Distinct prognostic and molecular profiles of fat versus vein invasion in T3a renal cell carcinoma.

To study the accuracy of CT for staging T3a (TNM 2009) renal cell carcinoma (RCC). Unenhanced and nephrographic phase CT studies of 117 patients (male:female = 82:35; age range, 21-86 years) with T1-T3a RCC were independently reviewed by 2 readers. The presence of sinus or perinephric fat, or renal vein invasion and tumour characteristics were noted. Median (range) tumour size was 5.5 (0.9-19.0) cm; and 46 (39%), 16 (14%) and 55 (47%) tumours were pT1, pT2 and pT3a RCC, respectively. The sensitivity/specificity for sinus fat, perinephric fat and renal vein invasion were 71/79%, 83/76% and 59/93% (Reader 1) and 88/71%, 68/72% and 69/91% (Reader 2) with κ = 0.41, 0.43 and 0.61, respectively. Sinus fat invasion was seen in 47/55 (85%) cases with T3a RCC vs 16/55 (29%) and 33/55 (60%) for perinephric fat and renal vein invasion. Tumour necrosis, irregularity of tumour edge and direct tumour contact with perirenal fascia or sinus fat increased the odds of local invasion [odds ratio (OR), 2.5-3.7; p < 0.05; κ = 0.42-0.61]. Stage T3a tumours were centrally located (OR, 3.9; p = 0.0009). Stage T3a RCC was identified with a sensitivity of 59-88% and specificity of 71-93% (κ = 0.41-0.61). Sinus fat invasion was the most common invasive feature. Centrally situated renal tumours with an irregular tumour edge, inseparable from sinus structures or the perirenal fascia and CT features of tumour necrosis should alert the reader to the possibility of Stage T3a RCC (OR, 2.5-3.9).

Prognostic Significance of Perinephric Fat Infiltration and Tumor Size in Renal Cell Carcinoma

The renal sinus is the fatty compartment located within the confines of the kidney not delineated from the renal cortex by a fibrous capsule. Because it contains numerous veins and lymphatics, invasion into this compartment may permit dissemination of a tumor otherwise regarded as renal-limited. Thirty-one consecutive renal carcinomas were studied: 22 clear cell renal cell carcinomas (3 multilocular cystic renal cell carcinomas), 4 chromophobe renal carcinomas, and 5 papillary renal carcinomas. The entire interface between the neoplasm and the sinus was embedded. Seventeen carcinomas did not invade the renal sinus and 16 were pT1 or pT2 tumors. Fourteen carcinomas, 13 clear cell renal cell carcinoma and one chromophobe renal carcinoma, invaded the renal sinus fat, and 9 of 14 invaded the lumen of renal sinus veins (all clear cell renal carcinomas). Although 14 of 22 clear cell renal carcinomas appeared to be renal limited pT1 and pT2 cancers, 6 of 14 carcinomas invaded sinus fat and 4 invaded into the lumen of renal sinus veins. Compared with the nine sinus-negative clear cell renal cell carcinomas, the 13 sinus-positive cancers were larger, exhibited more frequent renal capsule and renal vein involvement, and had higher nuclear grades. Renal sinus invasion was most common in clear cell renal cell carcinomas but was uncommon (one in 12) in 3 more indolent renal cell carcinomas: multilocular cystic renal cell carcinoma, chromophobe renal carcinoma, and papillary renal carcinoma. The follow-up period was short (1-17 months), but metastases developed in four of 31 cases. In three cases with metastases, carcinoma had involved the lumen of sinus veins but not the main renal vein, although two of three had also invaded through the renal capsule. This study shows that in carcinomas which appear to be renal limited (pT1/pT2), seven of 23 (30.4%) had invaded sinus fat and four of 23 (17.4%) had invaded sinus veins. We conclude that renal sinus invasion, especially sinus vein invasion, could identify a patient at risk for metastases even in a putative renal limited tumor, and suggest that all cases be examined for this feature. Renal sinus invasion merits further investigation to establish its prognostic importance and possible incorporation into future revisions of the TNM staging system for renal cell carcinomas.

