Perioperative nivolumab versus observation in patients with renal cell carcinoma undergoing nephrectomy (PROSPER ECOG-ACRIN EA8143): an open-label, randomised, phase 3 study.

BACKGROUND: The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only. METHODS: In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, with previously untreated clinical stage T2 or greater or Tany N+ renal cell carcinoma of clear cell or non-clear cell histology planned for partial or radical nephrectomy. Selected patients with oligometastatic disease, who were disease free at other disease sites within 12 weeks of surgery, were eligible for inclusion. We randomly assigned (1:1) patients using permuted blocks (block size of 4) within stratum (clinical TNM stage) to either nivolumab plus surgery, or surgery only followed by surveillance. In the nivolumab group, nivolumab 480 mg was administered before surgery, followed by nine adjuvant doses. The primary endpoint was investigator-reviewed recurrence-free survival in patients with renal cell carcinoma assessed in all randomly assigned patients regardless of histology. Safety was assessed in all randomly assigned patients who started the assigned protocol treatment. This trial is registered with ClinicalTrials.gov, NCT03055013, and is closed to accrual. FINDINGS: Between Feb 2, 2017, and June 2, 2021, 819 patients were randomly assigned to nivolumab plus surgery (404 [49%]) or surgery only (415 [51%]). 366 (91%) of 404 patients assigned to nivolumab plus surgery and 387 (93%) of 415 patients assigned to surgery only group started treatment. Median age was 61 years (IQR 53-69), 248 (30%) of 819 patients were female, 571 (70%) were male, 672 (88%) were White, and 77 (10%) were Hispanic or Latino. The Data and Safety Monitoring Committee stopped the trial at a planned interim analysis (March 25, 2022) because of futility. Median follow-up was 30·4 months (IQR 21·5-42·4) in the nivolumab group and 30·1 months (21·9-41·8) in the surgery only group. 381 (94%) of 404 patients in the nivolumab plus surgery group and 399 (96%) of 415 in the surgery only group had renal cell carcinoma and were included in the recurrence-free survival analysis. As of data cutoff (May 24, 2023), recurrence-free survival was not significantly different between nivolumab (125 [33%] of 381 had recurrence-free survival events) versus surgery only (133 [33%] of 399; hazard ratio 0·94 [95% CI 0·74-1·21]; one-sided p=0·32). The most common treatment-related grade 3-4 adverse events were elevated lipase (17 [5%] of 366 patients in the nivolumab plus surgery group vs none in the surgery only group), anaemia (seven [2%] vs nine [2%]), increased alanine aminotransferase (ten [3%] vs one [<1%]), abdominal pain (four [1%] vs six [2%]), and increased serum amylase (nine [2%] vs none). 177 (48%) patients in the nivolumab plus surgery group and 93 (24%) in the surgery only group had grade 3-5 adverse events due to any cause, the most common of which were anaemia (23 [6%] vs 19 [5%]), hypertension (27 [7%] vs nine [2%]), and elevated lipase (18 [5%] vs six [2%]). 48 (12%) of 404 patients in the nivolumab group and 40 (10%) of 415 in the surgery only group died, of which eight (2%) and three (1%), respectively, were determined to be treatment-related. INTERPRETATION: Perioperative nivolumab before nephrectomy followed by adjuvant nivolumab did not improve recurrence-free survival versus surgery only followed by surveillance in patients with high-risk renal cell carcinoma. FUNDING: US National Institutes of Health National Cancer Institute and Bristol Myers Squibb.

Clinical safety and efficacy of microwave ablation for small renal masses.

PURPOSE: CT-guided MWA is a safe and effective tool that should be utilized in the treatment of small renal masses (SRMs). We aim to clarify the utility of CT-guided MWA by examining patient outcomes such as recurrence, treatment success, changes in renal function, and complications. METHODS: A retrospective review of consecutive patients with SRMs who underwent same day renal mass biopsy (RMB) and CT-guided MWA between 2015 and 2022 was performed. Treatment safety was assessed by 30-day complications according to the Clavien-Dindo system and change in eGFR >30 days post-procedure. Treatment efficacy was defined by local recurrence and incomplete treatment rates and calculated using the Kaplan-Meier method. RESULTS: A total of 108 renal masses were found in 104 patients. The overall complication rate was 7.4% (8/108), of which 4 were major complications (3.7%). For those with renal function available >30 days post ablation, the median eGFR was 47.2 (IQR: 36.0, 57), compared to 52.3 (IQR: 43.7, 61.5) pre-ablation, p<0.0001. 5-year local recurrence free survival was 86%. Among those with biopsy proven malignancy (n= 66), there were five local recurrences (7.54%) occurring at a median of 25.1 months (IQR 19.9, 36.2) and one case (1.5%) of incomplete treatment. CONCLUSIONS: As the medical field continues to evolve towards less invasive interventions, MWA offers a valuable tool in the management of renal masses. With low major complication and recurrence rates, our findings support the utility of CT-guided MWA as a tool for treatment of SRMs.

