Cell Carcinoma Database Consortium Model Research Articles

Anemia in patients ≥ 75 years with metastatic clear cell renal cell carcinoma: an important poor prognostic factor in the international metastatic renal cell carcinoma database consortium model

BackgroundDue to an increase in life expectancy, the incidence of metastatic renal cell carcinoma (mRCC) in patients aged ≥75 years has been increasing. In this study we investigated the characteristics before treatment and the outcomes of systemic therapies for patients aged ≥75 years with mRCC and compared the results with those for patients aged < 75 years in order to determine whether differences in age influenced survival.MethodsA total of 206 consecutive Japanese patients with mRCC, including 47 patients aged ≥75 years, who received systemic therapy were included. Clinical data from medical records were retrieved and analyzed retrospectively. Survival analyses were determined using a Kaplan–Meier method, and analyzed with a log-rank test.ResultsElderly patients categorized as favorable risk group based on the International Metastatic RCC Database Consortium (IMDC) stratification system were significantly lower. Among IMDC risk factors, the rate of anemia was significantly higher in elderly patients. No statistically significant benefit in progression free survival for first and second line treatment was observed, whereas improvements in overall survival as well as cancer specific survival were seen in patients aged < 75 years.ConclusionsFor mRCC patients aged ≥75 years, a higher proportion of base line anemia, which resulted in higher rates of IMDC intermediate/poor risk, would be responsible for shorter OS/CSS. Furthermore, mRCC patients aged ≥75 years tend to receive BSC instead of second line active treatment. Overcoming under-treatment in elderly patients might help to prolong survival in mRCC.

Outcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary First-line Combination Therapies for Metastatic Renal Cell Carcinoma

BackgroundThe combination of immuno-oncology (IO) agents ipilimumab and nivolumab (IPI-NIVO) and vascular endothelial growth factor targeted therapies (VEGF-TT) combined with IO (IO-VEGF) are current standard of care first-line treatments for metastatic renal cell carcinoma (mRCC). ObjectiveTo establish real-world clinical benchmarks for IO combination therapies based on the International mRCC Database Consortium (IMDC) criteria. Design, setting, and participantsPatients with mRCC who received first-line IPI-NIVO, IO-VEGF, or VEGF-TT from 2002 to 2021 were identified using the IMDC database and stratified according to IMDC risk groups. Outcome measurements and statistical analysisOverall survival (OS), time to next treatment (TTNT), and treatment duration (TD) were calculated using the Kaplan-Meier method and compared between IMDC risk groups within each treatment cohort by the log-rank test. The overall response rate (ORR) was calculated by physician assessment of the best overall response. The primary outcome was OS at 18 mo. Results and limitationsIn total, 728 patients received IPI-NIVO, 282 IO-VEGF, and 7163 VEGF-TT. The median follow-up times for patients remaining alive were 14.3 mo for IPI-NIVO, 14.9 mo IO-VEGF, and 34.4 mo for VEGF-TT. OS at 18 mo for favorable, intermediate, and poor risk was, respectively, 90%, 78%, and 50% for those receiving IPI-NIVO; 93%, 83%, and 74% for IO-VEGF; and 84%, 64%, and 28% for VEGF-TT. ORRs in favorable-, intermediate-, and poor-risk groups were 41.3%, 40.6%, and 33.0% for those receiving IPI-NIVO; 60.3%, 56.8%, and 40.9% for IO-VEGF; and 39.3%, 33.5%, and 20.9% for VEGF-TT, respectively. The IMDC model stratified patients into statistically distinct risk groups for the three endpoints of OS, TTNT, and TD within each treatment cohort. Limitations of this study were the retrospective design and short follow-up. ConclusionsThis study demonstrated that the IMDC model continues to risk stratify patients with mRCC treated with contemporary first-line IO combination therapies and provided real-world survival benchmarks. Patient summaryThe International Metastatic Renal Cell Carcinoma Database Consortium model continues to stratify patients with metastatic renal cell carcinoma receiving modern combination treatments in the real-world setting.

Assessment of prognostic factors in previously treated Japanese patients with metastatic renal cell carcinoma who received nivolumab: An observational multi-institute study.

