Differences in the expression of the phosphatase PTP-1B in patients with localized prostate cancer with and without adverse pathological features.

Introduction: Patients with adverse pathological features (APF) at radical prostatectomy (RP) for prostate cancer (PC) are candidates for adjuvant treatment. Clinicians lack reliable markers to predict these APF preoperatively. Protein tyrosine phosphatase 1B (PTP-1B) is involved in migration and invasion of PC, and its expression could predict presence of APF. Our aim was to compare PTP-1B expression in patients with and without APF, and to explore PTP-1B expression as an independent prognostic factor. Methods: Tissue microarrays (TMAs) were constructed using RP archival specimens for immunohistochemical staining of PTP-1B; expression was reported with a standardized score (0-9). We compared median PTP-1B score between cases with and without APF. We constructed two logistic regression models, one to identify the independence of PTP-1B score from biologically associated variables (metformin use and type 2 diabetes mellitus [T2DM]) and the second to seek independence of known risk factors (Gleason score and prostate specific antigen [PSA]). Results: A total of 73 specimens were suitable for TMA construction. Forty-four (60%) patients had APF. The median PTP-1B score was higher in those with APF: 8 (5-9) vs 5 (3-8) (p=0.026). In the logistic regression model including T2DM and metformin use, the PTP-1B score maintained statistical significance (OR 1.21, 95% CI 1.01-1.45, p=0.037). In the model including PSA and Gleason score; the PTP-1B score showed no independence (OR 1.68, 95% CI 0.97-1.41, p=0.11). The area under the curve to predict APF for the PTP-1B score was 0.65 (95% CI 0.52-0.78, p=0.03), for PSA+Gleason 0.71 (95% CI 0.59-0.82, p=0.03), and for PSA+Gleason+PTP-1B score 0.73 (95% CI 0.61-0.84, p=0.001). Discussion: Patients with APF after RP have a higher expression of PTP-1B than those without APF, even after adjusting for T2DM and metformin exposure. PTP-1B has a good accuracy for predicting APF but does not add to known prognostic factors.

Envisioning Academic Global Oncologists: Proposed Competencies for Global Oncology Training From ASCO.

Recognizing the rising incidence, prevalence, and mortality of cancer in low- and middle-resource settings, as well as the increasingly international profile of its membership, ASCO has committed to expanding its engagement at a global level. In 2017, the ASCO Academic Global Oncology Task Force sought to define the potential role for ASCO in supporting global oncology as an academic field. A set of recommendations to advance the status of global oncology as an academic discipline were created through a consensus-based process involving participation by a diverse group of global oncology and global health practitioners; these recommendations were then published. The recommendations included developing a set of global oncology competencies for trainees and faculty interested in a career in academic global oncology. Here, we describe the global oncology competencies developed by this task force. These competencies consist of knowledge and skills needed in general global health as well as cancer-specific care and research, including understanding global cancer health disparities, defining unique resources and needs in low- and middle-resource settings, and promoting international collaboration. Although the competencies were originally developed for US training programs, they are intended to be widely applicable globally. By formalizing the training of oncologists and supporting career pathways in the field of global oncology, we can make progress in achieving global equity in cancer care and control.

Papillary Renal Cell Carcinoma: Outcomes for Patients Receiving First-line Immune-based Combinations or Tyrosine Kinase Inhibitors from the ARON-1 Study.

