway (403/950, 42% vs 559/1015, 55%; difference -13%, 95% CI -17% to -8.3%; p < 0.01). Among men with elevated risk, more GG ≥2 cancers were detected in the MRI group than in the US group (52% vs 43%; difference 9.2%, 95% CI 3.0-15%; p < 0.01). CONCLUSIONS: Risk-adapted US-directed and MRI-directed pathways detected GG ≥2 cancers equally well. The risk-adapted US-directed pathway performs well for prostate cancer diagnosis if prostate MRI capacity and expertise are not available. If prostate MRI availability is sufficient, risk assessment should preferably be performed using MRI, as this avoids more biopsies and detects fewer cases of GG 1 cancer. PATIENT SUMMARY: Among men with suspected prostate cancer, relevant cancers were equally well detected by risk-based pathways using either ultrasound or magnetic resonance imaging (MRI) to guide biopsy of the prostate. If prostate MRI availability is sufficient, risk assessment should be performed with MRI to reduce unnecessary biopsies and detect fewer irrelevant cancers.

End-fire versus side-fire: a randomized controlled study of transrectal ultrasound guided biopsies for prostate cancer detection.

Objectives: To compare prostate cancer detection rates between end-fire and side-fire ultrasound guided prostate biopsy techniques.Methods: A prospective randomized controlled trial was performed in patients who underwent prostate biopsy between 2009 and 2014. Patients were randomly assigned to the end-fire or side fire biopsy groups and underwent transrectal ultrasound guided prostate biopsy. The overall prostate cancer detection rate was compared between the two probe configurations. Trial was registered at Clinical Trials.gov with identifier: NCT00851292.Results: A total of 730 patients were included and randomized, 371 patients underwent prostate biopsy with side-fire probe and 359 patients with the end-fire probe. Prostate cancer detection rates were 52.4% in the end fire group and 45.6% in the side fire group (p = .066).Conclusions: No significant difference was found in detection rate of prostate cancer between the end-fire and side-fire probe in transrectal ultrasound guided prostate biopsy, neither for detection rate of prostate cancer in the apex.

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.

Repeat dynamic sentinel node biopsy in locally recurrent penile carcinoma.

OBJECTIVE: To explore the role of repeat dynamic sentinel-node biopsy (SNB) in clinically node-negative patients with locally recurrent penile carcinoma after previous penile surgery and SNB. PATIENTS AND METHODS: Between 1994 and 2008, 12 patients (4% of the 304 in our prospectively maintained dynamic sentinel node database) with clinically node-negative groins had a repeat SNB for locally recurrent penile carcinoma after previous penile surgery and SNB. Five of these patients had previously had a unilateral inguinal node dissection for groin metastases. The median disease-free interval was 18 months. The protocol and technique of primary dynamic SNB and the repeat procedure were similar, including preoperative lymphoscintigraphy and blue-dye injection. Completion inguinal node dissection was only done if there was an involved sentinel node. RESULTS: No sentinel nodes were seen on preoperative lymphoscintigraphy in the five groins that had previously been dissected. A sentinel node was visualized on lymphoscintigraphy in the remaining 19 undissected groins. In 15 of these groins (79%) the sentinel node was identified during surgery. Histopathological analysis showed involved sentinel nodes in four groins of three patients. Additional metastatic nodes were found in one completion inguinal lymph node dissection specimen. During a median follow-up of 32 months after the repeat SNB, one patient developed a groin recurrence 14 months after a tumour-negative sentinel node procedure. CONCLUSIONS: Repeat dynamic SNB is feasible in clinically node-negative patients with locally recurrent penile carcinoma despite previous SNB.

Lymph node metastasis in intermediate-risk penile squamous cell cancer: a two-centre experience.