The aim of the present study was to evaluate the prognosis of Japanese patients with metastatic renal cell carcinoma (mRCC) receiving nivolumab and to identify factors predicting the overall survival (OS) in this cohort of patients. This study retrospectively assessed the outcomes of 77 consecutive Japanese patients with mRCC who were treated using either 1 or 2 molecular-targeted agents followed by nivolumab in routine clinical practice. The best responses to nivolumab observed were as follows: Complete response in 3 patients, partial response in 27, stable disease in 33 and progressive disease in 14; therefore, the objective response rate in the 77 patients was 39.0%. During the median follow-up period of 11 months after the introduction of nivolumab, the median progression-free survival and OS were 7 months and not reached, respectively. On multivariate analysis of several parameters, age, Karnofsky Performance Status (KPS) and neutrophil counts were demonstrated to be independently associated with OS in the 77 patients. By dividing these patients into 3 groups according to 3 risk factors, it was possible to stratify the OS; however, the International Metastatic Renal Cell Carcinoma Database Consortium model was unable to classify the OS. These results suggested that age, KPS and neutrophil counts were useful predictors of OS in previously treated patients with mRCC who received nivolumab.

Efficacy and Safety of Nivolumab and Ipilimumab for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Cohort Study.

We conducted a multicenter, retrospective study to evaluate the efficacy and safety of combination nivolumab plus ipilimumab (NIVO+IPI) in 35 patients with advanced or metastatic renal cell carcinoma (mRCC). In this study, we focused on patients who received NIVO+IPI and were stratified into intermediate- or poor-risk disease according to the International Metastatic Renal Cell Carcinoma Database Consortium model at five institutions in Japan. The primary endpoint was overall survival (OS). Secondary endpoints were disease control rate (DCR), best overall response (BOR), objective response rate (ORR), and progression-free survival (PFS). In addition, we evaluated the role of inflammatory cell ratios, namely neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as predictive biomarkers in patients with mRCC. The median follow-up period was 1 year, and the 1-year OS rate was 95.8%. The ORR and DCR were 34.3% and 80.0%, respectively. According to BOR, four patients (11.4%) achieved complete response. According to NLR stratification, the 1-year PFS rates were 82.6% and 23.7% when the NLR was ≤4.6 and >4.6, respectively (p = 0.04). Based on PLR stratification, the 1-year PFS rates were 81.7% and 34.3% when the PLR was ≤188.1 and >188.1, respectively (p = 0.033). Although 71.4% of the patients experienced treatment-related adverse events (TRAEs) with NIVO+IPI, only four patients discontinued NIVO+IPI due to grade 3/4 TRAEs. Patients treated with NIVO+IPI as a first-line therapy for advanced or mRCC achieved relatively better oncological outcomes. Therefore, NIVO+IPI may have potential advantages and may lead to a treatment effect compared to those receiving targeted therapies. In addition, PLR >188.1 may be a useful predictive marker for mRCC patients who received NIVO+IPI.

External validation of the albumin, C-reactive protein and lactate dehydrogenase model in patients with metastatic renal cell carcinoma receiving second-line axitinib therapy in a Japanese multi-center cohort.

To externally validate the utility of the albumin, C-reactive protein and lactate dehydrogenase model to predict the overall survival of previously treated metastatic renal cell carcinoma patients. The ability of the albumin, C-reactive protein and lactate dehydrogenase model to predict overall survival was validated and compared with those of other prognostication models using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib therapy at 36 hospitals belonging to the Japan Urologic Oncology Group. The following factors in this cohort were independently associated with poor overall survival in a multivariate analysis: a low Karnofsky performance status, <1year from diagnosis to targeted therapy, a high neutrophil count, and low albumin, elevated C-reactive protein, and elevated lactate dehydrogenase, and the Japan Urologic Oncology Group model was newly developed based on the presence/absence of these independent factors. In this cohort, 151 (35.9%), 125 (27.7%) and 145 (34.4%) patients were classified into the favorable, intermediate and poor risk groups, respectively, according to the albumin, C-reactive protein and lactate dehydrogenase model; however, the proportions of patients in the intermediate risk group stratified by the Japan Urologic Oncology Group, Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models were>50%. The superiority of the albumin, C-reactive protein and lactate dehydrogenase model to the Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models, but not the Japan Urologic Oncology Group model, was demonstrated by multiple statistical analyses. The utility of the albumin, C-reactive protein and lactate dehydrogenase model as a simple and objective prognostication tool was successfully validated using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib.

