Improving Quality of Life and Psychosocial Health for Penile Cancer Survivors: A Narrative Review.

Treatment of penile cancer (PC) focuses on organ preservation, employing various surgical and non-surgical approaches. These interventions may lead to disfigurement, impacting patients' functional outcomes and psychosocial well-being. We reviewed studies related to penile health and PC up to February 2024, limited to studies published in English. Studies employing health-related quality of life (HRQoL) assessments have identified a detrimental association between aggressive treatment and overall health status, physical functioning, and relationships. In contrast, organ-sparing demonstrates improved measures related to HRQoL and sexual function. Assessment through validated questionnaires reveals diverse voiding outcomes, and varying impacts on QoL and sexual activity, emphasizing the necessity for multidisciplinary personalized care. Studies highlight substantial variations in sexual function, with patients reporting adaptations, reduced satisfaction, and concerns about body image and sexual well-being. Furthermore, unmet needs include challenges in patient-clinician communication, obtaining information, and accessing psychosocial support. Patient experiences underscore the importance of timely diagnosis, treatment access, and addressing psychological consequences. Organ-sparing approaches have higher QoL preservation and sexual function. Individualized support, including sexual therapy, support groups, and family counseling, is essential for post-treatment rehabilitation. Timely diagnosis and comprehensive care are paramount in addressing the multifaceted impact of PC on patients and families.

Neighborhood social vulnerability and disparities in time to kidney cancer surgical treatment and survival in Arizona.

BACKGROUND: Hispanics and American Indians (AI) have high kidney cancer incidence and mortality rates in Arizona. This study assessed: (1) whether racial and ethnic minority patients and patients from neighborhoods with high social vulnerability index (SVI) experience a longer time to surgery after clinical diagnosis, and (2) whether time to surgery, race and ethnicity, and SVI are associated with upstaging to pT3/pT4, disease-free survival (DFS), and overall survival (OS). METHODS: Arizona Cancer Registry (2009-2018) kidney and renal pelvis cases (n = 4592) were analyzed using logistic regression models to assess longer time to surgery and upstaging. Cox-regression hazard models were used to test DFS and OS. RESULTS: Hispanic and AI patients with T1 tumors had a longer time to surgery than non-Hispanic White patients (median time of 56, 55, and 45 days, respectively). Living in neighborhoods with high (≥75) overall SVI increased odds of a longer time to surgery for cT1a (OR 1.54, 95% CI: 1.02-2.31) and cT2 (OR 2.32, 95% CI: 1.13-4.73). Race and ethnicity were not associated with time to surgery. Among cT1a patients, a longer time to surgery increased odds of upstaging to pT3/pT4 (OR 1.95, 95% CI: 0.99-3.84). A longer time to surgery was associated with PFS (HR 1.52, 95% CI: 1.17-1.99) and OS (HR 1.63, 95% CI: 1.26-2.11). Among patients with cT2 tumor, living in high SVI neighborhoods was associated with worse OS (HR 1.66, 95% CI: 1.07-2.57). CONCLUSIONS: High social vulnerability was associated with increased time to surgery and poor survival after surgery.

Prostate Cancer Disparities in Metastatic and Treatment Status for Hispanic Americans Based on Country of Origin Compared to Non-Hispanic Whites Using the National Cancer Database.

