Association between prior nephrectomy and efficacy of immune checkpoint inhibitor therapy in metastatic renal cell carcinoma - A systematic review and meta-analysis

BackgroundImmune checkpoint-inhibitor (ICI)-based therapy is the standard of care for first-line treatment of metastatic renal cell carcinoma (mRCC). It is unclear whether prior removal of the primary tumor influences the efficacy of these treatments. We performed a systematic review and meta-analysis of studies of first-line ICI in mRCC to determine whether the efficacy of ICI-therapy, compared to sunitinib, is altered based on receipt of prior nephrectomy.MethodsWe systematically reviewed studies indexed in MEDLINE (PubMed), Embase, and Scopus and conference abstracts from relevant medical societies as of August 2020 to identify randomized clinical trials assessing first-line immunotherapy-based regimes in mRCC. Studies were included if overall survival (OS) and progression-free survival (PFS) outcomes were reported with data stratified by nephrectomy status. We pooled hazard ratios (HRs) stratified by nephrectomy status and performed random effects meta-analysis to assess the null hypothesis of no difference in the survival advantage of immunotherapy-based regimes based on nephrectomy status, while accounting for study level correlations.ResultsAmong 6 randomized clinical trials involving 5,121 patients, 3,968 (77%) had undergone prior nephrectomy. We found an overall survival benefit for immunotherapy-based regimes, compared to sunitinib, among both patients who had undergone nephrectomy (HR 0.75, 95% CI 0.63 –0.88) and those who had not (HR 0.74, 95% CI 0.59 –0.92), without evidence of difference based on nephrectomy history (P = 0.70; I² = 36%). Results assessing PFS were similar (P = 0.45, I² = 0%).ConclusionsThese clinical data suggest that prior nephrectomy does not affect the efficacy of ICI-based regimens in mRCC relative to sunitinib.     

The effect of metastasectomy on overall survival in metastatic renal cell carcinoma: A systematic review and meta-analysis

PurposeMetastasectomy (MTS) is a treatment option for patients diagnosed with metastatic Renal Cell Carcinoma (mRCC). Nevertheless, the benefits of MTS as they pertain to survival remain controversial. This systematic review aims to compare the survival outcomes of patients who underwent MTS, as well as discover which clinical factors were related to the results.MethodsFrom their inception up to August 2020, a systematic review of the EMBASE, PubMed, Cochrane library, and Web of science databases was performed. Studies which reported outcomes on patients who underwent MTS for the treatment of mRCC were included. The sites, times, amount, histology types of metastasis, and prior nephrectomy were also analyzed. The primary efficacy end point was Overall Survival (OS). A meta-analysis was performed to calculate hazard ratio, 95% confidence intervals, and I² values. Forest plots were constructed for each analysis group.ResultsThe systematic review and reference list search identified 294 articles, with 17 meeting studies as inclusion criteria. The MTS group showed a competitive advantage in OS, in that the non-MTS group was negatively associated with an overall survival rate (HR [non-MTS vs. MTS] = 2.15, 95% CI: 1.59–2.92, P< 0.001). Moreover, patients treated with the most recently available target therapy without MTS showed a significantly increased risk compared with the MTS group (HR = 1.82, 95% CI:1.23–2.70, P= 0.003). Additionally, meta-analysis revealed HR elevating in patients with nonlung only metastasis (HR = 1.87, 95% CI: 1.55–2.26, P< 0.001), synchronous metastasis (HR = 1.28, 95% CI: 1.10–1.49, P= 0.001), and multiple metastases (HR = 2.06, 95% CI: 1.64–2.59, P< 0.001). Clear-cell type mRCC (HR = 0.62, 95% CI: 0.48–0.82, P= 0.0006) and prior nephrectomy (HR = 0.37, 95% CI: 0.15–0.91, P= 0.03) were positively associated with a better overall survival rate.ConclusionsMTS is a treatment option for mRCC patients with prolonged overall survival time. The operation has additional advantages, particularly in patients with lung only metastasis, asynchronous metastasis, fewer metastasis sites, clear-cell type mRCC, and the patients who had received nephrectomy.     