BACKGROUND AND OBJECTIVE: Papillary renal cell carcinoma (pRCC) is the most frequent histological subtype of non-clear cell RCC (nccRCC). Owing to the heterogeneity of nccRCC, patients are often excluded from large phase 3 trials focused on clear cell RCC, so treatment options for nccRCC remain limited. Our aim was to investigate the efficacy of first-line treatment with tyrosine kinase inhibitors (TKIs) or immuno-oncology (IO)-based combinations in patients with pRCC. METHODS: We performed a multicenter retrospective analysis of real-world data collected for patients with advanced pRCC treated in 40 centers in 12 countries as part of the ARON-1 project (NCT05287464). The primary endpoints were overall survival (OS), progression-free survival (PFS), the overall response rate (ORR), and time to second progression (PFS2). OS, PFS, and PFS2 were estimated using the Kaplan-Meier method and results were compared between the treatment groups using a log-rank test. Univariate and multivariable analyses were carried out using Cox proportional-hazard models. KEY FINDINGS AND LIMITATIONS: We included 200 patients with metastatic pRCC, of whom 73 were treated with IO-based combinations and 127 with TKIs. Median OS was 22.5 mo in the TKI group 28.8 mo in the IO group (p = 0.081). Median PFS was 6.4 mo in the TKI group and 17.4 mo in the IO group (p < 0.001). The ORR was higher in the IO group than in the TKI group (41% vs 27%; p = 0.037). CONCLUSIONS AND CLINICAL IMPLICATIONS: Our results show that IO-based combinations have superior efficacy outcomes to TKIs for first-line treatment of metastatic pRCC. PATIENT SUMMARY: The ARON-1 project collects clinical data for patients with kidney cancer treated in multiple centers worldwide to assess outcomes in the real-world setting. We analyzed data for patients with metastatic kidney cancer of a specific subtype to evaluate the efficacy of different first-line treatments. Patients treated with immune-based combinations had better outcomes than patients treated with tyrosine kinase inhibitors.

Efficacy of immune checkpoint inhibitors combinations as first-line systemic treatment in patients with advanced urothelial carcinoma: A systematic review and network meta-analysis.

BACKGROUND: Combinations of immune checkpoint inhibitors (ICI) with platinum-based chemotherapy (PlatinumCT) or with another ICI in the first-line setting for patients with metastatic urothelial carcinoma (mUC) have mixed results. METHODS: Records were searched electronically from January 2019 to January 2024. A meta-analysis was performed to evaluate OS, progression-free survival (PFS), and overall response rate (ORR). RESULTS: Immune-based combinations were associated with an OS (HR: 0.75; 95% CI: 0.61-0.92; p < 0.001; I2= 84.1%) and PFS benefit in the intention-to-treat population (HR: 0.67; 95%CI: 0.51-0.89; p < 0.001; I2 = 89.7%). There was no ORR improvement with immune-based combinations (HR: 1.36; 95% CI:0.84-2.20; p < 0.001; I2 = 92.6%). CONCLUSION: This systematic review and study-level meta-analysis demonstrated that the immune-based combinations in first-line treatment for patients with mUC are associated with survival benefit.

Management of Metastatic Urothelial Carcinoma in Emerging Markets (EM): An Expert Opinion.

Urothelial carcinoma (UC) is the 10th most common cancer globally with an almost 4 times higher prevalence in men. The main risk factors for development of urothelial carcinoma are advanced age, smoking, arsenic contamination, exposure to carcinogens. Metastatic urothelial carcinoma (mUC) has overall poor prognosis with a 5-year overall survival rate of only < 5%. The standard of care comprises of platinum-based chemotherapy, but the responses are often not sustained. A working group was established with an objective to discuss the most recent clinical data on the genitourinary tumors of interest and comprised of experts across Latin America, Emerging Asia (except China, Japan, and South Korea), Africa, and the Middle East (known as Emerging Markets or EM). There is an evident disparity in terms of uneven mortality and incidence rate distribution among various regions. There is a lack and/or insufficient data on epidemiology, treatment, and outcomes in the EM. The lack of registries impacts the healthcare decisions and the lower incidence from the region might not be reflective of the true disease burden. The treatment outcomes of mUC can be improved by understanding the current disease burden and treatment approach of mUC and identifying the gaps and challenges associated with management. Hence, a literature review was developed to summarize the current disease burden and treatment approach of mUC across EM. The review also highlights the unmet needs for mUC management in EM and suggests a way forward to improve the current situation in order to better serve the patients.

Latin American Consensus for the Evaluation and Treatment of Patients With Metastatic/Locally Advanced Urothelial Carcinoma.

