pT1 Renal Cell Carcinoma Research Articles

Impact of the COVID-19 pandemic on diagnosis of renal cell carcinoma and disease stage at presentation.

Renal cell carcinoma (RCC) is often associated with significant morbidity and mortality, with overall survival contingent on multiple factors - most importantly, disease stage at diagnosis. Disruptions in healthcare delivery during the COVID-19 pandemic have resulted in various reported diagnostic and treatment delays, which have had detrimental impacts on malignancies such as RCC. Surgically managed cases of RCC at our center were identified using a retrospective chart review of all nephrectomies conducted from March 1, 2018, to February 28, 2023. Examination of disease characteristics in three time period cohorts (before, during, and following the COVID-19 pandemic) was undertaken. Timeframes were consistent with implementation and abolition of public health restrictions in the province of Newfoundland and Labrador. A total of 483 surgically managed RCC cases were identified during the study period. The median age was 65 years (interquartile range [IQR] 56-71), and 62.3% of patients were male. Demographics did not vary across timeframes. Before and during the pandemic, pathologic stage 3 (pT3) disease was reported in 38.9% and 35.4% of cases, respectively, whereas the post-pandemic period saw this presentation in 50.0% of patients. Surgical wait times increased significantly across study timeframes (p=0.003). The first year following the COVID-19 pandemic saw an 11.1% increase in patients presenting with pT3 RCC. These findings are suggestive of a clinically significant stage migration, which paired with prolonged wait times for surgery, provide critical consideration in the urgency of diagnostic and treatment decisions for RCC in the immediate future.

Is chest imaging needed as part of pT1a renal cell carcinoma surveillance after surgical resection?

IntroductionFollowing surgical excision of pT1a renal cell carcinoma (RCC), 2% to 5% will recur, with 50% to 60% being lung metastases. The ideal surveillance strategy to identify recurrences is unclear. Guidelines are mixed, with NCCN and AUA recommending surveillance via chest x-ray (CXR) at least annually for 5 years, while EAU guidelines do not specifically recommend the use of CXR. In an effort to clarify the utility of surveillance CXR, we retrospectively evaluated pT1a patients following surgical treatment at a single institution. MethodsWe performed retrospective analysis of unique patients who underwent surgical excision of pT1 RCC between January 2000 and January 2020. In addition to demographic information, we collected RCC pathology, recurrence details, and most recent chest imaging. We excluded non-RCC pathology, and patients with pulmonary nodules on baseline imaging. ResultsWe identified 463 unique patients (mean age 58.3 years, range 23–87) that underwent surgical excision of pT1a RCC with mean follow-up of 47.6 months (range 1–201). On the most recent pulmonary surveillance imaging, 72.4% (335/463) had CXR while 27.6% (128/463) had chest CT performed. Regardless of modality, pulmonary recurrence was not detected on any surveillance imaging (0/463). ConclusionIn patients without baseline preoperative lung pathology, we found that there is questionable clinical value in surveillance for pulmonary recurrence after resection of pT1a RCC.

Predictors of disease recurrence in high-risk non-metastatic renal cell carcinoma patients post-surgical resection A single-center, retrospective study.

Approximately 20-40% of kidney cancer patients treated for localized disease experience post-surgical recurrence. Several prognostic models exist to help clinicians determine the risk of distant recurrence, but these models vary in criteria and endpoints. We aimed to examine the recurrence rate and clinicopathologic factors as predictors of recurrence in high-risk renal cell carcinoma (RCC) patients. We conducted a single-center, retrospective chart review of pT3 RCC patients who underwent a nephrectomy between January 2000 and December 2015. Patients registered in clinical trials for adjuvant therapy and those with fewer than three years of followup were excluded. Kaplan-Meier survival analysis and univariate and multivariate Cox regression were performed to identify the rate and predictors of disease recurrence. Eighty-eight pT3 RCC patients were included, and 39 patients had recurrence with a median of 23.5 months (range 1.6-127.5). Nine patients had disease recurrence beyond 58 months. Kaplan-Meier log-rank tests identified patients with negative surgical margins and low Fuhrman nuclear grades had greater recurrence-free survival. Univariate Cox regression revealed positive surgical margins, high Fuhrman nuclear grade, and large tumor sizes were significant predictors. In the multivariate Cox regression model, high Fuhrman nuclear grade and positive surgical margins were significant predictors of recurrence. Disease recurrence occurred in 44% of pT3-staged patients. High Fuhrman nuclear grade and positive surgical margins were associated with time to recurrence. Physicians should use prognostic models to facilitate conversations about disease recurrence and continue to monitor high-risk patients beyond the recommended five-year followup period. We recommend monitoring pT3 resected patients for up to 10 years post-surgery.