Prevalence and predictors of probable depression in prostate cancer survivors.

BACKGROUND: The early diagnosis and treatment of depression are cancer care priorities. These priorities are critical for prostate cancer survivors because men rarely seek mental health care. However, little is known about the epidemiology of depression in this patient population. The goal of this study was to describe the prevalence and predictors of probable depression in prostate cancer survivors. METHODS: The data were from a population-based cohort of North Carolinian prostate cancer survivors who were enrolled from 2004 to 2007 in the North Carolina-Louisiana Prostate Cancer Project (n = 1031) and were prospectively followed annually from 2008 to 2011 in the Health Care Access and Prostate Cancer Treatment in North Carolina study (n = 805). Generalized estimating equations were used to evaluate an indicator of probable depression (Short Form 12 mental composite score ≤48.9; measured at enrollment and during the annual follow-up) as a function of individual-level characteristics within the longitudinal data set. RESULTS: The prevalence of probable depression fell from 38% in the year of the cancer diagnosis to 20% 6 to 7 years later. Risk factors for probable depression throughout the study were African American race, unemployment, low annual income, younger age, recency of cancer diagnosis, past depression, comorbidities, treatment decisional regret, and nonadherence to exercise recommendations. CONCLUSIONS: Depression is a major challenge for prostate cancer survivors, particularly in the first 5 years after the cancer diagnosis. To the authors' knowledge, this is the first study to demonstrate an association between treatment decisional regret and probable depression.

Multimedia psychoeducation for patients with cancer who are eligible for clinical trials: A randomized clinical trial.

BACKGROUND: Supporting patients' decision making about clinical trials may enhance trial participation. To date, few theory-based interventions have been tested to address this issue. The objective of the current study was aimed to evaluate the effect of a multimedia psychoeducation (MP) intervention, relative to a print education (PE) intervention, on patients' decision support needs and attitudes about clinical trials. METHODS: Patients with cancer who were eligible for participation in a National Cancer Institute therapeutic cancer clinical trial were recruited through the nationwide University of Rochester Cancer Center National Cancer Institute Community Oncology Research Program from 2014 to 2016 and were randomized to the MP or PE intervention. Assessments at baseline (before intervention), postintervention, and at a 2-month follow-up visit included patients' decision support needs, attitudes regarding clinical trials, and clinical trial participation. RESULTS: In total, 418 patients with various types of cancer were recruited (ages 26-89 years). Relative to the PE intervention, the MP intervention did not significantly affect decision support needs. However, patients in the MP arm reported significantly more positive attitudes about clinical trials and were more likely to participate in a clinical trial than those in the PE arm (69% vs 62%; P = .01). Furthermore, an improvement in attitudes about clinical trials significantly mediated the effect of the intervention on participation in clinical trials. CONCLUSIONS: The MP intervention was able to improve patient attitudes toward clinical trials compared with the PE intervention, and this improvement led to increased rates of participation in trials. The MP intervention could be disseminated to improve attitudes about clinical trials among patients with cancer.

Impact of rural location on receipt of standard of care treatment and survival for locally advanced bladder cancer in Louisiana.

