Locally-advanced Renal Cell Carcinoma Research Articles

Preoperative prognostic model for localized and locally advanced renal cell carcinoma: Michinoku Japan Urological Cancer Study Group.

The Modified International Metastatic Renal Cell Carcinoma Dataset Consortium model (mIMDC) is a preoperative prognostic model for pT3cN0M0 renal cell carcinoma (RCC). This study aimed to validate the mIMDC and to construct a new model in a localized and locally advanced RCC (LLRCC). A database was established (the Michinoku Japan Urological Cancer Study Group database) consisting of 79 patients who were clinically diagnosed with LLRCC (cT3b/c/4NanyM0) and underwent radical nephrectomy from December 2007 to May 2018. Using univariable and multivariable analyses, we retrospectively analyzed disease-free survival (DFS) and overall survival (OS) in this database, constructed a new prognostic model according to these results, and estimated the model fit using c-index on the new and mIMDC models. Independent poorer prognostic factors for both DFS and OS include the following: ≥ 1 Eastern Cooperative Oncology Group performance status, 2.0mg/dL C-reactive protein, and > upper normal limit of white blood cell count. The median DFS in the favorable (no factor), intermediate (one factor), and poor-risk group (two or three factors) was 76.1, 14.3, and 4.0 months, respectively (P < 0.001). The 3-year OS in the favorable, intermediate, and poor-risk group were 92%, 44%, and 0%, respectively (P < 0.001). The c-indices of the new and mIMDC models were 0.67 and 0.60 for DFS (P = 0.060) and 0.74 and 0.63 for OS (P = 0.012), respectively. The new preoperative prognostic model in LLRCC can be used in patient care and clinical trials.

Crisis Averted: Clinical T1b Renal Mass with Concurrent Arteriovenous Malformation and Renal Vein Thrombus

Arteriovenous malformations (AVMs) secondary to renal-cell carcinoma (RCC) are well-described in the literature. Independently, renal vein and inferior vena cava tumor thrombi can be detected in locally-advanced RCC. A 67-year-old gentleman presented with a cT1b renal mass detected on workup for elevated creatinine. Multiphase CT imaging obtained for partial nephrectomy surgical-planning revealed an initially-missed renal cortical AVM. This drastically changed the plan for intervention, including use of an open approach with AVM embolization by interventional radiology prior and avoidance of a nephron-sparing approach. Final pathology confirmed the AVM and a subclinical renal vein thrombus masked by arterial flow on CT imaging, making this the first concurrent case described in the literature. Herein, we describe avoidance of catastrophic intraoperative hemorrhage by careful review of preoperative imaging and provide a literature review of imaging modalities for both renal surgical-planning and detection of tumor thrombi in RCC.

T cell infiltration (TCI) in matched renal biopsy (bx) and nephrectomy (nx) samples in renal cell carcinoma (RCC).

4587 Background: TCI in tumors has been investigated as a biomarker of response to checkpoint inhibitors. A neo-adjuvant trial of checkpoint inhibition in locally-advanced RCC is ongoing at Cleveland Clinic, where TCI in pre-treatment renal mass bx will be compared to post-treatment nx specimens. However, there are no data regarding the association of TCI in matched bx and nx samples without intervening treatment. Understanding this association will enable further study of this potential biomarker in future studies. Methods: Matched bx and nx samples (without intervening systemic therapy) were identified from patients with non-metastatic RCC. Selected tissue sections from bx and nx samples were reviewed, and marked for intra-tumoral lymphocytes by the Pathologist. Immunohistochemistry (IHC) was utilized to stain these selected tissue sections for T cell markers (CD3, CD4 and CD8), and additional immune markers including PD-1, PDL-1 and CD11b. Intra-tumoral staining was then quantified in the pre-marked tissue sections as counts per total tumor area surveyed. Spearman correlation (ρ) was used to measure the strength of association. Results: 30 matched pairs were investigated. The median interval between bx and nx was 2.8 (0.2-87.7) months. Clear cell was the most common histology (29/30; 97%). There was a positive correlation between the frequency of CD8+T cells between matched bx and nx samples (ρ= 0.39; p=0.03). CD3, CD4 and CD11b did not show significant correlation. (Table) PD-1 (bx 4/29, nx 16/29) and PDL-1 (bx 5/28, nx 10/28) expression was positive in the minority of samples. Conclusions: Bx material can potentially be used to assess the degree of CD8+ TCI in RCC nx samples. However the utility of bx evaluation for CD4+TCI and expression of PD-1, PDL-1 and CD11b requires further study. [Table: see text]

T cell infiltration in matched renal biopsy (bx) and nephrectomy (nx) samples in renal cell carcinoma (RCC).

