Neoadjuvant Therapy to Enable Partial Nephrectomy in Patients With High-Complexity or Locally Advanced Non-metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

414 Background: Receipt of adjuvant therapy has become a standard of care for management of high risk localized renal cell carcinoma (RCC), with emerging literature demonstrating longer disease-free survival. Neoadjuvant approaches have been utilized investigationally to facilitate complete surgical resections in high risk and complex renal masses. We sought to evaluate outcomes of patients treated with neoadjuvant or adjuvant therapy in non-metastatic RCC utilizing a propensity score model. Methods: We queried the INMARC database for patients with localized surgically treated RCC who underwent systemic neoadjuvant or adjuvant therapy. Neoadjuvant therapy was defined as presurgical therapy given in the setting of localized disease and adjuvant therapy as systemic therapy given postoperatively in the absence of documented metastases. Patients with metastases at time of diagnosis were excluded from the analysis. A propensity score match (PSM) model in a 1:3 ratio was conducted within a caliper width of 0.1 including: age, sex, hypertension, Charlson Comorbidity Index, tumor size, tumor necrosis, stage, surgical margin, tumor grade and type of surgery [radical vs. partial nephrectomy]. Primary outcome was all-cause mortality (ACM), and secondary outcome was cancer-specific mortality (CSM). Multivariable analysis (MVA) via Cox regression was fitted for the outcomes of interest. Kaplan-Meier analysis (KMA) for overall (OS), cancer specific survival (CSS) was conducted for 5-year survival assessment. Results: After PSM 293 patients were analyzed [adjuvant n=203, (69.2%), 109 targeted therapy (TT) vs. 94 immunotherapy; neoadjuvant n=90, (30.7%), 59 TT vs. 31 immunotherapy]; median follow up was 50 (IQR 20-76) months from surgery . MVA revealed adjuvant vs. neoadjuvant (HR 1.98, p=0.007) and positive margin (HR 2.01, p=0.046) to be associated with increased risk of ACM; immunotherapy vs. TT (HR 0.47, p=0.001) was associated with a decreased risk. MVA for CSM revealed that adjuvant vs. neoadjuvant (HR 2.18, p=0.016) and positive margin (HR 2.41, p=0.028) were associated with increased risk of CSM, while immunotherapy vs. TT (HR 0.35, p<0.001) was associated with decreased risk. KMA comparing neoadjuvant vs. adjuvant 5-year OS was 80.4% vs. 64.8% (p=0.04), while CSS was 88.1% vs. 76.2% (p=0.03). Conclusions: In a comparison of patients with localized RCC who underwent adjuvant or neoadjuvant systemic therapy, receipt of neoadjuvant therapy was associated with superior survival outcomes. These findings are hypothesis generating and call for consideration for a clinical trial to compare outcomes of adjuvant vs. neoadjuvant therapy in high-risk localized RCC.

The R.E.N.A.L. Nephrometry Score: A Comprehensive Standardized System for Quantitating Renal Tumor Size, Location and Depth

Laparoscopic Partial Nephrectomy in Solitary Kidney

439 Background: Cytoreduction via systemic neoadjuvant therapy is an emerging investigational strategy in localized renal cell carcinoma (RCC). We analyzed our single institutional experience with neoadjuvant therapy. Methods: ingle institutional retrospective analysis of patients with T2-T3N0M0 RCC. Patients received confirmatory biopsy for clear cell histology prior to receipt of systemic therapy and underwent radical (RN) or partial nephrectomy (RN). Neoadjuvant therapy consisted of tyrosine kinase inhibitor (TKI) or Immuno-oncology (IO) therapy and/or combination (TKI-IO). Neoadjuvant therapy was given prior to planned partial nephrectomy for complex renal mass with imperative indications for nephron preservation and prior to planned radical nephrectomy in setting of locoregional disease with possible adjacent organ or great vessel involvement where multiorgan system resection was risked. Primary outcome was percentage cytoreduction comparing pre-treatment and post treatment mass size. Secondary outcome included partial response (PR) rate as per RECIST criteria, negative surgical margins, and lack of major 30-day complications (Clavien ≥3). Comparative analysis was conducted for outcomes between groups for overall survival (OS), cancer specific survival (CSS), and progression free survival utilizing Kaplan Meier Analyses (KMA). Results: A total of 50 patients (33 TKI, 17 IO + TKI-IO) were analyzed (median follow up 31.1 months). Overall PR and cytoreduction rates were 18.0% and 4.2%. No differences in tumor size were noted (7.7 vs. 10.4 cm, p= 0.08). There were no differences in % cytoreduction (12.2 vs. 11.8, p=0.13) and % PR (17.8% vs. 30.7%, p=0.73) between the groups. Overall, 18 patients and 30 patients underwent PN and RN, respectively. 30-day major complication rate was 28.0% and 20.5% was PSM rate. KMA revealed 3-year OS, CSS and PFS of 74%, 75%, and 14%. No differences were noted between TKI and IO/IO-combination groups for PFS (16.7% vs. 10.0%, p=0.45), CSS (70.9% vs. 93.3%, p=0.20), and OS (68.3% vs. 93.3%, p=0.06). Conclusions: Neoadjuvant therapy prior to surgery for complex and locoregional disease resulted in cytoreduction and was associated with acceptable safety, surgical quality, and short term oncological outcomes. Further investigation is requisite to delineate role of neoadjuvant therapy in localized RCC.