Sarcopenia as a predictor of postoperative outcomes after urologic oncology surgery: A systematic review and meta-analysis

AimSarcopenia as a reliable prognostic predictor in urologic oncology surgery remains controversial, and no consensus amongst researchers exists regarding the management of patients with sarcopenia. This meta-analysis was conducted to investigate the association between sarcopenia and postoperative outcomes after urologic oncology surgery.MethodsA systematic search in MEDLINE (via PubMed), Embase, Web of Science and Cochrane Library databases was conducted to identify the potential studies published before August 2019. Odds ratios and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated through inverse variance with random or fixed effects models.ResultsSeventeen retrospective cohorts comprising 3,948 patients were included with sarcopenia prevalence between 25% and 68.9%. Patients with sarcopenia had significantly shorter overall survival (OS; HR = 2.06, 95% CI: 1.44–2.95; P < 0.001; I-square (I²) = 86%) and cancer-specific survival (HR = 2.16, 95% CI: 1.60–2.92; P < 0.001; I² = 49.4%) than those without sarcopenia. Sarcopenia was independently associated with increased all-cause mortality (HR = 1.50, 95% CI: 1.26–1.80; P < 0.001; I² = 0%) and cancer-specific mortality (HR = 1.50, 95% CI: 1.12–2.01; P = 0.006; I² = 0%). No prognostic difference was observed in the postoperative risk of total complications and systemic progression except lymphovascular invasion status.ConclusionsSarcopenia is an independent poor prognostic factor for patients undergoing urologic oncology surgery, particularly postoperative risks of short survival and increased mortality. Thus, preoperative sarcopenia evaluation can provide clinicians with important information to guide and individualise patient management and improve surgical outcomes.     

Efficacy and safety of immunological checkpoint inhibitors combined with anti-angiogenic drugs in first-line treatment of metastatic renal cell carcinoma: a systematic review and meta-analysis

BackgroundImmune checkpoint inhibitors (ICIs) have shown promising results for the second-line treatment of metastatic renal cell carcinoma (mRCC). Several randomized controlled trials have so far also evaluated the efficacy of ICIs for first-line treatment of mRCC. In this study, we conducted a meta-analysis of relevant studies to further clarify the efficacy and safety of ICIs combined with anti-angiogenic drugs for the treatment of mRCC.MethodsWe searched the PubMed, Embase, and Cochrane libraries for RCT trials of ICIs combined with anti-angiogenic drugs for first-line treatment of mRCC published before November 20, 2019. A meta-analysis was conducted based on methodological recommendations by the Cochrane Collaboration.ResultsFour articles with a total of 2,967 patients met the inclusion criteria. Our meta-analysis revealed that progression-free survival (PFS) and objective response rate (ORR) were significantly improved in the experimental group while there was no significant difference in overall survival (OS) (HR 0.75, 95% CI: 0.67–0.84; HR 1.43, 95% CI: 1.07–1.91; HR 0.74, 95% CI: 0.53–1.03). After stratification for PD-L1 expression, OS, PFS, and ORR of PD-L1 positive patients were significantly increased in the experimental group (HR 0.74, 95% CI: 0.56–0.96; HR 1.66, 95% CI: 1.11–2.49; HR 0.65, 95% CI: 0.57–0.75).ConclusionsImmunological checkpoint inhibitors combined with anti-angiogenic drugs as a first-line treatment for mRCC improve PFS and ORR. This effect is more pronounced in PD-L1 positive patients, where ICIs also improve OS. ICIs do not increase the incidence of adverse events.     

The impact of cytoreductive nephrectomy on survival outcomes in patients treated with tyrosine kinase inhibitors for metastatic renal cell carcinoma in a real-world cohort

BackgroundTyrosine kinase inhibitor therapy (TKI) has changed the treatment paradigm of metastatic renal cell carcinoma (mRCC). The recent CARMENA and SURTIME trials challenged the role of the cytoreductive nephrectomy (CN).ObjectiveTo assess the impact of CN prior to TKI therapy in patients with mRCC in a real-world setting.MethodsOverall, 262 consecutive patients with mRCC were treated with CN plus TKI or TKI only at our institution between 2000 and 2016. Patients with prior immunotherapy or metastasectomy were excluded. Multiple imputation and inverse probability of treatment weighting (IPTW) were performed to account for missing values and imbalances between the treatment groups, respectively. Unadjusted and adjusted Kaplan-Meier estimates were used to determine differences in progression-free (PFS), overall (OS), and cancer-specific survival (CSS).ResultsOverall, 104 (40%) patients received CN before TKI treatment. Most frequent first line therapy was Sunitinib (66%), followed by Sorafenib (20%) and Pazopanib (10%). After adjustment with IPTW, there was no difference in PFS, CSS, and OS (all P > 0.05) between the treatment groups. In subgroup analyses, CSS was improved when CN was performed in patients with sarcomatoid features and clear cell histology (P = 0.04 and P = 0.03) and PFS was improved in patients with clear cell histology when CN was performed [0.04]). CN did not improve OS in any subgroup analysis.ConclusionThe role of CN remains controversial. We found no difference in survival outcomes between patients treated with and without CN before TKI therapy. However, CN was associated with improved survival in specific patient subgroups. Tailored, individualized treatment is key to further improve oncological outcomes for mRCC.     

