FDG PET/CT in a Patient With Syphilis Suspected of Having Penile Cancer.

ABSTRACT: A 58-year-old man with large penile wound and enlarged regional lymph node was suspected of having disseminated penile cancer. FDG PET/CT for primary staging showed high FDG uptake on penis and in several enlarged lymph nodes. However, biopsies revealed no signs of malignancy, but ulceration, inflammation, fibrosis, and spirochetes. Furthermore, Wassermann test was positive. The patient was then treated for syphilis. To our knowledge, this is the first report on FDG PET/CT in a patient suspected of having penile cancer that turned out to be syphilis. Thus, syphilis can be added to the list of benign pitfalls in FDG PET/CT.

Quality of life, voiding and sexual function of penile cancer patients: DaPeCa-10-a cross-sectional questionnaire survey.

Objectives: To assess prevalence of voiding and sexual symptoms and quality of life in penile cancer patients. Methods: From 1 January 2013 to 31 December 2015, we approached three separate groups of Danish penile cancer patients and asked them to complete a face-validated questionnaire at diagnosis (Group 1), after 1 year (Group 2) and after 2 years (Group 3). We analysed symptom prevalence and bother and quality of life items and explored differences between groups. Results: In total, we analysed 157 questionnaires. The response rates at diagnosis, after 1 year and after 2 years were 29%, 46% and 30%. The pad use (p = 0.001) and occurrence of nocturia twice a night or more (p = 0.006) was significantly decreasing 2 years after treatment. There was an increasing trend in sexual thoughts and importance of sexuality from 1 to 2 years after treatment, but the proportion of patients reporting a frequency of orgasm at more than once in the past 6 months was significantly decreasing after treatment (p = 0.03). Likewise, the trend for erectile dysfunction worsened after treatment with 49% of patients reporting an erection never sufficient for intercourse at diagnosis increasing to 62% after 1 year and 69% after 2 years. We observed trends towards lower self-esteem with increasingly mutilating treatment. Conclusion: Pad use, nocturia and frequency of orgasm were significantly reduced after penile cancer treatment. We observed trends towards lower self-esteem with increasingly mutilating treatment and increase in erectile dysfunction after treatment.

Lymphovascular and perineural invasion are risk factors for inguinal lymph node metastases in men with T1G2 penile cancer.

PURPOSE: To analyse the risk of inguinal lymph node (ILN) metastases in T1G2 penile cancer stratified by lymphovascular invasion (LVI), perineural invasion (PNI) and tumour size. METHODS: Retrospective study of men with localised T1G2 penile cancer with non-palpable lymph nodes and no local recurrence during follow-up at six European institutional high-volume centres was performed. ILN involvement was defined as cancer detected during ultrasound-guided fine-needle aspiration cytology, core needle biopsy, dynamic sentinel lymph node biopsy, ILN dissection or inguinal recurrence during follow-up. Uni- and multivariable logistic regression analyses were performed. RESULTS: In the cohort of 554 men with T1G2 penile cancer, from 6 European institutions, ILN metastases were observed in 46/554 men (8%, 95% confidence interval (CI) 6-11%). Men with both, LVI- and PNI- primary cancers had the lowest risk of ILN involvement (6%) whereas men with LVI + or PNI + showed ILN metastases in 22% and 30%. In multivariable regression, men with LVI + or PNI + had higher odds for ILN metastases compared to men with LVI- and PNI- (OR 3.9, 95% CI 1.6-9.0, p value < 0.01) Tumour size was not associated with ILN risk (OR 1.01 95% CI 0.99-1.04, p = 0.17). CONCLUSION: Approximately, one out of ten men with T1G2 overall and one out of four men with either LVI + or PNI + still have ILN metastases despite being clinically node negative. Therefore, invasive ILN staging should strongly be recommended in T1G2 with LVI + or PNI + but importantly, must be discussed in patients with T1G2 with LVI- or PNI-.

Sentinel Node Methods in Penile Cancer - a Historical Perspective on Development of Modern Concepts.

