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Penile cancer is a rare malignancy, particularly in industrialized nations. In the United States, rates are approximately less than 1 per 100,000 men per year with just over 2000 new cases per year. However, there is significantly increased prevalence in developing nations, with limited treatment expertise and reduced access to care, further driving an unmet clinical need. The most noteworthy risk factor for penile cancer is the association with human papillomavirus infection, which may be present in up to 50% of all penile carcinomas. In addition to local primary tumor approaches, multimodality treatment strategies are vital to patients with clinical regional nodal disease, locally advanced disease. Presence and degree of lymph node involvement remains the most important prognostic factor and patients may benefit from multiple treatment strategies. Interim analysis data from the first randomized clinical trial is expected to yield results in mid/late 2024–early 2025. These treatment approaches include neoadjuvant chemotherapy, adjuvant therapy, including chemotherapy and radiation. Systemic therapy for distant recurrent or metastatic disease is primarily a platinum-based chemotherapy, however with poor overall response. As poor outcomes remain high, particularly in indigent populations, there remains an unmet need for these patients, particularly for high level randomized trials and novel therapeutics. In this review, we will highlight treatment updates for penile cancer. In addition to standard of care, we will review novel lines of therapies including immunotherapies and targeted therapies as well as sequencing approaches.

Squamous cell carcinoma (SCC) of the penis is a rare malignancy in the United States, with a significantly higher incidence -- up to 20 to 30 times greater -- in areas of Africa and South America. This can be explained in part by the significantly greater prevalence of sexually transmitted diseases among high-risk males often having unprotected sex with multiple sexual partners. Human papillomavirus (HPV) has been implicated as the infectious pathway by which several these penile neoplasms originate from precursor lesions. In this regard, a fundamental understanding of HPV in penile carcinogenesis can have meaningful implications in understanding 1) the diagnosis of HPV-related precursor penile lesions, 2) targeting HPV-specific molecular pathways, and 3) cancer prevention. Using vaccination programs not only may improve patient outcomes but also may minimize the need for highly aggressive and often debilitating surgical resection.

Genomic alterations (GA) in NF2 tumor-suppressor gene have been associated with aggressive behavior in kidney tumors. We used comprehensive genomic profiling (CGP) to evaluate the frequencies of NF2 GA in histologic subtypes of kidney tumors and co-occurring GA in other genes and biomarkers. Advanced kidney tumors included 1875 clear cell (ccRCC), 405 papillary (pRCC), 108 chromophobe (chRCC), 171 sarcomatoid (sRCC), 61 collecting duct (cdRCC), 49 medullary (mRCC), 134 unclassified (uRCC), 906 urothelial carcinoma of renal pelvis (UC), and 147 Wilms tumors underwent hybrid-capture based CGP to evaluate all classes of GA. 192 (4.9%) of kidney tumors featured NF2 GA which were predominantly structural variant mutations (89%), followed by copy number alterations (9%). Gender and age were similar between NF2-mutant (NF2mut) and NF2-wild type (NF2wt) cohorts with male preponderance. NF2 GA frequency was highest in cdRCC (30%), sRCC (21%), uRCC (15%), and pRCC (12%) while lowest in ccRCC (3%), UC (3%) Wilms tumor (1%), and chRCC (0%). NF2 mutational status was associated with loss of Ch 22 (P < .001). NF2mut RCC harbored co-occurring GA including CDKN2A, CDKN2B, SETD2, and BAP1. VHL, PBRM1, PTEN, and FGFR3 GA were significantly more frequent in NF2wt than in NF2mut tumors. MTOR pathway GAs were uncommon in NF2mut tumors. No NF2 mutated RCC featured MSI-high or high TMB. sRCC was associated with high PD-L1 expression. PD-L1 SP142 tumoral (P = .04) and immune cells (P = .013) were more frequent in NF2mut as compared to NF2wt group. Among histologic subtypes of RCC, cdRCC, sRCC, pRCC, and uRCC are enriched in NF2 GA. Co-occurrent GA in CDKN2A/B, SETD2, and BAP1 may represent potential therapeutic targets. Higher level of PD-L1 expression in NF2mut cohort suggests that these tumors might be sensitive to immune checkpoint inhibitor therapies. In this study, comprehensive genomic profiling (CGP) was used to evaluate the frequency of NF2 genomic alterations in histologic subtypes of kidney tumors and co-occurring genomic alterations in other genes and biomarkers.