Presence of lymphovascular invasion in urothelial bladder cancer specimens after transurethral resections correlates with risk of upstaging and survival: A systematic review and meta-analysis

ObjectivesThis study aimed to elucidate the relationship between lymphovascular invasion (LVI) at transurethral resection of bladder tumor (TURBT) and the risk of pathologic upstaging as well as the clinical outcomes.Materials and methodsPubMed, Scopus, Web of Science, and Cochrane Library databases were searched from the respective dates of inception until November 11, 2013.ResultsA total of 16 articles met the eligibility criteria for this systematic review, which included a total of 3,905 patients. LVI was detected in 18.6% of TURBT specimens. A significant association was found between LVI at TURBT and pathologic upstaging of bladder cancer (odds ratio = 2.21, 95% CI: 1.44–3.39) without heterogeneity (I² = 45%, P = 0.14). The pooled hazard ratio (HR) was statistically significant for recurrence-free survival (HR = 1.47, 95% CI: 1.24–1.74), progression-free survival (HR = 2.28, 95% CI: 1.45–3.58), and disease-specific survival (HR = 1.35, 95% CI: 1.01–1.81), but not for overall survival (HR = 1.55, 95% CI: 0.90–2.67). Tests of inconsistency for disease-specific survival (I² = 66%, P = 0.007) and overall survival (I² = 72%, P = 0.03) could not exclude a significant heterogeneity. The results of the Begg and the Egger tests showed that there was evidence of publication bias on pathologic upstaging and progression-free survival.ConclusionsThe data obtained in this meta-analysis indicate that the presence of LVI at TURBT portends the increased risk of pathologic upstaging and may provide additional prognostic information. However, a large, well-designed, prospective study is needed to investigate potential treatment options for bladder cancer with LVI.     

Prognostic value of preoperative blood-based biomarkers in upper tract urothelial carcinoma treated with nephroureterectomy: A systematic review and meta-analysis

Purpose: This systematic review and meta-analysis assessed the prognostic value of preoperative blood-based biomarkers in patients with upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy. Methods: PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched in June 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared cancer-specific survival in UTUC patients with and without pretreatment laboratory abnormalities. Formal meta-analyses were performed for this outcome. Results: The review identified 54 studies with 23,118 patients, of these, 52 studies with 22,513 patients were eligible for the meta-analysis. Several preoperative blood-based biomarkers were significantly associated with cancer-specific survival as follows: neutrophil-lymphocyte ratio (pooled hazard ratio [HR]: 1.66, 95% confidence interval [CI]: 1.34−2.06), C-reactive protein (pooled HR: 1.17, 95% CI: 1.07−1.29), platelet-lymphocyte ratio (pooled HR: 1.68, 95% CI: 1.30−2.17), white blood cell (pooled HR: 1.58, 95% CI: 1.02−2.46), De Ritis ratio (pooled HR: 2.40, 95% CI: 1.92−2.99), fibrinogen (pooled HR: 2.23, 95% CI: 1.86−2.68), albumin-globulin ratio (pooled HR: 3.00, 95% CI: 1.87−4.84), hemoglobin (pooled HR: 1.51, 95% CI: 1.22−1.87), and estimate glomerular filtration rate (pooled HR: 1.52, 95% CI: 1.19−1.94). The Cochrane's Q test and I² test revealed significant heterogeneity for neutrophil-lymphocyte ratio, C-reactive protein, white blood cell, hemoglobin, and estimated glomerular filtration rate (P = 0.022; I² = 50.7%, P = 0.000; I² = 80.4%, P = 0.000; I² = 88.3%, P = 0.010; I² = 62.0%, P = 0.000; I² = 83.9%, respectively). Conclusions: Several pretreatment laboratory abnormalities in patients with UTUC were associated with increased risks of cancer-specific mortality. Therefore, blood-based biomarkers may have the potential to serve as prognostic factors to assist patients and physicians in selecting appropriate treatment strategies for UTUC. However, considering the study limitations including heterogeneity and retrospective nature of the primary data, the conclusions should be interpreted with caution.     

