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.     

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.     

Clinical outcome in patients receiving systemic therapy for metastatic sarcomatoid renal cell carcinoma: A retrospective analysis☆

ObjectivesSarcomatoid metastatic renal cell carcinoma (mRCC) represents an aggressive subset of disease, and a definitive therapeutic strategy is lacking. We seek to define outcomes associated with systemic therapy (including immunotherapy, cytotoxic therapy, and targeted agents) for sarcomatoid mRCC, with attention to novel prognostic schema.Materials and methodsFrom an institutional database including 270 patients with mRCC, we identified 34 patients with documented sarcomatoid features. Within this cohort, we assessed 21 patients who received systemic therapy. Survival was assessed in the overall cohort and in subgroups divided by clinicopathologic characteristics, including the extent of sarcomatoid features, Memorial Sloan-Kettering Cancer Center (MSKCC) risk criteria, Heng criteria, and the nature of systemic therapy rendered.ResultsOf the 21 patients assessed, 2 patients received chemotherapy, 7 patients received immunotherapy, and 12 patients received targeted agents as their first line treatment. Median overall survival (OS) in the overall cohort was 18.0 months (95% CI 6.9–22.0). By MSKCC criteria, patients with poor-risk disease had a median OS of 4.7 months, compared with 20.1 months for patients with intermediate-risk disease [hazard ratio (HR) 0.02, 95%CI 0.003–0.15; P = 0.0001]. A similar difference in median OS was seen poor- and intermediate-risk groups when stratifying by Heng criteria (HR 0.17, 95%CI 0.001–0.12). There was no significant difference in survival in patients with sarcomatoid predominant disease vs. nonpredominant disease (HR 0.62, 95%CI 0.23–1.65; P = 0.34), nor was there a difference amongst patients who received targeted therapies vs. nontargeted therapies (HR 1.0, 95%CI 0.61–1.40; P = 0.36).ConclusionsCompared with previous series and prospective trials assessing patients with sarcomatoid mRCC, the observed survival was prolonged. Although both Heng and MSKCC risk scores may be useful in determining prognosis, further studies are needed to identify relevant biomarkers and define the optimal therapeutic strategy for this disease.     

Prognostic impact of metastasectomy in renal cell carcinoma in the postcytokine therapy era

ObjectivesTo explore the real-world data regarding survival following metastasectomy (MS) for renal cell carcinoma (RCC) in the postcytokine therapy era.Patients and MethodsPatients diagnosed with metastatic renal cell carcinoma (mRCC) between January 2008 and December 2018 at our institutions were retrospectively evaluated. The patients were classified into three groups according to their MS status: (1) complete MS (cMS), (2) incomplete MS (icMS), and (3) without MS (nonMS). Factors for overall survival (OS) after diagnosis were analyzed.ResultsOverall, 314 patients were evaluated. During the follow-up period (median: 25.3 months), a total of 98 patients (31.2%) underwent at least one MS. The cMS group (n = 45, 14.3%) had a significantly longer OS (median: not reached [N.R.]) than the icMS (n = 53, 16.9%) (81.5 months, P= 0.0042) and nonMS groups (28.1 months, P< 0.0001). The icMS group had a significantly longer OS than the nonMS group did (P= 0.0010). Multivariate analysis showed that the MS status was an independent factor for OS (cMS vs. nonMS: P= 0.0004; icMS vs. nonMS: P= 0.0176), together with histopathological type, International Metastatic Renal Cell Carcinoma Database Consortium risk, liver metastasis status, and prior nephrectomy status (all, P< 0.05). In addition, the OS was comparable throughout the eras of systemic therapy (early molecular-targeted therapy, late molecular-targeted therapy, and immune checkpoint inhibitor eras) in the MS group (median: 121.9 vs. N.R. vs. N.R. months, P= 0.948).ConclusionsMS, especially cMS improved survival in selected patients with mRCC in the postcytokine therapy era. In addition, MS still plays a significant role in the current systemic therapy.     

Upfront Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors or Targeted Therapy: An Observational Study from the International Metastatic Renal Cell Carcinoma Database Consortium