BACKGROUND: The risk of lymph node (LN) metastasis in G2T1 penile cancer has been previously reported as 0-50% and is classified as "intermediate" in the European Association of Urology (EAU) guidelines. The management of impalpable regional nodes in this cohort of patients remains contentious and varies among treatment centres depending on tumour factors and local resources. OBJECTIVES: To establish the risk of LN metastasis in G2T1 disease. DESIGN, SETTINGS, AND PARTICIPANTS: We interrogated the databases of two referral centres for penile cancer. MEASUREMENTS: Out of 902 patients, 117 (13%) patients were identified with G2T1 cancers. Those with palpable inguinal nodes (cN1) underwent early inguinal LN dissection (iLND). Those with clinically node negative (cN0) inguinal basins were either observed or surgically staged with iLND or by dynamic sentinel LN biopsy (DSLNB). Median follow-up was 44 mo, with minimum follow-up of 6 mo. RESULTS AND LIMITATIONS: Fifteen of 117 (13%) patients with G2T1 cancer had LN metastasis at initial staging or during follow-up. Six of 12 (50%) cN1 patients had histologically proven LN metastasis on iLND. One hundred five patients were cN0 at presentation. Ten cN0 patients had prophylactic iLND, none of which yielded LN metastasis; 5 of 64 (8%) cN0 patients who had DSLNB had tumour-positive LNs, and 4 of 31 (13%) cN0 patients who were observed developed LN metastasis during follow-up. In cN0 patients, the risk of LN metastasis at initial staging or during surveillance was 9%. CONCLUSIONS: We consider that in cN0 patients with G2T1 penile cancer, the risk of developing metastases during surveillance warrants surgical and potentially curative staging. However, the morbidity of prophylactic bilateral iLND is too great to justify a detection rate of 9%. Less morbid alternatives such as DSLNB are advisable in G2T1 disease.

Scanning with 18F-FDG-PET/CT for detection of pelvic nodal involvement in inguinal node-positive penile carcinoma.

BACKGROUND: Penile carcinoma patients with inguinal lymph node involvement (LNI) have an increased risk for pelvic nodal involvement with or without distant metastases. OBJECTIVE: To evaluate the diagnostic accuracy of fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) with computed tomography (CT; 18F-FDG PET/CT) scanning in determining further metastatic spread in patients with tumour-positive inguinal nodes. DESIGN, SETTING, AND PARTICIPANTS: Eighteen patients with penile squamous cell carcinoma with unilateral or bilateral cytologically tumour-positive inguinal disease underwent whole-body 18F-FDG-PET/CT scanning for tumour staging. MEASUREMENTS: Images were blindly assessed by two nuclear medicine physicians. All scans were evaluated for pelvic nodal involvement per basin and for distant metastases. Histopathology (when available), radiologic imaging, and clinical follow-up (with a minimum of 1 yr) served as a reference standard. The diagnostic value of PET/CT scanning for predicting pelvic nodal involvement was evaluated using standard statistical methods. RESULTS AND LIMITATIONS: The reference was available in 28 of the 36 pelvic basins. Of the 11 tumour-positive pelvic basins, 10 were correctly predicted by PET/CT scan, as were all 17 tumour-negative pelvic basins. PET/CT scan showed a sensitivity of 91%, a specificity of 100%, a diagnostic accuracy of 96%, a positive predictive value of 100%, and a negative predictive value of 94% in detecting pelvic nodal involvement. Additionally, PET/CT scans showed distant metastases in five patients. In four patients, the presence of distant metastases could be confirmed, while in one patient, no radiologic confirmation was found for that particular lesion. A potential limitation is that the diagnostic accuracy of PET/CT scanning was calculated on 28 pelvic basins only. Furthermore, no comparison was made with conventional CT scans, as not all patients had undergone contrast-enhanced CT scans. CONCLUSIONS: PET/CT scanning appears promising for detecting pelvic lymph node metastases with great accuracy, and it identifies distant metastases in penile carcinoma patients with inguinal LNI. In our practice, PET/CT scanning has become part of routine staging in such patients.