Association of preoperative serum De Ritis ratio with oncological outcomes in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma

PurposeIdentifying which patients are likely to benefit from cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is important. We tested the association between preoperative serum De Ritis ratio (DRR, Aspartate Aminotransferase/Alanine Aminotransferase) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.Material and methodsmRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment DRR cut‐off value, we found 1.2 to have the maximum Youden index value. The overall population was therefore divided into 2 DRR groups using this cut‐off (low, <1.2 vs. high, ≥1.2). Univariable and multivariable Cox regression analyses tested the association between DRR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). The clinical value of the DRR was evaluated with decision curve analysis.ResultsAmong 613 mRCC patients, 239 (39%) patients had a DRR ≥1.2. Median follow-up was 31 (IQR 16–58) months. On univariable analysis, high DRR was significantly associated with OS (hazard ratios [HR]: 1.22, 95% confidence interval [CI]: 1.01–1.46, P = 0.04) and CSS (HR: 1.23, 95% CI: 1.02–1.47, P = 0.03). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, high DRR remained significantly associated with both OS (HR: 1.26, 95% CI: 1.04-1.52, P = 0.02) and CSS (HR: 1.26, 95% CI: 1.05–1.53, P = 0.01). The addition of DRR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.633 vs. C-index = 0.629). On decision curve analysis, the inclusion of DRR did not improve the net-benefit beyond that obtained by established subgroup analyses stratified by IMDC risk groups, type of systemic therapy, body mass index and sarcomatoid features, did not reveal any prognostic value to DRR.ConclusionDespite the statistically significant association between DRR and OS as well as CSS in mRCC patients treated with CN, DRR does not seem to add any further prognostic value beyond that obtained by currently available features.     

Validating the total cancer location density metric for stratifying patients with low-risk localized prostate cancer at higher risk of grade group reclassification while on active surveillance

PurposeTo validate a previously proposed prognostic metric, Total Cancer Location (TCLo) density, in a contemporary cohort of men with grade group (GG) 1 prostate cancer (PCa) on active surveillance (AS).MethodsWe evaluated 123 patients who entered AS with maximum GG1 PCa at diagnostic and/or confirmatory biopsy. TCLo was defined as the total number of PCa locations identified on both biopsy sessions. TCLo density was calculated as TCLo / prostate volume [ml]. Primary endpoint was progression-free survival (PFS), defined as time from confirmatory biopsy to grade group reclassification (GGR) on repeat biopsy or prostatectomy. Optimal cut-point for TCLo density was predefined in a previously reported cohort and applied to this contemporary cohort. Kaplan-Meier and multivariable Cox regression analysis were used to estimate the association of predictors with PFS.ResultsDuring median follow-up of 7.8 years, (IQR 7.3–8.2) 34 men had GGR. Using previously defined cut-points, PFS at 5-years was 60% (95% CI: 44%–81%) vs. 89% (95% CI: 83%–96%) in men with high (≥0.06 ml^?1) vs. low (<0.06 ml^?1) TCLo density, and 63% (95% CI: 48%–82%) vs. 90% (95% CI: 83%–96%) in men with high (≥3) vs. low (≤2) TCLo (log-rank test: P < 0.0001, respectively). Adjusting for age, prostate volume, percent of positive cores and PSA, both higher TCLo density (HR [per 0.01 ml^?1 increase]: 1.18, 95% CI: 1.05–1.33, P = 0.005) and TCLo (HR: 1.69, 95% CI: 1.20–2.38, P = 0.002) were associated with shorter PFS.ConclusionThe previously suggested prognostic value of TCLo density was confirmed in this validation cohort. TCLo alone performed similarly well. Patients with high TCLo density (≥0.06 ml^?1) or TCLo (>2) were at greater risk of GGR while on AS. With external validation, these metric may help guide risk-adapted surveillance protocols.     

