Perioperative nivolumab versus observation in patients with renal cell carcinoma undergoing nephrectomy (PROSPER ECOG-ACRIN EA8143): an open-label, randomised, phase 3 study.

BACKGROUND: The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only. METHODS: In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, with previously untreated clinical stage T2 or greater or Tany N+ renal cell carcinoma of clear cell or non-clear cell histology planned for partial or radical nephrectomy. Selected patients with oligometastatic disease, who were disease free at other disease sites within 12 weeks of surgery, were eligible for inclusion. We randomly assigned (1:1) patients using permuted blocks (block size of 4) within stratum (clinical TNM stage) to either nivolumab plus surgery, or surgery only followed by surveillance. In the nivolumab group, nivolumab 480 mg was administered before surgery, followed by nine adjuvant doses. The primary endpoint was investigator-reviewed recurrence-free survival in patients with renal cell carcinoma assessed in all randomly assigned patients regardless of histology. Safety was assessed in all randomly assigned patients who started the assigned protocol treatment. This trial is registered with ClinicalTrials.gov, NCT03055013, and is closed to accrual. FINDINGS: Between Feb 2, 2017, and June 2, 2021, 819 patients were randomly assigned to nivolumab plus surgery (404 [49%]) or surgery only (415 [51%]). 366 (91%) of 404 patients assigned to nivolumab plus surgery and 387 (93%) of 415 patients assigned to surgery only group started treatment. Median age was 61 years (IQR 53-69), 248 (30%) of 819 patients were female, 571 (70%) were male, 672 (88%) were White, and 77 (10%) were Hispanic or Latino. The Data and Safety Monitoring Committee stopped the trial at a planned interim analysis (March 25, 2022) because of futility. Median follow-up was 30·4 months (IQR 21·5-42·4) in the nivolumab group and 30·1 months (21·9-41·8) in the surgery only group. 381 (94%) of 404 patients in the nivolumab plus surgery group and 399 (96%) of 415 in the surgery only group had renal cell carcinoma and were included in the recurrence-free survival analysis. As of data cutoff (May 24, 2023), recurrence-free survival was not significantly different between nivolumab (125 [33%] of 381 had recurrence-free survival events) versus surgery only (133 [33%] of 399; hazard ratio 0·94 [95% CI 0·74-1·21]; one-sided p=0·32). The most common treatment-related grade 3-4 adverse events were elevated lipase (17 [5%] of 366 patients in the nivolumab plus surgery group vs none in the surgery only group), anaemia (seven [2%] vs nine [2%]), increased alanine aminotransferase (ten [3%] vs one [<1%]), abdominal pain (four [1%] vs six [2%]), and increased serum amylase (nine [2%] vs none). 177 (48%) patients in the nivolumab plus surgery group and 93 (24%) in the surgery only group had grade 3-5 adverse events due to any cause, the most common of which were anaemia (23 [6%] vs 19 [5%]), hypertension (27 [7%] vs nine [2%]), and elevated lipase (18 [5%] vs six [2%]). 48 (12%) of 404 patients in the nivolumab group and 40 (10%) of 415 in the surgery only group died, of which eight (2%) and three (1%), respectively, were determined to be treatment-related. INTERPRETATION: Perioperative nivolumab before nephrectomy followed by adjuvant nivolumab did not improve recurrence-free survival versus surgery only followed by surveillance in patients with high-risk renal cell carcinoma. FUNDING: US National Institutes of Health National Cancer Institute and Bristol Myers Squibb.

Discrepancies between genitourinary cancer patients' and clinicians' characterization of the Eastern Cooperative Oncology Group performance status.

