Phase I/IIa trial of 18F-prostate specific membrane antigen (PSMA) 1007 PET/CT in healthy volunteers and prostate cancer patients.

OBJECTIVE: 18F-PSMA 1007 is a promising PET tracer for prostate cancer. We aimed to examine the safety, biodistribution, radiation dosimetry, and clinical effectiveness in Japanese healthy volunteers and patients with prostate cancer. METHODS: Part A evaluated the pharmacokinetics and exposure doses in three healthy volunteers. Part B evaluated the diagnostic accuracy in patients with untreated preoperative prostate cancer (Cohort 1, n = 7) and patients with biochemical recurrence (Cohort 2, n = 3). All subjects received a single dose of 3.7 MBq/kg 18F-PSMA 1007. Results: 18F-PSMA 1007 was found to be safe and well tolerated in all subjects. No serous AEs or drug-related AEs were identified during the present study. The average blood radioactivity concentration reached a maximum of 47.87 ± 1.05 (percentage of injected dose [%ID]/ml) at 5 min and then decreased to 1.60 ± 0.78 in 6 h. The systemic radioactivity reached a maximum of 211.05 ± 6.77 (%ID$\times$103) at 5 min and decreased to 7.18 ± 3.91 in 6 h. The sensitivity and positive predictive value were 100% and 100% based on both pathologic and imaging confirmation as gold standard. In Cohort 1, 15 primary foci (11.9%) were >5 mm in the largest diameter and identified in 39 of 126 segments (30.1%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for 60 min uptake time acquisition were 80.0, 96.5, 91.4, 91.2 and 91.3%, respectively. CONCLUSIONS: Our study revealed that 18F-PSMA 1007 was safe, well tolerated and showed high accuracy in the diagnosis of prostate cancer.

Stepwise algorithm using computed tomography and magnetic resonance imaging for differential diagnosis of fat-poor angiomyolipoma in small renal masses: A prospective validation study.

OBJECTIVES: To validate the diagnostic accuracy of a stepwise algorithm to differentiate fat-poor angiomyolipoma (fp-AML) from renal cancer in small renal masses (SRMs). METHODS: We prospectively enrolled 223 patients with solid renal masses <4 cm and no visible fat on unenhanced computed tomography (CT). Patients were assessed using an algorithm that utilized the dynamic CT and MRI findings in a stepwise manner. The diagnostic accuracy of the algorithm was evaluated in patients whose histology was confirmed through surgery or biopsy. The clinical course of the patients was further analyzed. RESULTS: The algorithm classified 151 (68%)/42 (19%)/30 (13%) patients into low/intermediate/high AML probability groups, respectively. Pathological diagnosis was made for 183 patients, including 10 (5.5%) with fp-AML. Of these, 135 (74%)/36 (20%)/12 (6.6%) were classified into the low/intermediate/high AML probability groups, and each group included 1 (0.7%)/3 (8.3%)/6 (50%) fp-AMLs, respectively, leading to the area under the curve for predicting AML of 0.889. Surgery was commonly opted in the low and intermediate AML probability groups (84% and 64%, respectively) for initial management, while surveillance was selected in the high AML probability group (63%). During the 56-month follow-up, 36 (82%) of 44 patients initially surveyed, including 13 of 18 (72%), 6 of 7 (86%), and 17 of 19 (89%) in the low/intermediate/high AML probability groups, respectively, continued surveillance without any progression. CONCLUSIONS: This study confirmed the high diagnostic accuracy for differentiating fp-AMLs. These findings may help in the management of patients with SRMs.

Novel utility of Vesical Imaging-Reporting and Data System in multimodal treatment for muscle-invasive bladder cancer.

