Serum very long-chain fatty acid-containing lipids predict response to immune checkpoint inhibitors in urological cancers.

Checkpoint inhibitors (CPI) have significantly changed the therapeutic landscape of oncology. We adopted a non-invasive metabolomic approach to understand immunotherapy response and failure in 28 urological cancer patients. In total, 134 metabolites were quantified in patient sera before the first, second, and third CPI doses. Modeling the association between metabolites and CPI response and patient characteristics revealed that one predictive metabolite class  (n = 9/10) were very long-chain fatty acid-containing lipids (VLCFA-containing lipids). The best predictive performance was achieved through a multivariate model, including age and a centroid of VLCFA-containing lipids prior to first immunotherapy (sensitivity: 0.850, specificity: 0.825, ROC: 0.935). We hypothesize that the association of VLCFA-containing lipids with CPI response is based on enhanced peroxisome signaling in T cells, which results in a switch to fatty acid catabolism. Beyond use as a novel predictive non-invasive biomarker, we envision that nutritional supplementation with VLCFA-containing lipids might serve as an immuno sensitizer.

Synchronous primary cancers: Renal cell carcinoma and rectal cancer.

Although cancers of rectum and kidney are common malignancies, the occurrence of primary synchronous neoplasms of these organs has been reported rarely. Very few case reports are available in literature till date. The relationship between these two events remains unclear, probably because of the rarity of the association. In this report, we describe incidentally detected renal cell carcinoma in an elderly man, during staging workup of rectal adenocarcinoma and both malignancies were surgically managed simultaneously with curative intent.

Association between coffee consumption and risk of renal cell carcinoma: a meta-analysis.

BACKGROUND/OBJECTIVES: The risk of renal cell carcinoma (RCC) in individuals who regularly drink coffee is controversial. Several antioxidant compounds in coffee have been proposed to reduce the risk of RCC, while the findings from several studies raise concerns regarding a potential increased risk of RCC with coffee consumption. AIM: This meta-analysis aims to evaluate the association between coffee consumption and RCC. METHODS: A literature search was performed using MEDLINE, EMBASE and Cochrane Database of Systematic Reviews from inception until December 2016. Studies that reported odd ratios or hazard ratios comparing the risk of RCC in individuals who consumed a significant amount of coffee (at least one cup of coffee per day) versus those who did not consume coffee were included. Pooled risk ratios (RR) and 95% confidence intervals (CI) were computed using a random-effect, generic inverse variance method. RESULTS: Twenty-two observational studies (16 case-control and 6 cohort studies) were included in our analysis to assess the association between RCC and coffee consumption. The pooled RR of RCC in individuals consuming coffee was 0.99 (95% CI, 0.89-1.11). Subgroup analyses stratified by gender showed pooled RRs of RCC of 1.15 (95% CI, 0.85-1.55) in females and 0.87 (95% CI, 0.72-1.04) in males. CONCLUSIONS: Our study demonstrates no significant association between coffee consumption and RCC. Thus, coffee consumption is likely not a risk factor for RCC. Whether coffee consumption has a potential role in reduced risk of RCC, particularly in men, requires further investigations.

[Interdisciplinary Recommendations for the Treatment of Metastatic Renal Cell Carcinoma]. / Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms .

Thanks to the use of targeted therapies, the prognosis of patients with metastatic renal cell carcinoma (mRCC) has improved significantly. A median overall survival of more than 2 years is a realistic claim. These improvements are also reflected in recent discussions about 3 and more lines of therapy.Sunitinib, pazopanib, the combination of bevacizumab and interferon alpha, and temsirolimus are approved for first-line therapy of mRCC. Sunitinib and pazopanib are also approved for second-line therapy, which, for pazopanib, is confined to the use after cytokine failure. Everolimus (after tyrosine kinase inhibitor (TKI) treatment), sorafenib (after cytokines) and axitinib (after treatment with sunitinib or cytokines) are other compounds available for second-line therapy.3 new substances have recently been approved for second-line therapy: Nivolumab, cabozantinib, and lenvatinib combined with everolimus can be used after VEGF-targeted treatment has failed. It is for the first time that targeted immunotherapy and a combination of targeted substances are available for the treatment of mRCC.There is no new insight as to an optimal sequence therapy. Study results from a phase III trial suggest that the sequences sorafenib-sunitinib and sunitinib-sorafenib are equally effective.The purpose of an interdisciplinary expert meeting on RCC was to work out joint treatment recommendations based on current data and clinical experience and to integrate them into clinical routine practice. The results are presented in this publication.