OBJECTIVE: We aim to determine the effect of region of residence (urban vs. rural) on the odds of receiving standard of care treatment for locally advanced BCa in Louisiana and its impact on survival outcomes. METHODS: Using the Louisiana Tumor Registry, we identified American Joint Committee on Cancer (AJCC) stage II or III, BCa diagnoses in Louisiana residents between 2010 and 2020. Treatment received was classified as standard or non-standard of care according to American Urological Association (AUA) guidelines and location of residence was determined using Rural Urban Commuting Area-Tract-level 2010 (RUCA). Multivariable logistic regression analyses and multivariate cox proportional hazard analyses were performed. RESULTS: Of 983 eligible patients, 85.6% (841/983) lived in urban areas. Overall, only 37.5% received standard-of-care (SOC) for the definitive management of locally advanced bladder cancer. Individuals living in rural areas (OR 0.53, 95% CI: 0.31-0.91, p = 0.02) were less likely to receive standard of care treatment. Both rural residence and receipt of non-standard of care therapy were associated with an increased risk of bladder cancer-specific (adj HR 1.53, 95% CI: 1.09-2.14, p = 0.01 and adj HR: 1.85, 95% CI: 1.43-2.39, <0.0001) and overall mortality (adj HR: 1.28, 95% CI: 1.01-1.61, p = 0.04 and adj HR: 1.73 95% CI: 1.44-2.07, p < 0.0001). CONCLUSIONS: Most patients with locally advanced bladder cancer in Louisiana do not receive SOC therapy. Individuals living in rural locations are more likely to receive non-standard of care therapy than individuals in urban areas. Nonstandard of care treatment and rural residence are both associated with worse survival outcomes for Louisiana residents with locally advanced bladder cancer.

Does Chemo-Radiotherapy Improve Survival Outcomes vs. Radiotherapy Alone for High-Grade cT1 Urothelial Carcinoma of the Bladder?

BACKGROUND: Non-muscle invasive bladder cancer (non-MIBC) that is high-grade and confined to the lamina propria (HGT1) often has an aggressive clinical course. Currently, there is limited data on the comparative effectiveness of RT vs. CRT for HGT1 non-MIBC. We hypothesized that CRT would be associated with improved overall survival (OS) vs. RT in HGT1 bladder cancer. METHODS: Patients diagnosed with HGT1 non-MIBC, and treated with transurethral resection of bladder tumor followed by either treatment with RT alone or CRT, were identified in the National Cancer Database. Inverse probability of treatment weighting (IPTW) was employed and weight-adjusted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) hazard ratios. OS was the primary endpoint, and was estimated using the Kaplan-Meier method and log-rank tests. RESULTS: A total of 259 patients with HGT1 UC were treated with: (i) RT alone (n = 123) or (ii) CRT (n = 136). Propensity-weighted MVA showed that combined modality treatment with CRT was associated with improved OS relative to radiation alone (Hazard Ratio [HR]: 0.62, 95% Confidence Interval (95% CI): 0.44-0.88, P = .007). Four-year OS for the CRT vs. RT alone was 36% and 19%, respectively (log-rank P <.008). CONCLUSION: For patients with HGT1 bladder cancer, concurrent CRT was associated with improved OS compared with radiation alone in a retrospective cohort. These results are hypothesis-generating. The NRG is currently developing a phase II randomized clinical trial comparing CRT to other novel, bladder preservation strategies.

Can a durable disease-free survival be achieved with surgical resection in patients with pathological node positive renal cell carcinoma?

PURPOSE: Patients with isolated regional nodal metastases from renal cell carcinoma are a distinct cohort for which resection of involved lymph nodes may be therapeutic. We assessed the outcomes of patients treated at our institution with pathological node positive renal cell carcinoma without concomitant metastatic disease (T(any)N+M0). MATERIALS AND METHODS: A total of 2,521 patients with nonmetastatic renal cell carcinoma (T(any)N(any)M0) of any histological subtype treated with nephrectomy were identified between 1995 and 2009. Pathological regional node positive disease in the absence of clinically detectable metastases (T(any)N(1-2)M0) was present in 68 patients (2.7%) and these patients formed our study cohort. Patients were assessed for timing and location of recurrence, disease specific survival and overall survival. Multivariate Cox regression analysis was performed to define factors predictive of recurrence and overall survival. RESULTS: Of the 68 patients with T(any)N(1-2)M0 renal cell carcinoma 22.1% were free of disease at a median followup of 43.5 months. In those patients experiencing recurrence, disease was detected within the first 4 months after surgery in 51% and was most commonly detected at multiple organ sites. The Kaplan-Meier estimated 5-year overall survival and disease specific survival was 37% and 39%, respectively. Predictors of a favorable outcome included an Eastern Cooperative Oncology Group performance status of 0, single node involvement, absence of sarcomatoid features and papillary histology. CONCLUSIONS: Nephrectomy with lymph node dissection can provide a durable disease-free survival in a proportion of patients with regionally advanced renal cell carcinoma and limited lymph node metastases.

Renal cell carcinoma: what the surgeon and treating physician need to know.