IJU this issue

This issue contains three Review Articles, four Original Articles and four Urological Notes. Huge differences in the incidence and mortality rate of prostate cancer were detected between the USA and Japan. Such differences, however, have been decreasing over time, and were only twofold in 2017. Ito et al. (Takasaki, Japan) describe the important issue of screening for prostate cancer. They propose their screening strategies based on baseline prostate-specific antigen with a reasonable incremental cost-effectiveness ratio. In their perspectives, prostate cancer management might not only be aimed at decreasing the mortality of prostate cancer, but also aimed at achieving a significant increase in the quality-adjusted life year with an acceptable incremental cost-effectiveness ratio. The cancer-specific mortality among patients with localized prostate cancer has been reported to be very low irrespective of the treatment modalities. Nakamura et al. (Hamamatsu, Japan) focus on the patients’ quality of life after external beam radiotherapy using X-ray for prostate cancer, compared with other modalities, including radical prostatectomy and brachytherapy. In conclusion, the patients’ quality of life after external beam radiotherapy is strongly related to the total dose, fractionation regimens, dose parameters of the critical organs, beam delivery techniques and treatment plan quality, with a trade-off between the radicality of external beam radiotherapy and potentially increased toxicity. Particle beam radiotherapy (RT) for prostate cancer in Japan has changed considerably, and it is eligible for insurance coverage as of April 2018. Ishikawa et al. (Tsukuba, Japan) review the results of previous particle beam RT studies compared with photon beam RT, and introduce ongoing studies and prospects to establish high-quality evidence for particle beam RT for prostate cancer. Androgen deprivation therapy (ADT), a standard treatment for metastatic and locally advanced prostate cancer, is known to increase the risks of osteoporosis and fractures. Kimura et al. (Tokyo, Japan) prospectively investigated changes in bone quality, turnover markers and bone mineral density before and after ADT in castration-sensitive prostate cancer. They found that bone quality markers did not change significantly after ADT, whereas bone mineral density decreased significantly after ADT. Bone turnover markers might play an important role in monitoring bone health during ADT. Simone et al. (Rome, Italy) carried out propensity score-matched analysis to compare long-term renal functional outcomes after either off-clamp partial nephrectomy (PN) or on-clamp PN in patients with cT1–2/N0 M0 renal tumors. This study shows that off-clamp PN is associated with a significantly higher probability of maintaining 100% estimated glomerular filtration rate after surgery compared with on-clamp PN in patients with good baseline renal function. It also showed that patients treated with on-clamp PN had a 7.3-fold increased risk of developing a severe chronic kidney disease during long-term follow up. Molecular-targeted therapies have been generally used for treatment of metastatic renal cell carcinoma (mRCC), resulting in improvement in prognoses of mRCC. Konishi et al. (Hirosaki, Japan) retrospectively investigated the impact of C-reactive protein/albumin ratio (CAR) on prognosis, and the effect of adding CAR in the International Metastatic Renal Cell Carcinoma Database Consortium model for prognosis discrimination in Japanese patients who were treated with first-line tyrosine kinase inhibitor for mRCC. They concluded that CAR is an independent predictor of prognosis in patients with mRCC. Predictive activity was significantly improved in the International Metastatic Renal Cell Carcinoma Database Consortium-CAR model compared with the International Metastatic Renal Cell Carcinoma Database Consortium model. Kam et al. (Sydney, Australia) compared the operative performance of two single-use digital flexible ureteroscopes (fURS) with a reusable video fURS in order to show that single-use fURS would have a similar performance to reusable fURS with a lower scope failure rate. In conclusion, these single-use scopes offer a feasible alternative to reusable fURS, especially in complex stone cases where the risk of scope damage is high. None declared.