OBJECTIVES: To examine the clinical significance of the Vesical Imaging-Reporting and Data System (VI-RADS) in predicting outcome of multimodal treatment (MMT) in muscle-invasive bladder cancer (MIBC) patients. METHODS: We reviewed 78 pathologically proven MIBC patients who underwent MMT including transurethral resection and chemoradiotherapy, followed by partial or radical cystectomy. Treatment response was assessed through histologic evaluation of cystectomy specimens. Two radiologists categorized the index lesions of pretherapeutic MRI according to the 5-point VI-RADS score. The associations of VI-RADS score with the therapeutic effect of MMT were analyzed. The diagnostic performance of VI-RADS scores with a cut-off VI-RADS scores ≤ 2 or ≤ 3 for predicting pathologic complete response to MMT (MMT-CR) was evaluated. RESULTS: MMT-CR was achieved in 2 (100%) of VI-RADS score 1 (n = 2), 16 (84%) of score 2 (n = 19), 12 (86%) of score 3 (n = 14), 7 (64%) of score 4 (n = 11), and 14 (44%) of score 5 (n = 32). VI-RADS score was inversely associated with the incidence of MMT-CR (p = 0.00049). The cut-off VI-RADS score ≤ 2 and ≤ 3 could predict the favorable therapeutic outcome of MMT with high specificity (0.89 with 95% confidence interval [CI]: 0.71-0.98 and 0.82 with 95% CI: 0.62-0.94, respectively) and high positive predictive value (0.86 with 95% CI: 0.64-0.97 and 0.86 with 95% CI: 0.70-0.95, respectively). CONCLUSION: VI-RADS score may serve as an imaging marker in MIBC patients for predicting the therapeutic outcome of MMT. CLINICAL RELEVANCE STATEMENT: Muscle-invasive bladder cancer patients with a lower Vesical Imaging-Reporting and Data System score can be a good candidate for bladder-sparing treatment incorporating multimodal treatment. KEY POINTS: • Vesical Imaging-Reporting and Data System (VI-RADS) score was potentially valuable for classifying pathologic tumor response in patients with muscle-invasive bladder cancer. • The likelihood of achieving complete response of multimodal treatment (MMT) decreased with increasing VI-RADS score. • VI-RADS score could serve as an imaging marker that optimizes patient selection for MMT.

Patterns of recurrence in genuine and induced oligometastatic castration-resistant prostate cancer treated with progressive site-directed therapy.

OBJECTIVES: To describe oncological outcomes after progressive site-directed therapy (PSDT) in genuine and induced oligometasatic (OM)-castration-resistant prostate cancer (CRPC). METHODS: Thirty-seven patients with OM-CRPC treated with PSDT were retrospectively analyzed, and oncological outcomes and recurrence patterns on whole-body diffusion-weighted MRI (WB-DWI) were evaluated. RESULTS: Twenty-two (59%) were classified as genuine OM-CRPC and 15 (41%) as induced OM-CRPC. A 50% decline in PSA after PSDT was observed in 21 (95%) genuine OM-CRPCs and 7 (47%) induced OM-CRPCs (p = 0.0005). At a median observation period of 7.3 months, median PSA progression-free survival were 10.9 months in the genuine OM-CRPCs and 4.8 months in the induced OM-CRPCs (p = 0.015). Among the patients who developed PSA progression after PSDT, 11 of 15 in the genuine OM-CRPCs (73%) and 11 of 14 in the induced OM-CRPCs (79%) underwent WB-DWI at PSA progression. The median numbers of newly detected metastases were 2 (range: 1-5) in the genuine OM-CRPCs and 4 (range: 1-40) in the induced OM-CRPCs (p = 0.049). Only one new metastasis appeared in 5 patients from the genuine OM-CRPCs (46%) and 1 from the induced OM-CRPCs (9.1%, p = 0.048). In 7 of 9 patients from the genuine OM-CRPCs (78%) and 7 of 8 patients from the induced OM-CRPCs (88%) who had bone metastases alone, the newly detected metastasis limited to the bone. CONCLUSIONS: Genuine OM-CRPC had better oncological outcomes after PSDT than induced OM-CRPC, and the number of lesions detected at recurrence was limited. Induced OM-CRPC might be a disseminated condition with micrometastases at OM diagnosis.