INTRODUCTION: Among Hispanic-American (HA) men, prostatic cancer (PCa) accounts for nearly one-quarter of the total cancer burden. We sought to identify differences in PCa presentation and treatment status for HA subgroups based on country/region of origin. MATERIAL AND METHODS: Using the National Cancer Database, we identified patients with histologically confirmed prostate adenocarcinoma with reported race/ethnicity, clinical staging, Gleason score ≥ 6, and PSA level at diagnosis from 2010 to 2016. HAs were divided into 4 subgroups: Mexican, Puerto Ricans, Cubans, and Central/South Americans. Non-Hispanic White (NHW) men were used as a reference group. Statistical analysis was derived from the Kruskal-Wallis test for continuous variables and χ2 test for categorical variables. Models were constructed to evaluate the association of Hispanic country of origin with metastatic presentation and treatment status. RESULTS: A total of 428,829 patients were included, with 5625 (1.3%) classified as HA. Within the Hispanic group, 2880 (51.2%) were Mexican, 999 (17.8%) Puerto Rican, 477 (8.5%) Cuban, and 1269 (22.6%) South/Central American. Mexican men presented with higher median PSA, more Gleason 8 to 10 disease, and higher rates of metastatic presentation compared to NHW and other HA subgroups (all, p < .01). Metastatic rates over the study period for Mexican, Puerto Rican, Cuban, and South/Central Americans were 6.4 (±1.2), 5.3 (±3.0), 3.2 (±2.0), and 4.6% (±1.7), respectively (p = .01). Treatment rates were 89.1, 89.6, 92.4, and 89.3% for Mexican, Puerto Rican, Cuban, and South/Central Americans, respectively (p = .19). Mexican men had higher odds of initial metastatic presentation (OR: 1.32; 95%CI: 1.07-1.63, p = .01) but lower odds of receiving treatment (0.68; 0.55-0.85, p < .01). CONCLUSION: Men of Mexican origin presented with more advanced PCa when compared to NHW and other Hispanic subgroups. Our results warrant further investigation into potential biological factors affecting Hispanic patients as well as the identification of treatment barriers for this vulnerable population.

Analysis of prognostic factors in patients diagnosed with bladder cancer complicated by hemorrhage treated by drug-eluting bead embolization.

Background: Transcatheter bladder arterial chemoembolization (TACE) is an alternative treatment used to control bladder cancer (BC) with bleeding, especially in older adult patients with comorbidities. This retrospective observational study evaluated the effect and prognostic factors of transcatheter drug-eluting bead (DEB) embolization in patients with advanced BC. Methods: We assessed 39 patients diagnosed with BC with hemorrhage who were either inoperable or unwilling to undergo surgery at our hospital between January 2018 and October 2022. All patients underwent TACE by DEB loaded with epirubicin and imaging scans after 2 months to evaluate the curative effect according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) standard to determine treatment. Re-examination and follow-up were performed every 3-6 months to observe hematuria recurrence and the curative effect. Results: A total of 95 interventional treatments were performed in 39 patients, and all participants achieved complete hemostasis within 5 days after the first intervention. Computed tomography or magnetic resonance imaging showed that the total effective rate [complete response (CR) + partial response (PR)] was 64.1%, and the disease benefit rate (CR +PR + stable disease) was 79.5%. A total of 30 patients (76.9%) had no hematuria recurrence. Logistic regression analysis indicated that the type of blood supply in BC may relate to whether the patients benefited from the intervention. Hematuria recurrence was significantly associated with the total number of tumors and the type of blood supply (P<0.05). Conclusions: Superselective embolization of bladder arteries with DEB can be used to treat BC with hemorrhage. However, hypovascular tumor blood supply may result in poor postoperative efficacy and hematuria recurrence. Additionally, multiple bladder tumors may be a risk factor for hematuria recurrence.

Gemcitabine as first-line therapy for high-grade non-muscle invasive bladder cancer: results from a tertiary center in the contemporary BCG-shortage era.

Background: To evaluate the safety profile and efficacy of intravesical gemcitabine as first-line adjuvant therapy for non-muscle invasive bladder cancer (NMIBC) in the setting of ongoing Bacillus Calmette-Guérin (BCG) shortage. Methods: We performed an institutional, retrospective review of patients treated with intravesical gemcitabine induction and maintenance therapy from March 2019 to October 2021. Patients with intermediate or high-risk NMIBC who were BCG-naïve or experienced a high-grade (HG) recurrence after 12 months since the last dose of BCG were included in the analysis. The primary endpoint was complete response (CR) rate at the 3-month visit. Secondary endpoints were recurrence-free survival (RFS) and assessment of adverse events. Results: A total of 33 patients were included. All had HG disease and 28 (84.8%) were BCG-naive. The median follow-up was 21.4 months (range, 4.1-39.4). Tumor stages were cTa in 39.4%, cT1 in 54.5%, and cTis in 6.1% of patients. Most patients (90.9%) were in the AUA high-risk category. The 3-month CR was 84.8%. Among patients who achieved CR with adequate follow-up, 86.9% (20/23) remained disease-free at 6 months. The 6-month and 12-month RFS were 87.2% and 76.5%, respectively. The estimated median RFS was not reached. Approximately 78.8% of patients were able to complete full induction. Common adverse events (incidence ≥10%) included dysuria and fatigue/myalgia. Conclusions: Intravesical gemcitabine for intermediate and high-risk NMIBC in areas where BCG supply is limited was safe and feasible at short-term follow-up. Larger prospective studies are needed to better ascertain the oncologic efficacy of gemcitabine.