PURPOSE: Urothelial cancer accounts for approximately 3% of new cancer cases worldwide, with a high burden of disease in countries with medium and low human development indexes where its incidence and mortality are increasing. The purpose of this consensus is to develop statements on the evaluation and treatment of locally advanced and metastatic urothelial carcinoma that would further guide the clinical practice in Latin America. METHODS: A systematic review of the literature was conducted by an independent team of methodologists. Then, a modified Delphi method was developed with clinical specialists from different Latin American countries. RESULTS: Forty-two consensus statements, based on evidence, were developed to address the staging, the evaluation (suitability for chemotherapy, risk assessment, and biomarkers), and systemic treatment (first-line and subsequent therapies) of locally advanced or metastatic urothelial carcinoma. The statements made in this consensus are suggested practice recommendations in the Latin American context; however, the importance of a complete and individualized patient evaluation as a guide for therapeutic selection is highlighted. The availability and affordability of support tools for the evaluation of the disease, as well as specific therapies, may limit the application of the best practices suggested. RECOMMENDATIONS: Therapeutic decisions need to be tailored to the context-specific clinical setting and availability of resources. Local research is promoted to improve outcomes for patients with this challenging cancer in Latin America.

Real-world Outcome of Patients with Advanced Renal Cell Carcinoma and Intermediate- or Poor-risk International Metastatic Renal Cell Carcinoma Database Consortium Criteria Treated by Immune-oncology Combinations: Differential Effectiveness by Risk Group?

BACKGROUND: Renal c carcinoma (RCC) is one of the most common urinary cancers worldwide, with a predicted increase in incidence in the coming years. Immunotherapy, as a single agent, in doublets, or in combination with anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs), has rapidly become a cornerstone of the RCC therapeutic scenario, but no head-to-head comparisons have been made. In this setting, real-world evidence emerges as a cornerstone to guide clinical decisions. OBJECTIVE: The objective of this retrospective study was to assess the outcome of patients treated with first-line immune combinations or immune oncology (IO)-TKIs for advanced RCC. DESIGN, SETTING, AND PARTICIPANTS: Data from 930 patients, 654 intermediate risk and 276 poor risk, were collected retrospectively from 58 centers in 20 countries. Special data such as sarcomatoid differentiation, body mass index, prior nephrectomy, and metastatic localization, in addition to biochemical data such as hemoglobin, platelets, calcium, lactate dehydrogenase, neutrophils, and radiological response by investigator's criteria, were collected. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. The median follow-up was calculated by the inverse Kaplan-Meier method. RESULTS AND LIMITATIONS: The median follow-up time was 18.7 mo. In the 654 intermediate-risk patients, the median OS and PFS were significantly longer in patients with the intermediate than in those with the poor International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria (38.9 vs 17.3 mo, 95% confidence interval [CI] p < 0.001, and 17.3 vs 11.6 mo, 95% CI p < 0.001, respectively). In the intermediate-risk subgroup, the OS was 55.7 mo (95% CI 31.4-55.7) and 40.2 mo (95% CI 29.6-51.6) in patients treated with IO + TKI and IO + IO combinations, respectively (p = 0.047). PFS was 30.7 mo (95% CI 16.5-55.7) and 13.2 mo (95% CI 29.6-51.6) in intermediate-risk patients treated with IO + TKI and IO + IO combinations, respectively (p < 0.001). In the poor-risk subgroup, the median OS and PFS did not show a statistically significant difference between IO + IO and IO + TKI. Our study presents several limitations, mainly due to its retrospective nature. CONCLUSIONS: Our results showed differences between the IO + TKI and IO + IO combinations in intermediate-risk patients. A clear association with longer PFS and OS in favor of patients who received the IO + TKI combinations compared with the IO-IO combination was observed. Instead, in the poor-risk group, we observed no significant difference in PFS or OS between patients who received different combinations. PATIENT SUMMARY: Renal cancer is one of the most frequent genitourinary tumors. Treatment is currently based on immunotherapy combinations or immunotherapy with tyrosine kinase inhibitors, but there are no comparisons between these.In this study, we have analyzed the clinical course of 930 patients from 58 centers in 20 countries around the world. We aimed to analyze the differences between the two main treatment strategies, combination of two immunotherapies versus immunotherapy + antiangiogenic therapy, and found in real-life data that intermediate-risk patients (approximately 60% of patients with metastatic renal cancer) seem to benefit more from the combination of immunotherapy + antiangiogenic therapy than from double immunotherapy. No such differences were found in poor-risk patients. This may have important implications in daily practice decision-making for these patients.

