Current and Future Strategies in the Diagnosis and Management of Penile Cancer

Penile cancer is an uncommon malignancy that has a devastating effect on the patient while also being challenging to diagnose and treat. By implementing preventive measures, we can decrease the incidence of this disease and improve the quality of life of our patients. Early detection plays an important role in disease control and proper diagnostic modalities must be used in order to accurately identify the cancer and its progression. Primary penile lesions should be initially approached when surgically feasible and clinically appropriate with penile preserving surgical techniques. Advances in inguinal lymph node detection and management, has improved the clinical outcome of penile cancer. Advanced penile cancer still portends a poor prognosis and should be approached via a multimodal treatment regimen. In this review, we address the importance of prevention, early detection, and the contemporary management of primary penile lesions, as well as the advances in inguinal lymph node disease detection and surgical treatment, for both localized and advanced disease

Current and Future Strategies in the Diagnosis and Management of Penile Cancer

Penile cancer is an uncommon malignancy that has a devastating effect on the patient while also being challenging to diagnose and treat. By implementing preventive measures, we can decrease the incidence of this disease and improve the quality of life of our patients. Early detection plays an important role in disease control and proper diagnostic modalities must be used in order to accurately identify the cancer and its progression. Primary penile lesions should be initially approached when surgically feasible and clinically appropriate with penile preserving surgical techniques. Advances in inguinal lymph node detection and management, has improved the clinical outcome of penile cancer. Advanced penile cancer still portends a poor prognosis and should be approached via a multimodal treatment regimen. In this review, we address the importance of prevention, early detection, and the contemporary management of primary penile lesions, as well as the advances in inguinal lymph node disease detection and surgical treatment, for both localized and advanced disease

Penile Cancer Neoadjuvant Chemotherapy in Advanced Penile Carcinoma

e u r o p e a n u r o l o g y 5 2 ( 2 0 0 7 ) 4 8 8 -4 9 4 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m Please visit www.eu-acme.org/ europeanurology to read and answer questions on-line. The EU-ACME credits will then be attributed automatically. Article info Abstract 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

Reactivity to human papillomavirus type 16 Ll virus-like particles in sera from patients with genital cancer and patients with carcinomas at five different extragenital sites

A retrospective seroepidemiologic study was performed to examine the association between human papillomaviruses (HPV) 16 infection and carcinomas of the oropharynx, the oesophagus, penis and vagina. Sera were selected from the serum bank from the Antoni van Leeuwenhoek Hospital (Netherlands Cancer Institute) and the Slotervaart Hospital in Amsterdam, the Netherlands. Presence of HPV 16 specific antibody was assessed using HPV 16 L1 capsids. Sera positive for HPV 16 capsid antibody were further tested for antibody against HPV 16 E7 peptides. Prevalence of antibody against H PV 16 L1 capsids among both the negative control group without cancer and the negative control group with gastric cancer was 18%, while seroprevalence among the control group of patients with HPV-associated cervical squamous cell carcinoma was 47% (P < 0.001). Among the patients with penile squamous cell carcinoma seroprevalence was 38% (P < 0.001), among patients with oropharyngeal carcinoma 33% (P = 0.04) and among patients with oesophageal squamous cell carcinoma 14% (P = 0.7). The serological evidence for association between HPV 16 infection and both oropharyngeal carcinoma and penile carcinoma was established. The conclusion that no association was found between the presence of antibody against HPV 16 L1 capsids and oesophageal squamous cell carcinoma was in accordance with results of other studies carried out in the Netherlands using HPV DNA technology. In the subjects with HPV 16 L1 capsid antibody, no association was found between the antibody against HPV 16 E7 and clinical outcome

Arterio-ureteral fistula:a nationwide cross-sectional questionnaire analysis

PURPOSE: Arterio-ureteral fistula (AUF) is an uncommon diagnosis, but potentially lethal. Although the number of reports has increased over the past two decades, the true incidence and contemporary urologists’ experience and approach in clinical practice remains unknown. This research is conducted to provide insight in the incidence of AUF in The Netherlands, and the applied diagnostic tests and therapeutic approaches in modern practice. METHODS: A nationwide cross-sectional questionnaire analysis was performed by sending a survey to all registered Dutch urologists. Data collection included information on experience with patients with AUF; and their medical history, diagnostics, treatment, and follow-up, and were captured in a standardized template by two independent reviewers. Descriptive statistics were used. RESULTS: Response rate was 62% and 56 AUFs in 53 patients were reported between 2003 and 2018. The estimated incidence of AUF in The Netherlands in this time period is 3.5 AUFs per year. Hematuria was observed in all patients; 9% intermittent microhematuria, and 91% presenting with, or building up to massive hematuria. For the final diagnosis, angiography was the most efficient modality, confirming diagnosis in 58%. Treatment comprised predominantly endovascular intervention. CONCLUSION: The diagnosis AUF should be considered in patients with persistent intermittent or massive hematuria. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00345-021-03910-3