Gender, Racial and Ethnic Differences in Pathologic Response Following Neoadjuvant Chemotherapy for Bladder Cancer Patients.

OBJECTIVE: To evaluate trends and racial variations of pathologic complete response (CR) in patients with muscle-invasive bladder cancer undergoing cystectomy. MATERIALS AND METHODS: The National Cancer Database was queried for patients with non-metastatic muscle-invasive bladder cancer who underwent neoadjuvant chemotherapy and surgery. The primary endpoints, CR and mortality, were evaluated using the Cochran-Armitage test, multivariable regression, and Kaplan-Meier analyses. RESULTS: The cohort comprised 9955 patients. Non-Hispanic Black (NHB) patients were younger (P < .001), had a higher clinical tumor (P < .001), and had higher clinical node (P = .029) stages at presentation. CR for non-Hispanic White (NHW), NHB, and Hispanic patients were 12.6%, 10.1%, and 11.8%, respectively (P = .030). There was a significant increase in CR trends for NHW patients (P < .001) and increases in NHB (P = .311) and Hispanic patients (P = .236). On multivariable analysis, NHW females had lower odds of achieving CR (odds ratio: 0.83, 95% CI: 0.71-0.97); however, NHB males (hazard ratio: 1.21, 1.01-1.44) and NHB females (hazard ratio: 1.25, 1.03-1.53) had higher overall mortality in adjusted analysis. Survival differences were not observed in patients who achieved CR, regardless of racial background; however, for those with residual disease, the 2-year survival probabilities were 60.7%, 62.5%, and 51.1% for NHW, HW, and NHB patients, respectively (log-rank P = .010). CONCLUSION: Our findings revealed differences in chemotherapy response based on gender and race or ethnicity. The CR trends for all racial or ethnic groups increased over time. However, Black patients were found to have worse survival, particularly when residual disease was present. Clinical studies with more underrepresented minorities are needed to verify biological differences in response to neoadjuvant chemotherapy.

Targeting NEDDylation is a Novel Strategy to Attenuate Cisplatin-induced Nephrotoxicity.

Although cisplatin remains a backbone of standard-of-care chemotherapy regimens for a variety of malignancies, its use is often associated with severe dose-limiting toxicities (DLT). Notably, 30%-40% of patients treated with cisplatin-based regimens are forced to discontinue treatment after experiencing nephrotoxicity as a DLT. New approaches that simultaneously prevent renal toxicity while improving therapeutic response have the potential to make a major clinical impact for patients with multiple forms of cancer. Here, we report that pevonedistat (MLN4924), a first-in-class NEDDylation inhibitor, alleviates nephrotoxicity and synergistically enhances the efficacy of cisplatin in head and neck squamous cell carcinoma (HNSCC) models. We demonstrate that pevonedistat protects normal kidney cells from injury while enhancing the anticancer activity of cisplatin through a thioredoxin-interacting protein (TXNIP)-mediated mechanism. Cotreatment with pevonedistat and cisplatin yielded dramatic HNSCC tumor regression and long-term animal survival in 100% of treated mice. Importantly, the combination decreased nephrotoxicity induced by cisplatin monotherapy as evidenced by the blockade of kidney injury molecule-1 (KIM-1) and TXNIP expression, a reduction in collapsed glomeruli and necrotic cast formation, and inhibition of cisplatin-mediated animal weight loss. Inhibition of NEDDylation represents a novel strategy to prevent cisplatin-induced nephrotoxicity while simultaneously enhancing its anticancer activity through a redox-mediated mechanism. Significance: Cisplatin therapy is associated with significant nephrotoxicity, which limits its clinical use. Here we demonstrate that NEDDylation inhibition with pevonedistat is a novel approach to selectively prevent cisplatin-induced oxidative damage to the kidneys while simultaneously enhancing its anticancer efficacy. Clinical evaluation of the combination of pevonedistat and cisplatin is warranted.