The comparison of oncologic outcomes between metastatic upper tract urothelial carcinoma and urothelial carcinoma of the bladder after cisplatin-based chemotherapy

ObjectiveTo compare the oncologic outcomes and prognostic factors between metastatic upper tract urothelial carcinoma (UTUC) and UC of the bladder (UCB) after cisplatin-based chemotherapy.Materials and methodsWe retrospectively reviewed patients with metastatic UTUC and UCB after methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) or gemcitabine/cisplatin chemotherapy between 1997 and 2014 at Kaohsiung Chang Gung Memorial Hospital. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Univariate and multivariate analyses with Cox proportional hazard models were also performed to assess the effect of prognostic factors.ResultsTotally, 203 patients were enrolled into our study, including 120 patients with UTUC and 83 patients with UCB. For patients with UTUC, the median PFS was 7.3 months vs. 4.0 months (P<0.001), and the median OS was 17.0 months vs. 10.5 months (P<0.001) for MVAC and gemcitabine/cisplatin, respectively. For patients with UCB, the median PFS (P = 0.35) and OS (P = 0.06) of the 2 groups were insignificant. In multivariate analyses, number of metastatic sites was the identical prognostic factor for OS between UTUC (hazard ratio [HR] = 2.74; 95% CI: 1.63–4.62; P<0.001) and UCB (HR = 3.12; 95% CI: 1.52–6.39; P = 0.002). Presence of liver metastasis (HR = 1.84; 95% CI: 1.05–2.23; P = 0.03) and MVAC chemotherapy (HR = 0.54; 95% CI: 0.35–0.83; P<0.001) were significantly correlated to survival only for UTUC, not for UCB.ConclusionOur study suggests discordant oncologic outcomes and prognostic factors between metastatic UTUC and UCB after cisplatin-based chemotherapy. A prospective study is warranted to validate our results.     

Adjuvant therapy with tyrosine kinase inhibitors for localized and locally advanced renal cell carcinoma: an updated systematic review and meta-analysis

PURPOSETyrosine kinase inhibitors (TKIs) have been widely used in the management of patients with metastatic renal cell carcinoma (RCC). However, the use of systemic therapies in the adjuvant setting of localized and locally advanced RCC has shown conflicting results across the literature. Therefore, we aimed to conduct an updated systematic review and meta-analysis comparing the efficacy and safety of TKIs in the adjuvant setting for patients with localized and locally advanced RCC.MATERIALS AND METHODSThe MEDLINE and EMBASE databases were searched in December 2020 to identify phase III randomized controlled trials of patients receiving adjuvant therapies with TKI for RCC. Disease-free survival (DFS) and overall survival (OS) were the primary endpoints. The secondary endpoints included treatment-related adverse events (TRAEs) of high and any grade.RESULTSFive trials (S-TRAC, ASSURE, PROTECT, ATLAS, and SORCE) were included in our meta-analysis comprising 6,531 patients. The forest plot revealed that TKI therapy was associated with a significantly longer DFS compared to placebo (pooled HR: 0.88, 95% CI: 0.81–0.96, P= 0.004). The Cochrane's Q test (P = 0.51) and I2 test (I2 = 0%) revealed no significant heterogeneity. Adjuvant TKI was not associated with improved OS compared to placebo (pooled HR: 0.93, 95% CI: 0.83–1.04, P= 0.23). The Cochrane's Q test (P = 0.74) and I2 test (I2 = 0%) revealed no significant heterogeneity. The forest plot revealed that TKI therapy, compared to placebo, was associated with higher rates of high grade TRAEs (OR: 5.20, 95% CI: 4.10–6.59, P< 0.00001) as well as any grade TRAEs (OR: 3.85, 95% CI: 1.22–12.17, P= 0.02). The Cochrane's Q tests (P < 0.0001 and P < 0.00001, respectively) and I2 tests (I2 = 79% and I2 = 90%, respectively) revealed significant heterogeneity.CONCLUSIONSThe findings of our analyses suggest an improved DFS in patients with localized and locally advanced RCC receiving adjuvant TKI as compared to placebo; however, this did not translate into any significant OS benefit. Additionally, TKI therapy led to significant toxicity. Adjuvant TKI does not seem to offer a satisfactory risk and/orbenefit balance for all patients. Select patients with very poor prognosis may be considered in a shared decision-making process with the patient. With the successful arrival of immune-based therapies in RCC, these may allow a more favorable risk/benefit profile.     

