Survival prognoses of Heng intermediate-risk patients with metastatic renal cell carcinoma treated with immunotherapy or targeted therapy: A real-world, single-center retrospective study.
ABSTRACT: Purpose:This study aimed to compare progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS) in Heng intermediate-risk patients with metastatic renal cell carcinoma (mRCC) treated with first-line immunotherapy (IT) or targeted therapy (TT). Materials and Methods:From 2000 to 2017, a total of 186 intermediate-risk mRCC patients treated with first-line IT (n=64, 34.4%) or TT (n=122, 65.6%) were retrospectively evaluated for PFS, OS, and CSS using the Kaplan-Meier method with log-rank test and Cox proportional hazards models for their risk factors with a p-value for significance of <0.05. Results:During a median 5.08-month of systemic treatment and 92.22 months of follow-up, the median PFS, OS, and CSS were 5.16, 18.44, and 19.04 months, respectively. The comparison of baseline characteristics between the two groups showed a significantly higher rate of T3-4 stages, a lower rate of high nuclear grades, shorter follow-up, longer treatment durations, lesser rates of cytoreductive nephrectomy, a lower objective response rate, and no cases of complete response in the TT group compared with the IT group (p<0.05). The survival comparisons between the two groups showed that PFS was significantly different, whereas OS and CSS were not significantly different. The multivariate analyses showed that synchronous metastatic type(hazard ratio [HR], 2.285), IT (HR, 1.746), and treatment-free interval <1 year (HR, 1.926) were significant factors for PFS, whereas none of the risk factors were significant for OS or CSS. Conclusions:TT significantly prolonged PFS compared with IT, whereas long-term survival was not significantly different in intermediate-risk mRCC patients.
Project description:BACKGROUND:The differences in progression-free survival (PFS) and cancer-specific survival (CSS) of metastatic renal cell carcinoma (mRCC) patients according to treatment, type of metastasis, and Heng criteria risk are unclear. In this study, we compared survival according to various such parameters. METHODS:Between 2000 to 2014, 214 mRCC patients, of whom 171 (79.9%) were intermediate-risk and 43 (20.1%) were poor-risk, were retrospectively selected; 126 (58.9%) patients were treated with immunotherapy (IT) and 88 (41.1%) with targeted therapy (TT). Moreover, 144 patients had synchronous mRCCs (67.3%, SM) and 70 had metachronous mRCCs (32.7%, MM). The Kaplan-Meier method and log-rank test were used to compare progression-free survival (PFS) and CSS. RESULTS:During a median 4.2 (1.0-70.4) months of systemic treatment and 98.3 (4.8-147.6) months of follow-up, the median PFS and CSS were 4.7 (95% confidence interval [CI]: 3.8-5.5) and 13.8 (95% CI, 9.8-18.3) months, respectively. The PFS and CSS were significantly better in the MM (5.9 and 21.3 months) and intermediate-risk groups (5.2 and 18.3 months) than those in the SM (4.4 and 9.6 months) and poor-risk groups (2.7 and 5.8 months), respectively (p < 0.05). Further stratification showed that TT produced significantly better PFS than IT in intermediate-risk patients with SM and a treatment-free interval (TFI) < 1 year, and in those with MM with a TFI ≥1 year (p < 0.05). There were no differences in survival outcomes according to various other subgroup stratifications (p > 0.05). CONCLUSION:Dividing patients into specific subcategories helps to better predict therapeutic outcomes.
Project description:We compared progression-free survival (PFS) and overall survival (OS) among 292 metastatic renal cell carcinoma (mRCC) patients either undergoing nephrectomy (Nx, 61.6%) or not (non-Nx, 38.4%), stratified according to the MSKCC and Heng risk models, treated with either immunotherapy (IT, 45.2%) or targeted therapy (TT, 54.8%) between 2000 and 2015. During the follow-up duration of 16.6 months, PFS/OS of the Nx (6.0/30 months) and non-Nx (3.0/6.0 months) groups were significantly different despite differences among baseline parameters (p?<?0.05). The intermediate- and poor-risk patients defined using either model showed significantly longer PFS and OS in the Nx group than in the non-Nx group (p?<?0.05). After stratifying groups by systemic therapy and risk models, both the Nx and non-Nx groups showed no significant differences in intermediate and poor-risk models (p?>?0.05). In both synchronous and metachronous mRCC patients, both PFS and OS showed similar survivals; the Nx group had significantly longer PFS and OS than the non-Nx group, even after considering each systemic therapy and prognostic model. Nx showed a significant positive benefit in PFS and OS compared to no Nx upon patient stratification according to the MSKCC and Heng risk models. The metastatic type did not significantly affect survival between the two groups.