Augmented reality is widely used in aeronautics and is a developing concept within surgery. In this pilot study, we developed an application for use on Google Glass optical head-mounted display to train urology residents in how to place an inflatable penile prosthesis. We use the phrase Augmented Reality Assisted Surgery to describe this novel application of augmented reality in the setting of surgery. The application demonstrates the steps of the surgical procedure of inflatable penile prosthesis placement. It also contains software that allows for detection of interest points using a camera feed from the optical head-mounted display to enable faculty to interact with residents during placement of the penile prosthesis. Urology trainees and faculty who volunteered to take part in the study were given time to experience the technology in the operative or perioperative setting and asked to complete a feedback survey. From 30 total participants using a lO-point scale, educational usefulness was rated 8.6, ease of navigation was rated 7.6, likelihood to use was rated 7.4, and distraction in operating room was rated 4.9. When stratified between trainees and faculty, trainees found the technology more educationally useful, and less distracting. Overall, 81% of the participants want this technology in their residency program, and 93% see this technology in the operating room in the future. Further development of this technology is warranted before full release, and further studies are necessary to better characterize the effectiveness of Augmented Reality Assisted Surgery in urologic surgical training.

Introduction Obese patients with penile cancer may have more advanced disease. This study evaluated the association of obesity with penile cancer and the risk of lymph node metastases in patients who underwent inguinal lymphadenectomy. Methods We retrospectively reviewed the charts of 197 penile cancer (PC) patients from January 2000 to December 2011. Seventy underwent inguinal lymphadenectomy. For this subgroup, chi-square analysis evaluated the correlations of sociodemographic, clinical, and pathological variables with the presence of positive inguinal lymph nodes. Patients were divided into normal weight, overweight, and obese categories according to body mass index (BMI). The mean numbers of positive and resected lymph nodes were compared for each BMI category. Results The percentage of overweight men in the Brazilian population and among patients with PC was 52.6% and 42.8%, respectively. For patients who underwent lymphadenectomy, the mean BMIs were 25.9 ± 6. Most patients were white, married, had a lower education level, and had no history of smoking. Partial penectomy was the most frequently performed surgery; lymphovascular invasion occurred in 45.7%, and lymph node metastasis occurred in 52.9% of cases. The mean numbers of resected and positive lymph nodes for normal weight, overweight, and obesity were 21.1 and 2.2, 23.3 and 2.2, and 16.8 and 1.5, respectively. Conclusion Overweight and obesity were less frequently seen in patients with PC than in the Brazilian population. BMI was not a risk factor for developing lymph node metastasis; the only predictive factor for lymph node metastasis was the presence of lymphovascular invasion.

Rapid implementation of telehealth for cancer care during COVID-19 required innovative and adaptive solutions among oncology health care providers and professionals (HPPs). The aim of this qualitative study was to explore oncology HPPs' experiences with telehealth implementation during the COVID-19 pandemic. This study was conducted at Moffitt Cancer Center (Moffitt), an NCI (National Cancer Institute)-Designated Comprehensive Cancer Center. Prior to COVID-19, Moffitt piloted telehealth visits on a limited basis. After COVID-19, Moffitt rapidly expanded telehealth visits. Telehealth visits included real-time videoconferencing between HPPs and patients and virtual check-ins (ie, brief communication with an HPP by telephone only). We conducted semistructured interviews with 40 oncology HPPs who implemented telehealth during COVID-19. The interviews were recorded, transcribed verbatim, and analyzed for themes using Dedoose software (version 4.12). Approximately half of the 40 participants were physicians (n=22, 55%), and one-quarter of the participants were advanced practice providers (n=10, 25%). Other participants included social workers (n=3, 8%), psychologists (n=2, 5%), dieticians (n=2, 5%), and a pharmacist (n=1, 3%). Five key themes were identified: (1) establishing and maintaining patient-HPP relationships, (2) coordinating care with other HPPs and informal caregivers, (3) adapting in-person assessments for telehealth, (4) developing workflows and allocating resources, and (5) future recommendations. Participants described innovative strategies for implementing telehealth, such as coordinating interdisciplinary visits with multiple HPPs and inviting informal caregivers (eg, spouse) to participate in telehealth visits. Health care workers discussed key challenges, such as workflow integration, lack of physical exam and biometric data, and overcoming the digital divide (eg, telehealth accessibility among patients with communication-related disabilities). Participants recommended policy advocacy to support telehealth (eg, medical licensure policies) and monitoring how telehealth affects patient outcomes and health care delivery. To support telehealth growth, implementation strategies are needed to ensure that HPPs and patients have the tools necessary to effectively engage in telehealth. At the same time, cancer care organizations will need to engage in advocacy to ensure that policies are supportive of oncology telehealth and develop systems to monitor the impact of telehealth on patient outcomes, health care quality, costs, and equity.

