High-risk Renal Cell Carcinoma Patients Research Articles

Niemann-Pick C1-like 1 as a Prognostic Marker in Renal Cell Carcinoma: A Retrospective Cohort Study.

Renal cell carcinoma (RCC) is a highly aggressive malignancy accounting for the majority of kidney cancers. Despite recent advancements in therapeutic options, the prognosis for advanced-stage RCC remains poor. Niemann-Pick C1-Like 1 (NPC1L1) plays a crucial role in cholesterol absorption and has been implicated in cancer progression across various cancers. However, its expression patterns and prognostic significance in RCC remain unclear. In this study, NPC1L1 expression in normal and RCC tissues, including subtypes, was compared using TCGA, GEPIA2, and The Human Protein Atlas. Clinical correlations were assessed, and the impact of NPC1L1 on overall survival (OS) and progression-free survival (PFS) was evaluated. Gene effect scores were analyzed using the DepMap tool to determine the involvement of NPC1L1 in RCC progression. NPC1L1 expression was significantly lower in RCC tissues compared to normal tissues, particularly in the clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC) subtypes, but increased in advanced tumor stages. Higher NPC1L1 expression was associated with worse OS and PFS in RCC patients. Multivariable Cox regression confirmed NPC1L1 as an independent prognostic marker. Additionally, gene effect scores showed that NPC1L1 is essential for the survival of specific RCC cell lines. This study determines NPC1L1 as an independent prognostic indicator in RCC, with higher expression associated with poor survival outcomes. These findings suggest that NPC1L1 could serve as a valuable marker for identifying high-risk RCC patients. Further research is required to investigate the molecular mechanisms underlying the role of NPC1L1 in RCC progression.

Role of clinicopathological variables in predicting recurrence and survival outcomes after surgery for non-metastatic renal cell carcinoma: Systematic review and meta-analysis.

Renal cell carcinoma (RCC) represents 2% of all diagnosed malignancies worldwide, with disease recurrence affecting 20% to 40% of patients. Existing prognostic recurrence models based on clinicopathological features continue to be a subject of controversy. In this meta-analysis, we summarized research findings that explored the correlation between clinicopathological characteristics and post-surgery survival outcomes in non-metastatic RCC patients. Our analysis incorporates 99 publications spanning 140 568 patients. The study's main findings indicate that the following clinicopathological characteristics were associated with unfavorable survival outcomes: T stage, tumor grade, tumor size, lymph node involvement, tumor necrosis, sarcomatoid features, positive surgical margins (PSM), lymphovascular invasion (LVI), early recurrence, constitutional symptoms, poor performance status (PS), low hemoglobin level, high body-mass index (BMI), diabetes mellitus (DM) and hypertension. All of which emerged as predictors for poor recurrence-free survival (RFS) and cancer-specific survival. Clear cell (CC) subtype, urinary collecting system invasion (UCSI), capsular penetration, perinephric fat invasion, renal vein invasion (RVI) and increased C-reactive protein (CRP) were all associated with poor RFS. In contrast, age, sex, tumor laterality, nephrectomy type and approach had no impact on survival outcomes. As part of an additional analysis, we attempted to assess the association between these characteristics and late recurrences (relapses occurring more than 5 years after surgery). Nevertheless, we did not find any prediction capabilities for late disease recurrences among any of the features examined. Our findings highlight the prognostic significance of various clinicopathological characteristics potentially aiding in the identification of high-risk RCC patients and enhancing the development of more precise prediction models.

The Role of Targeted Therapy in the Management of High-Risk Resected Kidney Cancer: What Have We Learned and How Will It Inform Future Adjuvant Trials.

The primary treatment for localized renal cell carcinoma (RCC) is surgical resection with curative intent. Despite this, many patients, especially those with high-risk features, will develop recurrent or metastatic disease. Antiangiogenic therapies targeting vascular endothelial growth factor have been a mainstay of treatment of advanced RCC for more than 10 years. Evidence supporting the use of these therapies in the adjuvant setting is mixed, although one clinical trial, S-TRAC, has shown improvements in disease-free survival with 1 year of adjuvant sunitinib among patients with clear cell histology and high-risk features, leading to the first US Food and Drug Administration approval of an adjuvant therapy for high-risk RCC patients. Further investigation into combination therapies with immunotherapy, neoadjuvant approaches, and patient selection will be key to determining optimal adjuvant therapy regimens to improve outcomes and increase cure rates for patients with localized RCC.