Project description:<h4>Objective</h4>To evaluate the progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) treated with double- and triple-sequence targeted therapy (TT) using tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors (mTORi).<h4>Materials and methods</h4>Records of 292 patients with mRCC, treated with TT between January 2005 and July 2015, were analyzed retrospectively. Kaplan-Meier and log-rank analyses were used to calculate and compare the total PFS (tPFS) and OS when patients underwent double- or triple-TT using TKIs or mTORi.<h4>Results</h4>Eighty-one (27.7%) patients who underwent second-line TT were enrolled; 30 (10.3%) of whom underwent third-line TT. The tPFS and OS of double-TT using TKI-mTORi (5.4 and 30 months, respectively) were significantly better compared with TKI-TKI (0.3 and 2 months) or mTORi-TKI (2 and 6 months) (p <0.001). For triple-TT, the tPFS and OS of TKI-mTORi-TKI (22.8 and 25 months, respectively) were significantly superior compared with those for TKI-TKI-mTORi (4 and 9 months) (p <0.05).For patients with intermediate-risk according to the Heng or Memorial Sloan-Kettering Cancer Center risk models, TKI-mTORi was associated with a significantly longer tPFS and OS compared with TKI-TKI [expect for OS in the Heng group (p = 0.086)]. For the triple TT group, TKI-mTORi-TKI resulted in improved tPFS and OS compared with TKI-TKI-TKI or TKI-TKI-mTORi (p <0.05).<h4>Conclusion</h4>In patients with mRCC, sequential administration of TKI-mTORi led to a significantly superior tPFS compared with any other TT sequence. By contrast, OS did not differ significantly according to TT sequence.
Project description:Limited data exist on outcomes for metastatic renal cell carcinoma (mRCC) patients treated with multiple lines of therapy. Benchmarks for survival are required for patient counselling and clinical trial design.Outcomes of mRCC patients from the International mRCC Database Consortium database treated with 1, 2, or 3+ lines of targeted therapy (TT) were compared by proportional hazards regression. Overall survival (OS) and progression-free survival (PFS) were calculated using different population inclusion criteria.In total, 2705 patients were treated with TT of which 57% received only first-line TT, 27% received two lines of TT, and 16% received 3+ lines of TT. Overall survival of patients who received 1, 2, or 3+ lines of TT were 14.9, 21.0, and 39.2 months, respectively, from first-line TT (P<0.0001). On multivariable analysis, 2 lines and 3+ lines of therapy were each associated with better OS (HR=0.738 and 0.626, P<0.0001). Survival outcomes for the subgroups were as follows: for all patients, OS 20.9 months and PFS 7.2 months; for those similar to eligible patients in the first-line ADAPT trial, OS 14.7 months and PFS 5.6 months; for those similar to patients in first-line TIVO-1 trial, OS 24.8 months and PFS 8.2 months; for those similar to patients in second-line INTORSECT trial, OS 13.0 months and PFS 3.9 months; and for those similar to patients in the third-line GOLD trial, OS 18.0 months and PFS 4.4 months.Patients who are able to receive more lines of TT live longer. Survival benchmarks provide context and perspective when interpreting and designing clinical trials.
Project description:This study evaluated the effects of metastasectomy on overall survival (OS) and progression-free survival (PFS) in metastatic renal cell carcinoma (mRCC) according to metastatic organs. The medical records (2005-2017) of 273 patients with mRCC were analyzed retrospectively to evaluate OS and PFS according to metastatic organs and their metastasectomy states. The Cox proportional hazard model was used to determine the prognostic significance of metastasectomy. The Kaplan-Meier curve and log-rank test were used to compare groups with different modalities and metastatic organs at a statistical significance of p < 0.05. The overall median age was 57 years; 175 (64.3%) and 83 (30.4%) patients received cytoreductive nephrectomy and metastasectomy, respectively. The metastasectomy group was significantly younger and had a lower clinical T stage with significantly better PFS/OS (20.2/32.0 vs. 9.7/12.8 months) than that in the non-metastasectomy group (N = 190, p < 0.05). Liver with lung metastases were the worst metastatic combination for survivals in which liver metastasis was the only significant unfavorable risk factor for both PFS (HR 1.67) and OS (HR 1.74) (p < 0.05). Multivariable analysis confirmed that metastasectomy was a significant favorable risk factor for PFS (HR 0.70) and OS (HR 0.56) (p < 0.05) along with non-clear cell type (HR 0.61 for PFS), whereas the nuclear grade and poor Heng risk group were unfavorable risk factors (HR > 2.0) for both PFS and OS (p < 0.05). Metastasectomy and the affected metastatic organs significantly influenced prognostic survival in mRCC.