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.

Prospective evaluation of hybrid 18F-fluorodeoxyglucose positron emission tomography/computed tomography in staging clinically node-negative patients with penile carcinoma.

OBJECTIVE: To prospectively evaluate the performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to detect occult metastasis in patients with clinically node-negative (cN0) penile carcinoma, as there is little information on the use of (18)F-FDG-PET/CT in penile carcinoma. PATIENTS AND METHODS: In 24 patients, scheduled to undergo dynamic sentinel-node biopsy, hybrid PET/CT was used before surgery to assess the nodal status of the cN0-groins. Six of the 24 patients were unilaterally cN0. Thus, 42 cN0-groins were evaluated for occult metastasis using PET/CT. All scans were assessed by two experienced nuclear physicians. The histopathological tumour status of the removed sentinel node was used as the standard of care to evaluate the PET/CT-results. RESULTS: Histopathology was tumour-positive in five of the 42 (12%) evaluated cN0-groins, two of which contained only micrometastases (<2 mm). One of the five tumour-positive cN0-groins was correctly predicted on the PET/CT-images. All false-negative PET/CT scans contained metastasis of

Visualization of tumor blockage and rerouting of lymphatic drainage in penile cancer patients by use of SPECT/CT.

UNLABELLED: The reliability of sentinel node biopsy is dependent on the accurate visualization and identification of the sentinel node(s). It has been suggested that extensive metastatic involvement of a sentinel node can lead to blocked inflow and rerouting of lymph fluid to a "neo-sentinel node" that may not yet contain tumor cells, causing a false-negative result. However, there is little evidence to support this hypothesis. Recently introduced hybrid SPECT/CT scanners provide both tomographic lymphoscintigraphy and anatomic detail. Such a scanner enabled the present study of the concept of tumor blockage and rerouting of lymphatic drainage in patients with palpable groin metastases. METHODS: Seventeen patients with unilateral palpable and cytologically proven metastases in the groin underwent bilateral conventional lymphoscintigraphy and SPECT/CT before sentinel node biopsy of the contralateral groin. The pattern of lymphatic drainage in the 17 palpable groin metastases was evaluated for signs of tumor blockage or rerouting. RESULTS: On the CT images, the palpable node metastases could be identified in all 17 groins. Four of the 17 palpable node metastases (24%) showed uptake of radioactivity on the SPECT/CT images. In 10 groins, rerouting of lymphatic drainage to a neo-sentinel node was seen; one neo-sentinel node was located in the contralateral groin. A complete absence of lymphatic drainage was seen in the remaining 3 groins. CONCLUSION: The concept of tumor blockage and rerouting was visualized in 76% of the groins with palpable metastases. Precise physical examination and preoperative ultrasound with fine-needle aspiration cytology may identify nodes with considerable tumor invasion at an earlier stage and thereby reduce the incidence of false-negative results.

Non-invasive and minimally invasive staging of regional lymph nodes in penile cancer.

INTRODUCTION: The management of the regional lymph nodes in penile cancer patients, particularly when these lymph nodes are impalpable, remains controversial. Prophylactic bilateral inguinal lymphadenectomy is associated with high morbidity and is often unnecessary. However, there is no non-invasive or minimally invasive staging technique that can determine the lymph node status of penile cancer patients with 100% accuracy. METHODS: We reviewed the current literature to examine the role of non-invasive and minimally invasive techniques for staging regional lymph nodes in penile cancer with particular reference to clinically impalpable disease. RESULTS: Cross-sectional imaging (un-enhanced CT and MRI) modalities have a role in the assessment of patients with palpable inguinal basins and in locating distant metastases, but are unreliable in staging impalpable regional lymph nodes. The spatial resolution of lymphotropic nanoparticle enhanced MRI (LNMRI) and positron emission tomography (PET)/CT are limited to several millimetres and so these modalities cannot reliably detect micro-metastases (<2 mm). Ultrasound (US) and fine-needle aspiration cytology (FNAC) are indicated in staging palpable inguinal basins but are unreliable in isolation in the assessment of impalpable lymph nodes. They are, however, useful as an adjunct to dynamic sentinel lymph node biopsy (DSLNB) in lowering false-negative rates. CONCLUSIONS: While we await staging modalities that can equal the results of DSLNB with fewer disadvantages, histological staging in the form of DSLNB remains the best minimally invasive staging modality we can offer at risk patients presenting with clinically node negative groins.