Tumoral cubilin is a predictive marker for treatment of renal cancer patients with sunitinib and sorafenib.

PURPOSE: Tyrosine kinase inhibitors like sunitinib and sorafenib are commonly used to treat metastatic renal cell cancer patients. Cubilin is a membrane protein expressed in the proximal renal tubule. Cubilin and megalin function together as endocytic receptors mediating uptake of many proteins. There is no established predictive marker for metastatic renal cell cancer patients and the purpose of the present study was to assess if cubilin can predict response to treatment with tyrosine kinase inhibitors. METHODS: Cubilin protein expression was analyzsed in tumor tissue from a cohort of patients with metastatic renal cell cancer (n = 139) using immunohistochemistry. One hundred and thirty six of the patients were treated with sunitinib or sorafenib in the first- or second-line setting. Thirty of these were censored because of toxicity leading to the termination of treatment and the remaining (n = 106) were selected for the current study. RESULTS: Fifty-three (50%) of the tumors expressed cubilin in the membrane. The median progression-free survival was 8 months in patients with cubilin expressing tumors and 4 months in the cubilin negative group. In addition, the overall survival was better for patients with cubilin positive tumors. We also found that the fraction of cubilin negative patients was significantly higher in the non-responding group (PFS ≤3 months) compared to responding patients (PFS >3 months). CONCLUSIONS: We show for the first time that tumoral expression of cubilin is a positive predictive marker for treatment of metastatic renal cell cancer patients with sunitinib and sorafenib.

Pituitary Metastasis from Renal Cell Carcinoma: Description of a Case Report.

BACKGROUND Pituitary metastasis is uncommon, breast and lung cancers being the most frequent primary tumors. Renal cell carcinoma (RCC) is a rare cause of pituitary metastases, with only a few cases described to date. CASE REPORT We report a case of a 61-year-old man who presented with a progressive deterioration of visual acuity and field associated with a bitemporal hemianopsia. Two years ago, he underwent radical right nephrectomy for a clear cell RCC (ccRCC). The biological tests showed pan-hypopituitarism and diabetes insipidus. Brain MRI revealed a large sellar tumor lesion bilaterally infiltrating the cavernous sinuses, which was surgically resected. Histology confirmed a ccRCC pituitary metastasis. The patient received post-surgical radiotherapy. Considering the presence of concomitant extra-pituitary metastases, treatment with sunitinib was started, followed by several lines of therapy with axitinib, everolimus, and sorafenib because of tumor progression. The patient also presented with a pituitary tumor recurrence, which was treated by stereotaxic radiotherapy. He died five years after the initial diagnosis of RCC and 30 months after the diagnosis of the pituitary metastasis.  CONCLUSIONS There are no standardized treatment guidelines for management of pituitary metastases. Pituitary surgery plays a role in symptom palliation, and it does not have any relevant impact on survival. Exclusive radiotherapy or stereotaxic radiotherapy could be an alternative to surgery in patients whose general condition is poor or who have concomitant extra-pituitary metastases.

Late diagnosis of primary hyperoxaluria type III.

We report the case of a 78-year-old patient with late diagnosis of hyperoxaluria type III (PH3). He developed renal failure after nephrectomy for clear cell papillary renal carcinoma and complained of recurrent urolithiasis for some 30 years, whose aetiology was never identified. Biochemical laboratory investigations of urine and urolithiasis composition revealed marked hyperoxaluria but normal concentrations of urinary glyceric and glycolic acid as well as stones of idiopathic calcium-oxalate appearance. Furthermore, the dietary survey showed excessive consumption of food supplements containing massive amounts of oxalate precursors. However, the persistence of excessive hyperoxaluria after his eating habits was changed leading us to perform molecular genetic testing. We found heterozygous mutations of the recently PH3-associated HOGA1 gene when sequencing PH genes. This is the first description of late diagnosis primary PH3 in a patient with several additional pro-lithogenic factors. This case illustrates the importance of undertaking a complete biological work-up to determine the aetiology of hyperoxaluria. This may reveal underdiagnosed primary hyperoxaluria, even in older patients.

A decade of pharmacogenomics research on tyrosine kinase inhibitors in metastatic renal cell cancer: a systematic review.