Impact of healthcare inequities on survival in Mexican patients with metastatic renal cell carcinoma.

Introduction: The survival of patients with metastatic renal cell carcinoma (mRCC) has improved dramatically due to novel systemic treatments. However, mRCC mortality continues to rise in Latin America. Methods: A retrospective, multicenter study of patients diagnosed with mRCC between 2010-2018 in Mexico City was conducted. The aim of the study was to evaluate the impact of healthcare insurance on access to treatment and survival in patients with mRCC. Results: Among 924 patients, 55.4%, 42.6%, and 1.9% had no insurance (NI), social security, (SS) and private insurance (PI), respectively. De novo metastatic disease was more common in NI patients (70.9%) compared to SS (47.2%) and PI (55.6%) patients (p<0.001). According to IMDC Prognostic Index, 20.2% were classified as favorable, 49% as intermediate, and 30.8% as poor-risk disease. Access to systemic treatment differed by healthcare insurance: 36.1%, 99.5%, and 100% for the NI, SS, and PI patients, respectively (p<0.001). NI patients received fewer lines of treatment, with 24.8% receiving only one line of treatment (p<0.001). Median overall survival (OS) was 13.9 months for NI, 98.9 months for SS, and 147.6 months for NI patients (p<0.001). In multivariate analysis, NI status, brain metastases, sarcomatoid features, bone metastases, no treatment were significantly associated with worse OS. Conclusion: OS in mRCC was affected by insurance availability in this resource-limited cohort of Mexican patients. These results underscore the need for effective strategies to achieve equitable healthcare access in an era of effective, yet costly systemic treatments.

Geographical differences in the management of metastatic de novo renal cell carcinoma in the era of immune-combinations.

BACKGROUND: The upfront treatment of metastatic renal cell carcinoma (mRCC) has been revolutionized by the introduction of immune-based combinations. The role of cytoreductive nephrectomy (CN) in these patients is still debated. The ARON-1 study (NCT05287464) was designed to globally analyze real-world data of mRCC patients receiving first-line immuno-oncology combinations. This sub-analysis is focused on the role of upfront or delayed partial or radical CN in three geographical areas (Western Europe, Eastern Europe, America/Asia). METHODS: We conducted a multicenter retrospective observational study in mRCC patients treated with first-line immune combinations from 55 centers in 19 countries. From 1152 patients in the ARON-1 dataset, we selected 651 patients with de novo mRCC. 255 patients (39%) had undergone CN, partial in 14% and radical in 86% of cases; 396 patients (61%) received first-line immune-combinations without previous nephrectomy. RESULTS: Median overall survival (OS) from the diagnosis of de novo mRCC was 41.6 months and not reached (NR) in the CN subgroup and 24.0 months in the no CN subgroup, respectively (P<0.001). Median OS from the start of first-line therapy was NR in patients who underwent CN and 22.4 months in the no CN subgroup (P<0.001). Patients who underwent CN reported longer OS compared to no CN in all the three geographical areas. CONCLUSIONS: No significant differences in terms of patients' outcome seem to clearly emerge, even if the rate CN and the choice of the type of first-line immune-based combination varies across the different Cancer Centers participating in the ARON-1 project.

Erdafitinib in the Treatment of Metastatic Urothelial Carcinoma.

A Hispanic man, aged 42 years, was diagnosed with stage IV metastatic urothelial bladder cancer (MUBC) with nonregional lymphadenopathies and lung, bone, and skin involvement. He received first-line treatment with gemcitabine and cisplatin for 6 cycles, achieving a partial response (PR). Next, he received immunotherapy maintenance with avelumab for 4 months until disease progression. A next-generation sequencing test of paraffin-embedded tumor tissue identified a fibroblast growth factor receptor 3 (FGFR3) S249C missense mutation.

Global Real-World Outcomes of Patients Receiving Immuno-Oncology Combinations for Advanced Renal Cell Carcinoma: The ARON-1 Study.