El índice nutricional pronóstico como factor pronóstico independiente para la respuesta al tratamiento,la supervivencia y la elección del fármaco en el cáncer de próstata metastásico resistente a la castración tratado con acetato de abiraterona o enzalutamida

PurposeWe designed this study to identify the prognostic value of baseline prognostic nutritional index (PNI) in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate or enzalutamide.MethodsOne hundred one mCRPC patients were included. PNI was calculated using formula 10 × serum albumin value (g/dl) + .005 × total lymphocyte count (per mm³). ROC analysis was used for determining prognostic PNI value.ResultsThe statistically significant cut-off value for PNI was 46.62. Initial PSA response and PSA kinetics (early PSA response and 30-50%-90% PSA response at any time) were much better in PNI>46.62 group than the PNI ≤46.62 group (P<.01). In multivariate analysis, baseline PNI level >46.62 was an independent predictor of PSA-PFS (HR: .42; P<.01), radiologic PFS (HR: .53; P<.01), and OS (HR: .42; P<.01). In the PNI≤46.62 group, median OS was 7.4 months (95% CI: 4.1-10.7) for the abiraterone acetate subgroup vs. 17.6 months (95% CI: 10.1-25.1) for enzalutamide subgroups (P<.01).ConclusionPNI is a useful, independent prognostic marker for mCRPC patients treated with either abiraterone acetate or enzalutamide. Using pre-treatment PNI may help clinicians in the prediction of survival and decision making based on abiraterone acetate or enzalutamide.     

Prognostic effect of preoperative serum albumin to globulin ratio in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma

BackgroundAccurate identification of ideal candidates for cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is an unmet need. We tested the association between preoperative value of systemic albumin to globulin ratio (AGR) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.MethodsmRCC patients treated with CN were included. The overall population was therefore divided into two AGR groups using cut-off of 1.43 (low, <1.43 vs. high, ≥1.43). Univariable and multivariable Cox regression analyses tested the association between AGR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel’s concordance index (C-index). The clinical value of the AGR was evaluated with decision curve analysis (DCA).ResultsAmong 613 mRCC patients, 159 (26%) patients had an AGR <1.43. Median follow-up was 31 (IQR: 16–58) months. On univariable analysis, low preoperative serum AGR was significantly associated with both OS (HR: 1.55, 95% CI: 1.26–1.89, P<0.001) and CSS (HR: 1.55, 95% CI: 1.27–1.90, P<0.001). On multivariable analysis, AGR <1.43 was associated with worse OS (HR: 1.51, 95% CI: 1.23–1.85, P<0.001) and CSS (HR: 1.52, 95% CI: 1.24–1.86, P<0.001). The addition of AGR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index=0.640 vs. C-index=0.629). On DCA, the inclusion of AGR marginally improved the net benefit of the prognostic model. Low AGR remained independently associated with OS and CSS in the IMDC intermediate risk group (HR: 1.52, 95% CI: 1.16–1.99, P=0.002).ConclusionsIn our study, low AGR before CN was associated with worse OS and CSS, particularly in intermediate risk patients.     

Role of circulating tumor cells in patients with metastatic clear-cell renal cell carcinoma

PurposeCirculating tumor cells (CTC) have been demonstrated to have prognostic and predictive role in certain human cancers. However, studies exploring their role in metastatic renal cell carcinoma (mRCC) are scarce. We aimed to evaluate the prognostic and predictive role of CTC in mRCC.Materials and methodsIn this prospective study, 35 patients with mRCC were analyzed for the presence of CTC before starting tyrosine kinase inhibitors (TKI). Progression-free and overall survival rates were estimated using the Kaplan-Meier curves and log-rank test. The prediction to TKI therapy was calculated with the response to treatment determined by standard imaging techniques.ResultsOutcomes were assessed according to the CTC positivity at baseline, before the patients started TKI for mRCC. At a mean follow-up of 12.4 ± 4.1 months, disease progression was noted in 17 patients (48.6%) including 8 deaths (22.9%). CTC positive patients had a significantly lower progression-free survival rate (12.5% vs. 64.1%, respectively; P = 0.009) but not in the overall survival rate (75% vs. 76.3%, respectively; P = 0.88) in the Kaplan–Meier estimation curves. CTC positivity at baseline significantly predicted a poorer response to TKI (87.5% vs. 37.1%, P = 0.01). The multivariate Cox proportional hazards analysis showed that CTC at baseline was the most significant predictor of progression-free survival (hazard ratio 4.17, 95% confidence interval 1.41–11.99, P = 0.01).ConclusionsBaseline CTC detection can be an important prognostic factor of progression-free survival and significant predictor of poor response to TKI in patients with metastatic RCC.     