OBJECTIVE: The individual response to targeted tyrosine kinase inhibitors (TKIs) in the treatment of metastatic renal cell cancer (mRCC) is highly variable. Outlined in this article are findings on potential biomarkers for TKI treatment outcome in mRCC and an evaluation of the status of clinical implementation. METHODS: Articles were selected by two independent reviewers using a systematic search in five medical databases on renal cell carcinoma, TKIs, and pharmacogenetics. RESULTS: Many researchers have focused on predictive biomarkers for treatment outcome of targeted therapies in mRCC patients. Attempts to explain differences in efficacy and toxicity of TKIs by use of genetic variants in genes related to the pharmacokinetics and pharmacodynamics of the drug have been successful. CONCLUSION: Most findings on potential biomarkers have not been validated and therefore biomarker testing to guide choice of therapy and dose in mRCC is not yet feasible.

Outcome of genetic evaluation of patients with kidney cancer referred for suspected hereditary cancer syndromes.

OBJECTIVE: To analyze patients with kidney cancer referred for evaluation at a high-volume genetics service at a comprehensive cancer center and identify factors associated with positive tests for hereditary cancer syndromes. METHODS: A retrospective review of patients referred to the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center was performed, and patients with a personal history of kidney cancer were identified. Patient and disease characteristics were reviewed. In all, 4 variables including age at diagnosis of kidney tumor, presence of syndromic manifestations, family history of kidney cancer, and number of primary malignancies were evaluated for association with positive test results in 2 groups: patients tested for renal cell carcinoma syndromes and Lynch syndrome. Guidance for genetic testing strategy in patients with kidney cancer is provided. RESULTS: Between 1999 and 2012, 120 patients with a history of kidney cancer were evaluated by the Clinical Genetics Service. The mean age at kidney cancer diagnosis was 52 years (interquartile range: 42-63), with 57% being women. A family history of kidney cancer was reported by 39 patients (33%). Time between diagnosis of first cancer and genetic consultation was <1 year in 54%, 2 to 5 years in 23%, and>5 years in the remaining 23%. Overall, 95 patients were tested for genetic abnormalities with 27 (28%) testing positive. Testing for renal cell carcinoma (RCC)-related syndromes was performed on 43 patients, with 13 testing positive (30%). Lynch syndrome testing was positive in 9 patients (32%) after 28 were tested. In RCC-associated syndromes, young age of diagnosis was associated with positive test results. Conversely, syndromic manifestations and increasing number of primary malignancies were associated with positive Lynch testing. CONCLUSIONS: The discovery of inherited kidney cancer syndromes has provided a unique opportunity to identify patients at increased risk for cancer. Factors associated with positive genetic testing are unique to different syndromes. These data suggest that in kidney cancer patients evaluated for hereditary cancer syndromes, young age is associated with diagnosis of RCC syndromes, whereas syndromic manifestations and multiple primaries are found in Lynch syndrome. These results, along with clinical awareness, may be useful for practicing urologists to select patients with kidney cancer to refer for genetic counseling.

The impact of FGFR1 and FRS2α expression on sorafenib treatment in metastatic renal cell carcinoma.

BACKGROUND: Angiogenesis plays a role in tumor growth and is partly mediated by factors in both the fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) pathways. Durable clinical responses with VEGF tyrosine kinase inhibitors (TKIs) may be limited by intrinsic tumor resistance. We hypothesized that FGF signaling may impact clinical responses to sorafenib. METHODS: Nephrectomy material was available from 40 patients with metastatic renal cell carcinoma (RCC) enrolled in a phase II clinical trial of sorafenib ± interferon (ClinicalTrials.gov Identifier NCT00126594). Fibroblast growth factor receptor 1 (FGFR1) and fibroblast growth factor receptor substrate 2 alpha (FRS2α) expression was assessed by in situ hybridization and immunofluorescence, respectively. The relationship between fibroblast growth factor pathway marker levels and progression-free survival (PFS) was analyzed using Kaplan-Meier and Cox proportional hazards regression methods. RESULTS: Univariate analysis indicated that more intense FGFR1 staining was associated with shorter PFS (log-rank P = 0.0452), but FRS2α staining was not significantly associated with PFS (log-rank P = 0.2610). Multivariate Cox proportional hazards regression models were constructed for FGFR1 and FRS2α individually, adjusting for baseline Eastern Cooperative Oncology Group performance status, treatment arm and anemia status. When adjusted for each of these variables, the highest intensity level of FGFR1 (level 3 or 4) had increased progression risk relative to the lowest intensity level of FGFR1 (level 1) (P = 0.0115). The highest intensity level of FRS2α (level 3 or 4) had increased progression risk relative to the lowest intensity level of FRS2α (level 1) (P = 0.0126). CONCLUSIONS: Increased expression of FGFR1 and FRS2α was associated with decreased PFS among patients with metastatic RCC treated with sorafenib. The results suggest that FGF pathway activation may impact intrinsic resistance to VEGF receptor inhibition.