BACKGROUND: Patient-reported outcomes have been used to assess treatment effectiveness and actively engage patients in their disease management. This study was designed to describe the patient-reported performance status (PS) and the provider-reported PS. METHODS: Patients with metastatic genitourinary cancers were recruited from a single cancer center before the initiation of a new line of treatment. PS (Eastern Cooperative Oncology Group [ECOG]), quality of life (Functional Assessment of Chronic Illness Therapy-General), and distress (Patient-Reported Outcomes Measurement Information System Anxiety and Depression) were self-reported by patients. Clinical data (eg, age, sex, diagnosis, and physician-reported ECOG PS) were extracted from medical records. Multivariate analysis was used to determine the association between PS, quality of life, and psychological symptoms. RESULTS: One hundred forty-five patients were enrolled (76.6% male, 70.3% White, 81.4% married, and 76.6% well educated). The median age was 67 years; 66.9% were diagnosed with renal cell carcinoma, 20.0% were diagnosed with urothelial carcinoma, and 13.1% were diagnosed with prostate cancer. Clinicians more frequently classified patients' ECOG PS as 0 in comparison with the patients themselves (92.4% vs 64.1%; P = .001). Higher clinician-reported ECOG PS was associated with poorer physical and functional well-being and higher rates of depression (P < .01), whereas higher patient-reported ECOG PS was associated with worse psychosocial outcomes (P < .01). CONCLUSIONS: Discrepancies were noted between the patient- and provider-reported ECOG PS, with clinicians overestimating the ECOG PS in comparison with the patients themselves. This study's findings suggest that patients incorporate their social and emotional well-being into their PS score in addition to their physical well-being. This information is not immediately accessible to most clinicians from just a standard patient interview and likely accounts for the overestimation of the patients' ECOG PS by the clinicians.

Genetic risk assessment for hereditary renal cell carcinoma: Clinical consensus statement.

BACKGROUND: Although renal cell carcinoma (RCC) is believed to have a strong hereditary component, there is a paucity of published guidelines for genetic risk assessment. A panel of experts was convened to gauge current opinions. METHODS: A North American multidisciplinary panel with expertise in hereditary RCC, including urologists, medical oncologists, clinical geneticists, genetic counselors, and patient advocates, was convened. Before the summit, a modified Delphi methodology was used to generate, review, and curate a set of consensus questions regarding RCC genetic risk assessment. Uniform consensus was defined as ≥85% agreement on particular questions. RESULTS: Thirty-three panelists, including urologists (n = 13), medical oncologists (n = 12), genetic counselors and clinical geneticists (n = 6), and patient advocates (n = 2), reviewed 53 curated consensus questions. Uniform consensus was achieved on 30 statements in specific areas that addressed for whom, what, when, and how genetic testing should be performed. Topics of consensus included the family history criteria, which should trigger further assessment, the need for risk assessment in those with bilateral or multifocal disease and/or specific histology, the utility of multigene panel testing, and acceptance of clinician-based counseling and testing by those who have experience with hereditary RCC. CONCLUSIONS: In the first ever consensus panel on RCC genetic risk assessment, 30 consensus statements were reached. Areas that require further research and discussion were also identified, with a second future meeting planned. This consensus statement may provide further guidance for clinicians when considering RCC genetic risk assessment. LAY SUMMARY: The contribution of germline genetics to the development of renal cell carcinoma (RCC) has long been recognized. However, there is a paucity of guidelines to define how and when genetic risk assessment should be performed for patients with known or suspected hereditary RCC. Without guidelines, clinicians struggle to define who requires further evaluation, when risk assessment or testing should be done, which genes should be considered, and how counseling and/or testing should be performed. To this end, a multidisciplinary panel of national experts was convened to gauge current opinion on genetic risk assessment in RCC and to enumerate a set of recommendations to guide clinicians when evaluating individuals with suspected hereditary kidney cancer.

COVID-19 and financial toxicity in patients with renal cell carcinoma.