Patterns of Recurrence and Survival After Pelvic Treatment for Locally Advanced Penile Cancer

BACKGROUND: Penile cancer (PeCa) is rare, and the survival of patients with advanced disease remains poor. A better understanding of where treatment fails could aid the development of new treatment strategies. OBJECTIVE: To describe the disease course after pelvic lymph node (LN) treatment for PeCa. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analysed 228 patients who underwent pelvic LN treatment with curative intent from 1969 to 2016. The main treatment modalities were neoadjuvant chemotherapy, chemoradiation, and pelvic LN dissection. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In the case of multiple recurrence locations, the most distant location was taken and recorded as follows: local (penis), regional (inguinal and pelvic LN), and distant (any other location). A competing risk analysis was used to calculate the time to recurrence per location, and a Kaplan-Meier analysis was used for overall survival (OS). RESULTS AND LIMITATIONS: The median follow-up of the surviving patients was 79 mo. The reason for pelvic treatment was pelvic involvement on imaging (29%), two or more tumour-positive inguinal LNs (61%), or inguinal extranodal extension (52%). More than half of the patients (61%) developed a recurrence. The median recurrence-free survival was 11 mo. The distribution was local in 9%, regional in 27%, and distant in 64% of patients. The infield control rate of nonsystemically treated patients was 61% (113/184). From the start of pelvic treatment, the median OS was 17 mo (95% confidence interval 12–22). After regional or distant recurrence, all but one patient died of PeCa with median OS after a recurrence of 4.4 (regional) and 3.1 (distant) mo. This study is limited by its retrospective nature. CONCLUSIONS: The prognosis of PeCa patients treated on their pelvis who recur despite locoregional treatment is poor. The tendency for systemic spread emphasises the need for more effective systemic treatment strategies. PATIENT SUMMARY: In this report, we looked at the outcomes of penile cancer patients in an expert centre undergoing various treatments on their pelvis. We found that survival is poor after recurrence despite locoregional treatment. Therefore, better systemic treatments are necessary

Clinical outcome of robot-assisted residual mass resection in metastatic nonseminomatous germ cell tumor

Purpose: To evaluate the outcome of robot-assisted residual mass resection (RA-RMR) in nonseminomatous germ cell tumor (NSGCT) patients with residual tumor following chemotherapy. Patients and methods: Retrospective medical chart analysis of all patients with NSGCT undergoing RA-RMR at two tertiary referral centers between January 2007 and April 2019. Patients were considered for RA-RMR in case of a residual tumor between 10 and 50 mm at cross-sectional computed tomography (CT) imaging located ventrally or laterally from the aorta or vena cava, with normalized tumor markers following completion of chemotherapy, and no history of retroperitoneal surgery. Results: A total of 45 patients were included in the analysis. The Royal Marsden stage before chemotherapy was IIA in 13 (28.9%), IIB in 16 (35.6%), IIC in 3 (6.7%) and IV in 13 patients (28.9%). The median residual tumor size was 1.9 cm (interquartile range [IQR] 1.4–2.8; range 1.0–5.0). Five procedures (11.1%) were converted to an open procedure due to a vascular injury (n = 2), technical difficulty (n = 2) or tumor debris leakage (n = 1). A postoperative adverse event occurred in two patients (4.4%). Histopathology showed teratoma, necrosis and viable cancer in 29 (64.4%), 14 (31.1%), and two patients (4.4%), respectively. After a median follow-up of 41 months (IQR 22–70), one patient (2.2%) relapsed in the retroperitoneum. The one- and 2-year recurrence-free survival rate was 98%. Conclusion: RA-RMR is an appropriate treatment option in selected patients, potentially providing excellent cure rates with minimal morbidity. Long-term outcome data are needed to further support this strategy and determine inclusion and exclusion criteria

Additional surgical procedures and perioperative morbidity in post-chemotherapy retroperitoneal lymph node dissection for metastatic testicular cancer in two intermediate volume hospitals