Shortcomings of the current TNM classification for penile carcinoma: time for a change?

INTRODUCTION: Accurate tumor staging is essential in the management of malignancies. It provides a guide in selecting accurate treatment and gives an indication of prognosis based on the extent of disease. The current TNM classification for penile carcinoma has remained unchanged since 1987. In this article, we focus on several deficiencies of the current classification. MATERIALS AND METHODS: An analysis of the current literature regarding the current classification was done, focusing on known prognostic factors for survival. Furthermore, we discuss in detail the results from a recent analysis of more than 500 patients treated at our institute to evaluate the practical and prognostic value of the TNM-classification. RESULTS: We found that, using the current classification system, accurate clinical staging is often difficult, because the T and N categories are defined by structures that are not easily identified using physical examination or imaging. Furthermore, the prognostic stratification of the present staging system is not optimal and there is a substantial overlap in disease-specific survival between several categories. We give an overview of modifications that could improve clinical staging and prognostic ability. CONCLUSION: The current TNM classification for penile carcinoma has several shortcomings in terms of usability in clinical staging and prognostic value. With modifications clinical staging is facilitated, while the prognostic stratification of the classification is improved.

Evaluation of current TNM classification of penile carcinoma.

PURPOSE: The TNM classification is the most common tool for staging malignancies. The current classification for penile carcinoma has been unchanged since 1987. There are several shortcomings to this classification. Accurate clinical staging can be troublesome because several categories are defined by anatomical structures that cannot readily be identified by physical examination or imaging. A second drawback is substantial variability with respect to survival in certain T and N categories. We analyzed the prognostic value of the TNM classification in patients with penile carcinoma treated at our institute. We propose modifications to improve prognostic stratification and facilitate clinical staging. MATERIALS AND METHODS: The records of 513 patients treated between 1956 and 2006 were analyzed. All tumors were staged according to the most recent classification. We calculated disease specific survival in the different T and N categories. Survival in the different categories was compared using Kaplan-Meier analysis and the log rank test. RESULTS: Five-year disease specific survival in the entire group was 80.5% at a median followup of 58.7 months. There was no significant difference in survival between T2 and T3 tumors (p = 0.57). Furthermore, no significant survival difference was found between N1 and N2 categories (p = 0.18). Using a modified classification a significant difference in survival was found among all T and N categories. CONCLUSIONS: The current TNM classification for penile carcinoma does not adequately differentiate in terms of survival among several T and N categories. With some modifications prognostic stratification improves and clinical staging is facilitated.

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

OBJECTIVE: To determine the value of gene-expression profiling as a predictor of the status of the regional nodes in patients with penile carcinoma. PATIENTS AND METHODS: Tumour samples of 56 patients with penile squamous cell carcinoma were analysed for the gene expression on 35 k oligoarrays; 32 were from patients with histopathologically confirmed lymph node metastases and 24 from those with no lymph node involvement. The 56 patients were divided into a training and validation set. For the training set, 15 patients with histopathologically confirmed nodal metastases and 15 without were selected. The validation set consisted of the remaining 26 patients, containing 17 node-positive and nine with no nodal metastases. RESULTS: A 44-probe classifier had the best performance within the training set; this classifier correctly assigned 29 of 30 specimens in the training set to the two outcome groups. In the validation set of 26 tumours, the classifier correctly assigned 14 of the 26 (54%) specimens to the two outcome groups. Of the 17 specimens with histologically confirmed nodal involvement, 12 were classified as node-positive and five as node-negative, resulting in a sensitivity of 71%. Of the nine specimens from node-negative patients, two were correctly classified as node-negative and seven as node positive, resulting in a specificity of 22%. CONCLUSIONS: In this series, gene expression profiling did not produce a useful classifier to predict nodal involvement in patients with penile carcinoma.