MP04-02 BACTERIA-DERIVED DNA IN EXTRACELLULAR VESICLES OF SERUM COULD BECOME A NOVEL DIAGNOSTIC BIOMARKER FOR RENAL CELL CARCINOMA

You have accessJournal of UrologyCME1 Apr 2023MP04-02 BACTERIA-DERIVED DNA IN EXTRACELLULAR VESICLES OF SERUM COULD BECOME A NOVEL DIAGNOSTIC BIOMARKER FOR RENAL CELL CARCINOMA Toshihiro Uemura, Atsunari Kawashima, Kentaro Jingushi, Sassi Nesrine, Toshiki Oka, Yohei Okuda, Akinaru Yamamoto, Gaku Yamamichi, Eisuke Tomiyama, Yu Ishizuya, Yoshiyuki Yamamoto, Taigo Kato, Koji Hatano, and Norio Nonomura Toshihiro UemuraToshihiro Uemura More articles by this author , Atsunari KawashimaAtsunari Kawashima More articles by this author , Kentaro JingushiKentaro Jingushi More articles by this author , Sassi NesrineSassi Nesrine More articles by this author , Toshiki OkaToshiki Oka More articles by this author , Yohei OkudaYohei Okuda More articles by this author , Akinaru YamamotoAkinaru Yamamoto More articles by this author , Gaku YamamichiGaku Yamamichi More articles by this author , Eisuke TomiyamaEisuke Tomiyama More articles by this author , Yu IshizuyaYu Ishizuya More articles by this author , Yoshiyuki YamamotoYoshiyuki Yamamoto More articles by this author , Taigo KatoTaigo Kato More articles by this author , Koji HatanoKoji Hatano More articles by this author , and Norio NonomuraNorio Nonomura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003215.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There is no clinically established diagnostic biomarker for renal cell carcinoma (RCC) patients. This study aimed to identify a novel diagnostic biomarker using bacteria-derived DNA (b-DNA) in extracellular vesicles (EVs) of serum. METHODS: A total of 88 clear cell RCC patients underwent radical or partial nephrectomy, and 10 healthy controls were enrolled in cohort A. EVs were collected from serum just before surgery and prior to antibiotic administration, and metagenomic sequencing was performed after amplification of 16S ribosomal RNA gene. Linear discriminant analysis effect size was used to compare b-DNA from both groups (Figure 1). Significantly abundant b-DNA in serum EVs of RCC patients were used to establish an index for RCC diagnosis. A total of 32 RCC patients and 16 controls were enrolled in cohort B for validation. RESULTS: In cohort A, three kinds of b-DNA (Bacteroidia, TM7-1 and Sphingomonadales) were significantly abandant in serum EVs of RCC patients (Figure 2). In ROC analysis, the area under the curve (AUC) of each b-DNA was 0.66 (Bacteroidia), 0.68 (TM7-1), and 0.72 (Sphingomonadales), respectively. We established BTS index using three kinds of b-DNA to diagnose RCC patients, and it could distinguish RCC patients from healthy controls (AUC=0.88, sensitivity 89%, specificity 40%). Logistic regression analysis showed that BTS index was an independent factor for RCC diagnosis both in all patients (Odds ratio [OR] 5.9, 95% Confidence interval [CI] 1.3-26.1, p=0.02) and in early-stage (pT1) RCC patients (OR 6.0, 95% CI 1.2-29.7, p=0.03). Finally, also in cohort B, BTS index could distinguish RCC patients from healthy controls (sensitivity 91%, specificity 40%), and it was an independent factor for RCC diagnosis both in all patients (OR 6.0, 95% CI 1.2-28.8, p=0.03) and in pT1 RCC patients (OR 7.5, 95% CI 1.3-45.5, p=0.03). CONCLUSIONS: B-DNA in serum EVs could become a novel diagnostic biomarker for RCC. Source of Funding: This work was supported by a KAKENHI grant (22K09469, 22H03213) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e33 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Toshihiro Uemura More articles by this author Atsunari Kawashima More articles by this author Kentaro Jingushi More articles by this author Sassi Nesrine More articles by this author Toshiki Oka More articles by this author Yohei Okuda More articles by this author Akinaru Yamamoto More articles by this author Gaku Yamamichi More articles by this author Eisuke Tomiyama More articles by this author Yu Ishizuya More articles by this author Yoshiyuki Yamamoto More articles by this author Taigo Kato More articles by this author Koji Hatano More articles by this author Norio Nonomura More articles by this author Expand All Advertisement PDF downloadLoading ...