Feasibility of the ACL (albumin, C-reactive protein and lactate dehydrogenase) model as a novel prognostic tool in patients with metastatic renal cell carcinoma previously receiving first-line targeted therapy

PurposeTo develop a novel model to predict outcomes in patients with previously treated metastatic renal cell carcinoma. Patients and methodsThis study included 78 consecutive metastatic renal cell carcinoma patients receiving first- and second-line targeted therapies at our institution. Predictive factors of overall survival (OS) at the second-line setting in these patients were investigated, and a novel prognostic model was developed. ResultsMedian OS from the initiation of second-line therapy was 21.9 months. A multivariate analysis of several parameters identified the following independent predictors associated with poor OS: albumin (Alb, ≤3.5 g/dl), C-reactive protein (CRP, >0.5 mg/dl), and lactate dehydrogenase (LDH, >1.5 × upper limit of normal). When patients were divided into 3 groups based on the positive numbers of these 3 independent risk factors, named the ACL (Alb, CRP, and LDH) model, median OS durations were 50 months in the favorable risk group without risk factors (n = 26), 25 months in the intermediate-risk group with a single risk factor (n = 24), and 8 months in the poor risk group (n = 28) with multiple risk factors. The superiority of the ACL model as a prognostic tool to the Memorial Sloan Kettering Cancer Center model for previously treated patients and the International Metastatic Renal Cell Carcinoma Database Consortium model was demonstrated by Harrell's concordance index and a decision curve analysis. ConclusionsThe ACL model in the second-line targeted therapy setting may predict outcomes more accurately than the Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models.

C-reactive protein/albumin ratio is a predictive factor for prognosis in patients with metastatic renal cell carcinoma.

To evaluate the effect of pretreatment C-reactive protein/albumin ratio and modified Glasgow prognostic score on the prognosis in patients with metastatic renal cell carcinoma. A retrospective study was carried out in 176 patients with metastatic renal cell carcinoma who received first-line tyrosine kinase inhibitors. The effect of adding inflammatory prognostic scores to the International Metastatic Renal Cell Carcinoma Database Consortium model (International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio and International Metastatic Renal Cell Carcinoma Database Consortium-Glasgow prognostic score models) on overall survival was evaluated using receiver operating characteristic curves. The prognostic value of inflammatory prognostic scores (C-reactive protein/albumin ratio-modified Glasgow prognostic score) was tested using the Kaplan-Meier method and Cox proportional regression models. Patients were stratified into two groups using the cut-off value of 0.05: C-reactive protein/albumin ratio-low (<0.05) and C-reactive protein/albumin ratio-high (≥0.05). The area under the curve was significantly higher in the International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio model (0.720) than that of the International Metastatic Renal Cell Carcinoma Database Consortium model (0.689) and the International Metastatic Renal Cell Carcinoma Database Consortium-modified Glasgow prognostic score model (0.703). Significant differences were observed in overall survival stratified by the number of risk factors in the International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio risk model between one or two and three or four factors (P<0.001), and three or four and five or more factors (P=0.001). For the patients in the International Metastatic Renal Cell Carcinoma Database Consortium intermediate-risk group, overall survival was significantly different between the C-reactive protein/albumin ratio-low and -high groups (P=0.001), whereas it was not significantly different between the patients with one and two International Metastatic Renal Cell Carcinoma Database Consortium risk factors (P=0.106). The C-reactive protein/albumin ratio is a simple and independent predictor of overall survival in patients with metastatic renal cell carcinoma. The predictive activity was significantly improved in the International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio model compared with the International Metastatic Renal Cell Carcinoma Database Consortium/International Metastatic Renal Cell Carcinoma Database Consortium-modified Glasgow prognostic score models.

Sub-classification of patients with intermediate-risk metastatic renal cell carcinoma treated with targeted therapy.

International Metastatic Renal Cell Carcinoma Database Consortium model predicts the outcomes of metastatic renal cell carcinoma stratified into favorable, intermediate, and poor risk groups (FG, IG, and PG, respectively), with approximately 50% of patients being classified as IG. We aimed to generate better risk model based on the sub-classification of IG. We analyzed records of 213 consecutive patients receiving molecular targeted therapy. Age, gender, histology, type of initial molecular targeted therapy, serum laboratory data, previous nephrectomy and immunotherapy, and metastatic sites were used for IG sub-stratification. Modified and original models were compared using a concordance correlation coefficient analysis. Median follow-up was 17.8 months. Serum albumin, serum C-reactive protein, and bone metastases were independent predictors of overall survival (OS) in IG. IG was sub-classified into low-, middle-, and high-risk IG according to the number of predictors. The following modified model was developed: modified FG (FG & low-risk IG), modified IG (middle-risk IG), and modified PG (PG & high-risk IG). Concordance indices for original and modified models were 0.68 and 0.73, respectively (P < 0.001). OS was significantly longer in modified PG treated with mammalian target of rapamycin inhibitors as second-line therapy than with tyrosine kinase inhibitors, whereas this was not observed in the original model. We successfully developed modified IMDC model using a two-step process: the original IMDC plus an IG sub-stratification, and demonstrated that it predicts outcomes more accurately than original model.