Prognostic impact of the radiological infiltrative feature of primary renal tumor in metastatic renal cell carcinoma.

OBJECTIVES: Recent studies suggest that the radiological infiltrative feature (r-IF) of renal tumors is strongly correlated with poor oncologic outcomes in locally advanced renal cell carcinoma (RCC). This study investigated the prognostic impact of r-IF of primary renal tumors in metastatic RCC (mRCC) in comparison with International Metastatic RCC Database Consortium (IMDC) risk model. METHODS: We retrospectively analyzed 91 patients with previously untreated mRCC. Dynamic computed tomography of the primary renal tumor was reviewed to assess r-IF, defined as a focally/extensively ill-defined tumor interface with normal renal parenchyma. RESULTS: The median age was 67 years, and 69 patients (76%) were men. Prior nephrectomy was performed in 47 patients (52%). The median size of the primary renal tumor was 6.7 cm, and 50 patients (55%) presented with cT3-4 stage. Overall, 25 (28%)/52 (57%)/14 (15%) patients were classified into IMDC favorable/intermediate/poor-risk groups, respectively. An image review identified r-IFs in the primary renal tumor in 40 patients (44%). The incidences of r-IFs were 28%/46%/64% in IMDC favorable/intermediate/poor-risk groups, respectively. During a median follow-up of 2.6 years, 31 patients (34%) died of RCC. On multivariable analysis, r-IF and IMDC intermediate-poor risks were independently associated with poor cancer-specific survival (CSS). Two-year CSS were 64%/87% in patients with/without r-IF, respectively. C-index was improved from 0.73 to 0.81 by adding r-IF to the IMDC risk factors. CONCLUSIONS: R-IF of the primary renal tumor was an independent risk factor for poor CSS in patients with mRCC, which may improve the prognostic accuracy when combined with the IMDC risk model.

Usefulness of texture features of apparent diffusion coefficient maps in predicting chemoradiotherapy response in muscle-invasive bladder cancer.

OBJECTIVES: To examine the usefulness of the texture analysis (TA) of apparent diffusion coefficient (ADC) maps in predicting the chemoradiotherapy (CRT) response of muscle-invasive bladder cancer (MIBC). METHODS: We reviewed 45 MIBC patients who underwent cystectomy after CRT. CRT response was assessed through histologic evaluation of cystectomy specimens. Two radiologists determined the volume of interest for the index lesions on ADC maps of pretherapeutic 1.5-T MRI and performed TA using the LIFEx software. Forty-six texture features (TFs) were selected based on their contribution to the prediction of CRT sensitivity. To evaluate diagnostic performance, diagnostic models from the selected TFs were created using random forest (RF) and support vector machine (SVM), respectively. RESULTS: Twenty-three patients achieved pathologic complete response (pCR) to CRT. The feature selection identified first quartile ADC (Q1 ADC), gray-level co-occurrence matrix (GLCM) correlation, and GLCM homogeneity as important in predicting CRT response. Patients who achieved pCR showed significantly lower Q1 ADC and GLCM correlation values (0.66 × 10-3 mm2/s and 0.53, respectively) than those who did not (0.81 × 10-3 mm2/s and 0.70, respectively; p < 0.05 for both). The AUCs of the RF and SVM models incorporating the selected TFs were 0.82 (95% confidence interval [CI]: 0.67-0.97) and 0.96 (95% CI: 0.91-1.00), respectively, and the AUC of the SVM model was better than that of the mean ADC value (0.76, 95% CI: 0.61-0.90; p = 0.0037). CONCLUSION: TFs can serve as imaging biomarkers in MIBC patients for predicting CRT sensitivity. TAs of ADC maps can potentially optimize patient selection for CRT. KEY POINTS: • Texture analysis of ADC maps and feature selection identified important texture features for classifying pathologic tumor response in patients with muscle-invasive bladder cancer. • The machine learning model incorporating the texture features set, which included first quartile ADC, GLCM correlation, and GLCM homogeneity, showed high performance in predicting chemoradiotherapy response. • Texture features could serve as imaging biomarkers that optimize eligible patient selection for chemoradiotherapy in muscle-invasive bladder cancer.