Prevalence, disease-free (DFS) and overall (OS) survival of contemporary high-risk renal cell carcinoma (RCC) patients eligible for adjuvant checkpoint inhibitor trials: A RECUR database analysis.

636 Background: Designing adjuvant trials is challenging because of uncertainties of prevalence and outcome of high-risk RCC despite use of validated risk scores. Methods: RECUR is a European multicenter database capturing patient and tumour characteristics, recurrence patterns and survival of all patients treated with (partial) nephrectomy for non-metastatic RCC from 2006 to 2011 at each participating center. We evaluated prevalence, DFS and OS of RCC according to eligibility criteria of adjuvant trials IMMotion 010 (NCT03024996, IM), Checkmate 914 (NCT03138512, CM), Keynote-564 (NCT03142334, KN) and RAMPART (NCT03288532, RP), which all predominantly recruited high-risk clear cell RCC patients. Results: Of 2669 relevant patients in RECUR, 424(15.9%), 681(25.5%), 579(21.7%) and 1221(45.7%) met eligibility criteria for IM, CM, KN and RP respectively (p < 0.001). Median DFS and OS estimates (Kaplan-Meier) in RECUR corresponding to each trial placebo arm were 37.5 (95%CI 30.4–44.6) and 89.6 (95%CI 76.1–103.0) months for IM, 89.4 (95%CI 66.1–112.7) and 96.2 (95%CI 79.8–112.6) months for CM, 62.6 (95% CI39.6–85.6) and 86.6 (95%CI 74.3–98.9) months for KN and finally at 144 months (DFS not reached) and 123.8 (95% CI 110.1 – 137.4) months for RP. Additionally, at pairwise analysis of evaluated trials, DFS estimates were significantly different between all trials (p < 0.001) except between CM and KN (p = 0.125), while OS estimates did not differ significantly between all trials except between RP and the other three trials (p = 0.002). Conclusions: Percentages of eligible high-risk RCC patients in RECUR were low to moderate and, together with estimated placebo arm DFS and OS, varied due to differences in trial eligibility criteria. These differences may impact on the results and interpretation of the trials.

Sunitinib or Sorafenib as Neoadjuvant Therapy May not Improve the Survival Outcomes of Renal Cell Carcinoma with Tumor Thrombus

Objectives: The purpose of this work was to investigate the effect of sorafenib or sunitinib as neoadjuvant therapy on the survival outcomes of renal cell carcinoma (RCC) with tumor thrombus. Methods: A total of 92 RCC patients with tumor thrombus were included in this 2-center retrospective research from January 2007 to December 2014. Sorafenib and sunitinib were administered as neoadjuvant therapy in 9 patients and 14 patients, respectively, and 69 patients constituted non-neoadjuvant therapy groups. The Kaplan-Meier method was used to estimate the recurrence-free survival (RFS) and overall survival (OS). Log-rank test was used to compare the survival outcomes of patients with or without neoadjuvant therapy. Results: The overall median RFS and OS time for all 92 patients were 28 months (95% CI 17–39 months) and 42 months (95% CI 30–54 months). Patients with neoadjuvant therapy had no significantly longer median RFS (30 vs. 28 months, p = 0.376) and OS (45 vs. 42 months, p = 0.702) than those without neoadjuvant therapy. Conclusions: Neoadjuvant therapy of sorafenib or sunitinib might not improve survival outcomes for high risk RCC patients with tumor thrombus. Thus, neoadjuvant therapy for RCC with tumor thrombus should be considered cautiously.

Pathological High-risk Renal Cell Carcinoma: Trends in Clinical Characteristics Over 25 Years.