MP64-18 RECLASSIFICATION OF PATHOLOGICALLY UPSTAGED T3A RENAL CELL CARCINOMA IS LINKED WITH ENHANCED ALIGNMENT OF OUTCOMES: ANALYSIS OF THE NATIONAL CANCER DATABASE

You have accessJournal of UrologyCME1 Apr 2023MP64-18 RECLASSIFICATION OF PATHOLOGICALLY UPSTAGED T3A RENAL CELL CARCINOMA IS LINKED WITH ENHANCED ALIGNMENT OF OUTCOMES: ANALYSIS OF THE NATIONAL CANCER DATABASE Dhruv Puri, Luke Wang, Margaret Meagher, Aastha Shah, Franklin Liu, Saeed Ghassemzadeh, Mimi Nguyen, Kevin Hakimi, Cesare Saitta, Jonathan Afari, Sohail Dehanji, Ryan Nasseri, Juan Javier-Desloges, and Ithaar Derweesh Dhruv PuriDhruv Puri More articles by this author , Luke WangLuke Wang More articles by this author , Margaret MeagherMargaret Meagher More articles by this author , Aastha ShahAastha Shah More articles by this author , Franklin LiuFranklin Liu More articles by this author , Saeed GhassemzadehSaeed Ghassemzadeh More articles by this author , Mimi NguyenMimi Nguyen More articles by this author , Kevin HakimiKevin Hakimi More articles by this author , Cesare SaittaCesare Saitta More articles by this author , Jonathan AfariJonathan Afari More articles by this author , Sohail DehanjiSohail Dehanji More articles by this author , Ryan NasseriRyan Nasseri More articles by this author , Juan Javier-DeslogesJuan Javier-Desloges More articles by this author , and Ithaar DerweeshIthaar Derweesh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003322.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Pathological upstaging to pT3a disease can occur after surgical treatment of clinical T1 and T2 Renal Cell Carcinoma (RCC), and upstaging to T3 RCC is associated with poorer outcomes. Nonetheless pT3a RCC is a heterogeneous group with a wide variance in outcomes. With an intent to delve deeper into the disparateness in outcomes of pT3a disease, we investigated the outcomes of patients with an initial clinical stage of cT1, cT2 and cT3a. METHODS: Using the National Cancer Database, patients with RCC were categorized by pathological and clinical staging of RCC according to American Joint Committee on Cancer (AJCC) criteria. The primary outcome was measured as overall survival (OS). Kaplan-Meier Analysis (KMA) assessed differences between cT1 upstaged to pT3a RCC (cTa→pT3a), cT2 upstaged to pT3a RCC (cT2→pT3a), clinical/pathological T2 RCC (cT2→pT2), and clinical/pathological T3a RCC (T3a → pT3a). Multivariable cox regression (MVA) assessed predictors for OS evaluating clinical and pathological disease status. ROC/AUC analysis was utilized to compare predictive value of AJCC 8th edition TNM staging vs proposed staging. RESULTS: 53741 patients with pT3a disease were analyzed (10785 cT1→pT3a; 9675 cT2→pT3a, 22025 cT2→pT2; and 11256 cT3a→pT3a). MVA for OS [cT1→pT3a (referent)] demonstrated that cT2→pT3a (HR=1.33, p<0.001) and cT3a→pT3a (HR=1.35, p<0.001) were associated with worsened OS, while cT2→pT2 (HR=0.96, p=0.05) was not significantly different from referent. KMA revealed a difference in 5-year OS (cT1→pT3a 73.1%; cT2→pT2 78.0%; cT2→pT3a 60.8%; and cT3a→pT3a 59.9%, p<0.001). As such we proposed to align cT1→pT3a and cT2→pT2 into a new pT2 group while maintaining cT2→pT3a and cT3a→pT3a in a new pT3a (5 year OS new pT2 vs. new pT3a: 78.0% vs. 60.3%, p=0.003). ROC analysis revealed an AUC of 0.500 (p=0.005) for OS using the current AJCC 8th edition TNM staging and an AUC of 0.563 (p=0.003) for OS for our new proposal. CONCLUSIONS: Reclassification of cT1→pT3a and cT2→ pT2 into a new pT2 RCC while maintaining cT2→ pT3a and cT3a→pT3a RCC as a new pT3a RCC resulted in improved performance of realigned model for OS. Revision of TNM criteria for T2 and T3a RCC may lead to improved predictive ability and less heterogeneity in outcomes. Source of Funding: Insitutional © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e888 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Dhruv Puri More articles by this author Luke Wang More articles by this author Margaret Meagher More articles by this author Aastha Shah More articles by this author Franklin Liu More articles by this author Saeed Ghassemzadeh More articles by this author Mimi Nguyen More articles by this author Kevin Hakimi More articles by this author Cesare Saitta More articles by this author Jonathan Afari More articles by this author Sohail Dehanji More articles by this author Ryan Nasseri More articles by this author Juan Javier-Desloges More articles by this author Ithaar Derweesh More articles by this author Expand All Advertisement PDF downloadLoading ...