A Pilot Study Analyzing the Clinical Utility of Comprehensive Genomic Profiling Using Plasma Cell-Free DNA for Solid Tumor Patients in Japan (PROFILE Study).

BACKGROUND: The clinical utility of plasma cell-free DNA in precision cancer medicine has not been established. A pilot study was conducted to investigate the clinical utility of comprehensive genomic profiling by liquid biopsy in a Japanese population. METHODS: In this PROFILE study, 102 patients with advanced solid tumors who showed progression with standard systemic therapy underwent liquid biopsy between August 2017 and February 2020. Liquid biopsy was performed using Guardant360. RESULTS: Of the 102 patients, 56 were women, and the median age was 65 years. Regarding the types of cancer, 31 were hepatobiliary and pancreatic cancer, 17 were gastrointestinal cancer, and 13 were breast cancer. Frequently altered genes were TP53 (53.9%, 46/102), KRAS (25.5%, 26/102), PIK3CA (19.6%, 20/102), and EGFR (17.6%, 18/102). At least one genetic aberration was detected in 92 patients (90.2%). Actionable mutation was discovered in 88 patients (86.3%), and 67 patients (65.7%) were clinical trial candidates. Of the 102 patients, 22 (21.6%) were able to receive biomarker-matched therapy. Their best responses were as follows: 1 complete response, 3 partial responses, 7 stable diseases, and 11 progressive diseases. Additionally, the treated patients were divided on the basis of matching scores (≥ 50% vs. < 50%). The patients were divided into high and low groups. The high group had a higher disease control rate (DCR) of 75% compared with 20% in the low group (P = 0.010). CONCLUSIONS: The results indicate that liquid biopsy is useful for identifying actionable mutations associated with the clinical response of selected patients.

Virtual Interpolation Images of Tumor Development and Growth on Breast Ultrasound Image Synthesis With Deep Convolutional Generative Adversarial Networks.

OBJECTIVES: We sought to generate realistic synthetic breast ultrasound images and express virtual interpolation images of tumors using a deep convolutional generative adversarial network (DCGAN). METHODS: After retrospective selection of breast ultrasound images of 528 benign masses, 529 malignant masses, and 583 normal breasts, 20 synthesized images of each were generated by the DCGAN. Fifteen virtual interpolation images of tumors were generated by changing the value of the input vector. A total of 60 synthesized images and 20 virtual interpolation images were evaluated by 2 readers, who scored them on a 5-point scale (1, very good; to 5, very poor) and then answered whether the synthesized image was benign, malignant, or normal. RESULTS: The mean score of overall quality for synthesized images was 3.05, and that of the reality of virtual interpolation images was 2.53. The readers classified the generated images with a correct answer rate of 92.5%. CONCLUSIONS: A DCGAN can generate high-quality synthetic breast ultrasound images of each pathologic tissue and has the potential to create realistic virtual interpolation images of tumor development.

Infiltrative tumor interface with normal renal parenchyma in locally advanced renal cell carcinoma: Clinical relevance and pathological implications.