OBJECTIVE: The multimodality approach to treating both localized and metastatic renal cell carcinoma has led to a demand for improved imaging evaluation. We review the information needed from the radiologic studies used to determine treatment strategies. CONCLUSION: Adequate preoperative radiologic assessment provides the treating physician with information critical in determining the sequence of treatments, role of nephron-sparing surgery, surgical approach, and timing of systemic therapy for metastatic disease.

The role of lymph node dissection in renal cell carcinoma.

Due to the relatively heterogeneous metastatic spread of renal cell carcinoma (RCC) through both hematogenous and lymphatogenous routes, the surgical extirpation of regional lymph nodes in the treatment of RCC has long been a controversial topic. Individual risk is dependent on multiple variables including tumor stage, grade, and histologic sub-type, in addition to many others. Controversy exists over whether lymph node dissection (LND) simply provides improved staging or whether removal of pathologic nodes offers a therapeutic advantage. Herein, we evaluate the available data regarding the use of LND in the treatment of RCC. While we believe that LND may provide an opportunity for cure in a select group of patients, there are many variables to consider when determining its applicability to an individual patient.

The role of lymphadenectomy in renal cell carcinoma.

PURPOSE OF REVIEW: To critically appraise the current literature on the benefits of lymphadenectomy in patients with renal cell carcinoma. Many questions exist including: What is a 'standard' versus 'extended' lymph node dissection (LND)? What is the morbidity of a LND? What type of patient may derive the most benefit from LND? On the basis of preoperative staging, what is the benefit (therapeutic versus staging) for an individual patient? How does the performance of a LND impact current and future adjuvant and neoadjuvant studies? RECENT FINDINGS: Results from the EORTC 30881 trial did not show a therapeutic benefit to performing a 'standard' LND in patients with renal cell carcinoma, but the population predominantly comprised patients at the lowest risk of harboring lymph node metastasis. There are no prospective randomized trials with sufficient statistical power to analyze the therapeutic or staging effects in high-risk patients. SUMMARY: This review provides a synopsis of the available data regarding the therapeutic and staging benefits of lympadenectomy in the setting of renal cell carcinoma and should assist the urologist in educating affected patients as well as providing the urologist with the current evidenced-based data regarding this longstanding unanswered question.

Patterns and predictors of self-reported clinical diagnosis and treatment for depression in prostate cancer survivors.

BACKGROUND: Appropriate depression care is a cancer-care priority. However, many cancer survivors live with undiagnosed and untreated depression. Prostate cancer survivors may be particularly vulnerable, but little is known about their access to depression care. The goal of this study was to describe patterns and predictors of clinical diagnosis and treatment of depression in prostate cancer survivors. METHODS: Generalized estimating equations were used to evaluate indicators of self-reported clinical diagnosis and treatment depression as a function of individual-level characteristics within a longitudinal dataset. The data were from a population-based cohort of North Carolinian prostate cancer survivors who were enrolled from 2004 to 2007 on the North Carolina-Louisiana Prostate Cancer Project (N = 1,031), and prospectively followed annually from 2008 to 2011 on the Health Care Access and Prostate Cancer Treatment in North Carolina (N = 805). RESULTS: The average rate of self-reported clinical diagnosis of depression was 44% (95% CI: 39%-49%), which declined from 60% to 40% between prostate cancer diagnosis and 5-7 years later. Factors associated with lower odds of self-reported clinical diagnosis of depression include African-American race, employment, age at enrollment, low education, infrequent primary care visits, and living with a prostate cancer diagnosis for more than 2 years. The average rate of self-reported depression treatment was 62% (95% CI: 55%-69%). Factors associated with lower odds of self-reported depression treatment included employment and living with a prostate cancer diagnosis for 2 or more years. CONCLUSION: Prostate cancer survivors experience barriers when in need of depression care.

Robotic Cystectomy.

Retrospective observational studies support the utility of robotic-assisted radical cystectomy (RARC). Randomized controlled trials (RCTs) have shown that RARC with extracorporeal urinary diversion may lead to decreased estimated blood loss, decreased rate of transfusion, similar oncologic outcomes, cost-effectiveness, and variable increased operative times. Although RCTs comparing RARC with open radical cystectomy are currently ongoing, it may be several years before the utility of RARC is known. The discussion on the role of cystectomy, indications, outcomes, care pathways, access to high-volume care centers, and efforts to decrease complications may prove as important as the technique itself.

