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Background: Studies suggest that a hybrid indocyanine green (ICG)- 99m Tc-nanocolloid tracer improves sentinel node (SN) identification compared to conventional dynamic sentinel node biopsy (DSNB)., Objective: To investigate hybrid tracer-guided SN identification in a multicentre setting and determine false-negative (FN) and complication rates., Design, Setting, and Participants: A total of 130 patients with penile cancer scheduled for DSNB were prospectively included between February 2016 and December 2017 at two national Swedish referral centres. ICG- 99m Tc-nanocolloid hybrid tracer was used in the standard DSNB protocol., Intervention: SNs were identified intraoperatively using radioguidance, fluorescence imaging, and blue dye., Outcome Measurements and Statistical Analysis: The number of SNs identified by each tracer and the rates of complications and nodal recurrence during median follow-up of 34 mo were recorded. Differences in proportions between groups were compared using χ 2 and McNemar's tests., Results and Limitations: Overall, 453 SNs were identified preoperatively via single-photon emission computed tomography/computed tomography. Among the 425 SNs excised, radioguidance, fluorescence, and blue dye identified 414 (97%), 363 (85%), and 349 (82%), respectively. Fluorescence imaging helped to detect six SNs that were negative using the other tracers, two of which were from the same patient and contained metastases. Histopathological examination detected 33 metastatic SNs in 20/130 patients (15%). The FN rate was 12% per groin (95% confidence interval 8-16%)., Conclusions: Identification of SNs in patients with penile cancer relies mainly on radioguidance, while fluorescence (ICG) and blue dye methods for optical SN identification are comparable. However, the value of fluorescence imaging should be further evaluated in studies with long-term follow-up., Patient Summary: In this study, we investigated addition of a dye called indocyanine green (ICG) for assessment of lymph nodes in patients with cancer of the penis. ICG did not improve the rate of detection of nodes most likely to harbour cancer because of their location in the drainage pathway for lymphatic fluid, but did help in identifying additional metastases., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: To analyse the incidence, treatment strategies and complications associated with penile intraepithelial neoplasia (PeIN) in Sweden over a period of 20 years., Materials and Methods: Data on PeIN from the Swedish National Penile Cancer Register were analysed regarding treatment in relation to age, size of the PeIN lesion, localization of the PeIN lesion and complications using chi-squared tests and logistic regression. The incidence of PeIN was calculated and age-standardized according to the European Standard population., Results: Between 2000 and 2019 a total of 1113 PeIN cases were reported. The age-standardized incidence of PeIN was 1.40 per 100 000 men (95% confidence interval [CI] 1.32-1.49). An increase in incidence over time was seen, with a standardized incidence rate of 2.37 (95% CI 1.56-3.70) in 2019 compared to the baseline year, 2000. Surgical or topical treatments were given in 75.0% and 14.6% of cases, respectively. The complication rate was higher in laser surgery (12.1%, 7/58) compared to local surgery (4.6%, 16/348; P = 0.03) with an age-adjusted odds ratio (OR) of 2.82 (95% CI 1.10-7.19; P = 0.03). Local surgery was more common than laser surgery in the last 5 years compared to the first 5 years of the study period: OR 5.75 (95% CI 2.94-11.27). Treatments with imiquimod and topical 5-fluorouracil (5-FU) were more common than destructive methods such as photodynamic therapy, cryotherapy, curettage and electrocautery in the last 5 years compared to the first 5 years: OR 9.48 (95% CI 2.29-39.24)., Conclusions: A twofold increase in the age-standardized incidence of PeIN was seen in Sweden over 20 years. Complications were three times more common in laser surgery compared to local surgery. Changes in treatment showed an increase of treatment strategies such as local surgery and treatment with imiquimod and topical 5-FU over time., (© 2022 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Penile cancer is an uncommon disease with poor prognosis when spread to more than one inguinal lymph node. Recommendations on chemo- and radiotherapy in treatment guidelines are based on low-grade evidence. There are to our knowledge no described population-based cohort with detailed information on given oncological treatment and survival data. The aim of this study is to investigate in detail how men with metastatic penile cancer have been treated with chemotherapy and radiotherapy over time, and how survival varies with N-stage and given treatment., Material and Methods: For this observational cohort study all men in Sweden diagnosed with penile cancer with lymph node- or distant metastases 2000-2015 were identified through the Swedish National Penile Cancer Register (NPECR). Medical records were retrieved and 325 men were confirmed to have metastatic penile cancer (T any , c or pN1-3 and/or M1). Information on treatments was collected. Causes of death were retrieved from the National Cause of Death Register (CDR)., Results: Chemotherapy and/or radiotherapy were given to 172 (53%) of all men. The use of oncological treatments with curative intent increased significantly during the study period, from 30% of men with c/pN2-3 diagnosed 2000-2003 compared with 57% of men diagnosed 2012-2015. Ninety-three (29%) men received oncological treatments with curative intent of whom 85/93 (91%) had stage c/pN2-3M0. Survival decreased with higher N-stage, M1-stage, and absence of oncological treatment with curative intent. For men with c/pN3-stage, the engagement of pelvic lymph nodes was entailed with lower survival than pN3 based on extra-nodal extension (ENE)., Conclusion: The use of oncological treatment was below recommendations in guidelines but increased during the study period. Treatment was given predominantly to men with c/pN2-3 and M1-disease. Survival was higher among men treated with curative intent; this could be due to patient selection bias.