Anatomical mapping of lymphatic drainage in penile carcinoma with SPECT-CT: implications for the extent of inguinal lymph node dissection.

BACKGROUND: Knowledge regarding the lymphatic drainage pattern of penile cancer is the basis for the extent of inguinal lymph node dissection for this disease. OBJECTIVE: To prospectively analyze the lymphatic drainage pattern of penile carcinoma using SPECT-CT and evaluate the implications for the extent of inguinal lymph node dissection. DESIGN, SETTING, AND PARTICIPANTS: The lymphatic drainage patterns of 50 patients scheduled for dynamic sentinel node biopsy were analyzed using a hybrid SPECT-CT scanner. MEASUREMENTS: A total of 86 clinically node-negative (cN0) inguinal and pelvic regions was evaluated. The sentinel and higher-tier nodes on SPECT-CT were divided into different zones in the groin and pelvic region. The groin was divided according to Daseler's five zones, four zones obtained by drawing a vertical and horizontal line over the saphenofemoral junction and one zone directly overlying this junction. The nodes in the pelvic region were classified into three zones: the external iliac/obturator zone, the common iliac zone, and the paraaortal zone. RESULTS AND LIMITATIONS: Lymphatic drainage was visualised in 82 of the 86 cN0 groins (95.3%). A total of 115 sentinel nodes and 182 higher-tier nodes was found. All sentinel nodes were located in superior and central inguinal zones. The higher-tier nodes were located in the groin and pelvic region. No lymphatic drainage was seen to the inferior two regions of the groin. A potential limitation of the study is that the unilateral lymphatic drainage seen in some patients could be normal, but it could also be caused by blockage of lymphatic drainage due to a grossly involved metastatic lymph node. Another possible limitation is that this study relies on the quality and accuracy of lymphoscintigraphy and the subsequent sentinel node procedure. CONCLUSIONS: All sentinel and higher-tier nodes were located in the superior and central inguinal zones and the pelvic region. No lymphatic drainage to the inferior inguinal zones was seen. This suggests that the extent of inguinal node dissection in cN0 patients could be reduced to removal of the superior and central inguinal zones. This may decrease the extensive morbidity associated with this procedure.

Recurrence patterns of squamous cell carcinoma of the penis: recommendations for follow-up based on a two-centre analysis of 700 patients.

BACKGROUND: Current follow-up recommendations for patients with penile carcinoma are based on small numbers of patients. OBJECTIVES: To give further insight into the recurrence patterns of penile carcinoma in different treatment settings and provide recommendations for follow up. DESIGNS, SETTING, AND PARTICIPANTS: In this retrospective study, we analysed 700 patients from two referral centres for penile carcinoma for recurrences. MEASUREMENTS: Recurrences were categorized as local, regional, or distant. The rate of local recurrences was compared between patients undergoing penile-preserving treatments and partial/total amputation. Regional recurrences were compared between patients surgically staged as pN0 or pN+ and clinically node-negative (cN0) patients subjected to a wait-and-see policy. The total recurrence rate, type of recurrence, time to recurrence, and survival were calculated. RESULTS AND LIMITATIONS: 205 out of 700 patients (29.3%) had a recurrence, consisting of 18.6% local, 9.3% regional, and 1.4% distant recurrences. Of the recurrences, 92.2% occurred within 5 yr after primary treatment. All regional and distant recurrences occurred within 50 and 16 mo, respectively. The local recurrence rate was 27.7% after penile-preserving therapy and 5.3% after amputation. The regional recurrence rate was 2.3% in patients staged as pN0, 19.1% in patients staged as pN+, and 9.1% in patients undergoing a wait-and-see policy. The 5-yr disease-specific survival was 92% after a local recurrence and 32.7% after a regional recurrence. All patients with a distant recurrence died within 22 mo. Although the number of analysed patients is substantial, the results do not necessarily reflect those of other centres using different techniques for the management of penile carcinoma. CONCLUSIONS: Patients undergoing penile-preserving therapy, patients surgically staged as pN+, and those undergoing a wait-and-see policy for the nodal status are at high risk of developing a recurrence. Follow-up recommendations are provided based on the risk and impact on survival of a recurrence.