Malignant penile tumors are of squamous cell origin in more than 95% of cases and the occurrence of a distant metastasis without prior inguinal lymph node metastatic deposits is very rare. This makes inguinal lymph node staging very reliable and of great prognostic significance since undiscovered and untreated inguinal metastases may lead to a fatal clinical course. In lack of a sufficiently accurate noninvasive lymph node staging modality, penile cancer relies on surgical lymph node removal for regional staging. In this respect sentinel node biopsy offers a favourable minimally invasive alternative to prophylactic inguinal lymph node dissection which is associated with significant surgery-related morbidity. Today sentinel node biopsy is widely used in surgical oncology within high volume cancers such as breast cancer and melanoma. In rare cancers sentinel node biopsy is also emerging as a minimal invasive staging tool in patients with no obvious lymph node involvement. At several specialized units across Europe sentinel node biopsy has been practiced by dedicated specialist within vulva and penile cancer for more than two decades. In fact, the rare disease penile cancer was a model entity for development of the original sentinel node concept as early as the 1970'es due to work by the Paraguayan penile cancer pioneer, Cabañas, the sentinel node concept was subsequently successfully adapted in breast cancer and melanoma. This turned out mutually beneficial since the sequential development of sentinel node biopsy in penile cancer in the 1990s eventually adopted new insights and added conceptual details from the experiences harvested in the broader clinical application possible in these high-volume diseases. The prerequisite to conceptualising the sentinel node approach was the gradual anatomical and functional understanding of the lymphatic system which in western medicine rooted in ancient Greece and gradually increased in details and comprehension with significant contributions from many great notabilities during the last centuries including Hippocrates, Galen, Fallopio, Malpighi, Virchow, Starling, Cabañas, Hodgkin and Horenblas. Sentinel node biopsy in penile cancer is a complex multimodality procedure involving inguinal ultrasonography by radiologists, precise tracer-injection and interpretation of nuclear images by nuclear medicine physicians, radio-tracer- and dye guided open surgical biopsies by urologists and thorough step-sectioning, immunostaining and accurate lymph node specimen analysis by pathologists. This team effort requires well-tested protocols, experience and good collaboration and in rare diseases this calls for centralization of service.

Life satisfaction of patients with penile cancer.

INTRODUCTION: In penile cancer, both disease and treatment may be mutilating. We examined life satisfaction in three separate groups; at penile cancer diagnosis and one and two years later. METHODS: From 1 January 2013 to 31 December2015, Danish penile cancer patients completed the Life-Satisfaction Questionnaire-11 (LISAT-11) at diagnosis and after one year and after two years. Responders scored 11 domains of life on a six-point scale. We analysed the scores and compared scores with those of a Swedish control cohort from the literature with patients in the same age group. RESULTS: A total of 157 individual penile cancer patients completed the LISAT-11 checklist at one point in the trajectory and were considered for this study. We observed trends towards less life satisfaction in the years after diagnosis and with increasingly mutilating surgical treatment. The differences were not statistically significant. A difference was observed between the proportion of responders scoring "satisfied" on activities of daily living between penile cancer patients and a healthy control cohort, with a higher score being recorded for the healthy controls. No other LISAT-11 domains were scored significantly different between penile cancer patients and controls. CONCLUSIONS: Danish responders with penile cancer are less satisfied than a Swedish control cohort within the self-care domain. FUNDING: none. TRIAL REGISTRATION: not relevant.

Potential candidates for en bloc resection among patients with primary and recurrent bladder tumours.