C-reactive protein and neutrophil-lymphocyte ratio are prognostic in metastatic clear-cell renal cell carcinoma patients treated with nivolumab

ObjectiveTo evaluate the impact of markers of systemic inflammation such as C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) on outcomes of metastatic clear-cell renal cell carcinoma (m-ccRCC) patients treated with nivolumab.Patients and methodsWe retrospectively evaluated m-ccRCC patients treated with nivolumab and collected known prognostic factors and survival data. We used Kaplan-Meier survival analysis and cox proportional hazards regression analysis to study prognostic factors for overall survival (OS) and progression-free survival (PFS) since start of nivolumab. Harrell's C-index was used to evaluate the models.ResultsWe included 113 patients. Median OS and PFS after initiation of nivolumab was 15 (interquartile range 7–28) and 4 months (interquartile range 3–11), respectively.Elevated baseline CRP was associated with worse OS (HR per 25 mg/l 1.35, 95% CI 1.16–1.52, P < 0.001) and PFS (HR per 25 mg/l 1.19, 95% CI 1.08–1.35, P = 0.001), independent from the international metastatic renal cell carcinoma database consortium (IMDC) prognostic criteria, increasing the model's C-index from 0.72 to 0.77 for OS and 0.59 to 0.62 for PFS.Elevated NLR was associated with worse OS (HR 1.10, 95% CI 1.04–1.17, P = 0.002) and PFS (HR 1.06, 95% CI 1.01–1.11, P = 0.03) independent from the other IMDC prognostic criteria. The model's C-index decreased from 0.72 to 0.70 for OS and increased from 0.59 to 0.60 for PFS.ConclusionsElevated baseline CRP and NLR predict worse OS and PFS on nivolumab in m-ccRCC patients. Including baseline CRP in the IMDC prognostic model improves its discriminatory power to predict OS and PFS since start of nivolumab.     

A systematic review and meta-analysis of BRCA1/2 mutation for predicting the effect of platinum-based chemotherapy in triple-negative breast cancer

IntroductionPlatinum-based chemotherapy (PBC) remains the mainstay of treatments for triple-negative breast cancer (TNBC). TNBC is a heterogeneous group, the issue of whether BRCA1/2 mutation carriers have a particular sensitivity to platinum agents is inconclusive. We conducted a meta-analysis to explore the relationship between BRCA1/2 mutation and PBC susceptibility in individuals with TNBC, aiming to gain more information on the size of the benefit of PBC in BRCA1/2 mutation carriers.Materials and methodsAll studies applying PBC with a subgroup of BRCA1/2 status were included. All endpoints, including pCR and RCB in the neoadjuvant phase, DFS in the adjuvant phase, ORR, PFS, and OS in the advanced phase, were assessed using HRs and 95% Cl.ResultsFrom the 22 studies included, there were 2158 patients with TNBC, with 392 (18%) bearing the BRCA1/2 gene mutation. Based on 13 studies applying neoadjuvant PBC, we discovered that BRCA1/2 mutation was substantially associated with a 17.6% increased pCR rate (HR 1.32, 95% CI 1.17–1.49, p < 0.00001; I² = 51%). Same result was observed in RCB0/I index (HR 1.38, 95% CI 1.08–1.76, P = 0.009; I² = 0%). The meta-analysis of 6 trials addressing advanced therapy revealed that ORR rates were significantly higher in patients with BRCA1/2 mutation (HR 1.91, 95% CI 1.48–2.47, p < 0.00001; I² = 32%), as well as PFS(HR 1.13, 95% CI 0.81–1.57, P = 0.47; I² = 0%) and OS (HR 1.89, 95% CI 1.22–2.92, P = 0.004; I² = 0%).ConclusionAccording to our meta-analysis of 22 trials in TNBC, BRCA1/2 mutation carriers were significantly more sensitive to PBC regimens, especially in neoadjuvant and advanced therapy.     