Muscle mass change using linear measurement analysis after nephrectomy for pT3 and pT4 renal cell carcinoma is associated with mortality

AbstractBackgroundPreoperative skeletal muscle deficiency is an established risk factor for poor survival outcomes in patients with renal cell carcinoma (RCC). However, given the dynamic nature of skeletal muscle associated with malignancy, there is a need to evaluate the prognostic benefit of muscle area change from the preoperative to postoperative period. We hypothesize that an improvement in muscle area following nephrectomy, measured by linear segmentation of L3 psoas and paraspinal musculature, is associated with improvement in overall survival (OS) and cancer specific survival (CSS) for patients with pT3 and pT4 RCC.MethodsWe retrospectively analysed 270 pT3 and pT4 RCC patients who underwent nephrectomy from March 2004 to February 2020 with available preoperative and postoperative axial CT or MRI studies segmented at the L3 vertebrae. The majority were N0 (79%) and M0 (68%). Psoas and paraspinal muscles were measured bilaterally using a validated digital ruler tool. Total muscle area (TMA) was calculated by aggregating the area of all four muscles and total muscle area index (TMI) by dividing the TMA by height squared (m2). The prognostic value of postoperative muscle improvement, defined as any increase in muscle area index, was analysed using Kaplan–Meier and Cox proportional stepwise hazard models.ResultsMedian time between preoperative scans and surgery was approximately 22 days and between surgery and postoperative scans 172 days. One hundred twenty‐one patients (44.8%) had an increase in total muscle area index post‐nephrectomy (IQR = 33.4; P ≤ 0.0001). On Kaplan–Meier analysis, postoperative improvement in TMI was associated with decreased odds of mortality (P = 0.0024) with a median follow‐up of 38.6 months. In a multivariable Cox regression analysis, improvement of TMI was associated with increased OS (HR = 0.52, 95% CI 0.35–0.78, P &lt; 0.001) and increased CSS (HR = 0.55, 95% CI 0.32–0.94, P = 0.030). A 5% or more improvement in TMI was also associated with increased OS (HR = 0.53, 95% CI 0.34–0.84, P = 0.006) and increased CSS (HR = 0.46, 95% CI 0.24–0.86, P = 0.015).ConclusionsAny improvement in TMI between preoperative and initial postoperative imaging after nephrectomy was associated with increased OS and CSS in patients with pT3 and pT4 RCC. Perioperative linear segmentation is an efficient tool that may improve current prognostication methods and can be performed on any imaging software platform.

MP24-11 IS PATHOLOGICAL UPSTAGING TO T3 RENAL CELL CARCINOMA ASSOCIATED WITH A SIMILAR PROGNOSIS TO NON-UPSTAGED PATHOLOGIC T3 DISEASE? A MULTICENTER ANALYSIS

You have accessJournal of UrologyCME1 May 2022MP24-11 IS PATHOLOGICAL UPSTAGING TO T3 RENAL CELL CARCINOMA ASSOCIATED WITH A SIMILAR PROGNOSIS TO NON-UPSTAGED PATHOLOGIC T3 DISEASE? A MULTICENTER ANALYSIS Ryan Nasseri, Kevin Hakimi, Ava Saidian, Riccardo Autorino, Brian Lane, Yasuha Fujii, Michele Marchioni, Hajime Tanaka, Dattatraya Patil, Francesco Porpiglia, Sabrina Noyes, Chandru Sundaram, James Porter, Andrea Minervini, Umberto Capitianio, Francesco Montorsi, Viraj Master, and Ithaar Derweesh Ryan NasseriRyan Nasseri More articles by this author , Kevin HakimiKevin Hakimi More articles by this author , Ava SaidianAva Saidian More articles by this author , Riccardo AutorinoRiccardo Autorino More articles by this author , Brian LaneBrian Lane More articles by this author , Yasuha FujiiYasuha Fujii More articles by this author , Michele MarchioniMichele Marchioni More articles by this author , Hajime TanakaHajime Tanaka More articles by this author , Dattatraya PatilDattatraya Patil More articles by this author , Francesco PorpigliaFrancesco Porpiglia More articles by this author , Sabrina NoyesSabrina Noyes More articles by this author , Chandru SundaramChandru Sundaram More articles by this author , James PorterJames Porter More articles by this author , Andrea MinerviniAndrea Minervini More articles by this author , Umberto CapitianioUmberto Capitianio More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Viraj MasterViraj Master More articles by this author , and Ithaar DerweeshIthaar Derweesh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002563.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Pathological upstaging to T3a disease may occur following radical (RN) or partial nephrectomy (PN) for patients with T1/T2 renal cell carcinoma (RCC). Follow up and perceived prognosis for these patients is similar to those who initially presented with clinical T3 RCC. We sought to compare survival outcomes in patients who underwent surgical therapy for upstaged versus non-upstaged pT3 RCC. METHODS: We conducted a retrospective analysis of a multi-institutional dataset of patients who underwent radical (RN) or partial nephrectomy (PN) with final pathologic stage of pT3. Patients were classified as being upstaged (US) from cT1 or cT2 or non-upstaged (NUS) with cT3 disease. Primary outcome was cancer specific survival (CSS)/cancer specific mortality (CSM), with secondary outcomes being Overall Survival (OS)/all-cause mortality (ACM) and Progression/progression-free survival (PFS). Multivariable Cox regression analysis (MVA) was conducted for predictors of mortality outcomes and Kaplan Meier Analyses (KMA) were conducted for survival outcomes comparing US and NUS groups. RESULTS: 1232 patients were analyzed (853 US/379 NUS; median follow up 46.2 months). MVA for CSM found that clear cell RCC (HR 2.1, p <0.001), positive surgical margin (HR 1.7, p=0.047), and NUS (HR 1.5, p=0.003) were independently associated with worsened CSM. MVA for ACM revealed age (HR 1.01, p=0.002), RN (HR 2.5, p <0.001), preoperative GFR <60 (HR 1.4, p=0.007), clear-cell RCC (HR 1.4, p=0.007), positive surgical margin (HR 2.2, p <0.001), and NUS (1.27, p=0.023) were independently associated with worsened ACM. MVA for Progression revealed Age (HR 1.01, p=0.022), positive margin (HR 1.9, p=0.016), and NUS (HR 1.67, p <0.001) to be predictive. Comparing NUS and US groups, KMA revealed worsened 5 year CSS (56% vs. 75%, p <0.001; Figure), 5 year OS (42% vs. 58%, p <0.001) and 5 year PFS (33% vs. 58%, p <0.001). CONCLUSIONS: Pathologic upstaging of clinical T1/T2 to T3 RCC was associated with improved survival outcomes when compared to non-upstaged pathologic T3 RCC. Such differences need to be taken into account when designing follow up protocols and for refinement of risk stratification in the T3 RCC stage group. Further investigation is requisite. Source of Funding: Stephen Weissman Kidney Cancer Research Fund © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e396 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ryan Nasseri More articles by this author Kevin Hakimi More articles by this author Ava Saidian More articles by this author Riccardo Autorino More articles by this author Brian Lane More articles by this author Yasuha Fujii More articles by this author Michele Marchioni More articles by this author Hajime Tanaka More articles by this author Dattatraya Patil More articles by this author Francesco Porpiglia More articles by this author Sabrina Noyes More articles by this author Chandru Sundaram More articles by this author James Porter More articles by this author Andrea Minervini More articles by this author Umberto Capitianio More articles by this author Francesco Montorsi More articles by this author Viraj Master More articles by this author Ithaar Derweesh More articles by this author Expand All Advertisement PDF DownloadLoading ...