Proteins S100A8 and S100A9 are potential biomarkers for renal cell carcinoma in the early stages: results from a proteomic study integrated with bioinformatics analysis.

In order to investigate the two members of the EF­hand Ca2+ binding protein S100 family, S100A8 and S100A9, in renal cell carcinoma (RCC), serum samples were collected from patients with RCC, transitional cell carcinoma in the kidney, benign renal masses and normal controls. The samples were analyzed by isobaric tags for relative and absolute quantification technology to identify the differential expression of S100A8 and S100A9 in the respective groups. Hierarchical clustering analysis was then conducted for the samples and the relevant selected gene. The cross­platform analysis for the external validation was performed by means of The Cancer Genome Atlas database, containing the gene/microRNA expression pattern and clinical information of patients with RCC. Immunohistochemical staining was used to verify the expression of S100A8 and S100A9 in the four groups. As a result, serum and mRNA expression levels of S100A8 and S100A9 were found to be upregulated in patients with RCC compared with the other three groups, which was consistent with the result of the upregulated expression of mRNA levels in RCC tissue. The overexpression of S100A8 and S100A9 in cancer cells was also confirmed by immunohistochemistry. In addition, bioinformatics revealed that let­7, a microRNA formerly identified as an inhibiting factor of RCC was downregulated in RCC, which contrasted with S100A8. It was also complementary to the sequence at the 3' untranslated region terminal of S100A8. Therefore, indicating that S100A8 and S100A9 may serve as biomarkers for the detection of RCC.

Efficacy and toxicity of sunitinib for non clear cell renal cell carcinoma (RCC): a systematic review of the literature.

BACKGROUND: The randomized phase III trial of sunitinib versus interferon Alfa provided level-A evidence for the use of sunitinib in advanced clear cell renal cell carcinoma (RCC). This systematic literature review aims at the evaluation of the level of evidence for the use of sunitinib monotherapy for advanced non clear cell RCC in terms of efficacy and toxicity parameters. METHODS: Eligible studies were identified using MEDLINE, Google scholar, ASCO, ESMO and the Cochrane databases. Searches were last updated on 1 June 2014. Eligible studies reported survival and/or response data for patients with non clear cell RCC receiving sunitinib monotherapy. RESULTS: four hundred and five results were obtained from the searches in MEDLINE (n=319 studies) and other databases (n=86). Twelve studies (involving 980 patients) were considered eligible and were included in the final analysis: six phase II clinical trials, one expanded access prospective trial and five retrospective analyses. Median PFS was reported in 11 studies ranging from 1.6 to 8.9 months. Median OS was reported in 9 studies ranging from 12 months to 22 months. The disease control rate (DCR) was reported in 10 studies, and it ranged from 35% to 91%. The overall response rate (ORR) was reported in 10 studies and it ranged from 0% to 36%. Frequently reported Grade 3/4 toxicities were gastrointestinal toxicities, mucocutaneous toxicities and hematologic toxicities. CONCLUSION: There is insufficient evidence (level C) to recommend sunitinib monotherapy in advanced non clear cell RCC and the available data suggests it appears less efficacious than that in advanced clear cell RCC. Further prospective and randomized studies are needed to explore alternative therapies in this setting.

Prognostic factors in renal cell carcinoma patients treated with sorafenib: results from the Czech registry.