OBJECTIVES: Locally advanced renal cell carcinoma is considered clinically aggressive, despite heterogeneity in survival outcomes. We investigated the clinical relevance and pathological implications of infiltrative tumor interface with normal renal parenchyma on preoperative imaging in locally advanced renal cell carcinoma. METHODS: A total of 77 patients with locally advanced renal cell carcinoma (≥pT3a Nany M0) who underwent radical or partial nephrectomy (2008-2018) were analyzed. Preoperative dynamic computed tomography images were reviewed to assess radiological infiltrative features. A radiological infiltrative feature was defined as an ill-defined tumor interface with normal renal parenchyma. The tumor interfaces were analyzed histologically and compared with radiological findings. RESULTS: The median tumor size was 6.4 cm. Lymphadenopathy was observed in four patients (5.2%). Clear cell renal cell carcinoma was diagnosed in 66 patients (86%) and Fuhrman grade was 3-4 in 38 patients (49%). A total of 30 patients (39%) showed radiological infiltrative features, which were significantly associated with larger tumor size and higher clinical T stage. The specificity and sensitivity of radiological infiltrative features in predicting pathological renal parenchymal infiltration were 90 and 64%, respectively. During a median follow-up period of 3.8 years, 27 patients (35%) developed cancer recurrences, and six patients (7.8%) died of renal cell carcinoma. Multivariable analysis showed that the presence of radiological infiltrative features was an independent risk factor for cancer recurrence. Cancer recurrence and cancer-specific mortality were significantly stratified by the presence or absence of radiological infiltrative features (P < 0.001 and P = 0.02, respectively). CONCLUSIONS: Locally advanced renal cell carcinoma can show radiological infiltrative features preoperatively, which are significantly associated with unfavorable prognosis. Radiological infiltrative features on preoperative imaging correspond with a high specificity to pathological renal parenchymal infiltration.

Can Deep Learning-Based Volumetric Analysis Predict Oxygen Demand Increase in Patients with COVID-19 Pneumonia?

Background and Objectives: This study aimed to investigate whether predictive indicators for the deterioration of respiratory status can be derived from the deep learning data analysis of initial chest computed tomography (CT) scans of patients with coronavirus disease 2019 (COVID-19). Materials and Methods: Out of 117 CT scans of 75 patients with COVID-19 admitted to our hospital between April and June 2020, we retrospectively analyzed 79 CT scans that had a definite time of onset and were performed prior to any medication intervention. Patients were grouped according to the presence or absence of increased oxygen demand after CT scan. Quantitative volume data of lung opacity were measured automatically using a deep learning-based image analysis system. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of the opacity volume data were calculated to evaluate the accuracy of the system in predicting the deterioration of respiratory status. Results: All 79 CT scans were included (median age, 62 years (interquartile range, 46-77 years); 56 (70.9%) were male. The volume of opacity was significantly higher for the increased oxygen demand group than for the nonincreased oxygen demand group (585.3 vs. 132.8 mL, p < 0.001). The sensitivity, specificity, and AUC were 76.5%, 68.2%, and 0.737, respectively, in the prediction of increased oxygen demand. Conclusion: Deep learning-based quantitative analysis of the affected lung volume in the initial CT scans of patients with COVID-19 can predict the deterioration of respiratory status to improve treatment and resource management.

[Clinical Utility of Comprehensive Genome Profiling Using FoundationOne CDx in Japanese Population(PROFILE-F Study)].

BACKGROUND: FoundationOne CDx is a cancer genome profiling test that has already been approved by the FDA, but its clinical utility in Japanese patients is unknown. In this study, we examined the clinical utility of FoundationOne CDx. METHODS: 46 samples from 43 Japanese pretreated patients with advanced solid tumors were tested with FoundationOne CDx between September 2018-January 2019. RESULTS: The median age of 43 patients was 63 years(ranged 18 to 82 years), and among them 24 were males and 19 females. Major cancer types were hepato-biliary and pancreatic(8 cases)and other digestive organs(8 cases). All 27 cases in which genome cancer board had been completed by January 17, 2019 were analyzable, and the number of detected gene mutations(except VUS)was an average of 4.3(ranged 0 to 14)per case. Of the 27 cases, one or more mutations were found in 26 cases(96%), and in all such 26 cases actionable mutations with candidates for therapeutic agents were found. In 4(15%)of them, the treatment corresponding to the gene mutation was performed. Among the cases in which target disease matched and clinical trials of the drug were being conducted in Japan, only one case participated in the trial. The most common reason for not participating in the trial was disease deterioration and PS reduction (33%). CONCLUSIONS: The FoundationOne CDx test showed that it can detect gene mutations in various cancer types in Japanese patients.