Adjuvant and neoadjuvant therapy for renal cell carcinoma: A survey of the Society of Urologic Oncology

Original Articles: Bladder Cancer: Neoadjuvant Cisplatin Chemotherapy Before Radical Cystectomy in Invasive Transitional Cell Carcinoma of the Bladder: A Prospective Randomized Phase III Study

BACKGROUND: The number of older patients with kidney tumors is steadily increasing. Surgical methods are the main ones in the treatment of patients with localized forms of renal cell carcinoma, including the elderly. AIM: to conduct a comparative analysis of perioperative data and functional results of surgical interventions for renal cell carcinoma in patients of different age groups. MATERIALS AND METHODS: The study included 256 patients with kidney tumors (mean age 65.2 8.6 years). 146 (57.0%) patients aged 56 to 64 years made up group I, and 110 (43.0%) patients aged 65 to 75 years group II. In 210 (82.0%) patients, the tumor diameter did not exceed 4 cm (T1a), in 46 (18.0%) patients it ranged from 4 to 6.2 cm (T1b). Radical nephrectomy and partial nephrectomy were performed respectively in 44 (30.1%) and 102 (69.9%) patients of group I and 58 (52.7%) and 52 (47.3%) patients of group II. All operations were performed laparoscopically. RESULTS: In patients of group I, the duration of radical nephrectomy was 115.0 18.0 min, and partial nephrectomy 135.5 25.0 min (p 0.0001), in patients of group II, 120.0 20.5 and 138.0 25.5 min (p 0.0001), respectively. Warm ischemia time during partial nephrectomy was 17.6 1.2 min in patients of group I and 18.2 1.5 min in patients of group II (p = 0.25). The volume of blood loss in patients of both groups I and II was significantly higher during partial nephrectomy. The average volume of blood loss in patients of group I was 130.0 20.0 ml when performing radical nephrectomy and 236.5 20.0 ml when performing partial nephrectomy (p 0.0001), and in group II 125.0 18.5 ml for radical nephrectomy and 246.0 22.0 ml for partial nephrectomy (p 0.0001). The frequency of significant complications did not differ in patients of groups I and II. Grade IIIa complications according to the ClavienDindo classification of surgical complications were observed in 5 (3.4%) patients of group I and 4 (3.9%) patients of group II (p 0.05), and grade IIIb in 3 (2.1%) and 2 (1.8%) patients (p 0.05). Intraoperative bleeding developed in 19 (7.4%) patients: in 13 (8.4%) of 154 patients with partial nephrectomy, and in 6 (5.9%) of 102 patients with radical nephrectomy. In the early postoperative period in patients of group I after radical nephrectomy and partial nephrectomy, normal glomerular filtration rates was observed in 34.0% and 54.0% of patients, respectively, and in group II in 31.0% and 52.0% of patients, respectively. Renal function significantly decreased in patients of both groups after radical nephrectomy compared with partial nephrectomy (p 0.05). The results of GFR 3 months after surgery improved in patients after partial nephrectomy, and did not change significantly in the radical nephrectomy group. CONCLUSIONS: The results of the study showed no differences in perioperative parameters (volume of intraoperative blood loss, warm ischemia time) during radical nephrectomy and partial nephrectomy in patients aged 5664 and 6575 years. The functional results of partial nephrectomy in patients of both groups were better compared to patients after radical nephrectomy. Thus, our data indicate the justification for performing organ-preserving operations, including in elderly patients.