BACKGROUND: Immuno-oncology combinations have achieved survival benefits in patients with metastatic renal cell carcinoma (mRCC). OBJECTIVE: The ARON-1 study (NCT05287464) was designed to globally collect real-world data on the use of immuno-combinations as first-line therapy for mRCC patients. PATIENTS AND METHODS: Patients aged ≥ 18 years with a cytologically and/or histologically confirmed diagnosis of mRCC treated with first-line immuno-combination therapies were retrospectively included from 47 International Institutions from 16 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall clinical benefit (OCB). RESULTS: A total of 729 patients were included; tumor histology was clear-cell RCC in 86% of cases; 313 patients received dual immuno-oncology (IO + IO) therapy while 416 were treated with IO-tyrosine kinase inhibitor (IO + TKI) combinations. In the overall study population, the median OS and PFS were 36.5 and 15.0 months, respectively. The median OS was longer with IO+TKI compared with IO+IO therapy in the 616 patients with intermediate/poor International mRCC Database Consortium (IMDC) risk criteria (55.7 vs 29.7 months; p = 0.045). OCB was 84% for IO+TKI and 72% for IO + IO combination (p < 0.001). CONCLUSIONS: Our study may suggest that immuno-oncology combinations are effective as first-line therapy in the mRCC real-world context, showing outcome differences between IO + IO and IO + TKI combinations in mRCC subpopulations. CLINICAL TRIAL REGISTRATION: NCT05287464.

Germline DNA Repair Genes Pathogenic Variants Among Mexican Patients With Prostate Cancer.

BACKGROUND: Early identification of germline mutation carriers may be relevant for the optimal management of prostate cancer and to inform cancer risk in relatives. However, population minorities have limited access to genetic testing. The aim of this study was to describe the frequency of DNA repair gene pathogenic variants (PVs) among Mexican men with prostate cancer referred for Genomic Cancer Risk Assessment and testing. METHODS: Patients diagnosed with prostate cancer who meet criteria for genetic testing and enrolled in the Clinical Cancer Genomics Community Research Network at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City were included. Descriptive statistics were performed using frequency and proportions for categorical variables and median and range for quantitative variables. X2 and t test were used for group comparisons. RESULTS: A total of 199 men were enrolled, median age at diagnosis was 66 (range 44-88) years; 45% were de novo metastatic and 44% were high- very high and 10% were intermediate risk group. Four (2%) had a pathogenic germline variant; one each of the following genes: ATM, CHEK2, BRIP1, and MUTYH (all monoallelic). Younger men at diagnosis were more likely to carry a PV than older age at diagnosis (56.7 vs. 66.4 years, P = .01). CONCLUSION: Our results showed a low prevalence of known prostate cancer associated PVs and no BRCA PVs in Mexican men with prostate cancer. This suggests that the genetic and/or epidemiologic risk factors for prostate cancer are not well characterized in this specific population.

Racial differences in survival for early stage (T1) penile cancer: Analysis from the SEER database.

BACKGROUND: Penile cancer accounts for less than 1% of male cancers in the United States. Localized disease, particularly T1 tumors are potentially curable with local therapy. We present the racial differences in survival outcomes for T1, penile cancer from the SEER database. METHODS: From 2004 to 2016 all men with T1, N0, M0 penile cancer in the SEER-18 database were included. Kaplan-Meier analysis and multivariable Cox-Regression analysis were conducted to investigate prognostic variables for cancer specific survival (CSS). RESULTS: A total of 4,406 men were identified with penile cancer; 1,941 men had T1 disease. The Kaplan-Meier (KM) analysis showed those with primary site surgery had better 5-year CSS compared to those without primary site surgery (P <.0001) and a significant difference in CSS based on race (P= 0.0078). On multivariable analysis, Hispanic individuals had worse CSS (HR 1.92; P = 0.0057) compared to the White men. Black men were also found to have a poor CSS however this was not statistically significant (HR 1.53, P = 0.118). Men with penile cancer who had either penectomy (HR 0.45; P = 0.006) or penile preservation surgery (HR 0.25; P< 0.001) had improved CSS. CONCLUSION: Racial disparities in CSS exist among men with in early-stage penile cancer. KM analysis showed significant differences in CSS by race and in those receiving primary site surgery. On multivariable analysis, the CSS is worse in Hispanic compared to White men. There is a trend towards worse CSS in Black men however this was not statistically significant.