The aim of this study was to describe the characteristics and outcomes of a large cohort of patients treated with sorafenib in clinical practice and to identify predictive factors associated with prognosis. Patient data were obtained from the national Czech registry (RenIS). Data of virtually all Czech patients receiving targeted therapies are entered into this non-interventional post-registration database. Demographics and clinical data, as well as all treatment sequences and clinical outcomes, are reported in this registry. A total of 836 patients treated with sorafenib before March 2013 were included in the analysis. Median age was 63 years and 70% were men. Most patients had received prior treatment with cytokines, sunitinib or both. Sorafenib was the first-line treatment in 15% of patients. Median overall survival and progression-free survival were 21.7 months and 7.5 months, respectively. Median overall survival and progression-free survival was 26.3 and 8.3 months, respectively, in patients receiving sorafenib as first-line therapy. Cox proportional models identified several parameters associated with poor outcome including time ≤1 year from diagnosis to first-line systemic treatment, performance status ≥2, low hemoglobin, and LDH >1.5 times the upper limit of normal. Our data demonstrate that the outcomes of real-life patients are comparable to those enrolled in clinical trials. Prognostic factors identified in the present study were consistent with previously reported models.

Survival trends among patients with advanced renal cell carcinoma in the United States.

INTRODUCTION: Since the approval of sorafenib in December 2005, several targeted therapeutic agents have been approved by the FDA for the treatment of advanced renal cell carcinoma (RCC). This study was conducted to find out whether the improvements in survival of advanced RCC patients with targeted agents have translated into a survival benefit in a population-based cohort. METHODS: We analyzed the SEER 18 (Surveillance, Epidemiology and End RESULTS) registry database to calculate the relative survival rates for advanced RCC patients during 2001-2009, 2001-2005, 2006-2007 and 2008-2009. We also evaluated the survival rates by age (<65 and ≥65 years) and sex. RESULTS: The total number of advanced RCC patients during 2001-2009, 2001-2005, 2006-2007 and 2008-2009 were 7,047, 4,059, 1,548 and 1,440, respectively. During 2001-2009, the 1- and 3-year relative survival rates were 26.7±0.6 and 10.0±0.4%, respectively. There was no significant difference in 1-year relative survival rates for patients diagnosed during 2006-2007 and 2008-2009 compared to those diagnosed during 2001-2005. Similarly, the 3-year survival rates for patients diagnosed during 2006-2007 were similar to those diagnosed during 2001-2005. CONCLUSIONS: This population-based study showed that there was no significant improvement in relative survival rates among advanced RCC patients in the era of targeted agents.

Evaluation of changes in the tumor microenvironment after sorafenib therapy by sequential histology and 18F-fluoromisonidazole hypoxia imaging in renal cell carcinoma.

The mechanistic dissociation of 'tumor starvation' versus 'vascular normalization' following anti-angiogenic therapy is a subject of intense controversy in the field of experimental research. In addition, accurately evaluating changes of the tumor microenvironment after anti-angiogenic therapy is important for optimizing treatment strategy. Sorafenib has considerable anti-angiogenic effects that lead to tumor starvation and induce tumor hypoxia in the highly vascularized renal cell carcinoma (RCC) xenografts. 18F-fluoromisonidazole (18F­FMISO) is a proven hypoxia imaging probe. Thus, to clarify early changes in the tumor microenvironment following anti-angiogenic therapy and whether 18F-FMISO imaging can detect those changes, we evaluated early changes in the tumor microenvironment after sorafenib treatment in an RCC xenograft by sequential histological analysis and 18F-FMISO autoradiography (ARG). A human RCC xenograft (A498) was established in nude mice, for histological studies and ARG, and further assigned to the control and sorafenib-treated groups (80 mg/kg, per os). Mice were sacrificed on Days 1, 2, 3 and 7 in the histological study, and on Days 3 and 7 in ARG after sorafenib treatment. Tumor volume was measured every day. 18F-FMISO and pimonidazole were injected intravenously 4 and 2 h before sacrifice, respectively. Tumor sections were stained with hematoxylin and eosin and immunohistochemically with pimonidazole and CD31. Intratumoral 18F-FMISO distribution was quantified in ARG. Tumor volume did not significantly change on Day 7 after sorafenib treatment. In the histological study, hypoxic fraction significantly increased on Day 2, mean vessel density significantly decreased on Day 1 and necrosis area significantly increased on Day 2 after sorafenib treatment. Intratumoral 18F-FMISO distribution significantly increased on Days 3 (10.2-fold, p<0.01) and 7 (4.1-fold, p<0.01) after sorafenib treatment. The sequential histological evaluation of the tumor microenvironment clarified tumor starvation in A498 xenografts treated with sorafenib. 18F-FMISO hypoxia imaging confirmed the tumor starvation. 18F-FMISO PET may contribute to determine an optimum treatment protocol after anti-angiogenic therapy.