INTRODUCTION: Transurethral resection (TURB) is the gold standard treatment for non-muscle invasive bladder cancer (NMIBC). However, conventional TURB is possibly part of the mechanism leading to the high recurrence rate in NMIBC and the need for repeated procedures, as the method with piecemeal resection of the tumour violates basic oncological principles and compromises pathological examination. En bloc resection (EBR) could potentially overcome these flaws by improving pathological quality and thereby reducing the need for re-resections and could potentially also lower the risk of tumour seeding leading to early recurrences. With this study, we aimed to evaluate tumour characteristics in a consecutive cohort of patients undergoing conventional TURB in order to estimate the proportion of procedures eligible for EBR, findings at re-resection, and early recurrence rate. METHODS: All TURBs performed at a single large University Hospital in a 12 month period were manually reviewed. Based on tumour size and appearance, patients were registered as candidates or non-candidate for EBR. RESULTS: A total of 600 TURBs were reviewed. Overall, 25% of procedures were found to be eligible for EBR. The most frequent reason for not being a candidate was tumour diameter <1 cm. Re-resections were done after 10.5% of the procedures, where the residual tumour was found in 28.6% of these. Within 6 months, 21.2% had a recurrence. CONCLUSION: We found approximately 25% of all TURBs to be eligible for EBR. Based on a relatively low recurrence rate, we conclude that future studies on EBR with recurrence rate as the primary endpoint will require large patient cohorts.

DaPeCa-8: drawing the map of lymphatic drainage in patients with invasive penile cancer - evidence from SPECT/CT and sentinel node surgery.

BACKGROUND: Anatomy of the lymphatic drainage guides the extent of inguinal lymph node dissection in penile cancer. OBJECTIVE: To prospectively assess the lymphatic drainage of penile cancer with single-photon emission computed tomography CT (SPECT-CT) and implications for the extent of inguinal lymph node dissection. METHODS: We assessed the lymphatic drainage of 62 patients with at least unilateral clinical lymph node-negative (cN0) status with SPECT-CT at our tertiary referral centre. We evaluated 122 cN0 inguinal basins and compared them to the histopathological outcome. The inguinal regions were divided into ten different Daseler zones on SPECT-CT. The surgical team filled in a corresponding scheme at sentinel node biopsy and sent lymph nodes from each Daseler zone individually for histopathological examination. RESULTS: SPECT-CT successfully visualized lymphatic drainage in 116 of the 122 cN0 inguinal basins (95.1%). The vast majority of sentinel nodes and all metastatic nodes were located in central and superior inguinal zones, including six metastatic nodes in lateral superior zones. Minimal lymphatic drainage was seen to the inferior Daseler zones and no metastatic deposits were located here. No direct pelvic drainage was observed. CONCLUSIONS: Penile cancer lymphatic drainage is primarily to sentinel in the superior and central zones of Daseler. Colleagues practicing a modified inguinal lymph node dissection as a standard in cN0 patients are encouraged to include all these zones, while the inferior zones can be omitted. This study confirms the absence of lymphatic drainage directly to the pelvic region and supports the practice of omitting pelvic nodes from sentinel node biopsy.

DaPeCa-9 - cohabitation and socio-economic conditions predict penile cancer-specific survival in a national clinical study from Denmark.

BACKGROUND: Cohabitation and social conditions predict prognosis in several cancers; recent data suggest this might also be the case in penile cancer. OBJECTIVE: To assess the prognostic significance of cohabitation, living arrangements and socio-economic conditions for cancer-specific survival (CSS) in patients with penile squamous cell carcinoma (pSCC). METHODS: We retrospectively evaluated CSS in 429 pSCC patients from a 10-year period. We assessed cohabitation, living arrangements and socio-economic conditions(SEC) as prognostic predictors. Kaplan-Meier estimates and Cox hazard rates (HR) with 95% confidence intervals were used for analysis. RESULTS: Out of 429 pSCC patients, 137 (32%) were living alone and 292 (68%) were cohabiting. With a Cox HR at 1.91 (95% CI 1.3-2.98) patients living alone had a significantly lower median five-year survival rate at 69% (95% CI 60-77%) compared to cohabiting patients at 83% (95% CI 78-87%), p = 0.002. Comparing 60 (14%) from higher to 202 (47%) from medium and 95 (22%) patients from lower socio-economic groups we found Cox HRs at 1, 2.4 (95% CI 1.0-5.7, p = 0.04) and 3.4 (95% CI 1.4-8.1, p < 0.01) respectively. When comparing living arrangements, the trend that patients living in apartments and institutions had poorer outcomes than patients living in a house did not reach statistical significance. CONCLUSIONS: Living alone and in poor socio-economic conditions predict poor prognosis in penile cancer in this national study. We make the case for further research in efforts to minimize cancer inequality pSCC patients.