Clinico-Pathological Features Influencing the Prognostic Role of Body Mass Index in Patients With Advanced Renal Cell Carcinoma Treated by Immuno-Oncology Combinations (ARON-1).

BACKGROUND: Obesity has been associated with improved response to immunotherapy in cancer patients. We investigated the role of body mass index (BMI) in patients from the ARON-1 study (NCT05287464) treated by dual immuno-oncology agents (IO+IO) or a combination of immuno-oncology drug and a tyrosine kinase inhibitors (TKI) as first-line therapy for metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Medical records of patients with documented mRCC treated by immuno-oncology combinations were reviewed at 47 institutions from 16 countries. Patients were assessed for overall survival (OS), progression-free survival (OS), and overall clinical benefit (OCB), defined as the sum of the rate of partial/complete responses and stable disease. Univariate and multivariate analyses were used to explore the association of variables of interest with survival. RESULTS: A total of 675 patients were included; BMI was >25 kg/m2 in 345 patients (51%) and was associated with improved OS (55.7 vs. 28.4 months, P < .001). The OCB of patients with BMI >25 kg/m2 versus those with BMI ≤25 kg/m2 was significantly higher only in patients with nonclear cell histology (81% vs. 65%, P = .011), and patients with liver metastases (76% vs. 58%, P = .007), Neutrophil to lymphocyte ratio >4 (77% vs 62%, P = .022) or treated by nivolumab plus ipilimumab (77% vs. 64%, P = .044). In the BMI ≤25 kg/m2 subgroup, significant differences were found between patients with NLR >4 versus ≤4 (62% vs. 82%, P = .002) and patients treated by IO+IO versus IO+TKIs combinations (64% vs. 83%, P = .002). CONCLUSION: Our study suggests that the prognostic significance and the association of BMI with treatment outcome varies across clinico-pathological mRCC subgroups.

A Matching-adjusted Indirect Comparison of Nivolumab Plus Cabozantinib Versus Pembrolizumab Plus Axitinib in Patients with Advanced Renal Cell Carcinoma.

BACKGROUND: The comparative efficacy and health-related quality of life (HRQoL) outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib as first-line treatments for advanced renal cell carcinoma (aRCC) have not been assessed in head-to-head trials. OBJECTIVE: To assess the efficacy and HRQoL outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib. DESIGN, SETTING, AND PARTICIPANTS: Patient-level data for nivolumab plus cabozantinib from the CheckMate 9ER trial and published data for pembrolizumab plus axitinib from the KEYNOTE-426 trial were used. CheckMate 9ER data were reweighted to match the key baseline characteristics as reported in KEYNOTE-426. INTERVENTION: Nivolumab (240 mg every 2 wk) plus cabozantinib (40 mg once daily) and pembrolizumab (200 mg every 3 wk) plus axitinib (5 mg twice daily, initially). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Hazard ratios (HRs) for progression-free survival (PFS), duration of response, overall survival (OS), and deterioration in HRQoL were assessed using weighted Cox proportional-hazard models, with sunitinib as a common anchor. Objective response rates (ORRs) and changes in HRQoL scores from baseline were assessed as difference-in-differences for the two treatments relative to sunitinib. RESULTS AND LIMITATIONS: After balancing patient characteristics between the trials, nivolumab plus cabozantinib was associated with significantly improved PFS (HR [95% confidence interval {CI}] 0.70 [0.53-0.93]; p = 0.01) and a significantly decreased risk of confirmed deterioration in HRQoL (Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms: HR [95% CI] 0.48 [0.34-0.69]) versus pembrolizumab plus axitinib. OS was similar between treatments (HR [95% CI] 0.99 [0.67-1.44]; p = 0.94). Nivolumab plus cabozantinib was associated with numerically greater ORRs (difference-in-difference [95% CI] 8.4% [-1.7 to 18.4]; p = 0.10) and longer duration of response (HR [95% CI] 0.79 [0.47-1.31]; p = 0.36) than pembrolizumab plus axitinib. Comparative studies using data with a longer duration of follow-up are warranted. CONCLUSIONS: Nivolumab plus cabozantinib significantly improved PFS and HRQoL compared with pembrolizumab plus axitinib as first-line treatment for aRCC. PATIENT SUMMARY: This study was conducted to indirectly compare the results of two immunotherapy-based combinations-nivolumab plus cabozantinib versus pembrolizumab plus axitinib-for patients who have not received any treatment for advanced renal cell carcinoma. Patients who received nivolumab plus cabozantinib had a significant improvement in the length of time without worsening of their disease and in their perceived physical and mental health compared with pembrolizumab plus axitinib; patients remained alive for a similar length of time from the start of either treatment. This analysis further adds to our current knowledge of the relative benefits of these two treatment regimens and will help with physician and patient treatment decisions.