472 Background: T cell infiltration in tumors has been investigated as a biomarker of response to checkpoint inhibitors. A neo-adjuvant trial of checkpoint inhibition in locally-advanced RCC is ongoing at Cleveland Clinic, where T cell infiltration in pre-treatment renal mass bx will be compared to post-treatment nx specimens. However, there are no data regarding the association of T cell infiltration in matched bx and nx samples without intervening treatment. Understanding this association will enable further study of this potential biomarker in future neo-adjuvant studies. Methods: Matched bx and nx samples (without intervening systemic therapy) were identified from patients with non-metastatic RCC. Demographic and pathological data were collected from chart review. Selected tissue sections from bx and nx samples of each patient were reviewed, and marked for tumor and intra-tumoral lymphocytes by the pathologist. Immunohistochemistry (IHC) was utilized to stain these selected tissue sections for T cell markers (CD3, CD4 and CD8). Intra-tumoral T cells were then quantified in the pre-marked tissue sections as counts per total tumor area surveyed, using Image-Pro Plus (Media Cybernetics, Inc.). Spearman correlation (ρ) was used to measure the strength of association of T cell infiltration between matched samples. Results: 30 matched pairs were investigated. The median interval between bx and nx was 2.8 (0.2-87.7) months. Clear cell was the most common histology (29/30; 97%). 15/30 (50%) had grade 3-4 tumors, 2/19 (11%) patients had sarcomatoid features, 7/25 (29%) had necrosis, and 8/28 (29%) had lymphovascular invasion. We found a positive correlation between the frequencies of CD8+ T cells between matched bx and nx samples (ρ= 0.39; p=0.03). CD3+ and CD4+T cells did not show significant correlation. (Table) Conclusions: Bx material can be used to accurately assess the degree of CD8+T cell infiltration in RCC. [Table: see text]

Association of chronic kidney disease and locally-advanced RCC.

e16078Background: Chronic kidney disease (CKD) is classified according to cause, glomerular filtration rate (GFR), and proteinuria. In renal cell carcinoma (RCC) patients, reduced GFR has been rela...

Factor-inhibiting hypoxia-inducible factor expression in patients with high-risk locally advanced renal cell carcinoma and its relationship with tumor progression

Hypoxia-inducible factor (HIF) plays an important role in renal cell carcinoma (RCC) associated with angiogenesis. Factor-inhibiting HIF (FIH), which is the upstream mediator protein of HIF, is receiving more attention today. In the present study, the role of FIH expression in high-risk locally advanced renal cell carcinoma (LARCC) was explored. Eighty-eight high-risk LARCC cases were divided into two groups based on their prognosis. Using immunohistochemical staining, the correlations of FIH expression along with clinicopathological factors, progression-free survival (PFS), and overall survival (OS) were analyzed. FIH was mainly located in the cytoplasm (34/88) and nucleus (31/88) of the renal tumor cell. Nuclear negative expression or cytoplasmic positive expression of FIH were associated with an increased risk of disease progression (p = 0.007 and p < 0.001, respectively) and worse OS (p = 0.020 and p = 0.008, respectively). Using the group with nuclear and cytoplasmic FIH negative expression as reference, further stratified analysis found that the exclusive nuclear FIH expression group had a better PFS and OS [hazard ratio (HR) = 0.153, p = 0.07 and HR = 0, p = 0.961, respectively], and the exclusive cytoplasmic FIH positive group experienced the worst PFS and OS (HR = 2.876, p = 0.005 and HR = 2.799, p = 0.034, respectively). In addition, nuclear negative expression of FIH was associated with a significant negative predictive value for the effect of interferon-alpha (IFN-α) on PFS (p = 0.045). The nuclear negative and cytoplasmic positive expressions of FIH were identified not only as risk factors for disease progression in high-risk LARCC postoperative patients, but also to be associated with poor OS. Furthermore, the nuclear negative expression of FIH may be a promising biomarker for postoperative adjuvant therapy.

Evaluation of treatment options for patients with advanced renal cell carcinoma: Assessment of appropriateness, using the validated semi-quantitative RAND corporation/University of California, Los Angeles methodology

A diverse range of treatment options and interventions are available for the management of renal cell carcinoma (RCC), allowing clinicians to tailor therapy to best meet their patient’s needs and situation. However, choosing from the plethora of options can be problematic. RCC treatment guidelines advise on the most efficacious agents based upon specific clinical trial populations, but these do not always take into account all the patient factors that influence the suitability of treatment options for individual patients.This study used the validated RAND/UCLA (RAND corporation/University of California, Los Angeles) ‘appropriateness methodology’ to integrate clinical efficacy data with expert opinion concerning the use of specific RCC treatment options for particular patient scenarios, in an attempt to facilitate the widespread implementation of patient-focussed treatment choices. Use of the methodology has allowed us to develop treatment algorithms for patients with locally-advanced RCC and for those with metastatic disease post-nephrectomy or with primary tumour in situ. The algorithms take into account patient-specific characteristics such as tumour histology, prior treatment and known risk factors to advise whether a particular treatment intervention is appropriate, not appropriate or of uncertain appropriateness.Use of this methodology aims to develop a formalised process by which expert opinion can be integrated with clinical data and used as an additional source of information that can provide further guidance concerning difficult treatment decisions when data are absent or sparse.

