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Journal of Clinical Oncology : Official... Jul 2024Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma...
PURPOSE
Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts.
METHODS
This is an investigator-initiated, multicenter, phase I trial. CaboNivo doublet expansion cohorts included (1) mUC, (2) mRCC, and (3) adenocarcinoma of the bladder/urachal; CaboNivoIpi triplet expansion cohorts included (1) mUC, (2) mRCC, (3) penile cancer, and (4) squamous cell carcinoma of the bladder and other rare GU tumors (ClinicalTrials.gov identifier: NCT02496208).
RESULTS
The study enrolled 120 patients treated with CaboNivo (n = 64) or CaboNivoIpi (n = 56), with a median follow-up of 49.2 months. In 108 evaluable patients (CaboNivo n = 59; CaboNivoIpi n = 49), the ORR was 38% (complete response rate 11%) and the median duration of response was 20 months. The ORR was 42.4% for mUC, 62.5% for mRCC (n = 16), 85.7% for squamous cell carcinoma of the bladder (n = 7), 44.4% for penile cancer (n = 9), and 50.0% for renal medullary carcinoma (n = 2). Grade ≥ 3 treatment-related adverse events occurred in 84% of CaboNivo patients and 80% of CaboNivoIpi patients.
CONCLUSION
CaboNivo and CaboNivoIpi demonstrated clinical activity and safety in patients with multiple GU malignancies, especially clear cell RCC, urothelial carcinoma, and rare GU tumors such as squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, adenocarcinoma of the bladder, renal medullary carcinoma, and penile cancer.
PubMed: 38954785
DOI: 10.1200/JCO.23.02233 -
Oral Diseases Jun 2024Histopathological grading of oral epithelial dysplasia (OED) is the current standard for stratifying cancer progression risk but is associated with subjectivity and... (Review)
Review
OBJECTIVE
Histopathological grading of oral epithelial dysplasia (OED) is the current standard for stratifying cancer progression risk but is associated with subjectivity and variability. This problem is not commonly seen regarding the grading of epithelial dysplasia in other sites. This systematic review aims to compare grading systems for oral, anal, penile, and cervical epithelial dysplasia to determine their predictive accuracy for recurrence and malignant transformation (MT) outcomes.
METHODS
The review protocol was registered in PROSPERO (CRD42023403035) and was reported according to the PRISMA checklist. A comprehensive search was performed in the main databases and gray literature. The risk of bias in individual studies was analyzed using the Joanna Briggs Institute checklist for each study design.
RESULTS
Forty-six studies were deemed eligible and included in this systematic review, of which 45 were included in the quantitative analysis. Meta-analysis revealed that the binary system demonstrated a higher predictive ability for MT/recurrence of OED compared to multilevel systems. Higher predictive accuracy of MT was also observed for binary grading systems in anal intraepithelial neoplasia.
CONCLUSIONS
No significant difference was found between the current grading systems of epithelial dysplasia in different body parts. However, binary grading systems have shown better clinical outcomes.
PubMed: 38946217
DOI: 10.1111/odi.15052 -
The Journal of Sexual Medicine Jun 2024
Topics: Humans; Male; Nitric Oxide; Penis; Penile Erection; Erectile Dysfunction
PubMed: 38945686
DOI: 10.1093/jsxmed/qdae056 -
Urologic Oncology Jun 2024Penile cancer (PeCa) is a rare disease. HPV infection, smoking, phimosis, and lichen sclerosus represent well-known associated risk factors.
BACKGROUND
Penile cancer (PeCa) is a rare disease. HPV infection, smoking, phimosis, and lichen sclerosus represent well-known associated risk factors.
OBJECTIVES
Primary aim of our study is to evaluate the incidence and risk factors of PeCa and to outline the adopted diagnostic and therapeutic approaches. Secondary aim is to investigate risk factors associated with aggressive disease and to identify the complications arising from its surgical treatment.