Studies on risk factors for penile intraepithelial neo-plasia have been small in size, have not distinguished penile intraepithelial neoplasia from invasive cancer, and have relied on self-reported information. This study investigated risk factors for penile intraepithelial neoplasia in a cohort of 580 penile intraepithelial neoplasia cases and 3,436 controls using information from 7 Swedish registers. Cases with penile intraepithelial neoplasia had increased odds ratios (ORs) for inflammatory skin diseases (14.7, 95% CI 6.5-33.4) including lichen planus (12.0, 95% CI 3.0-48.0), indicating lichen planus to be an important risk factor. Increased ORs were also observed for diseases of the prepuce (4.0, 95% CI 2.2-7.4), immunosuppressive drugs (5.0, 95% CI 2.5-9.8), penile surgical procedures (4.8, 95% CI 2.2-10.8), balanitis (9.2, 95% CI 5.0-16.8), genital warts (9.9, 95% CI 4.3-22.7) and organ transplantation (7.0, 95% CI 2.4-20.8). This study demonstrates important risk factors for penile intraepithelial neoplasia, providing knowledge that can help prevent the development of penile cancer.

Objectives: To assess penile cancer incidence, stage distribution, adherence to guidelines and prognostic factors in a population-based setting., Patients and Methods: The population-based Swedish National Penile Cancer Register (NPECR) contains detailed information on tumour characteristics and management patterns. A total of 1 678 men with primary squamous cell carcinoma of the penis identified in the NPECR between 2000 and 2012 were included in the study., Results: The mean age-adjusted incidence of penile cancer was 2.1/100 000 men, remaining virtually unchanged during the study period. At diagnosis, 14 and 2% of the men had clinical N+ and M+ disease, respectively. Most men were staged pTis (34%), pT2 (19%), or pT1 (18%), while stage information was unavailable for 18% of the men. Organ-preserving treatment was used in 71% of Tis-T1 tumours. Of men with cN0 and ≥pT1G2 disease, 50% underwent lymph node staging, while 74% of men with cN1-3 disease underwent lymph node dissection. The overall 5-year relative survival rate was 82%. Men aged ≥40 years and those with pT2-3, G2-3 and N+ tumours had worse outcomes., Conclusions: The incidence of penile cancer in Sweden is stable. Most men presented with localized disease, and the proportion of non-invasive tumours was high. During the period under study, adherence to guidelines was suboptimum. The overall 5-year relative survival rate was 82%. Older age, increasing tumour stage and grade, and increasing lymph node stage were associated with poorer survival., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Objective: The aim of this study was to present early outcome data for patients treated for penile cancer with organ-sparing reconstructive surgery at two referral centres in Sweden., Material and Methods: Oncological, cosmetic and functional outcome and complications were analysed retrospectively during the period 2011-2013. Twelve patients with non-invasive penile cancer were treated with glans resurfacing (GR), while 15 patients with invasive penile cancer underwent total glansectomy with neoglans reconstruction (TGN)., Results: The 12 patients treated with GR had a median age of 66 years (range 35-83 years) and a median follow-up time of 16 months (range 4-40 months). All patients showed carcinoma in situ and negative surgical margins in the final pathology report. The 15 patients treated with TGN had a median age of 71 years (range 37-78 years) and the median follow-up time was 10 months (range 1-25 months). All patients had invasive penile cancer and the surgical margins were negative in all cases except one. Complications occurred in five of the 27 patients (18%), and in most cases these were minor and infection related. No recurrences were seen in either group during follow-up, and all patients except one, who had undergone GR, were satisfied with the functional and cosmetic results., Conclusions: GR and TGN seem to be oncologically safe procedures for treating carefully selected patients with penile cancer, and the functional and cosmetic results are promising. Based on these findings, the authors recommend that penile amputation should only be carried out in patients who are not suitable for organ-sparing reconstructive surgery.