Recurrence pattern in patients with locally advanced renal cell carcinoma: The implications of clinicopathological variables

ObjectivesRecurrence rates for patients with locally advanced renal cell carcinoma (LARCC) remain high. To date the predictors of recurrence in those patients remain controversial. The aim of the present study was to assess the relapse pattern in those patients and identify predictors for recurrence. Patients and methodsWe evaluated retrospectively 112 consecutive patients who underwent surgery for LARCC (T3–T4N0M0) between January 2000 and December 2010. Clinical and pathological data were collected from hospital medical records and compiled into a computerized database. Studied variables were age, mode of presentation, Tumour-Node-Metastasis (TNM) stage, Fuhrman nuclear grade, histological subtype, tumour size, venous thrombus level, collecting-system invasion and sarcomatoid differentiation. Recurrence-free survival (RFS) was estimated using the Kaplan–Meier method. Univariate and multivariate analyses were conducted. ResultsPatients were followed for a mean and median follow-up of 33 and 24 months, respectively, after surgery. During the follow-up, recurrences (distant and/or local) were recorded in 58 patients, representing 52% of the cohort. The mean and median times to recurrence were 25 and 13 months, respectively. Sites of recurrence were multiple in 36 patients (62%), lung only in 14 (24%), and local in eight (14%). RFS rates at 1, 2, and 5 years were 50%, 43% and 34%, respectively, while the median RFS was 23.7 months. Using univariate analysis, RFS after nephrectomy was significantly shorter in patients aged <70years, symptomatic at presentation, with larger tumours, higher nuclear grade, collecting-system invasion, and/or sarcomatoid differentiation. After multivariate analysis, T-stage, nuclear grade and sarcomatoid differentiation retained their power as independent predictors of RFS (P=0.032, <0.001 and 0.003, respectively). ConclusionsFor patients with LARCC, T-stage, grade and sarcomatoid differentiation independently dictate the risk of tumour recurrence. Considering these variables in the postoperative surveillance protocols and in the need for a multimodal therapeutic approach is highly recommended.

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

ObjectiveSeveral systemic agents have been approved for patients with advanced renal cell carcinoma (RCC) and others are in various stages of development. We surveyed members of the Society of Urologic Oncology (SUO) regarding the importance of adjuvant and neoadjuvant systemic therapy for RCC and their participation in such trials. Materials and methodsA survey was sent in October 2010 to 564 U.S. and Canadian members of the SUO and the SUO-Clinical Trials Committee with a valid e-mail address. A total of 136 urologic cancer specialists from a mixture of practice patterns responded to the questionnaire (24% participation rate). ResultsAt the time of the study, 75% participated in adjuvant or neoadjuvant treatment protocols, including 75% with adjuvant and 16% with neoadjuvant protocols. There was universal support for continued investigation of agents for adjuvant use in RCC with locoregional metastasis (100%) and nearly universal support for investigation of agents in patients with “high risk” (99%) and “intermediate risk” (91%) localized RCC after nephrectomy. The vast majority of respondents also supported investigation of neoadjuvant therapies in patients with advanced RCC (98%) or locally-advanced RCC (98%), with 70% also supporting neoadjuvant trials in patients with localized RCC. Importantly, 98% of respondents indicated interest in participating in future adjuvant and neoadjuvant trials. ConclusionUrologic cancer specialists surveyed in late 2010 demonstrated nearly universal support for trials to investigate the role of neoadjuvant and adjuvant therapies for RCC of all stages. With appropriate patient selection and outcome assessment, this widespread support indicates great potential for future clinical trials which will require the participation of urologic surgeons.

UP-01.162 Recurrence Pattern in Patients with Locally Advanced Renal Cell Carcinoma (LARCC): Implications of Clinico-Pathologic Variables

UP-01.162 Recurrence Pattern in Patients with Locally Advanced Renal Cell Carcinoma (LARCC): Implications of Clinico-Pathologic Variables

Management of Locally Advanced Renal Cell Carcinoma

Renal cell carcinoma accounts for approximately 3% of adult malignancies and over 90% of primary renal tumors. Recurrence rates for patients with locally advanced renal cell carcinoma (LARCC) remain high. The authors review literature regarding prognostic factors, potential biomarkers, surgical strategies, and adjuvant therapy trials for patients with LARCC. Molecular tumor markers may improve existing staging systems for predicting prognosis. Surgery is the best initial treatment for most patients with clinically localized renal tumors, although complete surgical resection can be challenging for patients with large tumors, bulky regional lymph node involvement, or inferior vena cava tumor thrombus. Significant recurrence rates for patients with LARCC undergoing nephrectomy indicate the presence of undetected micrometastases at the time of surgery. Adjuvant radiation, chemotherapy, and immunotherapy have been ineffective. Other trials of adjuvant therapy are ongoing. Aggressive surgical resection alone for LARCC is not sufficient to prevent disease recurrence in a significant number of patients. Adjuvant therapies are needed to improve cancer-specific survival.