DaPeCa-7: comparative assessment of fluorodeoxyglucose positron emission tomography/computed tomography (CT) and conventional diagnostic CT in diagnosis of lymph node metastases, distant metastases and incidental findings in patients with invasive penile cancer.

OBJECTIVES: To evaluate diagnostic accuracy of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) compared to contrast-enhanced CT in assessment of inguinal lymph node (ILN) metastases, distant metastases and synchronous cancers in patients with penile squamous cell carcinoma (pSCC). PATIENTS AND METHODS: During a 4-year period, patients with pSCC were scheduled for FDG PET/CT prior to surgical treatment at two referral centres that manage all penile cancers in Denmark. The primary endpoint was diagnostic accuracy of FDG PET/CT and of CT alone with histopathology or Response Evaluation Criteria In Solid Tumors (RECIST) as reference. RESULTS: We evaluated 171 patients for distant metastases and synchronous incident cancers and examined 286 groins in 143 patients for LN metastases by FDG PET/CT. Six groins disclosed false negatives. FDG PET/CT sensitivity was 85.4% per patient. In 135 patients (270 groins), CT images were evaluated separately and 22 groins disclosed false negatives. CT sensitivity was 47.5% per patient. FDG PET/CT detected pSCC distant metastases in seven patients. Distant metastases from other cancers were newly detected in three patients. In eight patients, an incidental synchronous cancer was detected. Seven out of the 18 distant malignancies detected depended on FDG PET information. CONCLUSION: This study underlines the increased diagnostic accuracy of FDG PET/CT compared to CT alone in the evaluation of ILN status. In patients with palpable LNs, the advantage of FDG PET/CT over CT is less pronounced. FDG PET/CT may play a role in penile cancer evaluation.

Management of penile cancer patients during the COVID-19 pandemic: An eUROGEN accelerated Delphi consensus study.

OBJECTIVES: To develop an international consensus on managing penile cancer patients during the COVID-19 acute waves. A major concern for patients with penile cancer during the coronavirus disease 2019 (COVID-19) pandemic is how the enforced safety measures will affect their disease management. Delays in diagnosis and treatment initiation may have an impact on the extent of the primary lesion as well as the cancer-specific survival because of the development and progression of inguinal lymph node metastases. MATERIALS AND METHODS: A review of the COVID-19 literature was conducted in conjunction with analysis of current international guidelines on the management of penile cancer. Results were presented to an international panel of experts on penile cancer and infection control by a virtual accelerated Delphi process using 4 survey rounds. Consensus opinion was defined as an agreement of ≥80%, which was used to reconfigure management pathways for penile cancer. RESULTS: Limited evidence is available for delaying penile cancer management. The consensus rate of agreement was 100% that penile cancer pathways should be reconfigured, and measures should be developed to prevent perioperative nosocomial transmission of COVID-19. The panel also reached a consensus on several statements aimed at reconfiguring the management of penile cancer patients during the COVID-19 pandemic. CONCLUSIONS: The international consensus panel proposed a framework for the diagnostic and invasive therapeutic procedures for penile cancer within a low-risk environment for COVID-19.

DaPeCa5 - obesity at the time of diagnosis does not predict poor cancer-specific survival in patients with penile squamous cell carcinoma - a Danish National study.