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

Renal cell carcinoma (RCC) accounts for 2%–3% of all adultmalignancies, representing the seventh most common cancer inmen and the ninth most common cancer in women [1].Worldwide, there are ∼209000 new cases and 102000 deathsper year. The incidence of all stages of RCC has increased overthe past several years, contributing to a steadily increasing mor-tality rate per unit population. Active and passive cigarettesmoking is an established risk factor for RCC as well as hyper-tension. However, anti-hypertensive medications such as diure-tics are not independently associated with RCC development.RCC also appears to be more common in patients with obesity,end-stage renal failure, acquired renal cystic disease and tuber-ous sclerosis.Approximately 2%–3% of RCC are hereditary and severalautosomal dominant syndromes are described, each with a dis-tinct genetic basis and phenotype, the most common one beingVon Hippel Lindau disease.In recent years, many new genes associated with RCC havebeen reported (such as PBRM1, SETD2, BAP1). Their roles inpathogenesis and as prognostic biomarkers are currently underinvestigation.

Metastatic Clear-cell Renal Cell Carcinoma With a Long-term Response to Sunitinib: A Distinct Phenotype Independently Associated With Low PD-L1 Expression.

Long-term responders (LTRs) are defined by at least 18 months of response to sunitinib in metastatic clear-cell renal cell carcinoma (ccRCC). Well-described by clinical studies, the phenotype of these tumors has never been explored. In a retrospective and multicenter study, 90 ccRCCs of patients with metastatic disease were analyzed. Immunohistochemistry (carbonic anhydrase IX, vascular endothelial growth factor, c-MET, programmed death-ligand 1 [PD-L1], and PD-1) and VHL status were performed. Progression-free survival and overall survival were calculated from sunitinib introduction and from progression. LTRs and their corresponding tumors were compared with others using univariate and multivariate analysis. Twenty-eight patients were LTRs. They had a median progression-free survival of 28 months versus 4 months for other patients (P< .001). Similarly, LTRs had a median overall survival of 49 months versus 14 months (P< .001), even from progression (median, 21 vs. 7 months; P= .029). They were associated with a favorable or intermediate risk (International Metastatic Renal Cell Carcinoma Database Consortium model) (P= .007) and less liver metastasis (P= .036). They experienced more frequent complete or partial responses at the first radiologic evaluation (P=.035). The corresponding ccRCCs were associated with less nucleolar International Society for Urological Pathology grade 4 (P= .037) and hilar fat infiltration (P= .006). They were also associated with low PD-L1 expression (P= .02). Only the International Metastatic Renal Cell Carcinoma Database Consortium model and PD-L1 expression remained significant after multivariate analysis (P= .014 and P= .029, respectively). Primary tumor characteristics of LTRs were studied for the first time and demonstrated a different phenotype. Interestingly, they were characterized by low expression of PD-L1, suggesting a potentially lower impact of targeted immunotherapy in these patients.

External validation of the systemic immune-inflammation index as a prognostic factor in metastatic renal cell carcinoma and its implementation within the international metastatic renal cell carcinoma database consortium model.