Unlabelled: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? According to the current European Association of Urology Guidelines, dynamic sentinel node biopsy is the recommended approach to assess lymph node status in men with cN0 intermediate and high risk penile cancer. Nevertheless, most encouraging results derive from a limited number of studies. The present study shows a false-negative rate of 15%, comparable with or better than several previous studies. Nevertheless, the aim should be a false-negative rate of no more than 5%. We conclude that increased overall experience and the use of the complete modern dynamic sentinel node biopsy protocol are paramount to improve results., Objective: •  To evaluate the false-negative rate and complication rate of dynamic sentinel node biopsy (DSNB) in penile cancer., Patients and Methods: •  In this retrospective study, 58 unilaterally or bilaterally clinically lymph node negative (cN0) patients with penile cancer (57 squamous cell carcinomas and one malignant melanoma), scheduled for DSNB at the Örebro University Hospital, Sweden, between 1999 and 2011, were analysed. •  Preoperative ultrasonography and fine-needle aspiration cytology of suspicious nodes were not introduced until 2008. •  Patients were assessed by lymphoscintigraphy using (99m) technetium nanocolloid on the day before surgery and the dissection of sentinel nodes was aided by the lymphoscintigraphic images and intraoperative detection of radiotracer and patent blue dye. •  The false-negative rate and complication rate were calculated per groin., Results: •  Of the 58 patients, 32 (55%) underwent preoperative ultrasonography. •  Two patients had positive fine-needle aspiration cytology and discontinued further DSNB protocol. Of the remaining 56 patients, all but one were bilaterally cN0 and hence 111 cN0 groins were assessed by lymphoscintigraphy. •  In the 55 bilaterally cN0 patients, lymphoscintigraphy visualized a bilateral sentinel node in 34 (62%). •  At surgery, all excised sentinel nodes were radioactive while 43% were additionally blue. In total, at least one sentinel node was harvested in 96 (86%) of the DSNB staged groins. •  A positive sentinel node was found in 11 groins (bilaterally in three patients). During a median follow-up of 21 months, two false-negative cases emerged, producing a false-negative rate of 15%. Both false-negative cases occurred during the first half of the study. The complication rate was 10%. The majority of complications were minor and transient., Conclusions: •  DSNB is a minimally invasive staging tool in men with cN0 penile cancer, enabling early detection of metastatic disease and thus optimal care. •  Our false-negative rate of 15% is comparable or even favourable in comparison with several previous studies, but far from the 5% or less that we aim for. The complication rate found is somewhat higher than previously reported. •  With increased overall experience and the continued use of the complete DSNB protocol, we believe our results will improve and the complication rate will decrease., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Objective: • To analyse the overall and type-specific human papillomavirus (HPV) prevalence and distribution in penile carcinoma and determine the correlation to histopathological parameters., Patients and Methods: • In this retrospective study, we analysed HPV status in 241 patients with penile carcinoma, treated at Örebro University Hospital, Örebro, Sweden, between 1984 and 2008. Age and date at diagnosis was recorded. • The tumour specimens were categorized according to the UICC 2002 TNM classification. A subset of patients was operatively staged with regard to lymph node status. • A commercially available Real Time PCR was used to detect 13 different types of HPV (6,11,16,18,31,33,35,45,51,52,56,58 and 59)., Results: • We excluded 25 patients due to low DNA quality. Of the remaining 216, 179 (82.9%) tumour specimens were HPV infected. The majority of cases positive for HPV (70.4%) were infected by a single-type. The most frequent type was HPV 16 followed by HPV 18. • No significant association between HPV status and pathological tumour stage, grade or lymph node status was found., Conclusion: • The HPV prevalence found is higher than in most other studies, further strengthening HPV as an etiological agent in penile carcinoma. Furthermore, the high prevalence of HPV 16 and 18 raises the question of what potential impact current HPV vaccines that target these specific HPV types might have on penile carcinoma. No significant association between HPV status and histopathological parameters was found in the present study. Additional investigations are needed to draw final conclusions on the prognostic value of HPV status in penile carcinoma., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)