PURPOSE: To ascertain renal cell carcinoma (RCC) financial toxicity on COVID-19 during the COVID-19 crisis as patients are struggling with therapeutic and financial implications. METHODS: An online survey was conducted from March 22 to March 25, 2020. It included baseline demographic, clinicopathologic, treatment-related information, anxiety levels related to COVID-19, questions related to financial concerns about COVID-19 as well as the validated 11-item COST measure. RESULTS: Five-hundred-and-thirty-nine patients (39%:58% male:female) from 14 countries responded. 23% of the patients did not feel in control of their financial situation but 8% reported being very satisfied with their finances. The median COST score was 21.5 (range 1-44). Metastatic patients who have not started systemic therapy had a COST score (19.8 range 2-41) versus patients on oral systemic therapy had a COST score (23.9 range 4-44). Patients in follow-up after surgery had a median COST score at 20.8 (range 1-40). A low COST scores correlated (p < 0.001) were female gender (r = 0.108), younger age (r = 0.210), urban living situation (r = 0.68), a lower educational level (r = 0.155), lower income (r = 0.165), higher anxiety about acquiring COVID-19 (r = 0.198), having metastatic disease (r = 0.073) and a higher distress score about cancer progression (r = 0.224). CONCLUSION: Our data highlight severe financial impact of COVID-19. Acknowledging financial hardship and thorough counseling of cancer patients should be part of the conversation during the pandemic. Treatment and surveillance of RCC patients might have to be adjusted to contemplate financial and medical needs.

Prevalence of Dietary Modification and Supplement Use in Patients with Metastatic Renal Cell Carcinoma Receiving Systemic Therapy.

Many patients diagnosed with cancer adopt dietary changes and supplement use, and a growing body of evidence suggests that such modifications can affect outcomes to cancer therapy. We sought to assess the prevalence of these practices and the surrounding physician-patient dialogue among patients with metastatic renal cell carcinoma. An online survey was administered by Kidney Cancer Research Alliance (KCCure), interrogating dietary modification patterns, supplement usage, out-of-pocket expenditure related to supplements, and patients' views toward alternative medicine practices. Patients with metastatic renal cell carcinoma receiving combination therapy were actively solicited. In total, 289 unique responses were collected. The most common first-line treatments were nivolumab/ipilimumab (32.4%) and axitinib/pembrolizumab (13.1%). Within the cohort, 147 (50.9%) started using supplements following diagnosis of renal cell carcinoma; the most utilized supplements were probiotics, cannabidiol (CBD) oil/marijuana, and Vitamin C, reported by 70 (47.6%), 61 (41.4%), and 54 (36.7%), respectively. Dietary modifications following cancer diagnosis were reported by 101 (34.9%) respondents, of which 19.8% followed the Mediterranean diet and 18.8% adopted a ketogenic diet. Most respondents (71.3%) noted that they consistently report supplement usage to their physicians. A substantial proportion of patients with metastatic renal cell carcinoma utilize dietary modification and supplements as an adjunct to antineoplastic therapy. Considering the widespread adoption of these practices and the reported effects on cancer treatment, it is crucial for healthcare providers to engage in discussions with patients regarding supplement use.

Addressing resistance to PD-1/PD-(L)1 pathway inhibition: considerations for combinatorial clinical trial designs.

With multiple PD-(L)1 inhibitors approved across dozens of indications by the US Food and Drug Administration, the number of patients exposed to these agents in adjuvant, first-line metastatic, second-line metastatic, and refractory treatment settings is increasing rapidly. Although some patients will experience durable benefit, many have either no clinical response or see their disease progress following an initial response to therapy. There is a significant need to identify therapeutic approaches to overcome resistance and confer clinical benefits for these patients. PD-1 pathway blockade has the longest history of use in melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). Therefore, these settings also have the most extensive clinical experience with resistance. In 2021, six non-profit organizations representing patients with these diseases undertook a year-long effort, culminating in a 2-day workshop (including academic, industry, and regulatory participants) to understand the challenges associated with developing effective therapies for patients previously exposed to anti-PD-(L)1 agents and outline recommendations for designing clinical trials in this setting. This manuscript presents key discussion themes and positions reached through this effort, with a specific focus on the topics of eligibility criteria, comparators, and endpoints, as well as tumor-specific trial design options for combination therapies designed to treat patients with melanoma, NSCLC, or RCC after prior PD-(L)1 pathway blockade.

Decisional Regret and Financial Toxicity among Patients with Benign Renal Masses.