Holmium laser lithotripsy for ureteral calculi: predictive factors for complications and success.

PURPOSE: To define possible predictive factors for success and complications for ureteroscopic holmium laser lithotripsy procedures. PATIENTS AND METHODS: All 105 ureteroscopic holmium laser lithotripsy procedures performed between 1996 and 2005 were analyzed. Data recorded were sex, age, stone size, stone location, complications, success rate (stone-free rate after 3 months), operative time, and surgeon experience for this procedure. For further analysis, surgeon experience was divided into four groups based on the number of procedures performed. Multivariate analysis was used to define possible predictive factors for complications and successful procedures. RESULTS: Total success rate was 84.8%. Complications were present in 13 patients (12.4%). Success rate was significantly (P = 0.03) related to surgeon experience, with 92.9% success in the most experienced group and 50% in the least experienced group. Furthermore, significantly more complications occurred with decreased experience (P = 0.03): complication rate was 4.2% in the highest experience group and 41.7% in the least experienced group. In our series, sex, stone location, size, and age did not significantly influence complication and success rates. CONCLUSION: Surgeon experience is a predictive factor for complications and success for ureteroscopic holmium laser lithotripsy for ureteric calculi. Experienced surgeons have fewer complications, and the success rate is higher. Sex, stone location, size, and age were not significantly related to complication or success rates.

Human papillomavirus-16 is the predominant type etiologically involved in penile squamous cell carcinoma.

PURPOSE: Human papillomavirus (HPV) infections are suggested to be involved in the development of penile squamous cell carcinoma (SCC), but comprehensive studies to define the association are limited. Therefore, we performed molecular and serologic analyses for a broad spectrum of HPV types on a large series of 83 penile SCCs, and we compared serological findings to those of age-matched male controls (N = 83). METHODS: Penile SCCs were subjected to detection and typing assays for mucosal and cutaneous HPVs and to subsequent, type-specific viral load and viral gene expression assays. Sera of patients and of controls were analyzed for type-specific mucosal and cutaneous HPV L1, E6, and/or E7 antibodies using bead-based, multiplex serology. RESULTS: HPV DNA of mucosal and/or cutaneous types was found in 46 of 83 (55%) penile SCCs. HPV16 was the predominant type, appearing in 24 (52%) of 46 of penile SCCs. The majority of HPV16 DNA-positive SCCs (18 of 24; 75%) demonstrated E6 transcriptional activity and a high viral load. Additionally, HPV16 molecular findings were strongly associated with HPV16 L1-, E6-, and E7-antibody seropositivity. Furthermore, serologic case-control analyses demonstrated that, in addition to the association of HPV16 with penile SCC, seropositivity against any HPV type was significantly more common in patients compared with in controls. HPV18 and HPV6 seropositivity were associated with HPV16-negative SCCs but were not correlated to molecular findings. CONCLUSION: HPV16 is the main HPV type etiologically involved in the development of penile SCC. Although individuals who develop penile SCC show a greater prior exposure to a broad spectrum of HPV types, insufficient evidence was found to claim a role for HPV types other than HPV16 in penile carcinogenesis.