Purpose: To evaluate the perioperative morbidity of PC-RPLND in two intermediate volume centers and to identify predictors of high morbidity. Methods: Retrospective analysis of 124 patients treated with open PC-RPLND at two tertiary referral centers between 2001 and 2018. Perioperative morbidity was determined by analyzing additional surgical procedures, intra-operative blood loss, and postoperative complications. Results: An additional procedure was necessary for 33 patients (26.6%). The risk was higher in patients with IGCCCG intermediate/poor prognosis (OR 3.56; 95% CI 1.33–9.52) and residual tumor size > 5 cm (OR 3.53; 95% CI 1.39–8.93). Blood loss was higher in patients with IGCCCG intermediate/poor prognosis (β = 0.177; p = 0.029), large residual tumor (β = 0.570; p < 0.001), an additional intervention (β = 0.342; p < 0.001) and teratoma on retroperitoneal histology (β = − 0.19; p = 0.014). Thirty-one patients had a postoperative complication Clavien-Dindo Grade ≥ 2 (25.0%). Complication risk was highest in patients undergoing an additional intervention (OR 3.46; 95% CI 1.03–11.60; p = 0.044). Conclusions: The rate of additional interventions in our series is comparable to what has been reported in high-volume centers. IGCCCG intermediate/poor prognosis patients with high-volume disease and patients undergoing an additional surgical procedure can be classified as high-risk patients

Dose-Dependent Effect of Platinum-Based Chemotherapy on the Risk of Metachronous Contralateral Testicular Cancer

PURPOSE: Patients with testicular germ cell tumor (TGCT) are at increased risk of developing a contralateral TGCT (CTGCT). Although some studies suggest that prior treatment with platinum-based chemotherapy affects CTGCT risk, a relationship between CTGCT risk and platinum dose has not previously been assessed. We analyzed the association between the number of platinum-based chemotherapy cycles and CTGCT risk. PATIENTS AND METHODS: The risk of developing a metachronous CTGCT was evaluated in a nationwide cohort of 4,755 patients diagnosed with primary TGCT in the Netherlands between 1989 and 2007. Standardized incidence ratios were computed to compare CTGCT incidence with expected TGCT on the basis of TGCT incidence in the general population. The cumulative incidence of CTGCT was estimated in the presence of death as competing risk. The effect of treatment with platinum-based chemotherapy on CTGCT risk was assessed using multivariable Cox proportional hazards regression models. RESULTS: CTGCT was diagnosed in 136 patients (standardized incidence ratio, 14.6; 95% CI, 12.2 to 17.2). The cumulative incidence increased up to 20 years after primary diagnosis, reaching 3.4% (95% CI, 2.8% to 4.0%) after 20 years of follow up. The risk of developing a CTGCT decreased with age (hazard ratio [HR], 0.93; 95% CI, 0.90 to 0.96), was lower after nonseminomatous germ cell tumor (HR, 0.58; 95% CI, 0.35 to 0.96) and decreased with every additional cycle of chemotherapy (HRper cycle, 0.74; 95% CI, 0.64 to 0.85). CONCLUSION: Approximately one in every 30 survivors of TGCT will develop a CTGCT, with CTGCT incidence increasing up to 20 years after a primary TGCT. Treatment with platinum-based chemotherapy shows a dose-dependent inverse association with CTGCT risk

Development of the First Patient-centred Set of Outcomes for Muscle-invasive and Metastatic Bladder Cancer: A Multicentre Initiative

Background: To improve and compare outcomes in healthcare, it is necessary to standardise outcome measurements. There are no widely accepted standardised outcome measures reflecting quality of care for bladder cancer (BCa) patients. Objective: The aim of this study was to create a standardised set of outcomes for patients with muscle-invasive or metastatic BCa, using the value-based healthcare principles. Design, setting, and participants: A multidisciplinary working group of 25 healthcare professionals and patient representatives was assembled, to develop the set. Outcome measurements and statistical analysis: We used an online RAND-modified Delphi process to prioritise, discuss, and reach consensus regarding the outcomes, case-mix variables, and treatment factors. Results and limitations: Recognising the heterogeneity of patients with BCa, the working group defined the scope as patients with muscle-invasive and metastatic BCa. A total of 24 outcomes, including ten patient-reported outcomes, were included in the standard set of outcomes, covering survival, complication rates, recurrence of disease, readmissions after treatment, and quality of life (QoL). Fourteen case-mix variables were included. The EQ-5D and European Organisation for Research and Treatment of Cancer quality of life (EORTC-QLQ) questionnaires were recommended to measure QoL. Conclusions: We developed the first standardised set of patient-centred outcomes for muscle-invasive and metastatic BCa. The sue of this set enables institutions to monitor, compare, and improve the quality of BCa care, on an international level. Patient summary: Our group of healthcare professionals and patient representatives recommended a standardised set of patient-centred outcomes to be followed during the treatment of patients with muscle-invasive or metastatic bladder cancer, in order to monitor, compare, and improve the quality of care