Grade 3/4 Adverse Event Costs of Immuno-oncology Combination Therapies for Previously Untreated Advanced Renal Cell Carcinoma.

BACKGROUND: Despite 4 approved combination regimens in the first-line setting for advanced renal cell carcinoma (aRCC), adverse event (AE) costs data are lacking. MATERIALS AND METHODS: A descriptive analysis on 2 AE cost comparisons was conducted using patient-level data for the nivolumab-based therapies and published data for the pembrolizumab-based therapies. First, grade 3/4 AE costs were compared between nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + axitinib using data from the CheckMate 214 (median follow-up [mFU]: 13.1 months), CheckMate 9ER (mFU: 12.8 months), and KEYNOTE-426 (mFU: 12.8 months) trials, respectively. Second, grade 3/4 AE costs were compared between nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + lenvatinib using data from the CheckMate 214 (mFU: 26.7 months), CheckMate 9ER (mFU: 23.5 months), and KEYNOTE-581 (mFU: 26.6 months) trials, respectively. Per-patient costs for all-cause and treatment-related grade 3/4 AEs with corresponding any-grade AE rates ≥ 20% were calculated based on the Healthcare Cost and Utilization Project database and inflated to 2020 US dollars. RESULTS: Per-patient all-cause grade 3/4 AE costs for nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + axitinib were $2703 vs. $4508 vs. $5772, and treatment-related grade 3/4 AE costs were $741 vs. $2722 vs. $4440 over ~12.8 months of FU. For nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + lenvatinib, per-patient all-cause grade 3/4 AE costs were $3120 vs. $5800 vs. $9285, while treatment-related grade 3/4 AE costs were $863 vs. $3162 vs. $5030 over ~26.6 months of FU. CONCLUSION: Patients with aRCC treated with first-line nivolumab-based therapies had lower grade 3/4 all-cause and treatment-related AE costs than pembrolizumab-based therapies, suggesting a more favorable cost-benefit profile.

Overview and characterization of penile cancer content across social media platforms.

Background: Social media platforms (SMP) are an emerging resource that allows physicians, patients, and families to converse on cancer prevention, diagnosis, and treatment. We aimed to characterize penile cancer (PC) content shared on SMP. Methods: We searched PC posts on Twitter, Facebook, and Instagram from July 1st, 2021, through June 30th, 2022. Two independent, blinded reviewers analyzed the hashtags: #PenileCancer, #PenileCancerAwareness, and #PenileNeoplasm. Descriptive statistics were used for posts characterization, Pearson´s correlation coefficient for associations, and Cohen's weighted kappa coefficient for inter-rater agreement rate. Results: A total of 791 posts were analyzed, with Twitter accounting for 52%, Facebook for 12.2%, and Instagram for 35.5%, and. Most posts originated from high-income countries, such as the United Kingdom (48.8%). We found no correlation between the number of posts with PC incidence (p = 0.64) or users on SMP (p = 0.27). Most accounts were classified as "support and awareness communities" (43.6%) and "physicians and clinical researchers" (38.2%). Urology was the most common medical specialty to post (60.9%), followed by oncology (11.3%). Most posts were classified as "prevention and awareness for users" (45.1%). Global inter-reviewer agreement rate was almost perfect (k=0.95; p ≤ 0.01). On Twitter, "physicians and clinical researchers" shared more content on "treatment updates and medical papers published in medical journals," while on Facebook and Instagram, "support and awareness communities" focused on "personal and support comments." Conclusion: Overall, the number of PC posts was low compared to other neoplasms across the SMP evaluated in this study. "Physicians and clinical researchers" shared more content on Twitter, while "support and awareness communities" on Facebook and Instagram. Encouraging the use of a common SMP among the medical community and general users could lead to a more effective communication between physicians, patients, and support groups, and to increased awareness of PC.