We conducted a study to validate the influence of the systemic immune-inflammation index (SII) on overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) and to verify whether the implementation of the SII in place of neutrophil and platelet counts within the International Metastatic Renal Cell Carcinoma Consortium (IMDC) model might increase its prognostic accuracy. We retrospectively analyzed consecutive patients with mRCC, who were treated with first-line tyrosine kinase inhibitors from 2008 to 2016 in two major oncology centres in Poland. We stratified patients into low SII (< 730) and high SII (≥ 730) groups according to a recent literature report. We used multivariable Cox proportional hazards regressions (CPHRs) to assess the impact of the SII on OS and concordance, global 'goodness-of-fit', calibration and reclassification measures to quantify a potential prognostic benefit from the modification of the IMDC model. Overall, 502 patients (294 with low and 208 with high SII) were included. Median OS was 36.7 months [95% confidence interval (CI) 30.4-41.5 months] and 17.0 months (95% CI 12.5-19.6 months) in the low and high SII groups, respectively. The SII status was significant in CPHRs with the hazard ratio ranging from 1.38 to 1.68. All prognostic accuracy measures favored the SII-modified-IMDC model over the original IMDC model. Using an external dataset, we showed that high SII was an independent factor for poor OS. The addition of the SII to the IMDC model in place of neutrophil and platelet counts increased the model's prognostic performance.

Spotlight on cabozantinib for previously untreated advanced renal cell carcinoma: evidence to date.

BackgroundIn the past few years, new drugs made their appearance in the first-line setting of treatment for metastatic renal cell carcinoma (mRCC), and cabozantinib is one among them. The present systematic review aims to point out any evidence published to date about first-line treatment with cabozantinib for mRCC patients, describing their outcome in all end points explored by the literature.MethodsPRISMA guidelines were followed. A systematic assessment of literature and peer- reviewed presentations was performed by searching PubMed and major oncology meeting resources, from the database inception until June 25, 2018. The following keywords were used: “cabozantinib or cabozantinib-s-malate or XL184” and “renal cell carcinoma or kidney cancer or clear cell renal carcinoma or renal cancer” and “first-line or untreated or treatment-naïve or primary treatment”. All types of original clinical studies were included, evaluating either cabozantinib monotherapy or any systemic drug combination containing cabozantinib for previously untreated patients with mRCC.ResultsFrom potential 75 titles and abstracts, seven publications were selected. One was the main report of a randomized clinical trial (the CABOSUN study); four papers reported updated results, secondary or subgroup analyses from the same study population; and further two reports consisted of network meta-analyses. From the additional search for ongoing clinical trials, six studies currently in progress were reported.ConclusionAccording to the reported evidence, cabozantinib may be a viable first-line option in mRCC patients with intermediate or poor risk according to International Metastatic Renal Cell Carcinoma Database Consortium model. It offers an undoubtful advantage in terms of progression-free survival, despite quite high rates of G3–4 toxicity, modest objective response rate, and no survival advantage. Nevertheless, given the availability of an immunotherapy combination that significantly improved overall survival for the same population in a Phase III trial and the indisputable efficacy of cabozantinib as second-line treatment, this drug may be devoted as a rescue option in patients progressive to primary therapy.

Significance of preoperative prognostic nutrition index as prognostic predictors in patients with metastatic renal cell carcinoma with tyrosine kinase inhibitors as first-line target therapy.

Prognostic nutritional index (PNI) is a recognized indicator of both immune and nutritional status. It was firstly used as a preoperative prognostic indicator, and its role in the prognosis of patients with metastatic renal cell carcinoma (mRCC) has not yet been investigated in large-scale study. The purpose of this work was to investigate the prognostic role of pretreatment PNI in patients with mRCC with sorafenib or sunitinib as first-line targeted therapy. In this retrospective single-center research, the Kaplan-Meier method was used to estimate the progression-free survival (PFS) and overall survival (OS) of 178 mRCC patients who received first-line therapy of sorafenib or sunitinib. Log-rank test was used to compare the survival outcomes of patients with low pretreatment PNI (PNI<51.62) and high pretreatment PNI (PNI≥51.62), and Cox proportional hazard regression model was used to compare PFS and OS between these two groups. Prognostic accuracy was determined using Harrell concordance index. The overall median PFS and OS time for all 178 patients were 11months (95% CI 9-12months) and 24months (95% CI 19-33months), respectively. Patients with low pretreatment PNI both had significantly shorter median PFS (7 vs 19months, P<0.001) and OS (14 vs 50months, P<0.001) than those with high PNI. Multivariate analysis showed that pretreatment PNI was an independent predictor of OS (HR 1.658, 95% CI 1.040-2.614, P=0.033) and an independent predictor of PFS as well (HR 1.842, 95% CI 1.226-2.766, P=0.003). The model built by the addition of pretreatment PNI improved predictive accuracy of PFS and OS compared with the International Metastatic Renal Cell Carcinoma Database Consortium Model (Heng model) (c-index: 0.68 and 0.70). Comparing to NLR (neutrophil-to-lymphocyte ratio) (0.69 and 0.72), PNI might be a preciser factor to predict PFS and OS (0.71 and 0.73). Low pretreatment PNI could be a significant risk factor for mRCC patients who received tyrosine kinase inhibitors as first-line target therapy and increase the accuracy of established prognostic model.