The incidence of renal cell carcinoma (RCC) has been increasing mainly due to the increase in the incidental detection of small renal masses. The aim of this study was to verify whether the trend towards early diagnosis changed the clinical characteristics of pathologically-defined high-risk RCC patients over the last decades. A total of 741 patients with pathologically-confirmed high-risk RCC (pT1-4, and/or pN1 and/or Fuhrman grade 3-4 and/or all M1 patients) treated with radical (RN) or partial nephrectomy (PN) at a single tertiary referral center between 1987 and 2011 were included in the study. The temporal trends of pre-operative clinical and tumor characteristics were assessed relying on the lowess smoother weighted function with corresponding 95% confidence interval. Estimated annual percentage changes (EAPC) were evaluated using a log linear regression model. The median age of patients increased from 57.5 to 67.3 years between 1987 and 2011 (EAPC 4.9%, p=0.002). Body mass index and gender rates remained stable during the study period. A constant trend towards patients with one or more comorbidity was observed. Moreover, the proportion of asymptomatic patients at diagnosis and of clinical T1 increased by 41.1 and 19.8%, respectively (all p≤0.007). The clinical tumor size dropped from 8.4 to 6.2 cm (EAPC -1.2%, p=0.001). This trend was accompanied by a clinically-relevant increase by 15.3% in the rate of patients without clinical metastases (p=0.07). Conversely, the rate of clinical lymphadenopathies remained stable over time. Finally, the rate of PNs performed increased by 23.3% (p<0.001). Over the years, pathologically-confirmed high-risk RCC patients are older, mostly asymptomatic, with smaller cancers, with a higher rate of tumors localized to the kidney and with a decreased rate of metastatic disease at diagnosis. These trends can explain the increasing number of PNs performed despite the presence of a high-risk cancer profile.

Adjuvant antiangiogenic agents in post-nephrectomy renal cell carcinoma (RCC): A systematic review and meta-analysis.

689 Background: The role of antiangiogenic agents in advanced RCC is well established. However, it is still not clear whether this benefit can be extrapolated to the adjuvant setting. In this meta-analysis of 3 randomized control trials (RCTs), we sought to determine the efficacy of these agents in RCC patients who underwent nephrectomy with high risk of relapse. Methods: We searched three databases, including Pubmed, Embase, and Cochrane Central Register of Controlled Trials to identify RCTs comparing antiangiogenic agents to placebo in post-nephrectomy RCC patients. We evaluated: 1) the effect of antiangiogenics in highest risk groups as defined by individual studies; 2) the role of each agent separately; and 3) the effect in clear-cell RCC population. Outcomes of interest included overall survival (OS) and disease-free survival (DFS). The overall effect was pooled using the DerSimonian and Laird random effects models Results: Three RCTs (N = 3693 patients) were identified. All studies were comparing placebo to antiangiogenics: sunitinib, sorafenib, and pazopanib. Overall, antiangiogenics did not improve DFS (HR 0.92, 95% CI 0.78 to 1.07) or OS (HR 0.99, 95% CI 0.79 to 1.25). These results persisted when restricting the analysis to patients with clear cell carcinoma and patients with highest risk of relapse. Similarly, sunitinib did not show any improvement in the entire studied group for either DFS (HR 0.89, 95% CI 0.67 to 1.19) or OS (HR 1.11, 95% CI 0.90 to 1.37). In addition, when restricting the analysis to the high risk group, sunitinib did not show any advantage in terms of DFS (HR 0.85, 95% CI 0.67 to 1.07) and OS (HR 1.04, 95% CI 0.83 to 1.31). Conclusions: Based on the available evidence, antiangiogenics do not seem to add an advantage over placebo in terms of OS and DFS in high risk RCC patients after nephrectomy. Further studies are needed to identify the patient population which might derive a benefit from antiangiogenics in the adjuvant setting.

Retrospective review of cytotoxic chemotherapy and anti-angiogenic combinations in renal cell carcinoma: A single institution experience.

523 Background: Despite many therapeutic advances, Renal Cell Carcinoma (RCC) still is a leading cause of cancer morbidity and mortality. A recent phase 2 study has examined the combination of Sunitinib and Gemcitabine in a poor risk RCC trial population (Michaelson et al., Cancer 2015). There is limited data on such combinations in a non-clinical trial population. This retrospective study examines our institutional experience in treating predominantly high risk RCC patients with a combination of gemcitabine and an anti-angiogenic agent. Methods: IRB approval was obtained in order to review pathological and clinical data of RCC patients. A retrospective cohort was identified of RCC patients treated with Gemcitabine as well as an anti-angiogenic agent (Sunitinib or Pazopanib) between January 2011 and December 2015 at the Winship Cancer Institute at Emory University. Patient data was reviewed for clinical and pathological characteristics, treatments, prognostic factors, and tolerance. Kaplan Meier analysis was used to assess treatment associated time-to-disease progression (TTP) and overall survival (OS). Results: 12 patients received Gemcitabine and either Sunitinib (n=11) or Pazopanib (n=1). Clear cell (n=5) and non-clear cell varieties including papillary (n=5), chromophobe (n=1), and collecting duct (n=1) RCC were represented. The median line of therapy was 2 (range 0-5 prior therapies). 50% of patients were poor risk, 33% were intermediate risk, and 17% of patients had good risk disease by Heng Criteria. The overall median TTP was 2.9 months (range 0.82-16.5 months) and overall median OS was 8.3 months (range 2.3-16.5 months). This regimen was well tolerated with the most common adverse effects being fatigue in 50% (6/12) of patients, fever in 33% (4/12) of patients, and nausea in 33% (4/12) of patients. Conclusions: Our experience suggests that this combination is effective in advanced and heavily pretreated RCC patients, including poor risk RCC patients outside of a clinical trial format. Additional prospective data using similar combinations, may provide improved outcomes of RCC patients, especially with non-clear cell RCC patients.