Concomitant vs Staged Therapeutic Inguinal Lymphadenectomy in Clinically Node Positive Penile Squamous Cell Carcinoma: Does It Make a Difference?

PURPOSE: Inguinal lymph node dissection within 3 months of primary tumor resection in penile cancer has been associated with longer recurrence-free and cancer-specific survival. However, the optimal timing and effect of lymphadenectomy performed concurrently at the time of primary lesion management on oncologic outcomes in clinically lymph node positive penile squamous cell carcinoma remains unknown. MATERIALS AND METHODS: An international, multicenter cohort of 966 penile cancer cases was queried for penile squamous cell carcinoma management after the year 2000, clinically lymph node positive status, and performance of penile surgery and inguinal lymph node dissection. Cohorts were stratified as concomitant if inguinal lymph node dissection and penile surgery occurred on the same date or staged when inguinal lymph node dissection was performed after penile resection. Rates and patterns of penile squamous cell carcinoma recurrence were reported. Distant recurrence-free, cancer-specific, and overall survival were estimated using Kaplan-Meier analyses and groups compared with log-rank testing. RESULTS: Of 253 contemporary men with clinically lymph node positive penile squamous cell carcinoma, 96 (38%) underwent concomitant inguinal lymph node dissection and 157 (62%) had inguinal lymph node dissection performed in a staged manner. Penile cancer was most likely to recur distantly (19%) followed by in the groin (14%) or pelvis (5%). There were no differences in distant recurrence-free, cancer-specific, or overall survival between management strategies. Multivariable analysis adjusting for stage, treatment center, and perioperative chemoradiation also demonstrated no recurrence-free, cancer-specific, or overall survival benefit between management strategies. CONCLUSIONS: Inguinal lymph node dissection performed concurrently with excision of the penile tumor for clinically node positive penile squamous cell carcinoma is not associated with differences in recurrence-free, cancer-specific, or overall survival compared to staged lymph node dissection.

Current Landscape of Immune Checkpoint Inhibitors for Metastatic Urothelial Carcinoma: Is There a Role for Additional T-Cell Blockade?

Urothelial carcinoma (UC) is the most common form of bladder cancer (BC) and is the variant with the most immunogenic response. This makes urothelial carcinoma an ideal candidate for immunotherapy with immune checkpoint inhibitors. Key immune checkpoint proteins PD-1 and CTLA-4 are frequently expressed on T-cells in urothelial carcinoma. The blockade of this immune checkpoint can lead to the reactivation of lymphocytes and augment the anti-tumor immune response. The only immune checkpoint inhibitors that are FDA-approved for metastatic urothelial carcinoma target the programmed death-1 receptor and its ligand (PD-1/PD-L1) axis. However, the overall response rate and progression-free survival rates of these agents are limited in this patient population. Therefore, there is a need to find further immune-bolstering treatment combinations that may positively impact survival for patients with advanced UC. In this review, the current immune checkpoint inhibition treatment landscape is explored with an emphasis on combination therapy in the form of PD-1/PD-L1 with CTLA-4 blockade. The investigation of the current literature on immune checkpoint inhibition found that preclinical data show a decrease in tumor volumes and size when PD-1/PD-L1 is blocked, and similar results were observed with CTLA-4 blockade. However, there are limited investigations evaluating the combination of CTLA-4 and PD-1/PD-L1 blockade. We anticipate this review to provide a foundation for a deeper experimental investigation into combination immune checkpoint inhibition therapy in metastatic urothelial carcinoma.

Importance of Addressing the Psychosocial Impact of Penile Cancer on Patients and Their Families.

OBJECTIVE: In this article we review the quality of life and the psychosocial and functional outcomes experienced by patients and their partners following penile cancer diagnosis and treatment. DATA SOURCES: A literature search for primary articles related to patient reported outcomes following penile cancer treatment was conducted using the electronic database PubMed. CONCLUSION: Penile cancer is a rare malignancy in the United States, and it carries an excellent prognosis if diagnosed early. However, increased survivorship carries devastating long-term consequences on the mental health of patients and their families. Factors impacting the quality of life of patients include sexual dysfunction, cosmetic changes, voiding dysfunction, depression, and anxiety. Treatment modalities vary depending on the extent of the cancer but include medical, interventional, and surgical options. IMPLICATIONS FOR NURSING PRACTICE: The multidisciplinary team can support patients and their partners to develop, test and deliver posttreatment survivorship interventions to optimize psychosocial well-being and quality of life outcomes for this rare disease.