Nephrectomy Delay of More than 10 Weeks from Diagnosis Is Associated with Decreased Overall Survival in pT3 RCC.

In this study, we aimed to evaluate the impact of surgical wait time (SWT) on outcomes of patients with renal cell carcinoma (RCC), and to investigate risk factors associated with prolonged SWT. Using the National Cancer Database, we retrospectively reviewed the records of patients with pT3 RCC treated with radical or partial nephrectomy between 2004 and 2014. The cohort was divided based on SWT. The primary outcome was 5-year overall survival (OS). Logistic regression analysis was used to investigate the risk factors associated with delayed surgery. Cox proportional hazards models were fitted to assess relations between SWT and 5-year OS after adjusting for confounding factors. A total of 22,653 patients were included in the analysis. Patients with SWT > 10 weeks had higher occurrence of upstaging. Using logistic regression, we found that female patients, African-American or Spanish origin patients, treatment in academic or integrated network cancer center, lack of insurance, median household income of <$38,000, and the Charlson–Deyo score of ≥1 were more likely to have prolonged SWT. SWT > 10 weeks was associated with decreased 5-year OS (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.15–1.33). This risk was not markedly attenuated after adjusting for confounding variables, including age, gender, race, insurance status, Charlson–Deyo score, tumor size, and surgical margin status (adjusted HR, 1.13; 95% CI, 1.04–1.24). In conclusion, the vast majority of patients underwent surgery within 10 weeks. There is a statistically significant trend of increasing SWT over the study period. SWT > 10 weeks is associated with decreased 5-year OS.

Reply to "Predictors of Recurrence for T3a RCC: A Recurring Conundrum".

We really appreciate Leopold et al's thoughtful comments in response to our manuscript regarding the prognostic value of pT3 renal cell carcinoma (RCC)-related features [...].

MP50-06 UTILIZATION OF RADIOMIC MARKERS IN LOCALIZED RENAL CELL CARCINOMA TO PREDICT STAGE

INTRODUCTION AND OBJECTIVE: Incidental pT3a upstaging following partial nephrectomy (PN) for cT1 renal masses is associated with inferior oncologic outcomes. The ability to identify tumor characteristics associated with pathologic upstaging using current imaging protocols is limited. The inclusion of quantitative radiomic imaging characteristics in pre-operative staging may improve the detection of adverse pathologic features. We sought to evaluate whether any radiomic features were associated with pathologic upstaging following PN for cT1 renal masses. METHODS: Pre-operative CT imaging from a total of 130 patients with cT1 renal masses and final pathology demonstrating either pT1 (n=92) or pT3a (n=45) renal cell carcinoma were retrospectively reviewed. T1 patients were matched by age and tumor size with pT3a patients in a 2:1 ratio. An Auto-Initialized Cascaded Level Set (AI-CALS) system was used to segment 139 renal lesions. 49 radiomic descriptors including morphological features (volume, shape) and gray level features were extracted from segmented lesions. A predictive model was developed using automatic feature selection and linear discriminant analysis classifier. A leave-one-lesion out cross validation method was used for model training and performance testing. The area under the receiver operating characteristic curve (AUC) was calculated for the predictor model to evaluate its performance in predicting cancer stage (pT1 or pT3a). RESULTS: We identified one gray level and 4 shape features of significance in our predictive model. Features related to surface irregularity of the renal mass appeared to be highly predictive in distinguishing between pT1a and pT3a cancers. The training AUC was 0.72 and the test AUC was 0.70. The results from the test AUC were graphed. The AUC for our training set was 0.72 dropping only slightly to 0.70 in our validation set (figure). CONCLUSIONS: Machine learning techniques show promise in decision support for renal cell carcinoma staging. The ability to predict pathologic stage prior to intervention could help guide treatment selection or identify patients for future neoadjuvant trials. Future work will focus on tool and feature optimization and incorporating clinical and biopsy data into the predictive model.Source of Funding: None