Guideline for Management of the Clinical T1 Renal Mass

826 THE EFFECT OF RADICAL VERSUS PARTIAL NEPHRECTOMY ON OTHER-CAUSE MORTALITY IN PATIENTS WITH T1A RENAL CELL CARCINOMA: RESULTS FROM THE SURVEILLANCE, EPIDEMIOLOGY AND END RESULTS DATABASE

Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.

420 Background: Partial nephrectomy (PN) is the standard of care for small renal masses (SRMs) whenever feasible. The occurrence of a positive surgical margin (PSM) on a pathological specimen is not uncommon and an ideal management is unknown. We conducted this study to examine the rate of PSM, predictors of PSM and their oncological outcomes after PN for renal cell carcinoma (RCC), using the Canadian Kidney Cancer information system (CKCis) database. Methods: We accessed the prospectively maintained CKCis database for 1066 patients who underwent PN for RCC in major academic centers all across Canada. Demographics, clinical, pathological and follow-up data were noted for patients with PSM and negative surgical margins (NSM). Multivariate logistic regression analysis was performed to assess predictors of PSM. Results: Out of 1066 patients, 59 (5.5%) had PSM, 928 (87%) had NSM and records of 79 (7.4%) patients were not available. Mean patient age was 61 years and 59 years in the PSM and NSM group respectively, and in each group 63% of the patients were males. Mean tumor size was 3.6cm (range 1.1 – 9.5) and 3.3cm (range 0.5 – 16.2) in PSM and NSM group respectively. PSM group had 5 (8%) grade 1, 28 (47%) grade 2, 16 (27%) grade 3 and 5 (8%) grade 4 tumors as compared to 127 (14%), 458 (50%), 207 (23%) and 27 (3%) respectively in NSM group. Four (6.7%) patients from the PSM group and 49 (5.3%) patients from the NSM group had local and/or systemic progression of disease. There were two cancer specific deaths in NSM group and none in PSM group. Fifty two (88%) and 861 (93%) patients were alive at mean follow-up of 18.5 (range 0 – 91.7) and 28.9 months (range 0 – 315.5) in PSM and NSM group respectively. For the multivariate logistic regression analysis; Fuhrman grade 4 predicted presence of PSM whereas age, operative technique, tumor size, tumor stage did not. Conclusions: Results from the CKCis database suggest that PSM after PN are common but does not result in adverse oncological outcomes. Presence of Fuhrman grade 4 may be associated with PSM on final pathological specimen.

Radiotherapy (RT) represents a treatment option for small renal masses with proven feasibility and tolerability. However, it has never been directly compared to partial nephrectomy (PN) with cancer-specific mortality (CSM) as an endpoint. Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified T1aN0M0 renal cell carcinoma (RCC) patients treated with RT or PN. We relied on 1:1 propensity score matching (PSM) for age, tumor size and histology. Subsequently, cumulative incidence plots and multivariable competing risks regression (CRR) models were fitted. The same methodology was then re-applied to a subset of patients with tumor size 21-40mm. Of 40,355 patients with T1aN0M0 RCC, 40,262 underwent PN (99.8%) vs 93 underwent RT (0.2%). RT patients were older (median age 72 vs 60years, p < 0.001) and harbored larger tumor size (median size 28 vs 25mm, p < 0.001) and a higher proportion of non-clear cell RCC (49% vs 22%, p < 0.001). After 1:1 PSM (92 RT versus 92 PN patients), cumulative incidence plots' derived CSM was 21.3 vs 4%, respectively. In multivariable CRR models, RT independently predicted higher CSM (hazard ratio (HR) 4.3, p < 0.001). In the subgroup with tumor size 21-40mm, after 1:1 PSM (72 RT versus 72 PN patients), cumulative incidence plots derived CSM was 21.3% vs 4%, respectively. In multivariable CRR models, RT also independently predicted higher CSM (HR 4.7, p = 0.001). In T1aN0M0 RCC patients, relative to PN, RT is associated with significantly higher absolute and relative CSM, even in patients with tumor size 21-40mm.

Matching might help interpretation of results of retrospective studies on neoadjuvant chemotherapy followed by surgery in patients affected by bulky cervical cancer

MP49-07 INCIDENCE AND RISK FACTORS OF POSTOPERATIVE HYPERTENSION AFTER PARTIAL NEPHRECTOMY FOR RENAL TUMORS

Sequential Sorafenib and Sunitinib for Renal Cell Carcinoma