INTRODUCTION: Treatment of benign renal masses may often be unnecessary and can lead to significant morbidity, mortality, and health care costs. However, individual burdens such as decisional regret and financial costs associated with treatment are not well understood. METHODS: Members of a support group who have been diagnosed with benign renal tumors were surveyed to evaluate demographic and clinical characteristics as well as decisional regret, using the modified Decision Regret Scale (DRS), and financial toxicity, using the Comprehensive Score for Financial Toxicity (COST). Predictors of decisional regret (DRS score >25) and financial toxicity were explored using logistic and linear regression analyses, respectively. RESULTS: Of 70 respondents with complete data, 49 (70%) received definitive treatment while 21 (30%) elected surveillance. Decisional regret was expressed by 34/70 (49%) of patients and was associated with increasing age, smaller tumor size, and use of surveillance vs active treatment in univariable analysis. Patients reported significant financial toxicity from the diagnosis of a benign renal mass with a median COST score of 24, similar to a historical cohort of patients with stage IV solid organ cancers undergoing chemotherapy. Qualitative analysis of patient responses identified a lack of discussion by the provider of the likelihood of benign disease, postoperative complications, and financial burden as common themes in their experiences. CONCLUSIONS: High levels of decisional regret and financial toxicity were found among individuals with benign renal lesions regardless of treatment approach. Improved counseling and diagnostic tools may limit the psychological and financial burdens from these benign entities.

Counterbalancing COVID-19 with Cancer Surveillance and Therapy: A Survey of Patients with Renal Cell Carcinoma.

BACKGROUND: While providers are challenged with treatment decisions during the coronavirus disease 2019 (COVID-19) crisis, decision making ultimately falls in the hands of patients-at present, their perspective is poorly understood. OBJECTIVE: To ascertain renal cell carcinoma (RCC) patients' perspectives on COVID-19 and understand the associated implications for treatment. DESIGN, SETTING, AND PARTICIPANTS: An online survey of RCC patients was conducted from March 22 to March 25, 2020, disseminated through social media and patient networking platforms. The survey comprised 45 items, including baseline demographic, clinicopathologic, and treatment-related information. Patients were additionally queried regarding their anxiety level related to COVID-19 and associated implications for their cancer diagnosis. INTERVENTION: An online survey study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive statistics with graphical outputs were used to characterize survey results. RESULTS AND LIMITATIONS: A total of 539 patients (male:female 39%:58%) from 14 countries responded. Of them, 71% felt that their risk of COVID-19 infection was higher than the general population, and 27% contacted their physician to establish this. Among patients with localized disease (40%), most (42%) had scheduled surveillance scans within 6 wk-65% were unwilling to delay scans. Among patients with metastatic disease, 76% were receiving active therapy. While most patients preferred not to defer therapy (51%), patients receiving immune therapy regimens were less amenable to deferring therapy than those receiving targeted treatment (20% vs 47%). CONCLUSIONS: Despite high levels of anxiety surrounding COVID-19, many patients with RCC were inclined to adhere to existing schedules of surveillance (localized disease) and systemic treatment (metastatic disease). PATIENT SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic has prompted many doctors to develop different treatment strategies for cancer and other chronic conditions. Given the importance of the patient voice in these strategies, we conducted a survey of patients with kidney cancer to determine their treatment preferences. Our survey highlighted that most patients prefer to continue their current strategies of kidney cancer treatment and monitoring.

Fear of Cancer Recurrence in Patients With Localized Renal Cell Carcinoma.

PURPOSE: Patients with cancer commonly report distress and fear of cancer recurrence (FCR) impacting quality of life and clinical outcomes. This study aims to test the association between emotional well-being and clinical characteristics of survivors with localized renal cell carcinoma (RCC). MATERIALS AND METHODS: Survivors with localized RCC were invited to participate in this study through social media by the Kidney Cancer Research Alliance. Participants self-reported clinical characteristics, distress (Distress Thermometer), and FCR (Fear of Cancer Recurrence-7). Ordinal regression was used to test the association between emotional well-being and patient characteristics. RESULTS: A total of 412 survivors were included in this analysis. Participants were mostly female (79.4%) and well educated (58.3%), with a median age of 54 years (range, 30-80 years) and median time since diagnosis of 17.5 months. More than one half were diagnosed with stage I disease (56.1%). Most patients (62.3%) had a clear understanding of their diagnosis. A high prevalence of moderate to severe distress (67.0%) and FCR (54.9%) was reported across all survivors of RCC. Higher FCR was associated with female gender, younger age, and lack of understanding of their diagnosis (P = .001), whereas more recent diagnosis was associated with higher distress levels (P = .01). CONCLUSION: Our findings suggest that FCR is a common problem that is persistent after therapy and that certain individuals, including female and younger patients, may be at particular risk of experiencing clinically relevant FCR.