Outcomes and prognosticators of stage 4 renal cell carcinoma with pathological T4 primary lesion using a large, Canadian, multi-institutional database.

The primary objective of this study was to evaluate outcomes and prognosticators in patients who underwent radical nephrectomy (RN) or cytoreductive nephrectomy (CN), depending on the clinical stage of disease preoperatively, with a pathological T4 (pT4) renal cell carcinoma (RCC) outcome. There is little data on the outcome of this specific subset of patients. From 2009-2016, we identified patients in the Canadian Kidney Cancer information system (CKCis) who underwent RN or CN and were found to have pT4 RCC. Clinical, operative, and pathological variables were analyzed with univariable and multivariable Cox proportional hazard models to identify factors associated with overall survival (OS). Survival curves were created using Kaplan-Meier methods and compared using the log-rank test. A total of 82 patients were included in the study cohort. Median patient age was 62 years (interquartile range [IQR] 55, 70). Fifty (61%) patients had clear-cell histology and 14 (17%) had sarcomatoid characteristics. Median followup was 12 months (IQR 3, 24). At last followup, eight (10%) patients are alive with no evidence of disease, 27 (33%) are alive with disease, four (5%) were lost to followup, 36 (44%) died of disease, and seven (8%) died of other causes. Tumor histological subtype (clear-cell vs. non-clear-cell) (p=0.0032), larger tumor size (cm) (p=0.012), and Fuhrman grade (G4 vs. G2-G3) (p=0.045) were significantly associated with mortality in a multivariable Cox regression model. For patients with pT4 RCC after RN or CN, survival is poor. Sarcomatoid features, non-clear-cell histology, and presence of systemic symptoms were associated with worse OS.

Radical Nephrectomy with or without Lymph Node Dissection for pT3 Renal Cell Carcinoma: A Propensity Score-based Analysis.

Objectives: To study whether radical nephrectomy (RN) with lymph node dissection (LND) can benefit pT3 renal cell carcinoma (RCC) patients versus no LND under the 2018 American Joint Committee on Cancer TNM classification system.Subjects/Patients and Methods: We performed a retrospective cohort study of clinicopathological data for 245 T3 RCC patients, who underwent radical nephrectomy between January 2006 and December 2013 at our center, including 67 (27.1%) who underwent LND. The relationships between the LND and progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) were evaluated using 1:1 propensity score (PS) matching. Then, Kaplan-Meier survival analysis and Cox regression analysis were conducted to study whether these patients can benefit from LND. Depending on the LND number, we divided the cohort into two groups for further comparation. At last, we validated the results with the TCGA database KIRC patients.Results: The median follow-up time was 4.9 years. Sixty-seven pairs of patients were screened by the PS and were further analyzed. We conducted a Cox regression with the survival data and found that the LND group, compared with the non-LND group, showed no survival benefit on PFS, CSS, and OS (p = 0.444, 0.809, and 0.816, respectively). However, the removal of 5 or more LNs showed negative effect on OS (p = 0.0387). TCGA cohort results are mostly consistent with our findings.Conclusion: RN with LND cannot improve the PFS, CSS, or OS for pT3 renal cell carcinoma patients.

Risk-adjusted proposal for >60months follow up after surgical treatment of organ-confined renal cell carcinoma according to life expectancy.

To determine the long-term oncological outcome of organ-confined (<pT3) renal cell carcinoma. We identified 889 patients with complete long-term follow-up data, who had been surgically treated for renal cell carcinoma (<T3) at our institution between 1976 and 2009. Kaplan-Meier analysis was used to assess the incidence and time interval of recurrence defined as local recurrences or metastases. We further compared patients who had tumor progression before or after 60months. After a median follow-up period of 74.33months (range 3-329months), 44 patients (4.9%) had disease recurrence. A total of 38.6% of the recurrences occurred after 60months; 76.2% of patients had distant metastases and 23.8% of patients had local recurrences. In patients with low-grade (G1) and low-stage (pT1a) tumors, there was a trend to develop recurrence or metastases after longer intervals. Patients with lung metastasis and patients with multiple metastatic locations developed these metastases earlier than patients with bone metastasis. The risk of dying of other causes correlated with age, but the time interval to metastases did not. Current guidelines recommend a follow-up period of 60months after surgical treatment of organ-confined renal cell carcinoma. Our data shows that one-third of recurrences of <pT3 renal cell carcinoma occur after 60months. According to our oncological analysis, we suggest an age-adjusted strategy of follow-up balancing the risk of tumor recurrence and the life expectancy of the patient.