Oncofertility and Fertility Preservation in Cancer Patients Across the Twitterverse.

Purpose: Infertility is a major problem affecting children, adolescents, and young adults (AYAs) with cancer, either due to the disease itself or because of oncologic treatment. Oncofertility (OF) focuses on counseling cancer patients about fertility risks and preservation options. However, OF and fertility preservation (FP) conversations on Twitter and their impact are unknown. We aim to characterize the users and type of content of these conversations. Materials and Methods: This observational study analyzed tweets with the hashtags "#Oncofertility" and "#FertilityPreservation" over eight months. We classified Twitter accounts by user type and country. Tweets were categorized by content type, and retweets and likes were quantified. Descriptive statistics were used for analysis. Results: A total of 399 tweets from 223 different accounts were evaluated. Twitter accounts comprised 22 countries and stemmed from high, upper-middle, and lower-middle-income countries in 86.5%, 5.4%, and 6.3%, respectively; no accounts from low-income countries were found. Accounts were mostly from physicians (37%) and healthcare centers (20%); we did not find any patient accounts. The most common content category was informative tweets directed to patients (30.8%), followed by discussion/sharing of medical papers (25.6%). Only 14.5% of tweets contained information about children and adolescents. Still, only 4.5% were aimed at children. Retweets were absent in 16.5% of the tweets, and 80.7% did not have comments. Conclusion: OF and FP discussions on Twitter were limited to interactions among medical professionals. Also, advocacy groups showed limited activity on social media. Even though a significant proportion of tweets directed to patients were found, no active involvement of patients was observed. Finally, limited number of tweets (4.5%) were directed to children and adolescents. There is a need to raise awareness about the effects of cancer on fertility in this group. Currently, Twitter is not a resource of information for children and AYAs with cancer who need OF counseling and fertility preservation. Our results open a debate on how to promote the use of social media in the future to improve the quality of OF information available, awareness, and care since there is an unmet need for fertility preservation access in young cancer patients.

Patterns of Treatment and Outcomes in Older Men With Penile Cancer: A SEER Dataset Analysis.

Purpose: To evaluate clinicopathologic and treatment characteristics from a population-based cohort of penile cancer, with an emphasis in older adults, due to incomplete evidence to guide therapy in this age subgroup. Materials and Methods: Patients with malignant penile tumors diagnosed 2004-2016 were identified in the Surveillance, Epidemiology and End Results Program (SEER)-18 dataset. Demographic and treatment characteristics were obtained. Population was analyzed by age at diagnosis (<65 vs ≥65 years). We examined univariate associations between age groups with Chi-square analysis. To study survival, we calculated Kaplan-Meier survival curves, but due to the high number of competing events, we also performed a univariate competing risk analysis using the cumulative incidence function, and a multivariate analysis using the Fine-Gray method. We also described competing mortality due to penile cancer and other causes of death. Results: We included 3,784 patients. Median age was 68 years, 58.7% were aged ≥65. Older patients were less likely to have received chemotherapy (p<0.001), primary site surgery (p = 0.002), or therapeutic regional surgery (p <0.001). Median overall survival (OS) in patients <65 years was not reached (95% CI incalculable) vs 49 months in those ≥65 years (95% CI 45-53, p <0.0001). On univariate analysis, age was associated with a lower incidence of penile cancer death. On multivariate analysis, stage at diagnosis, and receipt of primary site surgery were associated with a higher incidence of penile cancer death. Estimated penile cancer-specific mortality was higher in patients <65 years in stages II-IV. Estimated mortality due to other causes was higher in older patients across all stages. Conclusions: Older patients are less likely to receive surgery, chemotherapy and radiotherapy for penile cancer. Primary surgical resection was associated with better penile cancer-specific mortality on multivariate analysis. Competing mortality risks are highly relevant when considering OS in older adults with penile cancer. Factors associated with undertreatment of older patients with penile cancer need to be studied, in order to develop treatment strategies tailored for this population.