Clinical study of neoadjuvant therapy of tyrosine kinase inhibitor in high–risk renal cell carcinoma

Objective To investigate the safety and clinical significance in presurgical application of tyrosine kinase inhibitor (TKI) targeted therapy in high–risk renal–cell–carcinoma patients. Methods TKI targeted therapy was applied to 33 high–risk renal–cell–carcinoma patients from Jun. 2010 to Dec. 2013, 7 cases with paraneoplastic symdromes and 1 with bilateral lesions received surgical treatments. There were 6 males and 2 females in this group with average age of 50 (42–56) years. They were high–risk patients because of renal tumor and vena caval tumor thrombus in 3 cases, renal tumor and vena caval tumor thrombus and hypercalcinemia in 1 case, renal tumors with metastasis to lung and lymph nodes in 2 cases, renal tumor with metastasis to lung and bones in 1 cases, and bilateral kidney cancer in 1 case. The clinical stages included 3 cases of T3aN1M1 and T3bN0M0 respectively, and 1 case of T3bN0M1 and T3aN0M0, respectively. The primary metastasis sites were lymph nodes and lung (3 cases respectively), and another 1 in bone. 4 cases suffered from vena cava tumor thrombi with 3 staged Mayo Ⅲ and 1 Mayo Ⅳ. 7 cases with paraneoplastic syndromes were contra–indicated for surgery due to poor ECOG performance score (with score 3 in 3 cases and 2 in 4 cases). 4 cases received Sorafinib 400mg po bid and the other 4 Sunitinib 50 mg po qd, 4 weeks on and 2 weeks off, with duration of 8–12 weeks. Medical therapy ceased 6 to 16 days (median 12 days) before operation. Results Patients with neoadjuvant therapy experienced good toleration. The 7 cases with poor ECOGs improved during medical therapy. The tumor sizes in the bilateral lesions shrunk remarkably. All 7 patients received surgery: 3 radical nephrectomies, 4 nephrectomies and resections of Vena Caval tumor thrombus, and 1 bilateral lesions underwent nephron sparing surgery. Operations were successful though with mild to moderate adhesion, and the blood loss ranged from 120 to 500 ml, with averaged of 280 ml. Pathologic results were clear–cell renal carcinomas. All incisions were well–healed. 4 patients with metastasis continued TKI therapy. All patients were alive without recurrence during the follow–up of 4 to 42 mon. Conclusions Presurgical application of targeted therapy is safe and may increase the opportunity of surgery for some patients with poor general situation, also patients with bilateral lesions may benefit from it for its possibility of nephron sparing. Key words: Tyrosine kinase inhibitor targeted therapy; High–risk renal cell carcinoma; Presurgical treatment; Paraneoplastic syndrome

Clinical efficacy of sunitinib as post-operative adjuvant therapy in patients with high-risk renal cell carcinoma.