MATERIALS AND METHODS
We conducted a retrospective analysis using the PearlDiver™ Mariner database, from January 1, 2011, to December 31, 2021, identifying all patients diagnosed with PeCa and PeIN, evaluating comorbidities, risk factors, and social and economic conditions. We evaluated the imaging modalities employed for staging as well as the treatment strategies. Finally, we evaluated the most frequent complications associated with inguinal lymphadenectomy (ILND).
RESULTS
During the study period, 17,494 patients were diagnosed with PeCa and 5,965 with penile intraepithelial neoplasia (PeIN). US was the most frequently utilized imaging modality, followed by PET and PET/CT. Use of CT and MRI was around 5%. Surgical treatment was the predominant strategy, utilized in 31.3% of PeCa and 22.9% of PeIN. Wide Local Excision/Glansectomy emerged as the most common surgical procedures. MLR analysis identified smoking as a risk factor for metastatic PeCa (OR; 95% CI = 1.49; 1.379-1.609), HPV infections were associated with a 35% decrease in risk (OR; 95% CI = 0.65; 0.562-0.744) (all P < 0.001). Lichen sclerosus and phimosis were associated with a doubled risk of demolitive surgery. Approximately 40% of patients experienced complications associated with ILND.
CONCLUSION
Despite advances in PeCa management, there's no significant move toward more conservative treatments. Surgical treatments are still marked by high rates of complications, potentially affect the sexual and psychosocial health of patients. These issues may foster a tendency toward avoidance behaviors, contributing to a delayed clinical presentation and treatment.
PubMed: 38944595
DOI: 10.1016/j.urolonc.2024.05.013 -
Advances in Pediatrics Aug 2024Undescended testis is the most common genital disorder identified at birth. Boys who do not have spontaneous descent of the testis at 6 months of age, adjusted for... (Review)
Review
Undescended testis is the most common genital disorder identified at birth. Boys who do not have spontaneous descent of the testis at 6 months of age, adjusted for gestational age, should be referred to pediatric urology for timely orchiopexy. Retractile testes are at risk for secondary ascent of the testes and should be monitored by physical examination annually. If there is concern for ascent of the testis, pediatric urology referral is recommended. Most cases of phimosis can be managed medically with topical corticosteroids and manual retraction of the foreskin.
Topics: Humans; Male; Cryptorchidism; Phimosis; Child; Orchiopexy; Infant; Infant, Newborn; Child, Preschool
PubMed: 38944481
DOI: 10.1016/j.yapd.2023.12.001 -
BMC Urology Jun 2024TIP is the most common preformed type of Urethroplasty. The intermediate barrier is used as a waterproofing layer to prevent fistula formation. Many tissues have been... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
TIP is the most common preformed type of Urethroplasty. The intermediate barrier is used as a waterproofing layer to prevent fistula formation. Many tissues have been utilized as a barrier layer, with varying success rates. The search for a better intermediate layer will continue. In this study, we aim to evaluate the role of Buck's Fascia as a covering for the neo-urethra to prevent fistula formation in patients who underwent Snodgrass Urethroplasty.
METHODS
This prospective study was conducted between 2018 and 2022. Patients were randomly assigned to either Group 'A' or Group 'B'. Group A included patients who underwent the Snodgrass procedure with a Buck's Fascia cover, while Group B included patients whose neo-urethra was covered with the dartos flap. These patients were closely monitored for the development of short- and long-term complications in both groups, and the results were recorded.
RESULTS
The study involved 164 patients, who underwent midpenile and distal hypospadias repair using the Snodgrass technique. In Group 'A' (84 patients), the neo-urethra was covered with Buck's Fascia, while in Group 'B' (80 patients), the neo-urethra was covered with the dartos flap. The mean age of the children was (23.06 ± 16.12) months in group 'A' & (26.06 ± 14.07) months in group 'B'. mean operating time was (40 ± 11.43) minutes, in Group 'A', and (70 ± 17.43) minutes, in Group 'B'. Meatal stenosis occurred in 3.57% of children in Group 'A' and 10% of patients in Group 'B'. Urethral fistulas were encountered in 2.35% of cases in Group 'A'and 10% in Group 'B'. The difference between the groups was statistically significant.