624 Background: Pathological T3a (pT3a) renal cell carcinoma (RCC) is often diagnosed at the time of final pathological analysis, though impact of lack pre-treatment detection on surgical outcomes is unclear. We sought to compare outcomes of pathologically upstaged pT3a RCC with pT3a RCC recognized clinically. Methods: We queried the National Cancer Database for incident cases of pT3a pN0/x pM0/x renal cell carcinoma (RCC) treated with radical (RN) or partial nephrectomy (PN) between 2009-2015. Tumors were staged using the AJCC staging system, 7th edition. Pathologically upstaged tumors were defined as those that had a clinical stage of T1 or T2. Non-upstaged tumors had a clinical stage of T3a. Multivariable Cox proportional hazards and Kaplan-Meier survival analysis were performed to study the impact of clinical to pathological upstaging in pT3a tumors on overall survival (OS) in patients treated with RN and PN. Results: A total of 19,538 pT3a tumors were identified of which 7,231 (37%) had concordant clinical stage (non-upstaged) and 12,307 (63%) had lower clinical stage (upstaged). Patients with upstaged tumors had longer time from diagnosis to surgery (31.5 vs. 23.8 days; p&lt;0.001), smaller tumor size (6.7 vs. 7.4 cm; p&lt;0.001), higher rates of treatment with partial nephrectomy (18% vs. 11%; p&lt;0.001), and higher rates of negative margins (92% vs. 89%; p&lt;0.001). On multivariate analysis, age (HR 1.06; p&lt;0.001), Charlson Comorbidity Index (HR 1.51; p=0.006) and positive margin status (HR 1.55; p&lt;0.001) were associated with worse OS. Pathological upstaging was an independent predictor of improved OS following both PN (HR 0.74; 95% CI 0.59-0.91; p=0.006) and RN (HR 0.87; 95% CI 0.82-0.93; p&lt;0.001). Kaplan-Meier analysis showed higher OS for tumors that were upstaged following both PN (5-year OS 73 vs. 70%; p=0.0083) and RN (5-year OS 67 vs. 64%; p&lt;0.001). Conclusions: Most pT3a RCC are pathologically upstaged. Pathological pT3a tumors that were correctly detected clinically were associated with worsened outcomes. While our findings require further confirmation, they call for consideration and refinement of risk stratification protocols in pT3a RCC.

In the current Tumor-Node-Metastasis (TNM) classification system for renal cell carcinoma (RCC), both perinephric fat invasion (PFI) and renal sinus fat invasion (SFI) are classified at the T3a stage. However, their associated prognoses are clinically controversial. The present study proposes a new sub-classification criterion for pathological T3a (pT3a) RCC with SFI or PFI to resolve this dispute. Data were collected from consecutive records of 2,765 patients with T1a renal cancer, who had undergone partial nephrectomy (PN) between 2001 and 2015 at one of four hospitals. Among these patients, 127 cases were diagnosed with stage pT3a RCC with SFI or PFI, according to final pathological examination. The pathological characteristics, clinical data and follow-up observations were analyzed. Of the 127 patients, with an average follow-up duration of 56 months (range, 15–60 months), 17 cases of tumor recurrence were found. After analysis of the pathological findings, the following new sub-classification criteria was proposed for pT3a RCC with SFI or PFI: i) Type A, renal tumor invades the pseudo-capsule and contacts with the perinephric adipose tissues directly (3 recurrences out of 57 patients); ii) type B, tumor protrudes into the perinephric adipose tissues like a tongue (4 recurrences out of 29 patients); and iii) type C, tumor nodules distribute in perinephric adipose tissues (10 recurrences out of 41 patients). There was statistically significant difference between the three subtypes in terms of recurrence rate (P=0.023). In conclusion, controversies remain in the current TNM classification system for pT3a RCC. The present study added to the available data and found that pT3a RCC with tumor nodules in perinephric adipose or/and with an irregular tumor protruding into adipose tissues showed a higher recurrence rate. Thus, it is recommended that pT3a RCC should be carefully analyzed and should be considered differently to other stages of RCC.

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

Prognostic significance of pT3a staging subclassifications in renal cell carcinoma: Not all pT3a are equal

Aim: This single centre, retrospective study aims to determine whether performing a partial nephrectomy is oncologically safe for stage T3a renal cell carcinomas. Introduction: Radical Nephrectomy is the gold standard surgical approach for T3a Renal Cell Carcinomas. However, a small but not insignificant number of patients pre-operatively staged cT1/cT2 are treated with a partial nephrectomy but at final pathology are subsequently upstaged to pT3a. Materials and Method: Data was collected retrospectively using the Royal Free database. 16 of the 306 partial nephrectomies demonstrated stage T3a at final histology. Primary outcome analysed was Recurrence-Free Survival. Secondary outcome analysed was Renal Function Preservation (post-operative eGFR/ pre-operative eGFR). Results: Of the 16 patient, 14 patients presented with localised T3a RCC at presentation with an average follow up of 17.3 months. No evidence of local or metastatic recurrence was found in this series of 14 patients. 2 patients were excluded as they presented with metastatic disease. This study found a respectable Renal Function Preservation. In this series, the eGFR±SD (mL/ min/1.73m2) was 77.3±18.8 pre-operatively and 69.7± 19.7 post-operatively, displaying a Renal Function Preservation (post/pre eGFR) of 90.2%. Conclusion: This pilot study concluded that a partial nephrectomy is oncologically safe for certain T3a kidney renal cell carcinomas. The main implications are that: 1) Current practice should shift and start considering a partial nephrectomy in certain selected patients with clinical T3a tumours, especially in patients with imperative reasons for nephron-sparing surgery as long as a negative margin can be achieved. 2) This study seeks to advise that surgeons should not be deterred from carrying out a partial nephrectomy for fear of pathological upstaging.