e15547 Background: To evaluate the efficacy and safety of Sunitinib as post-operative adjuvant therapy in patients with high-risk renal cell carcinoma (RCC). Methods: A total of 60 patients with resected, histologically confirmed clear cell RCC were enrolled in this study. Patients received orally Sunitinib either at a dose of 50mg on treatment schedule 4/2 (once daily for 4 weeks followed by 2 weeks off) or at a dose of 37.5mg once daily for three 6-week cycles from 1 month after surgery. Results: All 60 patients tolerated Sunitinib treatment well and no patient discontinued treatment due to adverse events. Most adverse events were grade 1 to 2. The most frequently reported adverse events were neutropenia (56.7%), thrombocytopenia (53.3%), leucopenia (48.3%), hand-foot syndrome (46.7%) and hypertension (36.7%). The most frequently reported grade 3 or 4 toxicities were thrombocytopenia (25%), neutropenia (15%), hand-foot syndrome (11.7%) and leucopenia (8.3%). The majority of adverse events occurred within the first 1-2 cycles of Sunitinib treatment, and was ameliorated 1 month after 3 cycles finished. No irreversible adverse event was observed. As of January 31, 2013, recurrence occurred in 3 of 60 (5%) patients except one death due to cerebrovascular accident unrelated to treatment, with 12-month disease-free survival (DFS) rate of 96.6% (RCC recurred 7 months after surgery in 2 patients and recurred 14 months after surgery in 1 patient). Conclusions: Myelosuppression occurred less frequently in high-risk RCC patients treated with Sunitinib as operative adjuvant therapy than in advanced RCC patients, with a better benefit trend. Long-term follow-up data are needed to further confirm the efficacy of Sunitinib in the adjuvant setting.

Clinical efficacy of sunitinib as post-operative adjuvant therapy in patients with high-risk renal cell carcinoma

Objective To evaluate the efficacy and safety of sunitinib as post-operative adjuvant therapy in patients with high-risk renal cell carcinoma (RCC).Methods A total of 60 patients with resected,histologically confirmed clear cell RCC were enrolled in this study.Patients received orally sunitinib either at a dose of 50 mg on treatment schedule (once daily for 4 weeks followed by 2 weeks off) or at a dose of 37.5 mg once daily for three 6-week cycles from 1 month after surgery.Results All the 60 patients tolerated Sunitinib treatment well and no patient discontinued treatment due to adverse events.Most adverse events were grade Ⅰ to Ⅱ.The most frequently reported adverse events were neutropenia (56.7％),thrombocytopenia (53.3％),leucopenia (48.3％),hand-foot syndrome (46.7％) and hypertension (36.7％).The most frequently reported grade 3 or 4 toxicities were thrombocytopenia (25.0％),neutropenia (15.0％),hand-foot syndrome (11.7％) and leucopenia (8.3％).The majority of adverse events occurred within the first 1-2 cycles of sunitinib treatment,and was ameliorated 1 month after 3 cycles finished.No irreversible adverse event was observed.As of April 5,2012,no recurrence occurred in patients except one death due to cerebrovascular accident unrelated to treatment,with both 6-month and 9-month disease-free survival rate of 100％.Conclusions Myelosuppression occurred less frequently in high-risk RCC patients treated with sunitinib as operative adjuvant therapy than in advanced RCC patients,with a better benefit trend.However,long-term follow-up data are needed to further confirm the efficacy of sunitinib in the adjuvant setting. Key words: Carcinoma, renal cell; Sunitinib; Adjuvant therapy; High-risk renal cell carcinoma

847P - Clinical Efficacy of Sunitinib as Post-Operative Adjuvant Therapy in Patients with High-Risk Renal Cell Carcinoma

ABSTRACT Objective To evaluate the efficacy and safety of Sunitinib as post-operative adjuvant therapy in patients with high-risk renal cell carcinoma (RCC). Methods A total of 60 patients with resected, histologically confirmed clear cell RCC were enrolled in this study. Patients received orally Sunitinib either at a dose of 50mg on treatment schedule 4/2 (once daily for 4 weeks followed by 2 weeks off) or at a dose of 37.5mg once daily for three 6-week cycles from 1 month after surgery. Results All 60 patients tolerated Sunitinib treatment well and no patient discontinued treatment due to adverse events. Most adverse events were grade I to II. The most frequently reported adverse events were neutropenia (56.7%), thrombocytopenia (53.3%), leucopenia (48.3%), hand-foot syndrome (46.7%) and hypertension (36.7%). The most frequently reported grade 3 or 4 toxicities were thrombocytopenia (25%), neutropenia (15%), hand-foot syndrome (11.7%) and leucopenia (8.3%). The majority of adverse events occurred within the first 1-2 cycles of Sunitinib treatment, and was ameliorated 1 month after 3 cycles finished. No irreversible adverse event was observed. As of April 5, 2012, no recurrence occurred in patients except one death due to cerebrovascular accident unrelated to treatment, with both 6-month and 9-month disease-free survival (DFS) rate of 100%. Conclusion Myelosuppression occurred less frequently in high-risk RCC patients treated with Sunitinib as operative adjuvant therapy than in advanced RCC patients, with a better benefit trend. However, long-term follow-up data are needed to further confirm the efficacy of Sunitinib in the adjuvant setting. Disclosure All authors have declared no conflicts of interest.