Early assessment by FDG-PET/CT of patients with advanced renal cell carcinoma treated with tyrosine kinase inhibitors is predictive of disease course.

BACKGROUND: We reported previously that (18)F-2-fluoro-2-deoxyglucose positron emission tomography/ computed tomography (FDG PET/CT) had potential for evaluating early response to treatment by tyrosine kinase inhibitors (TKIs) in advanced renal cell carcinoma (RCC). This time we investigated the relation of the early assessment by FDG PET/CT to long-term prognosis with an expanded number of patients and period of observation. METHODS: Patients for whom TKI treatment for advanced RCC was planned were enrolled. FDG PET/CT was performed before TKI treatment and after one month of TKI treatment. The relations of the FDGPET/CT assessment to progression free survival (PFS) and overall survival (OS) were investigated. RESULTS: Thirty-five patients were enrolled (sunitinib 19 cases, sorafenib 16 cases). The patients with RCC showing high SUVmax in pretreatment FDG PET/CT demonstrated short PFS (P =0.024, hazard ratio 1.137, 95% CI 1.017-1.271) and short OS (P =0.004, hazard ratio 1.210 95% CI 1.062-1.379). Thirty patients (sunitinib 16 cases, sorafenib 14 cases) were evaluated again after 1 month. The PFS of the patients whose SUVmax decreased<20% was shorter than that of the patients whose SUVmax decreased<20% (P = 0.027, hazard ratio 3.043, 95% CI 1.134-8.167). The PFS of patients whose tumor diameter sum increased was shorter than that of the patient with tumors whose diameter sum did not (P =0.006, hazard ratio 4.555, 95% CI 1.543-13.448). The patients were classified into three response groups: good responder (diameter sum did not increase, and SUVmax decreased ≥ 20%), intermediate responder (diameter sum did not increase, and SUVmax decreased<20%), and poor responder (diameter sum increased, or one or more new lesions appeared). The median PFS of good, intermediate, and poor responders were 458 ± 146 days, 131 ± 9 days, and 88 ± 26 days (good vs. intermediate P = 0.0366, intermediate vs. poor P = 0.0097, log-rank test). Additionally the mean OSs were 999 ± 70 days, 469 ± 34 days, and 374 ± 125 days, respectively (good vs. intermediate P = 0.0385, intermediate vs. poor P = 0.0305, log-rank test). CONCLUSIONS: The evaluation of RCC response to TKI by tumor size and FDG uptake using FDG PET/CT after 1 month can predict PFS and OS.

Baseline patient-reported kidney cancer-specific symptoms as an indicator for median survival in sorafenib-refractory metastatic renal cell carcinoma.

INTRODUCTION: The goal of the study was to determine the relationship of baseline Functional Assessment of Cancer Therapy-Kidney Cancer Symptom Index (FKSI) scores with median progression-free survival (mPFS) and median overall survival (mOS) after treatment with axitinib in patients with sorafenib-refractory metastatic renal cell carcinoma. METHODS: As part of a multicenter, open-label, phase II study, patients (N = 62) reported symptoms at baseline using the FKSI, with higher scores indicating less severe symptoms. A Weibull (fully parametric) model was fit to time-to-event data to establish the relationship of baseline FKSI score with mPFS and mOS. Kaplan-Meier curves were obtained as sensitivity analyses. RESULTS: Longer progression-free and overall survivals were associated with higher (more favorable) baseline FKSI-15 and FKSI disease-related symptoms (FKSI-DRS) subscale specific to kidney cancer scores. For example, for FKSI-15 scores of 0 (most symptoms), 30, and 60 (no symptoms), the mPFS were 0.72, 3.83, and 20.43 months, respectively, and the mOS were 1.05, 6.27, and 37.53 months. Similar patterns and interpretations were observed for the FKSI-DRS scores. The results from the Kaplan-Meier analyses supported the parametric model. DISCUSSIONS/CONCLUSIONS: Baseline patient-reported kidney cancer symptoms are linked to mPFS and mOS in a clear and interpretable way. These results support the evaluation of patient-reported symptoms at baseline in clinical trials and in clinical practice to measure symptom severity and potentially predict progression-free and overall survival outcomes. IMPLICATIONS FOR CANCER SURVIVORS: The results provide a heightened opportunity to use patient data not only to assist in medical treatment planning but also to prepare patients, who have advanced disease and an already reduced expected lifespan, with an opportunity to deal with the psychosocial aspects of the dying process.