Project description:Purpose: To investigate the effect of bone metastasis (BM) on survival outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with first-line tyrosine kinase inhibitors (TKI) by performing propensity-score matching (PSM) analysis. Materials & Methods: We retrospectively reviewed 1,151 patients with mRCC who were treated with first-line TKI from December 2006 to September 2016. After excluding 135 patients, 1,016 patients with mRCC were finally analyzed. The primary and secondary end points were overall survival (OS) and progression-free survival (PFS), respectively. After 1:1 PSM analysis, survival outcomes were compared between patients with BM (n=237) and without BM (n=237). Multivariate Cox regression analysis was used to determine predictors of survival. Results: Among 1,016 total patients, 27.5% (n=279) had BM. Before PSM, patients with BM had worse OS outcomes than those without BM. Even after PSM, OS was significantly poorer in patients with BM compared to those without BM. Of note, the presence of BM was identified as an independent predictor of OS (HR=1.36), in addition to prior nephrectomy, sarcomatoid differentiation, and IMDC risk group. However, there were no differences in PFS according to the presence of BM after PSM. In the subgroup analysis, only intermediate IMDC risk group showed significant differences in OS according to the presence of BM. Conclusion: Based on PSM analysis, the presence of BM negatively affected OS outcomes in patients with mRCC treated with first-line TKI, particularly in the IMDC intermediate risk group.
Project description:The aim of the present study was to investigate the association between clinical parameters and the overall survival (OS) of Japanese patients with metastatic renal cell carcinoma (mRCC). The medical records of 59 consecutive mRCC patients receiving molecular-targeted therapy were retrospectively assessed. Kaplan-Meier and log-rank analyses were used to evaluate the progression-free survival (PFS) and OS, and a multivariate Cox proportional hazard model was used to analyze the clinical parameters for their prognostic relevance. The median OS for all patients was 23.7 months [95% confidence interval (CI): 17.9-30 months], and the median OS stratified by the Memorial Sloan Kettering Cancer Center risk classification was 28.5, 20.9 and 8.1 months for the favorable-, intermediate- and poor-risk groups, respectively (P=0.137; degree of freedom: 2). Univariate analyses identified prior nephrectomy, number of metastatic sites, anemia, best response to first-line treatment and PFS with first-line treatment as prognostic variables. Multivariate analyses identified number of metastatic sites [2: hazard ratio (HR)=3.351, 95% CI: 1.460-8.201, P=0.004; ≥3: HR=6.397, 95% CI: 1.939-20.209, P=0.003], time from diagnosis to therapy (≥1 year: HR=0.334, 95% CI: 0.137-0.755, P=0.008), PFS with first-line treatment (≥5.1 months: HR=0.353, 95% CI: 0.156-0.766, P=0.008) and number of lines of molecular-targeted agents (≥3: HR=0.248, 95% CI: 0.091-0.664, P=0.006) as independent prognostic factors. The results indicated that the PFS of first-line treatment may be a meaningful intermediate endpoint for OS in patients with mRCC who received treatment with molecular-targeted therapy.
Project description:<h4>Objective</h4>To compare survival outcomes for renal embolization (RE) to cytoreductive nephrectomy (CN) and no primary renal treatment (NT) among patients with synchronous metastatic renal cell carcinoma (mRCC) treated using either targeted therapy (TT) or immunotherapy (IT).<h4>Results</h4>The median follow-up duration was 81.3 months, with a duration of first-line treatment of 3.5 months. Among the 211 patients, the median PFS and OS were 4.4 and 10.6 months. Specifically for patients receiving TT (124 patients), the PFS and OS were 5.5 and 12.0 months. An intervention effect was identified only for OS, with a median OS of 20.1, 8.8 and 9.3 months for CN, RE and NT, respectively. After stratification by risk classification, CN provided a significant benefit on OS, compared to RE and NT, for patients with an intermediate risk (MSKCC). For those with a poor risk (Heng criteria), NT provided better survival than PFS (p=0.003), and a comparable survival to RE (p > 0.05).<h4>Materials and methods</h4>Retrospective analysis of 211 patients, 87 treated with IT and 124 with TT, retrieved from our RCC database. Patients' risk factors for survival was evaluated using the Heng and MSKCC criteria, with only patients with an intermediate or poor survival risk included in the analysis. Between-group comparisons were evaluated with respect to progression-free survival (PFS) and overall survival (OS).<h4>Conclusions</h4>The differential effect of CN and RE on OS appears to be modulated by risk classification. In patients with a poor risk, RE should be implemented after careful consideration of comorbidities and life expectancy.