BACKGROUND: Conflicting data on the prognostic significance of obesity in penile cancer have been presented in recent years. OBJECTIVE: The objective of this study was to investigate obesity as a prognostic factor in patients with penile squamous cell carcinoma (pSCC) in a large national Danish cohort. Furthermore we aimed to compare the BMI of pSCC patients to a large age-matched cohort of healthy men. METHODS: We evaluated 429 patients with invasive pSCC from a national retrospective penile cancer cohort and defined a body mass index (BMI) at 30 kg/m2 as obese. Furthermore, we considered if a fitted model for BMI and mortality could define a critical BMI tipping point for increasing mortality by the means of BMI categories of 1 kg/m2 width. We compared 29 pSCC patients with reported unintended weight loss at diagnosis to 400 with no reported weight loss. Cox regression with 95% confidence intervals was used for penile cancer-specific survival analysis. The comparison between 325 age-matched pSCC patients and 11,238 healthy men from an existing contemporary health database was done by nonparametric tests. RESULTS: There was no difference in cancer specific survival between patients with a BMI below and above 30 kg/m2, cox hazard ratio (HR) 0.74 (0.47-1.18), p = .20, but 37 kg/m2 was a tipping point for increasing mortality, HR = 2.10 (1.06-4.18), p = .035. Unintentional weight loss prior to diagnosis significantly predicted worse cancer specific outcome, cox hazard ratio 6.0 (3.5-10.0), p < 001 and cox hazard ratio adjusted for American Joint Committee of Cancer (AJCC)-stage at 1.8 (1.1-3.1), p = .03. Age-matched pSCC patients had a significantly higher BMI than healthy males, 28.4 ± 5.5 kg/m2 vs. 26.2 ± 3.6 kg/m2, p < .0001 and were more likely to smoke, p < .0001, and report alcohol intakes over 14 units/week, p < .0001. CONCLUSION: In this Danish cohort, BMI above 30 kg/m2 at diagnosis does not affect prognosis, but BMI at and above 37 kg/m2 at diagnosis predicts poor prognosis. Unintentional weight loss is a predictor of high stage and poor prognosis. PSCC patients have a significantly higher BMI than age-matched healthy males.

DaPeCa-4: outcome in penile cancer patients with N3 disease due to extra nodal extension treated with surgery and chemo-irradiation.

Objective: The role of pelvic lymph node dissection (PLND) is still debated in patients with N3 stage penile cancer. In Denmark this subgroup of patients is in general managed with an inguinal lymphadenectomy (ILND) and adjuvant chemoradiation and PLND is not offered as a standard. The objective of this study was to report treatment outcomes of this regimen and compare this with existing literature.Materials and methods: We retrospectively reviewed records of patients with pT1-T4, N3, M0 penile cancer diagnosed between 1st January 2010 and 31th December 2014 in Denmark and treated with curative intend.Results: 21 patients were identified with a median follow up of 74 months (CI 54-94). Management of the penile lesion was local resection in 5 (23.8%), partial penectomy in 10 (47.6%), and total penectomy in 6 (28.6%) of patients. Regarding the most extensive lymph node (LN) surgery: 4 patients (23,8%) went directly to oncological treatment from sentinel node biopsy with no further LN dissection, 6 patients (28.6%) were treated with unilateral ILND, 10 patients (47.6%) with bilateral ILND and a single patient (4.8%) was treated with ILND and PLND. In the adjuvant setting patients were treated with external beam therapy of involved regions and cisplatin-based chemotherapy. Median overall survival was 84 months (CI 0-176). The 5-year probability of surviving penile cancer was 57.1% (CI 36.0-78.3).Conclusion: Treatment with surgery and chemo-irradiation in this national cohort does not show inferior survival outcomes compared to historical cohorts.

Human papillomavirus and squamous cell carcinoma of the urinary bladder: DaBlaCa-10 study.