Erlotinib with sirolimus for advanced renal cell carcinoma: Preliminary efficacy results

e16037 Background: The mammalian target of rapamycin (mTOR) is an important therapeutic target in the treatment of renal cell carcinoma (RCC). Temsirolimus, an analog of rapamycin, prolongs survival when used to treat high-risk RCC patients and is approved for the treatment of advanced RCC. Oral rapamycin (sirolimus/Rapamune) is less expensive than temsirolimus and plasma levels can be routinely monitored. Pre-clinical data indicate that the combined inhibition of the epidermal growth factor receptor (EGFR) and mTOR results in enhanced anti-cancer activity, especially in cell lines with wt-VHL. Methods: All patients on this study had metastatic or unresectable renal cell carcinoma with progression despite sunitinib and/or sorafenib. Treatment was started with erlotinib (Tarceva) 150 mg po daily. On day 8, sirolimus was begun with a single 6 mg loading dose and then given as 2 mg daily. Radiographic assessments were performed every 8 weeks. Results: The current data set was obtained through July of 2008. Enrollment started in July of 2006 with the last patient accrued in March 2008; 25 patients have been treated. The median subject age was 60 years with an average of 2.6 previous medical treatments. The unconfirmed median progression free survival (PFS) was 12 weeks (range 2–52) with 4 patients remaining on active treatment and included in this analysis. No confirmed complete or partial responses were observed, but meaningful stable disease (SD) (e.g., &gt; 6 months) was noted in a small group of patients. The most common adverse events were rash and diarrhea with the majority of these observed as a grade 1 event. Grade 3 and 4 toxicities included rash, mucositis, neurological motor weakness, dehydration, worsening cardiac function, non-ST elevation MI, and anemia. Additional efficacy, toxicity and pharmacokinetic data will be presented. Conclusions: The combination of erlotinib and sirolimus produces a median PFS of 12 weeks in a significantly pretreated RCC population, which is not dissimilar to recent results with other mTOR inhibitors in this setting. The toxicity profile of this combination is consistent with the expectations of this pre-treated patient population with advanced RCC. [Table: see text]

A phase II study of GM-CSF, IFN alpha and IL-2 in adjuvant setting for high-risk renal cell carcinoma patients

16123 Background: Patients (pts) with high-risk RCC have a dismal prognosis. To date, no effective adjuvant therapy exists for this pts category. We suppose that combination of granulocyte-macrophage colony-stimulating factor (GM-CSF), IFNa and IL-2 stimulates immune system from dendritic cells to cytotoxic T-lymphocytes and eliminates residuary tumor cells. The primary end-point was median disease-free survival (DFS). Secondary end-points were progression rate, overall survival (OS) and toxicity. Methods: After radical surgery eligible pts with T3b-T4, or N1-N3, or M1 or T3a and tumor grade 3 were supposed to be disease-free. The interval between surgery and protocol therapy was 2–10 weeks. Pts received treatment during 6 months according to scheme: GM-CSF, 1 mcg/kg, 3 tiw, s.c., first week of each 1–6 months; IFN-a2b, 10 MIU, 3 tiw, s.c., second week of 1, 3, 6 months and 5 MIU, 3 tiw, s.c., second-third weeks of 2, 4, 5 months; IL-2, 1 MIU, 3 tiw, i.v. once a day, third week of 1, 3, 6 months. Fourth week of each month was free from treatment. Results: Between 5/2004 and 01/2006, 35 patients (28m/7f; median age = 46, range 21–71; ECOG 0; 12 (34.3%) pts with stage III and 23 (65.7%) pts with stage IV) underwent “radical” surgery and were treated with adjuvant cytokines for 6 planned months. Toxicity was minimal characterized by mainly flu-like syndrome (IFN) and erythema in injection site (GM-CSF). 3 pts (9,4%) had grade 2 hypotension (IL-2). There were neither hematological side effects no toxicity grade 3 or 4. At a median follow-up of 32.4 months, 21 (60%) patients have relapsed. Median DFS was 14.1 months. There was not a significant association between III and IV stages in median DFS (log rank p=0.2). Median OS has not yet been reached. Conclusions: These preliminary data do not demonstrate a marked improvement in DFS over historical controls. Low doses GM-CSF, IFNa and IL-2 during 6 months in adjuvant setting are feasible and tolerable. No significant financial relationships to disclose.