The use of PET/CT in prostate cancer.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) has recently emerged as a promising diagnostic imaging platform for prostate cancer. Several radiolabelled tracers have demonstrated efficacy for cancer detection in various clinical settings. In this review, we aim to illustrate the diverse use of PET/CT with different tracers for the detection of prostate cancer. METHODS: We searched MEDLINE using the terms 'prostate cancer', 'PET', 'PET/CT' and 'PET/MR'). The current review was limited to 18F-NaF PET/CT, choline-based PET/CT, fluciclovine PET/CT and PSMA-targeted PET/CT, as these modalities have been the most widely adopted. RESULTS: NaF PET/CT has shown efficacy in detecting bone metastases with high sensitivity, but relatively low specificity. Currently, choline PET/CT has been the most extensively studied modality. Although having superior specificity, choline PET/CT suffers from low sensitivity, especially at low PSA levels. Nevertheless, choline PET/CT was found to significantly improve upon conventional imaging modalities (CIM) in the detection of metastatic lesions at biochemical recurrence (BCR). Newer methods using fluciclovine and PSMA-targeted radiotracers have preliminarily demonstrated great promise in primary and recurrent staging of prostate cancer. However, their superior efficacy awaits confirmation in larger series. CONCLUSIONS: PET/CT has emerged as a promising staging modality for both primary and recurrent prostate cancer. Newer tracers have increased detection accuracies for small, incipient metastatic foci. The clinical implications of these occult PET/CT detected disease foci require organized evaluation. Efforts should be aimed at defining their natural history as well as responsiveness and impact of metastasis-directed therapy.

Klinefelter Syndrome with Poor Risk Extragonadal Germ Cell Tumor.

Germ cell tumors are the most common malignancy in men aged 15-35 years old, with a small percentage presenting in an extragonadal location. These tumors are seldom identified in the gastrointestinal tract. There is increased risk of extragonadal germ cell tumors (EGCT) in men with Klinefelter syndrome (KS). We report a rare case of a 37-year-old male with KS and EGCT discovered in the duodenum and pelvis. After treatment with Bleomycin-Etoposide-Cisplatin (BEP), he developed growing teratoma syndrome (GTS) and myelodysplasia. Despite surgical excision of the pelvic growing teratoma, he unfortunately died secondary to complications of severe bone marrow suppression.

Outcome of patients with clinically node-positive bladder cancer undergoing consolidative surgery after preoperative chemotherapy: The M.D. Anderson Cancer Center Experience.

PURPOSE: Patients with urothelial cancer with nodal metastasis have a poor prognosis, with many deemed incurable. We report outcomes of a prospective clinical protocol of patients with clinically node-positive disease treated via a multimodality treatment approach. PATIENTS AND METHODS: A total of 55 patients with bladder urothelial carcinoma with concurrent node-positive disease including pelvic nodal and retroperitoneal lymph node (RPLN) involvement underwent preoperative chemotherapy followed by consolidative surgery between 1995 and 2010. Associations between clinicopathologic factors and outcomes were analyzed using log-rank test and Cox regression analysis. RESULTS: Median cancer-specific survival (CSS) was 26 months (95% CI: 12.9-not applicable) for all patients. A total of 30 (55%) patients had pN0 category disease at the time of surgical extirpation. Despite radiologic complete response after chemotherapy, 6 of 21 patients (29%) had pN+category disease. The 5-year CSS rate was 66% for pN0 category disease vs. 12% for pN+category disease (P<0.001). Radiologic complete response to chemotherapy was associated with a 5-year CSS rate of 60% vs. 33% for a partial response (P = 0.038). Although no recurrences occurred within the lymphadenectomy template, 2 (14%) patients with cM1 RPLN disease who did not undergo RPLN dissection had recurrences in the RPLN basin and died within 6 months. CONCLUSION: Multimodality treatment approach with upfront chemotherapy followed by surgery can result in a 66% 5-year CSS rate for patients rendered as having pN0 category disease despite initially presenting with node-positive disease. However, as those with residual disease do so poorly, further efforts in refining selection of patients for surgical consolidation are needed.

The role of lymph node dissection in renal cell carcinoma.

The role of lymph node dissection (LND) in the staging and treatment of renal cell carcinoma has long been a topic of debate. The controversy has focused on whether LND is purely an adjunctive staging procedure or has a therapeutic role in the management of this disease. Potential benefits include enhanced staging, better selection for adjuvant therapies/clinical trials, a decrease in recurrence rates, and improved disease-specific and overall survival. This article reviews the available literature on LND in renal cell carcinoma and discusses the potential benefits of aggressive surgical resection in select high-risk patients.