Topics: Humans; Male; Urologic Surgical Procedures, Male; Prospective Studies; Hypospadias; Urethra; Infant; Treatment Outcome; Child, Preschool; Fascia; Surgical Flaps; Postoperative Complications
PubMed: 38937743
DOI: 10.1186/s12894-024-01468-x -
Journal of Personalized Medicine Jun 2024Inflatable penile prosthesis (IPP) surgery is an effective treatment for erectile dysfunction (ED), but infections pose a significant threat to its success. Current... (Review)
Review
Inflatable penile prosthesis (IPP) surgery is an effective treatment for erectile dysfunction (ED), but infections pose a significant threat to its success. Current guidelines lack antifungal recommendations, despite rising fungal infection rates post-IPP surgery. This review examines epidemiology, risk factors (including diabetes mellitus, immunosuppression, and obesity), and pathogenesis, highlighting the role of biofilm formation in device contamination. Clinical manifestations vary from acute to delayed, with fungal biofilms presenting challenges in diagnosis. Prophylactic strategies, including broad-spectrum antibiotics and antifungals, are crucial, with evidence suggesting a 92% reduction in infections. With fungal infections showing lower salvage rates, management involves culture-guided treatment, irrigation, and oral antibiotics. Future research aims to understand biofilm mechanisms and develop biomaterials to reduce infection rates. Implementing antifungal therapy, along with standard practices like the no-touch technique and antibiotic dips, is crucial in preventing IPP infections.
PubMed: 38929865
DOI: 10.3390/jpm14060644 -
The Urologic Clinics of North America Aug 2024
Topics: Humans; Male; Testicular Neoplasms; Penile Neoplasms
PubMed: 38925747
DOI: 10.1016/j.ucl.2024.05.001 -
The Urologic Clinics of North America Aug 2024Penile cancer is a rare malignancy with a poor prognosis. Studies with single-agent immune checkpoint inhibitors (ICIs) have demonstrated efficacy, but response rates... (Review)
Review
Penile cancer is a rare malignancy with a poor prognosis. Studies with single-agent immune checkpoint inhibitors (ICIs) have demonstrated efficacy, but response rates are low. Studies combining ICIs with both chemotherapy and targeted therapy are ongoing. Up to 50% of penile cancer cases are associated with human papillomavirus (HPV). HPV-targeting therapies, such as HPV-targeting vaccines and T-cell receptor therapies, are an area of active investigation. Penile cancer cells also express cell surface antigens that may be targeted by the emerging class of antibody-drug conjugates.
Topics: Humans; Penile Neoplasms; Male; Immune Checkpoint Inhibitors; Papillomavirus Infections; Immunotherapy; Neoplasm Metastasis; Molecular Targeted Therapy
PubMed: 38925739
DOI: 10.1016/j.ucl.2024.03.005 -
The Urologic Clinics of North America Aug 2024This article reviews penile squamous cell carcinoma (PSCC), a rare genitourinary cancer that has been increasing in prevalence. It discusses emerging therapies, focusing... (Review)
Review
This article reviews penile squamous cell carcinoma (PSCC), a rare genitourinary cancer that has been increasing in prevalence. It discusses emerging therapies, focusing on immunotherapy, vaccine therapy, and cell-based treatments, especially in the context of human papillomavirus-related PSCC. Factors influencing these therapies are discussed. These include the immune microenvironment, programmed cell death ligand-1 expression, and tumor immune cell infiltration. This article also highlights immune checkpoint inhibitors and related clinical trials. This review supports the use of personalized medicine in treating PSCC. It stresses the need for collaborative studies and data sharing to create specific treatment plans and achieve better outcomes.
Topics: Humans; Penile Neoplasms; Male; Immunotherapy; Carcinoma, Squamous Cell; Immune Checkpoint Inhibitors; Tumor Microenvironment
PubMed: 38925738
DOI: 10.1016/j.ucl.2024.03.014