Project description:This prospective randomized comparative trial study aimed to evaluate the therapeutic outcomes of radical nephroureterectomy and adjuvant chemotherapy (ACT) used in combination in high risk upper tract urothelial carcinoma (UTUC) patients with cardiovascular comorbidity. Based on the inclusion criteria of high-risk UTUC in EAU guidelines (updated in 2014), all eligible patients treated in our hospital from January 2014 to March 2018 were included, and cases with late disease, renal dysfunction, severe cardiopulmonary disease or other malignant tumors were excluded. The cases were randomized into two groups based on treatment regimen. Multivariate analyses were performed to analyze the influencing factors of survival outcome in the enrolled patients. The Cox proportional-hazards model and the Kaplan-Meier method were employed to assess progression free survival (PFS), overall survival (OS) and cancer specific survival (CSS). In addition, the potential adverse effects of chemotherapy were actively monitored. A total of 176 high-risk UTUC individuals with cardiovascular comorbidity were enrolled and evaluated in this study. Median follow-up durations were 30 months (range 6-54) in the RNU (n?=?82) group and 36 months (range 6-54) in the RNU?+?ACT (n?=?94) group. Multivariable analysis indicated that peri-operative cardiovascular events risk grade was independent prognostic factor for OS. Tumor size was independent prognostic factor for PFS and CSS. BMI and lymphovacular invasion were significant predictors of PFS. Clinical stage, lymph node involvement, and tumor grade were significant predictors of PFS, OS and CSS in these patients. Especially, chemotherapy was helpful in improving PFS [P?<?0.001, HR?=?6.327 (5.115-7.793)], OS [P?=?0.013, HR?=?2.336 (1.956-2.883)] and CSS [P?=?0.008, HR?=?3.073 (2.533-3.738)]. Kaplan-Meier analysis demonstrated that the oncologic outcomes of RNU treated high-risk UTUC patients were improved much significantly by ACT, including PFS [P?=?0.0033, HR?=?3.78 (3.13-4.55)], OS [P?=?0.0397, HR?=?1.39 (1.01-1.75)] and CSS [P?=?0.0255, HR?=?1.26 (1.07-1.45)]. Further analysis of the lymph node positive subgroup showed that the median time of oncologic events was enhanced in RNU?+?ACT treated individuals in comparison with the RNU group, including PFS (11.4 months vs. 31.9 months, P?=?0.0018), OS (26.8 months vs. 36.3 months, P?=?0.0255) and CSS (28.2 months vs. 39.3 months, P?=?0.0197). In the T3/4 cohort, significantly increased median PFS (13.9 months vs. 36.3 months, P?=?0.0217), OS (20.6 months vs. 32.2 months, P?=?0.0183) and CSS (21.9 months vs. 38.4 months, P?=?0.0226) were obtained in the combination group. Additionally, no severe adverse events (over grade 4) associated with chemotherapy were detected in the RNU?+?ACT group. In conclusion, ACT after radical surgery has statistically significant therapeutic effects on PFS, OS and CSS in high-risk UTUC patients with cardiovascular comorbidity.
Project description:BACKGROUND: The relationship between progression-free survival and time to progression (PFS/TTP) and overall survival (OS) has been demonstrated in a variety of solid tumours but not in metastatic renal cell carcinoma (mRCC). METHODS: A systematic literature search was conducted to identify controlled trials of cytokine or targeted therapies for mRCC reporting information on treatment effects on PFS/TTP and OS for one or more comparison. The associations between treatment effects on PFS/TTP and OS were analysed using linear regression. RESULTS: Thirty-one studies representing 10943 patients, 75 treatment groups, and 41 comparisons were identified. The correlation coefficient between the negative log of the hazard ratio (HR) for PFS/TTP (-ln HR(PFS/TTP)) vs the negative log of the HR for OS (-ln HR(OS)) was 0.80 (P<0.0001). In linear regression, the coefficient on -ln HR(PFS/TTP) vs -ln HR(OS) was 0.64 (95% confidence interval (CI): 0.470.81; R(2)=0.63), suggesting each 10% relative risk reduction (RRR) for PFS/TTP was associated with a 6% RRR for OS. A 1-month gain in median PFS/TTP was associated with a 1.17-month gain in median OS (95% CI: 0.59,1.76; R(2)=0.28). CONCLUSION: In trials of treatments for mRCC, treatment effects on PFS/TTP are strongly associated with treatment effects on OS.