Neoadjuvant chemotherapy in advanced penile carcinoma.

OBJECTIVE: Little data on the role of neoadjuvant chemotherapy for advanced penile carcinoma are available. We describe the experiences at our institute. METHODS: A total of 20 patients received neoadjuvant chemotherapy for downstaging of irresectable disease in the period from 1972 until August 2005. During this 34-yr period, five different chemotherapeutic regimens were used. We evaluated clinical tumour response, chemotherapeutic toxicity, rate and type of subsequent surgery, histopathologic features, and long-term clinical outcome. RESULTS: An objective tumour response was achieved in 12 of 19 evaluable patients. Overall 5-yr survival was 32%. A significant difference (p=0.012) in survival was found between responders (5-yr survival 56%) and nonresponders (all patients died within 9 mo). Nine responders underwent subsequent surgery with curative intent. Eight of them were long-term survivors without evidence of recurrent disease. Three nonresponders were operated on to improve local control. All died within 8 mo after surgery. Toxicity of chemotherapy was high with three toxic deaths and discontinuation of treatment in one patient. CONCLUSIONS: Of 20 patients with advanced penile carcinoma, 12 were responsive to neoadjuvant chemotherapy and 8 were long-term survivors after subsequent surgery. These results suggest that neoadjuvant chemotherapy is a valuable treatment option for patients with irresectable penile carcinoma, which is otherwise considered incurable. Surgery should be performed only in patients showing clinical response to chemotherapy because prognosis for nonresponding patients who underwent surgery was dismal and local control was not improved.

Reliability and safety of current dynamic sentinel node biopsy for penile carcinoma.

OBJECTIVES: Dynamic sentinel node biopsy (DSNB) has been performed at our department since 1994 to assess status of inguinal lymph nodes of clinically node-negative (cN0) patients with penile carcinoma. Over time, several modifications were made to reduce the false-negative rate and thus increase sensitivity. We compared the false-negative and complication rates of the current procedure, as performed at our institute since 2001, with the prior procedures. MATERIALS AND METHODS: The patients who underwent DSNB for penile carcinoma in the period from 1994 until July 2004 were divided into two cohorts: cohort A: patients treated from 1994 until 2001; cohort B: patients treated from 2001 until 2004. Cohort A consisted of 92 patients, in whom 157 groins were explored. Cohort B consisted of 58 patients, with a total of 105 explored groins. Medians for follow-up in cohorts A and B were 83 (range: 24-130) and 30 (range: 24-49) mo, respectively. The false-negative and complication rates were determined in both cohorts. RESULTS: In cohort A, 21 of 157 explored groins contained tumour-positive sentinel nodes, and five false-negative procedures were encountered, resulting in a false-negative rate of 19.2%. In cohort B, 20 of 105 explored groins contained tumour-positive sentinel nodes, and one procedure was false-negative. The false-negative rate was 4.8%. The rate of complications dropped from 10.2% in cohort A to 5.7% in cohort B. All complications were minor and transient. CONCLUSIONS: The false-negative and complication rates of DSNB have decreased since the procedure was modified. The current procedure has false-negative and complication rates of 4.8% and 5.7%, respectively. DSNB has matured into a reliable and safe method for assessing status of lymph nodes in cN0 penile carcinoma patients.

Use of positron emission tomography in spindle cell carcinoma of the penis.

A 60-year-old man presented with spindle cell carcinoma of the penis. He underwent surgery and additional positron emission tomography and computed tomography scans to evaluate for possible metastases. Positron emission tomography showed a left inguinal and paravesical hot spot on the right. Only the left inguinal lesion could be confirmed on computed tomography. The patient underwent additional surgery with curative intent. Three months later, the patient underwent repeat computed tomography, which revealed an osteolytic process in the right acetabulum. This lesion corresponded with the right paravesical hot spot on the positron emission tomography scan 3 months earlier.