The use of partial nephrectomy in the treatment of patients with pT1/pT2 renal cell carcinoma: a trend analysis from a tertiary referral centre

In patients with localised renal cell carcinoma, the only curative treatment option is surgical tumour excision. Current national and European guidelines recommend partial nephrectomy in the form of an open or minimally-invasive procedure in case of small tumours. The aim of this study was to examine the use of radical (RN) or partial (PN) nephrectomy performed as open or minimally-invasive procedures in patients with pT1 /pT2 renal cell carcinoma at a tertiary referral centre. This retrospective study included a total of 758 patients with localised renal cell carcinoma (pT1/pT2), who underwent PN or RN between 01/2008 and 10/2014. Nephrectomy was either performed as an open (OPN, ORN), laparoscopic (LPN, LRN) or robot-assisted laparoscopic (RAPN) procedure. Out of 758 patients, 439 (57.9 %) underwent PN performed as an LPN in n = 254 (57.9 %) and OPN in n = 185 (42.1 %). 319 patients (42.1 %) underwent RN performed as an LRN in n = 250 (78.4 %) and ORN in n = 69 (21.6 %). Between 2008 and 2014, there was a trend towards the use of PN, especially in patients with pT1a and pT1b. The majority of patients with pT2 underwent RN, performed as an LRN in 40 - 53.9 %. The results of this trend analysis from a tertiary referral centre demonstrate an increased use of PN and minimally-invasive procedures over time, as recommend by national and European guidelines.

Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with locally advanced renal cell carcinoma (RCC) (PROTECT).

4507 Background: PROTECT (NCT01235962) evaluated the efficacy and safety of pazopanib (PAZ) versus placebo in patients (pts) with locally advanced renal cell carcinoma (RCC) post nephrectomy. Methods: 1538 pts with resected pT2 (high grade), pT3 or greater clear cell RCC were randomly assigned to PAZ or placebo for 1 year. The starting dose (800 mg) following treatment of 403 pts was lowered to 600 mg to improve tolerability and primary endpoint was changed to disease-free survival (DFS) with PAZ 600 (N = 1135). Primary analysis was performed after 350 DFS events in intent-to-treat (ITT) PAZ 600, and DFS follow-up analysis was performed after an additional 12 months. Secondary endpoints included DFS with ITT PAZ 800 and ITT ALL, and safety. Results: Disease characteristics were similar between arms. The primary analysis results of DFS ITT 600 were not significant [HR: 0.862; 95% CI, 0.699, 1.063; p = 0.165] (Table). The secondary endpoint of DFS in ITT PAZ 800 and ITT ALL yielded 31% and 20% risk reduction, respectively. Updated DFS analysis in ITT 600 showed a higher HR with longer follow up. Increased ALT and AST were the most common adverse events leading to treatment discontinuation in the PAZ 600 (ALT 16% and AST 5%) and PAZ 800 (ALT 18% and AST 7%) groups. Conclusions: The study did not meet the primary DFS endpoint in ITT 600; however, a 31% decrease in the risk of recurrence was observed in ITT 800. The safety profiles in the 600 mg and 800 mg groups were similar and consistent with PAZ prior experience. Clinical trial information: NCT01235962. [Table: see text]

Clinical and pathological prognostic factors for the long-term survival of patients with pT1 renal cell carcinoma

Introduction The incidence of renal cell carcinoma (RCC) has been increasing over the past few decades. Simultaneously, due to improved imaging, small renal masses at stage pT1 have been diagnosed more frequently. However, it is known that even small RCCs may recur and metastasize at a late point of time. This study aimed to identify easy-to-assess clinical and histopathological prognostic markers for long-term survival. Patients/Methods We performed a retrospective analysis of patients who underwent surgical treatment of a pT1 RCC in a single centre between 1993 and 2007. The prognostic impact of clinical and histopathological parameters was investigated regarding recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). Univariate Kaplan-Meier analysis and multivariate Cox regression analysis were performed using SPSS 23. Results Overall, 571 patients were included with a median follow-up of 111 months. Univariate analysis revealed that higher grading (p = 0.031) and stage pT1b (p < 0.001) were statistically significantly associated with worse RFS. Likewise, stage pT1b (p = 0.001) and grading G2/3 (p = 0.019) were significantly associated with shorter CSS. Multivariate analysis revealed that stage pT1b was the only predictor for reduced RFS (p = 0.001) and CSS (p = 0.009). Total nephrectomy (p = 0.024), and diabetes (p < 0.001) were significantly associated with reduced OS. Multivariate analysis revealed that multifocal tumours (p = 0.041) and diabetes (p < 0.001) were the best predictive factors for OS. Conclusion The identified prognostic parameters may help to provide a risk-adapted after follow-up for patients with small renal tumours.