A diagnostic approach of various urethral diseases using multimodal imaging findings: comprehensive overview.

In clinical practice, urethral diseases are not as frequent as conditions affecting other components of the urinary system. Radiological imaging tests, such as retrograde urethrography, CT, MRI, and PET/CT, along with patient history, are crucial for accurately assessing relatively rare urethral lesions. This article aimed to provide a comprehensive overview of urethral lesions, from traumatic changes to neoplasms, and discuss the multimodal imaging findings of various urethral lesions that radiologists should know. To this end, the normal imaging anatomy of the urethra and a step-by-step approach that can be used in clinical practice have been presented to help in the systematic understanding of urethral lesions.

Detection support of lesions in patients with prostate cancer using 18 F -PSMA 1007 PET/CT.

PURPOSE: This study proposes a detection support system for primary and metastatic lesions of prostate cancer using 18 F -PSMA 1007 positron emission tomography/computed tomography (PET/CT) images with non-image information, including patient metadata and location information of an input slice image. METHODS: A convolutional neural network with condition generators and feature-wise linear modulation (FiLM) layers was employed to allow input of not only PET/CT images but also non-image information, namely, Gleason score, flag of pre- or post-prostatectomy, and normalized z-coordinate of an input slice. We explored the insertion position of the FiLM layers to optimize the conditioning of the network using non-image information. RESULTS: 18 F -PSMA 1007 PET/CT images were collected from 163 patients with prostate cancer and applied to the proposed system in a threefold cross-validation manner to evaluate the performance. The proposed system achieved a Dice score of 0.5732 (per case) and sensitivity of 0.8200 (per lesion), which are 3.87 and 4.16 points higher than the network without non-image information. CONCLUSION: This study demonstrated the effectiveness of the use of non-image information, including metadata of the patient and location information of the input slice image, in the detection of prostate cancer from 18 F -PSMA 1007 PET/CT images. Improvement in the sensitivity of inactive and small lesions remains a future challenge.

Kidney R2* Mapping for Noninvasive Evaluation of Iron Overload in Paroxysmal Nocturnal Hemoglobinuria.

PURPOSE: The kidney iron deposition can cause kidney damage and renal insufficiency in paroxysmal nocturnal hemoglobinuria (PNH) patients. Assessment of iron deposition in the kidney is essential for the early diagnosis of renal damage in PNH patients. The purpose of this study was to evaluate kidney R2* (T2* reciprocals) values in PNH patients using the iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ). METHODS: Two radiologists measured the R2* values of the renal cortex in 14 PNH patients and 13 healthy volunteers using IDEAL-IQ. Lactate dehydrogenase (LDH), a reliable marker of intravascular hemolysis, was also measured in all participants. RESULTS: The kidney R2* values were significantly higher in PNH patients compared with those in healthy volunteers (P < 0.001). High inter-operator reproducibility of the measurements was also acquired using IDEAL-IQ. LDH levels were also significantly higher in PNH patients compared with those in healthy volunteers (P < 0.001). Kidney R2* values strongly correlated with LDH levels in PNH patients. CONCLUSION: IDEAL-IQ has a possibility of becoming a useful method for the noninvasive evaluation of renal iron overload in PNH patients.

Motility Mapping Quantification Using the Classical Optical Flow Algorithm for Small Bowel Crohn's Disease: Comparison with Balloon-assisted Enteroscopy Findings.