Immune infiltration is typically quantified using cellular density, not accounting for cellular clustering. Tumor-associated macrophages (TAM) activate oncogenic signaling through paracrine interactions with tumor cells, which may be better reflected by local cellular clustering than global density metrics. Using multiplex immunohistochemistry and digital pathologic analysis we quantified cellular density and cellular clustering for myeloid cell markers in 129 regions of interest from 55 samples from 35 patients with metastatic ccRCC. CD68+ cells were found to be clustered with tumor cells and dispersed from stromal cells, while CD163+ and CD206+ cells were found to be clustered with stromal cells and dispersed from tumor cells. CD68+ density was not associated with OS, while high tumor/CD68+ cell clustering was associated with significantly worse OS. These novel findings would not have been identified if immune infiltrate was assessed using cellular density alone, highlighting the importance of including spatial analysis in studies of immune cell infiltration of tumors. Significance : Increased clustering of CD68+ TAMs and tumor cells was associated with worse overall survival for patients with metastatic ccRCC. This effect would not have been identified if immune infiltrate was assessed using cell density alone, highlighting the importance of including spatial analysis in studies of immune cell infiltration of tumors.

ABSTRACT We describe the novel use of dynamic sentinel node biopsy (DSNB) in five patients with primary urethral squamous cell carcinoma (U-SCC) and no evidence of inguinal node disease across two centers in North America and Europe between 03/2021 and 06/2024. Each of these referral centers sees over 75 cases of penile cancer per year and approximately 10 cases of U-SCC per year. Patients underwent DSNB concomitant to surgical resection of the primary tumor (n=3), or in a deferred manner (n=2), six weeks after primary surgery. In the five DSNBs performed, clinically occult nodal metastasis was discovered in one patient. In this patient DSNB was performed after local recurrence and repeat imaging confirming cN0 status. Only one minor complication with DSNB was observed. Awaiting further investigations in larger series, this study highlights the feasibility of DSNB in primary U-SCC with clinically node negative disease.

ABSTRACT Purpose: There is a bidirectional relationship between chronic kidney disease and the incidence of renal cell carcinoma. Despite the frequency of patients with both chronic kidney disease and renal cell carcinoma, there are limited systematic reviews detailing the nuanced treatment. This review provides comprehensive insights for clinicians for managing chronic kidney disease, and renal cell carcinoma. Methods and Methods: We reviewed published literature that examined either chronic kidney disease and renal cell carcinoma or an indirect contributor of both. Results: We compare and contrast renal cell carcinoma treatment with partial and radical nephrectomies, ablative techniques, and radiation and their impact on glomerular filtration rate, recurrence rate, and contraindications. We discuss when and how to intervene with treatment with emphasis on the delicate balance between eradicating malignancy and preserving renal function. Specifically, we detail the appropriate use of renal biopsies in incidentally discovered tumors, active surveillance, and postoperative surveillance including imaging sensitivity and specificity. We offer insight into the limitations of current systemic therapy, including renal toxicity. Conclusions: Our investigation into the intricate relationship between chronic kidney disease and renal cell carcinoma has many multifaceted challenges for both patients and healthcare providers face. This comprehensive review serves as an extensive synopsis of the current literature and offers patients the best possible long-term renal-based outcomes.

Penile cancer (PC) is a rare malignancy predominantly of squamous cell origin. Approximately 40% of penile tumors are associated with human papillomavirus (HPV) infection. Diagnosing PC remains challenging due to its rarity and variety of clinical presentations. Furthermore, the impact of HPV on the tumor immune microenvironment complicates clinical management, although recent advancements in immune checkpoint inhibitors (ICIs) have shown some efficacy in treating HPV-associated PC. Ongoing research efforts aim to develop oncologic treatments that target HPV-induced cellular modifications. Additionally, novel therapeutic vaccines and adoptive T-cell therapies targeting HPV oncoproteins represent emerging treatment modalities. Our review highlights the complex interplay between HPV and penile carcinogenesis, emphasizing its epidemiology, etiology, clinicopathological characteristics, and potential therapeutic implications.