Renal Cell Carcinoma Surgical Treatment Disparities in American Indian/Alaska Natives and Hispanic Americans in Arizona.

American Indians/Alaska Natives (AI/AN) and Hispanic Americans (HA) have higher kidney cancer incidence and mortality rates compared to non-Hispanic Whites (NHW). Herein, we describe the disparity in renal cell carcinoma (RCC) surgical treatment for AI/AN and HA and the potential association with mortality in Arizona. A total of 5111 stage I RCC cases diagnosed between 2007 and 2016 from the Arizona Cancer Registry were included. Statistical analyses were performed to test the association of race/ethnicity with surgical treatment pattern and overall mortality, adjusting for patients' demographic, healthcare access, and socioeconomic factors. AI/AN were diagnosed 6 years younger than NHW and were more likely to receive radical rather than partial nephrectomy (OR 1.49 95% CI: 1.07-2.07) compared to NHW. Mexican Americans had increased odds of not undergoing surgical treatment (OR 1.66, 95% CI: 1.08-2.53). Analysis showed that not undergoing surgical treatment and undergoing radical nephrectomy were statistically significantly associated with higher overall mortality (HR 1.82 95% CI: 1.21-2.76 and HR 1.59 95% CI: 1.30-1.95 respectively). Mexican Americans, particularly U.S.-born Mexican Americans, had an increased risk for overall mortality and RCC-specific mortality even after adjusting for neighborhood socioeconomic factors and surgical treatment patterns. Although statistically not significant after adjusting for neighborhood-level socioeconomic factors and surgical treatment patterns, AI/AN had an elevated risk of mortality.

Impacts of Neighborhood Characteristics and Surgical Treatment Disparities on Overall Mortality in Stage I Renal Cell Carcinoma Patients.

Racial/ethnic minority groups in the United States have high renal cell carcinoma (RCC) mortality rates. This study assessed surgical treatment disparities across racial/ethnic groups and impacts of neighborhood socioeconomic characteristics on surgical treatments and overall mortality. Stage I RCC patients diagnosed between 2004 and 2016 from National Cancer Database were included (n = 238,141). We assessed differences in associations between race/ethnicity and treatment patterns using logistic regression and between race/ethnicity and overall mortality using Cox regression with and without neighborhood characteristics in the regression models. When compared to non-Hispanic Whites (NHWs), American Indians/Alaska Natives and non-Hispanic Blacks (NHBs) were more likely not to receive surgical care and all racial/ethnic minority groups had significantly increased odds of undergoing radical rather than partial nephrectomy, even after adjusting for neighborhood characteristics. Including surgical treatment and neighborhood factors in the models slightly attenuated the association, but NHBs had a significantly increased risk of overall mortality. NHBs who underwent radical nephrectomy had an increased risk of mortality (HR 1.15, 95% CI: 1.08-1.23), but not for NHBs who underwent partial nephrectomy (HR 0.92, 95% CI: 0.84-1.02). Neighborhood factors were associated with surgical treatment patterns and overall mortality in both NHBs and NHWs. Neighborhood socioeconomic factors may only partly explain RCC disparities.

National trends and survival outcomes of penile squamous cell carcinoma based on human papillomavirus status.