Incidence and risk factors of suicide among patients diagnosed with bladder cancer: A systematic review and meta-analysis

Background: Patients with bladder cancer have a high risk of suicide. This study aimed to assess how bladder cancer increases suicide risk and to identify the demographic and clinical factors associated with suicidal death among patients with bladder cancer. Methods: Literature search of MEDLINE, PsycINFO, Embase, Web of Sciences and Cochrane Library databases was conducted up to April 2020 to identify eligible studies related to the incidence and risk factors of suicide after bladder cancer diagnosis. Summary multivariate-adjusted risk estimates and their associated 95% confidence intervals (CIs) were calculated using inverse variance method with random or fixed-effect modeling. Results: Five retrospective cohorts comprising 563,680 patients with bladder cancer were included. Higher risk of suicide by 1.90-fold was observed among patients with bladder cancer (hazard ratio, HR = 1.90, 95% CI: 1.29–2.81; P = 0.001; I² = 81.2%), especially in those aged 70 years or older (HR = 1.36, 95% CI: 1.29–1.43; P < 0.001; I² = 0%), unmarried (HR = 1.72, 95% CI: 1.61–1.83; P < 0.001; I² = 0%), and those with regional bladder cancer (HR = 1.88, 95% CI: 1.10–3.21; P = 0.021; I² = 96.3%), compared with those without bladder cancer. Furthermore, gender and race were not associated with increased suicide risk among patients with bladder cancer. Conclusions: Suicide risk is increased among patients with bladder cancer, particularly those aged 70 years or older, unmarried and those with regional bladder cancer. Hence, early psychological support must be provided during the follow-up period of these special populations with a high suicide risk.     

PSA time to nadir as a prognostic factor of first-line docetaxel treatment in castration-resistant prostate cancer: Multicenter validation in patients from the Chinese Prostate Cancer Consortium

ObjectiveDocetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China. We have previously shown that time to nadir (TTN) of prostate-specific antigen (PSA) is an important prognostic factor in patients from a single center in Northwestern China. In this study, we performed a multicenter validation of the prognostic role of TTN in additional Chinese patients with mCRPC receiving docetaxel treatment.Materials and methodsThe data were gathered from 170 eligible Chinese patients who received docetaxel chemotherapy from January 2007 to October 2018 in 11 Chinese Prostate Cancer Consortium member hospitals in China. TTN was defined as the time from start of chemotherapy to the nadir of PSA level during the treatment. Multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS) and progression-free survival (PFS).ResultsPatients with a TTN ≥ 15 weeks had a longer OS and PFS compared to those with a TTN < 15 weeks (43 vs. 15 months, P < 0.001; 24 vs. 6 months, P < 0.001, respectively). In addition, Patients with a TTN ≥ 15 weeks and PSA nadir <4.55ng/ml were associated with longer OS than others (HR 0.093, 95% CI 0.044-0.188, P < 0.001; HR 4.002, 95% CI 1.890–8.856, P = 0.001, respectively) and TTN, PSA nadir, PSA baseline (optimal threshold 56.07 ng/ml), and PSA reduction (optimal threshold 50%) were associated with PFS (HR 0.238, 95% CI 0.149–0.382, P < 0.001; HR 1.676, 95% CI 1.033–2.722, P = 0.037; HR 1.770, 95% CI 1.134–2.763, P = 0.012; HR 0.573, 95% CI 0.428–0.756, P < 0.001; respectively). Furthermore, patients with a PSA nadir <4.55 ng/ml had longer OS and PFS compared to other patients when TTN was ≥15 weeks.ConclusionIn this multicenter validation study, TTN and PSA nadir remain important prognostic markers in predicting therapeutic outcomes in Chinese men who receive chemotherapy for mCRPC.     

Preoperative apolipoprotein B/A1 ratio is an independent prognostic factor in metastatic renal cell carcinoma

Objectives

We aimed to explore the prognostic value of preoperative apolipoprotein B/apolipoprotein A1 (Apo B/A1) ratio in metastatic renal cell carcinoma (mRCC).

Association among metabolic syndrome,inflammation, and survival in prostate cancer

Background

Metabolic syndrome (MS) and inflammation (INF) alterations are among the factors involved in cancer progression. The study aimed to assess the relationship between MS and INF and its effect on progression-free/overall survival (PFS/OS) in metastatic castration-resistant prostate cancer (mCRPC) treaed with abiraterone or enzalutamide.