OBJECTIVE: To evaluate a potential association between Human Papillomavirus (H.P.V.) and squamous cell carcinoma (S.C.C.) urinary bladder cancer (B.C.). Furthermore, the relation between p16INK4a, H.P.V. and B.C. was examined. PATIENTS AND METHODS: Patients were included and divided into three groups based on the histological diagnosis of B.C. SPECIMENS: An extensive exclusion was performed, including accepted casual risk factors for S.C.C. B.C., such as long-term use of catheters, cystolithiasis and Schistosoma hematobium infection. A total of 100 patients were included: 50 with pure S.C.C., 25 with urothelial carcinomas (U.C.) and 25 with squamous differentiation of U.C. (Sq.D.). The patients were operated at one of four major Danish hospitals in the period January 2005 to December 2016. Clinical information was collected from the medical records. Presence of H.P.V. was analyzed using the INNO-LiPA H.P.V. Genotyping Extra II. p16INK4a was analyzed using immunohistochemical (I.H.C.) staining. A p-value <0.05 was considered statistically significant. RESULTS: An overall H.P.V. prevalence of 12/100 (12%) was observed. H.P.V. was demonstrated in 9/50 (18%) of the S.C.C. PATIENTS: Overall, p16INK4a over-expression was observed in 52/100 (52%) patients. However, concomitant H.P.V. positivity and p16INK4a over-expression were observed in only 4/100 (4%) patients. CONCLUSION: The presence of H.P.V. in one fifth of patients with S.C.C. B.C. was demonstrated. H.P.V. infection could have a significant association with S.C.C. B.C. without other known casual risk factors for S.C.C. B.C.

Correlation between organ-specific co-morbidities and complications in bladder cancer patients undergoing radical cystectomy.

OBJECTIVE: To evaluate the association between patients' organ-specific co-morbidities and post-operative complications following radical cystectomy for bladder cancer. PATIENTS AND METHODS: All patients who underwent radical cystectomy at Aarhus University Hospital during the period from January 2006 to February 2014 were included retrospectively. A total of 40 comorbidities and 59 complications were registered meticulously. Univariate and multivariate analyses were used to detect associations between the individual comorbidities and specific post-operative complications. RESULTS: Ninety-two per cent (575/625) of patients experienced one or more complications following radical cystectomy. Clavien-Dindo grade 3-5 complications were observed in 40.8% of patients, and 6.2% had severe complications (Clavien-Dindo grade 4-5). The mortality rate was 2.2%. High BM, previous myocardial infarction and chronic obstructive pulmonary disease were noted to be associated with moderate-to-severe post-operative complications (Clavien-Dindo grade 3-5), while diabetes and lymphoproliferative disorders were significantly associated with severe complications (Clavien-Dindo grade 4-5). CONCLUSION: This study demonstrates that overall complications to radical cystectomy are high (92%). The associations between specific comorbidities and complications need to be further investigated in order to evaluate whether pre-operative assessment can be more optimally used in a prevention strategy tailored to the individual patient.

The Danish National Penile Cancer Quality database.

AIM OF DATABASE: The Danish National Penile Cancer Quality database (DaPeCa-data) aims to improve the quality of cancer care and monitor the diagnosis, staging, and treatment of all incident penile cancer cases in Denmark. The aim is to assure referral practice, guideline adherence, and treatment and development of the database in order to enhance research opportunities and increase knowledge and survival outcomes of penile cancer. STUDY POPULATION: The DaPeCa-data registers all patients with newly diagnosed invasive squamous cell carcinoma of the penis in Denmark since June 2011. MAIN VARIABLES: Data are systematically registered at the time of diagnosis by a combination of automated data-linkage to the central registries as well as online registration by treating clinicians. The main variables registered relate to disease prognosis and treatment morbidity and include the presence of risk factors (phimosis, lichen sclerosus, and human papillomavirus), date of diagnosis, date of treatment decision, date of beginning of treatment, type of treatment, treating hospital, type and time of complications, date of recurrence, date of death, and cause of death. DESCRIPTIVE DATA: Registration of these variables correlated to the unique Danish ten-digit civil registration number enables characterization of the cohort, individual patients, and patient groups with respect to age; 1-, 3-, and 5-year disease-specific and overall survival; recurrence patterns; and morbidity profile related to treatment modality. As of August 2015, more than 200 patients are registered with ∼65 new entries per year. CONCLUSION: The DaPeCa-data has potential to provide meaningful, timely, and clinically relevant quality data for quality maintenance, development, and research purposes.

DaPeCa-2: Implementation of fast-track clinical pathways for penile cancer shortens waiting time and accelerates the diagnostic process--A comparative before-and-after study in a tertiary referral centre in Denmark.