PURPOSE: To quantify bowel motility shown on cine MRI using the classical optical flow algorithm and compare it with balloon-assisted enteroscopy (BAE) findings in patients with Crohn's disease (CD). METHODS: This retrospective study included 29 consecutive patients with CD who had undergone MR enterocolonography (MREC) and BAE between March and May 2017. We developed computer software to present motion vector magnitudes between consecutive cine MR images as bowel motility maps via a classical optical flow algorithm using the Horn-Schunck method. Cine MR images were acquired with a balanced steady-state free precession sequence in the coronal direction to capture small bowel motility. The small bowels were divided into three segments. In total, 63 bowel segments were assessed via BAE and MREC. Motility scores on the maps, simplified MR index of activity (sMaRIA), and MREC score derived from a 5-point MR classification were assessed independently by two radiologists and compared with the CD endoscopic index of severity (CDEIS). Correlations were assessed using Spearman's rank coefficient. The areas under the receiver-operating characteristic curve (AUCs) of motility score for differentiating CDEIS was calculated; a P value < 0.05 was considered statistically significant. RESULTS: Motility score was negatively correlated with CDEIS (r = -0.59 [P < 0.001] and -0.54 [P < 0.001]), and the AUCs of motility scores for detecting CDEIS ≥ 3 were 88.2% and 78.6% for observers 1 and 2, respectively. There were no significant differences in the AUC for detecting CDEIS ≥ 3 and CDEIS ≥ 12 between motility and sMaRIA or MREC score. CONCLUSION: The motility map was feasible for locally quantifying the bowel motility. In addition, the motility score on the map reflected the endoscopic inflammatory activity of each small bowel segment in patients with CD; hence, it could be used as a tool in objectively interpreting cine MREC to predict inflammatory activity in CD.

Defining Tumour Shape Irregularity for Preoperative Risk Stratification of Clinically Localised Renal Cell Carcinoma.

Background: Unexpected adverse pathology is a major concern in surgical management of clinically localised renal cell carcinoma (RCC). Further studies are needed to improve preoperative risk stratification. Objective: To define and classify tumour shape irregularity (TSI) based on preoperative imaging, and to investigate its effect on pathological and oncological outcomes in clinically localised RCC. Design setting and participants: We retrospectively analysed 474 patients with cT1-2N0M0 RCC managed by partial or radical nephrectomy. Preoperative dynamic computed tomography was used to define and classify TSI, graded as 1 (completely elliptical shape), 2 (elliptical shape with minor and focal protrusions), or 3 (nonelliptical shape presenting with major and/or extensive protrusions). Intervention: Partial or radical nephrectomy. Outcome measurements and statistical analysis: A logistic regression analysis evaluated the risk factors for pT3a upstaging and Fuhrman grade 3-4. A Cox proportional hazard analysis assessed preoperative variables for recurrence-free survival (RFS). Results and limitations: The median tumour size was 3.5 cm, and 94 patients (20%) had (R)adius (tumour size as maximal diameter), (E)xophytic/endophytic properties of tumour, (N)earness of tumour deepest portion to collecting system or sinus, (A)nterior (a)/posterior (p) descriptor, and (L)ocation relative to polar lines (RENAL) score ≥10. TSI was graded as 1, 2, and 3 in 214 (45%), 151 (32%), and 109 (23%) patients, respectively. Higher TSI was significantly associated with a larger tumour size and a higher RENAL score. Overall, pT3a upstaging and Fuhrman grade 3-4 were observed in 45 (9.5%) and 116 patients (31% in 380 clear cell RCC cases), respectively. The incidence of pT3a upstaging and Fuhrman grade 3-4 was significantly higher in patients with higher TSI (0.5%, 8.6%, and 28% for pT3a upstaging and 12%, 33%, and 60% for Fuhrman grade 3-4 in TSI 1, 2, and 3 groups, respectively). In multivariable analyses, higher TSI was independently associated with adverse pathological outcomes. During the median follow-up of 6.0 yr, 49 patients (10%) developed recurrence. Multivariable analyses demonstrated that older age and higher TSI were independent risk factors for worse RFS. The limitations include the retrospective design. Conclusions: TSI may be a useful adjunct in preoperative risk stratification for adverse pathology and recurrence after surgery in clinically localised RCC. Patient summary: Tumour shape irregularity is significantly associated with unfavourable pathological outcomes, that is, locally advanced stage or high-grade cancer, and with a higher recurrence rate after surgery in patients with clinically localised renal cell carcinoma. Preoperative evaluation of the tumour shape may help in patient counselling and treatment decisions.