Incorporating Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio in Place of Neutrophil Count and Platelet Count Improves Prognostic Accuracy of the International Metastatic Renal Cell Carcinoma Database Consortium Model.

PurposeThe study investigated whether a replacement of neutrophil count and platelet count by neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) within the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model would improve its prognostic accuracy.Materials and MethodsThis retrospective analysis included consecutive patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors. The IMDC and modified-IMDC models were compared using: concordance index (CI), bias-corrected concordance index (BCCI), calibration plots, the Grønnesby and Borgan test, Bayesian Information Criterion (BIC), generalized R2, Integrated Discrimination Improvement (IDI), and continuous Net Reclassification Index (cNRI) for individual risk factors and the three risk groups.ResultsThree hundred and twenty-one patients were eligible for analyses. The modified-IMDC model with NLR value of 3.6 and PLR value of 157 was selected for comparison with the IMDC model. Both models were well calibrated. All other measures favoured the modified-IMDC model over the IMDC model (CI, 0.706 vs. 0.677; BCCI, 0.699 vs. 0.671; BIC, 2,176.2 vs. 2,190.7; generalized R2, 0.238 vs. 0.202; IDI, 0.044; cNRI, 0.279 for individual risk factors; and CI, 0.669 vs. 0.641; BCCI, 0.669 vs. 0.641; BIC, 2,183.2 vs. 2,198.1; generalized R2, 0.163 vs. 0.123; IDI, 0.045; cNRI, 0.165 for the three risk groups).ConclusionIncorporation of NLR and PLR in place of neutrophil count and platelet count improved prognostic accuracy of the IMDC model. These findings require external validation before introducing into clinical practice.

The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study

Previous prognostic models for second-line systemic therapy in patients with metastatic renal cell carcinoma have not been studied in the setting of targeted therapy. We sought to validate the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in patients with metastatic renal cell carcinoma receiving next-line targeted therapy after progression on first-line targeted therapy. In this population-based study, we analysed patients who received second-line targeted therapy for metastatic renal cell carcinoma at 19 centres in Canada, USA, Greece, Japan, Singapore, South Korea, and Denmark. The primary endpoint was overall survival since the initiation of second-line therapy. We compared the prognostic performance of the IMDC model with the three-factor MSKCC model used for previously treated patients for overall survival since the start of second-line targeted therapy. Between Jan 1, 2005, and Nov 30, 2012, we included 1021 patients treated with second-line targeted therapy. Median overall survival since the start of second-line targeted therapy was 12·5 months (95% CI 11·3-14·3). Five of six predefined factors in the IMDC model (anaemia, thrombocytosis, neutrophilia, Karnofsky performance status [KPS] <80, and <1 year from diagnosis to first-line targeted therapy) were independent predictors of poor overall survival on multivariable analysis. The concordance index using all six prognostic factors (ie, also including hypercalcaemia) was 0·70 (95% CI 0·67-0·72) with the IMDC model and was 0·66 (95% CI 0·64-0·68) with the three-factor MSKCC model. When patients were divided into three risk categories using IMDC criteria, median overall survival was 35·3 months (95% CI 28·3-47·8) in the favourable risk group (n=76), 16·6 months (14·9-17·9) in the intermediate risk group (n=529), and 5·4 months (4·7-6·8) in the poor risk group (n=261). The IMDC prognostic model can be applied to patients previously treated with targeted therapy, in addition to previously validated populations in first-line targeted therapy. The IMDC prognostic model in the second-line targeted therapy setting has an improved prognostic performance and is applicable to a more contemporary patient cohort than that of the three-factor MSKCC model. DF/HCC Kidney Cancer SPORE P50 CA101942-01, Kidney Cancer Research Network of Canada, Canadian Institute for Health Research, Trust Family, Loker Pinard, Michael Brigham, and Gerald DeWulf.