Safety of presurgical targeted therapy in the setting of metastatic renal cell carcinoma.

BACKGROUND: In patients with metastatic renal cell carcinoma (mRCC), the timing of systemic targeted therapy in relation to cytoreductive nephrectomy (CN) is under investigation. OBJECTIVE: To evaluate postoperative complications after the use of presurgical targeted therapy prior to CN. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of all patients who underwent a CN at The University of Texas M.D. Anderson Cancer Center from 2004 to 2010 was performed. Inclusion in this study required documented evidence of mRCC, with treatment incorporating CN. INTERVENTIONS: Patients receiving presurgical systemic targeted therapy prior to CN were compared to those undergoing immediate CN. MEASUREMENTS: Complications were assessed using the modified Clavien system for a period of 12 mo postoperatively. RESULTS AND LIMITATIONS: Presurgical therapy was administered to 70 patients prior to CN (presurgical), while 103 patients had an immediate CN (immediate). A total of 232 complications occurred in 57% of patients (99 of 173). Use of presurgical systemic targeted therapy was predictive of having a complication>90 d postoperatively (p=0.002) and having multiple complications (p=0.013), and it was predictive of having a wound complication (p<0.001). Despite these specific complications, presurgical systemic targeted therapy was not associated with an increased overall complication risk on univariable or multivariate analysis (p=0.064 and p=0.237) and was not predictive for severe (Clavien ≥3) complications (p=0.625). This study is limited by its retrospective nature. As is inherent to any retrospective study reporting on complications, we are limited by reporting bias and the potential for misclassification of specific complications. CONCLUSIONS: Despite an increased risk for specific wound-related complications, overall surgical complications and the risk of severe complications (Clavien ≥3) are not greater after presurgical targeted therapy in comparison to upfront cytoreductive surgery.

The impact of targeted molecular therapies on the level of renal cell carcinoma vena caval tumor thrombus.

BACKGROUND: Targeted molecular therapies (TMTs) previously have demonstrated oncologic activity in renal cell carcinoma (RCC) by reducing the size of primary tumors and metastases. OBJECTIVE: To assess the cytoreductive effect of TMTs on inferior vena cava tumor thrombi. DESIGN, SETTING, AND PARTICIPANTS: A multi-institutional database of patients treated with TMTs for RCC was reviewed. The subset with in situ level II or higher caval thrombi (above renal vein) was assessed for radiographic response in thrombus size and level. Pre- and posttreatment characteristics of this population were assessed for predictors of response in height, diameter, and level of the tumor thrombi. MEASUREMENTS: The main outcome measured was a change in the clinical level of tumor thrombus following TMT. We also measured radiographic responses in thrombus size and location before and after TMT. RESULTS AND LIMITATIONS: Twenty-five patients met the inclusion criteria. Before TMT, thrombus level was II in 18 patients (72%), III in 5 patients (20%), and IV in 2 patients (8%). The first-line therapy was sunitinib in 12 cases; alternative TMTs were administered in 13. The median duration of therapy was two cycles (range: one to six cycles). Following TMT, 7 patients (28%) had a measurable increase in thrombus height, 7 (28%) had no change, and 11 (44%) had a decrease. One patient (4%) had an increase in thrombus-level classification, 21 (84%) had stable thrombi, and in 3 (12%) the thrombus level decreased. There was only one case (4%) where the surgical approach was potentially affected by tumor thrombus regression (level IV to III). No statistically significant predictors of tumor thrombus response to TMTs were found. Limitations include the descriptive and retrospective study design. Because TMTs were initiated according to physician and/or patient preferences, and not all patients were treated in anticipation of surgery, no conclusions could be drawn regarding selection and duration of therapy. Thus it may not be appropriate to extrapolate our experience to all patients with locally advanced RCC. Although this is the largest reported experience with in situ caval tumor thrombi treated with TMT, this series lacks sufficient statistical power to assess the usefulness of TMTs adequately in tumor thrombus cytoreduction. CONCLUSIONS: TMT had a minimal clinical effect on RCC tumor thrombi. Only patients treated with sunitinib had clinical thrombus regression; however, the clinical magnitude and relevance of this effect is not clear and should be investigated prospectively.