OBJECTIVE: The aim of this study was to examine the feasibility and impact of a fast-track referral pathway on clinical time intervals in penile cancer. MATERIALS AND METHODS: This observational study from a tertiary referral centre included 263 patients diagnosed before and after the introduction of an intervention to reduce clinical time intervals, the Cancer Patient Pathway (CPP). The CPP included fast-track referral and set time-frames for units participating in cancer diagnosis and treatment, and was introduced for penile cancer in Denmark on 1 January 2009. Median time intervals (in calendar days) with interquartile range were the main outcome measure. RESULTS: A trend towards reduction was observed in all clinical time intervals, with a statistically significant reduction in the system interval (p = 0.01) and tertiary centre interval (p < 0.0001). The proportion of patients treated within the maximum accepted time-frame of 37 days after referral steadily increased after implementation of the CPP. In particular, unjustified waiting time was reduced significantly. This was mainly achieved through pre-booking of appointments and diagnostic time slots by a dedicated clinical coordinator. CONCLUSIONS: To the authors' knowledge, this is the first study examining the feasibility and impact of an intervention to reduce clinical time intervals in penile cancer. The Danish CPP was successful in reducing system and tertiary centre intervals. Future interventions need to address the long patient interval. Longer follow-up is needed to study the impact of CPP on mortality.

DaPeCa-2: Implementation of fast-track clinical pathways for penile cancer shortens waiting time and accelerates the diagnostic process--A comparative before-and-after study in a tertiary referral centre in Denmark.

OBJECTIVE: The aim of this study was to examine the feasibility and impact of a fast-track referral pathway on clinical time intervals in penile cancer. MATERIALS AND METHODS: This observational study from a tertiary referral centre included 263 patients diagnosed before and after the introduction of an intervention to reduce clinical time intervals, the Cancer Patient Pathway (CPP). The CPP included fast-track referral and set time-frames for units participating in cancer diagnosis and treatment, and was introduced for penile cancer in Denmark on 1 January 2009. Median time intervals (in calendar days) with interquartile range were the main outcome measure. RESULTS: A trend towards reduction was observed in all clinical time intervals, with a statistically significant reduction in the system interval (p = 0.01) and tertiary centre interval (p < 0.0001). The proportion of patients treated within the maximum accepted time-frame of 37 days after referral steadily increased after implementation of the CPP. In particular, unjustified waiting time was reduced significantly. This was mainly achieved through pre-booking of appointments and diagnostic time slots by a dedicated clinical coordinator. CONCLUSIONS: To the authors' knowledge, this is the first study examining the feasibility and impact of an intervention to reduce clinical time intervals in penile cancer. The Danish CPP was successful in reducing system and tertiary centre intervals. Future interventions need to address the long patient interval. Longer follow-up is needed to study the impact of CPP on mortality.

Sentinel node biopsy in uro-oncology: a history of the development of a promising concept.

Lymph node staging is important in many urologic malignancies. The lack of a sufficiently accurate noninvasive lymph node staging modality has proven to be challenging as most urologic malignancies rely on surgical lymph node removal for regional staging. Penile cancer has been a model disease for the development of the sentinel node concept, which has subsequently been successfully adapted to breast cancer and melanoma studies. Currently, the sentinel node technique is standardized in many centers and under development for new indications. The introduction of near-infrared cameras and fluorescence techniques has paved the way for robot-assisted laparoscopic sentinel node biopsies in prostate cancer, urinary bladder cancer, and renal cancer. Fluorescence techniques have increased visual guidance towards lymph nodes during surgery and have challenged previously established templates for surgical lymph node removal. This review discusses the history of our understanding of the lymphatic system and the development of the sentinel node concept and highlights the importance of early and minimally invasive regional lymph node staging. Contemporary data on sentinel node biopsy in each of the urologic malignancies are assessed. Current trends towards robot-assisted sentinel lymph node removal are discussed, and the diagnostic accuracy and oncologic safety of sentinel node procedures are addressed. In an era of several new sentinel node indications, the importance of proper case selection, protocolled regimen, consequent follow-up, and back-up strategies in the case of radiotracer-silent or nonvisualized regions is stressed.