Impact of preoperative thrombocytosis on prognosis after surgical treatment in pathological T1 and T2 renal cell carcinoma: results of a multi-institutional comprehensive study.

BackgroundThe prognostic significance of preoperative thrombocytosis (TC) in renal cell carcinoma (RCC) is not without some debate. The aim of the present multi-institutional study was to determine the association of preoperative TC with the clinicopathological features and prognosis of localized RCC patients who underwent surgery in a large cohort.MethodsA study involving 8 institutions, and 4,376 patients with pT1 and pT2 RCC from the Korean renal cell carcinoma (KORCC) database, was conducted. TC was defined as a platelet count ≥400,000/μL. Patients were divided into 2 groups based on the presence of preoperative TC. Clinicopathological variables and survival rates were compared between the 2 groups.ResultsOut of the 4,376 patients in the study, 106 (2.4%) had preoperative TC. Compared to patients without TC, these patients had a lower body mass index. Additionally, these patients had more advanced stage tumors with a higher Fuhrman grade, and higher incidence of symptoms at the time of diagnosis. Kaplan-Meier curves revealed that patients with TC had a significantly lower rate of recurrence-free survival (RFS). Furthermore, a lower rate of overall survival (OS) was exhibited amongst patients with TC. Multivariate analysis revealed that TC was an independent prognostic factor in terms of the RFS and OS.ConclusionsTC appeared to be an important prognostic determinant in localized RCC. Furthermore, preoperative platelet count may be clinically useful for risk stratification of patients with surgically treated localized RCC.

651 - Utility of chest x-ray in follow-up of pT1 renal cell carcinoma

651 - Utility of chest x-ray in follow-up of pT1 renal cell carcinoma

Utility of prospective pathologic evaluation to inform clinical genetic testing for hereditary leiomyomatosis and renal cell carcinoma.

Patients with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) resulting from fumarate hydratase (FH) mutations may present with skin, uterine, and renal tumors, with each having unique pathologic features. This study investigated the association between prospectively identified suspicious pathology (SP) and FH mutations when patients were referred for genetic testing. This was an institutional review board-approved cohort study of patients receiving FH testing from 2008 to 2013. SP was defined as a report of HLRCC histologic features identified during a prospective pathologic assessment. The association between SP and FH mutations was analyzed. FH testing was performed in 29 patients with a median age of 37 years; 15 (52%) were female, and 18 (62%) were white. Pathologists reported SP from kidney tumors (11 of 18), leiomyomas (9 of 15: uterus [n = 8] and bladder [n = 1]), and metastatic tumors (3 of 6) in 23 of 39 associated specimens (59%) from 21 of the 29 patients (72%). Patients with SP were younger (35 vs 51 years; P = .010), and those with kidney tumors more often had stage pT3 or higher renal cell carcinoma than those without SP (100% vs 33%; P = .006). FH mutations were present in 8 patients with SP (38%) and in 1 patient without SP (13%; P = .37); 7 of these patients had kidney cancer (n for SP = 7), all with N1 disease. Analyzing SP by tissue type identified only SP from renal tumors as being significantly associated with positive testing for an FH mutation (P = .013). SP from kidney tumors was statistically associated with FH mutations. An expert pathologic assessment of renal tumors will facilitate the clinical identification of HLRCC cases, and this will result in genetic testing and targeted cancer screening for patients and at-risk family members. Cancer 2017;123:2452-58. © 2017 American Cancer Society.

Urinary collecting system invasion is associated with poor survival in patients with clear-cell renal cell carcinoma.

To evaluate the prognostic significance of urinary collecting system invasion (UCSI) in a large series of patients with clear-cell renal cell carcinoma (RCC). Patients with clear-cell RCC treated with nephrectomy between 2001 and 2010 were reviewed from a prospectively maintained registry. One urological pathologist re-reviewed all slides. Cancer-specific survival was estimated using the Kaplan-Meier method, and associations of UCSI with death from RCC were evaluated using Cox models. Of the 859 patients with clear-cell RCC, 58 (6.8%) had UCSI. At last follow-up, 310 patients had died from RCC at a median of 1.8 years after surgery. The median follow-up for patients alive at last follow-up was 8.2 years. The estimated cancer-specific survival at 10 years after surgery for patients with UCSI was 17%, compared with 60% for patients without UCSI (P < 0.001). In a multivariable model, UCSI remained independently associated with an increased risk of death from RCC (hazard ratio 1.5; P = 0.018). Further, among patients with pT3 RCC, those with USCI had survival outcomes similar to those of patients with pT4 RCC. Collecting system invasion is associated with poor prognosis among patients with clear-cell RCC. If validated, consideration should be given to including UCSI in future staging systems.