BACKGROUND: There are no series evaluating penile squamous cell carcinoma (pSCC) based on human papillomavirus (HPV) infection. Herein, we present national registry data on clinical and survival outcomes for pSCC based on HPV status. METHODS: We performed a retrospective review of 1224 pSCC patients with known HPV staining from the National Cancer Database. Patients with cM1 disease, those who did not receive treatment, or had missing follow-up data were excluded. Logistic regression identified factors associated with locally aggressive disease. Univariable, multivariable, and inverse probability of treatment weighting (IPTW)-Cox proportional hazard modeling were used to assess hazard ratios (HR) associated with overall survival (OS). RESULTS: After exclusion criteria, we identified 825 cases of which 321 (38.9%) were HPV positive. The HPV-positivity rate did not significantly change by year. HPV-positive patients were younger, had lower Charlson-Deyo performance score, and resided in areas with both lower median household income and lower school education completion. HPV-positive tumors presented with lower American Joint Committee on Cancer clinical T-stage (cT), poorer differentiation, lower rates of lymphovascular invasion (LVI), but more node-positive disease (cN+). For those who underwent lymph node surgery, there were no differences in final pathologic stage, upstaging, or presence of extranodal extension. Only tumor differentiation, LVI, and performance score were independent predictors for locally aggressive disease. HPV status was not a predictor of OS (IPTW-HR:0.89, p = 0.13). CONCLUSIONS: In the largest series evaluating pSCC based on HPV status, HPV-positive tumors were associated with lower cT stages, less LVI, but more cN + disease. More studies on prognostic factors are needed, and time may still be immature to use HPV information for risk stratification.

Racial and Ethnic Disparities in Preoperative Surgical Wait Time and Renal Cell Carcinoma Tumor Characteristics.

Racial/ethnic minority groups have a disproportionate burden of kidney cancer. The objective of this study was to assess if race/ethnicity was associated with a longer surgical wait time (SWT) and upstaging in the pre-COVID-19 pandemic time with a special focus on Hispanic Americans (HAs) and American Indian/Alaska Natives (AIs/ANs). Medical records of renal cell carcinoma (RCC) patients who underwent nephrectomy between 2010 and 2020 were retrospectively reviewed (n = 489). Patients with a prior cancer diagnosis were excluded. SWT was defined as the date of diagnostic imaging examination to date of nephrectomy. Out of a total of 363 patients included, 34.2% were HAs and 8.3% were AIs/ANs. While 49.2% of HA patients experienced a longer SWT (≥90 days), 36.1% of Non-Hispanic White (NHW) patients experienced a longer SWT. Longer SWT had no statistically significant impact on tumor characteristics. Patients with public insurance coverage had increased odds of longer SWT (OR 2.89, 95% CI: 1.53-5.45). Public insurance coverage represented 66.1% HA and 70.0% AIs/ANs compared to 56.7% in NHWs. Compared to NHWs, HAs had higher odds for longer SWT in patients with early-stage RCC (OR, 2.38; 95% CI: 1.25-4.53). HAs (OR 2.24, 95% CI: 1.07-4.66) and AIs/ANs (OR 3.79, 95% CI: 1.32-10.88) had greater odds of upstaging compared to NHWs. While a delay in surgical care for early-stage RCC is safe in a general population, it may negatively impact high-risk populations, such as HAs who have a prolonged SWT or choose active surveillance.

Impact of radiation therapy on perineal urethrostomy for penile cancer.

OBJECTIVE: A lack of demonstrated clinical benefit precludes radiotherapy (RT) from being recommended for pN1/pN2 penile cancer (PeCa) lesions; but it may be recommended in case of extranodal (pN3) disease or for positive resection margins. Perineal urethrostomy (PU) is a technique of urinary diversion in patients with PeCa requiring total or subtotal penectomy as primary therapy. Prior studies suggest PU failure rates of up to 30%, without specific mention of the potential role of RT. When RT is delivered for PeCa it is usually to the pre-pubic fat, groin and lateral pelvis, and not to the region of the PU. Here we describe the role of perioperative RT in a large, multi-institutional registry of PU for PeCa. METHODS: In our cohort, 299 patients from seven international, high-volume centers in Belgium, Brazil, China, Netherlands, United Kingdom and the United States underwent PU as urinary diversion for PeCa between 2000 and 2020. Demographic and clinicopathologic characteristics were reviewed. RESULTS: Median patient age was 67 years and median follow-up was 19 months. Seven patients (2.3%) received pre-operative RT; six of them with chemotherapy. 37 received RT post-operatively, 21 (57%) with chemotherapy. Stenosis of the PU occurred in 35 (12%) of the total population. The majority of these patients (74%) required surgical revision at a median of 6.1 months post-operatively. RT delivery was neither significantly related to PU stenosis (p = 0.16) or to subsequent revision (p = 0.75). CONCLUSION: Receipt of RT was not significantly associated with increased stenosis risk in PeCa patients who underwent PU.