Adjuvant therapy for high-risk renal cell carcinoma patients

For most cases of renal cell carcinoma (RCC), the standard of care is surgical resection as monotherapy or as part of a multimodal approach. In patients with early localized disease, radical nephrectomy is associated with a favorable prognosis, whereas patients with advanced disease are rarely cured. A significant number of patients undergoing surgery for localized RCC experience recurrence, suggesting that there are some individuals in whom surgical excision is necessary but insufficient. In these patients, the development of effective adjuvant strategies is imperative. In this article, we review the prognostic variables and comprehensive staging algorithms for identifying patients at high risk for disease recurrence. Additionally, we review data from completed adjuvant RCC trials and highlight relevant ongoing trials.

Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: Results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN): Atzpodien J, Schmitt E, Gertenbach U, Fornara P, Heynemann H, Maskow A, Ecke M, Wöltjen HH, Jentsch H, Wieland W, Wandert T, Reitz M, German Cooperative Renal Carcinoma Chemo-Immunotherapy Trials Group

We conducted a prospectively randomised clinical trial to investigate the role of adjuvant outpatient immunochemotherapy administered postoperatively in high-risk patients with renal cell carcinoma. In total, 203 renal carcinoma patients’ status post radical tumour nephrectomy were stratified into three risk groups: patients with tumour extending into renal vein/vena cava or invading beyond Gerota’s fascia (pT3b/c pN0 or pT4pN0), patients with locoregional lymph node infiltration (pN+), and patients after complete resection of tumour relapse or solitary metastasis (R0). Patients were randomised to undergo either (A) 8 weeks of outpatient subcutaneous interleukin-2 (sc-rIL-2), subcutaneous interferon-alpha2a (sc-rIFN-α2a), and intravenous 5-fluorouracil (iv-5-FU) according to the standard Atzpodien regimen (Atzpodien et al , 2004) or (B) observation. Two-, 5-, and 8-year survival rates were 81, 58, and 58% in the treatment arm, and 91, 76, and 66% in the observation arm (log rank P = 0.0278), with a median follow-up of 4.3 years. Two, 5-, and 8-year relapse-free survival rates were calculated at 54, 42, and 39% in the treatment arm, and at 62, 49, and 49% in the observation arm (log rank P = 0.2398). Stage-adapted subanalyses revealed no survival advantages of treatment over observation, as well. Our results established that there was no relapse-free survival benefit and the overall survival was inferior with an adjuvant 8-week-outpatient sc-rIL-2/sc-rIFN-α2a/iv-5-FU-based immunochemotherapy compared to observation in high-risk renal cell carcinoma patients following radical tumour nephrectomy.

Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: Results of a prospectively randomised Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN)

We conducted a prospectively randomised clinical trial to investigate the role of adjuvant outpatient immunochemotherapy administered postoperatively in high-risk patients with renal cell carcinoma. In total, 203 renal carcinoma patients' status post radical tumour nephrectomy were stratified into three risk groups: patients with tumour extending into renal vein/vena cava or invading beyond Gerota's fascia (pT3b/c pN0 or pT4pN0), patients with locoregional lymph node infiltration (pN+), and patients after complete resection of tumour relapse or solitary metastasis (R0). Patients were randomised to undergo either (A) 8 weeks of outpatient subcutaneous interleukin-2 (sc-rIL-2), subcutaneous interferon-alpha2a (sc-rIFN-α2a), and intravenous 5-fluorouracil (iv-5-FU) according to the standard Atzpodien regimen (Atzpodien et al, 2004) or (B) observation. Two-, 5-, and 8-year survival rates were 81, 58, and 58% in the treatment arm, and 91, 76, and 66% in the observation arm (log rank P=0.0278), with a median follow-up of 4.3 years. Two, 5-, and 8-year relapse-free survival rates were calculated at 54, 42, and 39% in the treatment arm, and at 62, 49, and 49% in the observation arm (log rank P=0.2398). Stage-adapted subanalyses revealed no survival advantages of treatment over observation, as well. Our results established that there was no relapse-free survival benefit and the overall survival was inferior with an adjuvant 8-week-outpatient sc-rIL-2/sc-rIFN-α2a/iv-5-FU-based immunochemotherapy compared to observation in high-risk renal cell carcinoma patients following radical tumour nephrectomy.