Sources of Frustration Among Patients Diagnosed With Renal Cell Carcinoma.

Despite numerous therapeutic advances in renal cell carcinoma (RCC), little is known about patients' perspectives on cancer care. An international survey was conducted to identify points of frustration associated with cancer care reported by patients with RCC. Data were obtained from an online survey, conducted from April 1 to June 15, 2017, through social media and patient networking platforms. This survey obtained baseline demographic, clinicopathologic, and treatment-related information. Open-ended questions accessed sources of frustration in cancer-related care and patients' suggestions for amelioration. Responses were categorized and reviewed by independent reviewers. A qualitative analysis was performed and the Kruskal-Wallis test was used to define associations between baseline characteristics and sources of frustration. Among 450 patients surveyed, 71.5% reported sources of frustration, classified as either emotional (48.4%) or practical (23.1%). The most common were fear of recurrence/progression (15.8%), distrust of their cancer care system (12.9%), and lack of appropriate information (9.8%). Female gender and non-clear cell histology were associated with both types of frustration, and older age was linked to practical sources of frustration. Patients suggested solutions included greater compassion among health care practitioners (20.7%), better access to information (15.1%) and research to improve their chances of being cured (14.7%). Sources of frustration related to emotional and practical causes were identified amongst patients with RCC. Certain demographic and clinical characteristics were associated with more sources of frustration. This study provides the first characterization of specific ways to improve the patient experience by addressing common frustrations.

The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC).

The approval of immunotherapeutic agents and immunotherapy-based combination strategies in recent years has revolutionized the treatment of patients with advanced renal cell carcinoma (aRCC). Nivolumab, a programmed death 1 (PD-1) immune checkpoint inhibitor monoclonal antibody, was approved as monotherapy in 2015 for aRCC after treatment with a VEGF-targeting agent. In April 2018, the combination of nivolumab and ipilimumab, a CTLA-4 inhibitor, was approved for intermediate- and poor-risk, previously untreated patients with aRCC. Then, in 2019, combinations therapies consisting of pembrolizumab (anti-PD-1) or avelumab (anti-PD-ligand (L) 1) with axitinib (a VEGF receptor tyrosine kinase inhibitor) were also approved to treat aRCC and are likely to produce dramatic shifts in the therapeutic landscape. To address the rapid advances in immunotherapy options for patients with aRCC, the Society for Immunotherapy of Cancer (SITC) reconvened its Cancer Immunotherapy Guidelines (CIG) Renal Cell Carcinoma Subcommittee and tasked it with generating updated consensus recommendations for the treatment of patients with this disease.

Team Leadership and Cancer End-of-Life Decision Making.

End-of-life decision making in cancer can be a complicated process. Patients and families encounter multiple providers throughout their cancer care. When the efforts of these providers are not well coordinated in teams, opportunities for high-quality, longitudinal goals of care discussions can be missed. This article reviews the case of a 55-year-old man with lung cancer, illustrating the barriers and missed opportunities for end-of-life decision making in his care through the lens of team leadership, a key principle in the science of teams. The challenges demonstrated in this case reflect the importance of the four functions of team leadership: information search and structuring, information use in problem solving, managing personnel resources, and managing material resources. Engaging in shared leadership of these four functions can help care providers improve their interactions with patients and families concerning end-of-life care decision making. This shared leadership can also produce a cohesive care plan that benefits from the expertise of the range of available providers while reflecting patient needs and preferences. Clinicians and researchers should consider the roles of team leadership functions and shared leadership in improving patient care when developing and studying models of cancer care delivery.