Differing Risk of Cancer Death Among Patients With Pathologic T3a Renal Cell Carcinoma: Identification of Risk Categories According to Fat Infiltration and Renal Vein Thrombosis

Prognostic heterogeneity in T3aN0M0 renal cell carcinoma according to the site of invasion

The recent eighth tumor-node-metastasis (TMN) staging system classifies renal cell carcinoma (RCC) with perirenal fat invasion (PFI), renal sinus fat invasion (SFI), or renal vein invasion (RVI) as stage pT3a. However, limited data are available on whether these sites have similar prognostic value or recurrence rate. We investigated the recurrence rate based on tumor size, pathological invasion sites including urinary collecting system invasion (UCSI), and clinically detected renal vein thrombus (cd-RVT) with pT3aN0M0 RCC. We retrospectively reviewed 91 patients with pT3aN0M0 RCC who underwent surgical treatment. Patients with tumor size > 7 cm, UCSI, three invasive sites (PFI + SFI + RVI), and cd-RVT showed a significant correlation with high recurrence rates (hazard ration (HR) 2.98, p = 0.013; HR 8.86, p < 0.0001; HR 14.28, p = 0.0008; and HR 4.08, p = 0.0074, respectively). In the multivariate analysis, tumor size of >7 cm, the presence of UCSI, and cd-RVT were the independent predictors of recurrence (HR 3.39, p = 0.043, HR 7.31, p = 0.01, HR 5.06, p = 0.018, respectively). In pT3a RCC, tumor size (7 cm cut-off), UCSI, and cd-RVT may help to provide an early diagnosis of recurrence.

Renal Cell Carcinoma: Diagnosis Based on Metastatic Manifestations

Renal Cell Carcinoma with Thrombus Extension into the Inferior Vena Cava and the Right Atrium: A Case Report

ABSTRACTPurpose:Radical nephrectomy (RN) is the standard surgical type for pathological stage T3a (pT3a) renal cell carcinoma (RCC). Recently, some studies have suggested equivalence between partial nephrectomy (PN) and RN for oncologic control and have shown the benefits of PN for better renal function. We conducted this meta-analysis to assess oncologic outcomes, perioperative outcomes and renal function between two groups among patients with pT3a RCC.Materials and methods:PubMed, Scopus, Web of Science, Science Direct, Ovid MEDLINE, The Cochrane Library, Embase and Google Scholar were searched for eligible articles. The endpoints of the final analysis included overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), surgical complications, operative time, estimated blood loss (EBL), serum creatinine and estimated glomerular filtration rate (eGFR).Results:Twelve studies of moderate to high quality, including 14.152 patients, were examined. PN showed superiority for renal functional preservation, providing higher eGFR (WMD=12.48mL/min; 95%CI: 10.28 to 14.67; P <0.00001) and lower serum creatinine (WMD=-0.31mg/dL; 95%CI: −0.40 to −0.21; P <0.00001). There were no significant differences between PN and RN regarding operative time, EBL, surgical complications, OS, RFS and CSS. Despite inherent selection bias, most pooled estimates were consistent in sensitivity analysis and subgroup analysis. More positive margins were found in the PN group (RR=2.42; 95%CI: 1.25-4.68; P=0.009).Conclusions:PN may be more suitable for treating pT3a RCC than RN because it provides a similar survival time (OS or RFS) and superior renal function. Nevertheless, this result is still disputed, and more high-quality studies are required.

To compare outcomes following laparoscopic renal surgery (LRS) and open renal surgery (ORS) in the treatment of pathologic T3a (pT3a) renal cell carcinoma (RCC) using a propensity matched analysis. The Canadian Kidney Cancer Information System is a prospectively maintained database for patients diagnosed with RCC from 15 Canadian institutions. Patients treated for nonmetastatic pT3a RCC between 2008 and 2015 were included. Propensity score matching for age, gender, tumor size, grade, histology, and surgical approach was performed to compare laparoscopic radical and partial nephrectomy (LRN or LPN) with open radical or partial nephrectomy (ORN or OPN). The primary endpoint was recurrence-free survival (RFS). Two hundred twenty-six (45%) patients underwent LRS (88% LRN and 12% LPN), and 275 (55%) underwent ORS (75% ORN and 25% OPN). After a median follow-up of 21.1 months, 155 (72 LRS and 83 ORS) patients experienced recurrence. The 3-year RFS was 63% and 50% for the LRS and ORS groups, respectively, p = 0.36. On subgroup analysis, there was no significant difference in RFS among patients who underwent radical nephrectomy (3-year RFS 61% in LRN compared with 46% in ORN group, p = 0.32) or partial nephrectomy (77% in LPN compared with 79% in OPN group, p = 0.82). This study is the largest matched analysis comparing LRS and ORS for pT3a RCC. In matched patients, LRS showed no difference in oncologic outcomes compared with ORS and should be considered when technically feasible.