BackgroundThe role of upfront cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the era of immune checkpoint inhibitors is unclear.ObjectiveTo evaluate the relationship between upfront CN and clinical outcomes in the setting of mRCC treated with immune checkpoint inhibitors or targeted therapy.Design, setting, and participantsUsing the International Metastatic RCC Database Consortium, we retrospectively identified patients diagnosed with de novo mRCC treated with immune checkpoint inhibitors or targeted therapy.Outcome measurements and statistical analysisOverall survival (OS) was compared between the two groups using the Kaplan-Meier method and multivariable Cox regressions adjusting for known prognostic factors.Results and limitationsWe identified a total of 4639 eligible patients with mRCC. Among the 4202 patients treated with targeted therapy and 437 patients treated with immune checkpoint inhibitors, 2326 (55%) and 234 (54%) patients received upfront CN prior to treatment start. In multivariable analyses, CN was associated with significantly better OS in both the immune checkpoint inhibitor–treated (hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.41–0.90, p = 0.013) and the targeted therapy treatment (HR: 0.72; 95% CI, 0.67–0.78, p < 0.001) group. There was no difference in OS benefit of CN between the immune checkpoint inhibitor and targeted therapy treatment groups (interaction p = 0.6). Limitations include selection of patients from large academic centers and the retrospective nature of the study.ConclusionsUpfront CN is associated with a significant OS benefit in selected patients treated by either immune checkpoint inhibitors or targeted therapy, and still has a role in selected patients in the era of immune checkpoint inhibitors.Patient summaryBefore effective systemic therapies were available for metastatic kidney cancer, surgical removal of the primary (kidney) tumor was the mainstay of treatment. The role of removing the primary tumor has recently been called into question given that more effective systemic therapies have become available. In this study, we find that removal of the primary kidney tumor still has a benefit for selected patients treated with highly effective modern systemic therapies, including targeted therapies and immune checkpoint inhibitors.     

Characteristics and follow-up of metastatic breast cancer in Ethiopia: A cohort study of 573 women

ObjectivesThere is little information on characteristics, treatment and outcome of metastatic breast cancer (mBC) patients in low-income countries. This study aims to describe mBC in the setting of Ethiopia.Materials and MethodsA retrospective cohort study was conducted among all female mBC patients from the only oncologic hospital in Addis Ababa 01/2006 to 12/2010. Time between first metastasis and known death or loss to follow-up for more than six months as surrogate for death were used for Cox proportional hazards model.ResultsA total of 573 patients were included; 188 (32.8%) women with de novo mBC (dnmBC) and 385 women with recurrent mBC (rmBC). The average age at time of first metastasis was 43.7 (standard deviation 11.9) years with an average survival probability of twelve months. Negative hormone receptor status, only present in 29% (Hazard ratio HR = 2.28 [95% confidence interval CI 1.56–3.32] p < 0.001), and grade 3 (HR = 1.72 [95% CI 1.15–2.55] p = 0.008) had significant influence on survival. Patients with initial bone metastasis (HR = 0.63 [95% CI 0.48–0.83] p = 0.001) had best chances of survival compared to more common initial visceral metastasis. About 35% of the patients received chemotherapy and 30.5% were on endocrine therapy.ConclusionThe lower survival for mBC in Addis Ababa compared to that from Western countries is presumably due to the later presentation at the hospital and lack of standard therapy. An unexpected high proportion of patients with hormone receptor positive mBC encourage consequent utilization of endocrine therapy to improve the quality of palliative care in this cohort.     

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.     

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.     

A population-based evaluation of tunica vaginalis mesothelioma: An analysis of the National Cancer Database

PurposePrimary mesothelioma of the tunica vaginalis (TVM) is a rare and poorly understood malignancy with insufficient population-level data to guide management decisions.Materials and MethodsA retrospective analysis of TVM cases recorded in the National Cancer Database from 2004 to 2015 was performed. Cases were identified using International Classification of Diseases for Oncology histology codes. Associations between demographic, clinical and therapeutic factors were analyzed using Kaplan-Meier survival estimates for overall survival (OS) and Cox proportional hazard modeling. Propensity score matching for receipt of systemic chemotherapy was performed to assess the impact on OS.ResultsOne hundred fifty-one men with a median age of 65 years (interquartile range [IQR] 51–78) were included. Median OS from diagnosis was 72.5 months (IQR 20.2–Not Reached [NR]) after a median follow up of 34.9 months. Multivariate analysis demonstrated an increased risk of death for patients in the fourth quartile of age (hazard ratio [HR] 5.57, 95% confidence interval [CI] 1.70–18.17, P = 0.004), those with biphasic or fibrous histology (HR 2.59, 95% CI 1.15–6.42, P = 0.04) and positive surgical margins (HR 3.27, 95% CI 1.61–6.63, P = 0.001). There was no significant difference in OS associated with receiving chemotherapy (P = 0.5) even after propensity score matching (P = 0.07).ConclusionsMargin-negative surgical resection is paramount to improving OS. There are insufficient data to recommend for or against adjuvant systemic chemotherapy or RT, although the limited available data does not suggest apparent benefit in terms of OS.     

Albumin levels predict prognosis in advanced renal cell carcinoma treated with tyrosine kinase inhibitors: a systematic review and meta-analysis

PurposeWith the development of therapy and prognostic criteria for metastatic Renal Cell Carcinoma (mRCC), the prognostic value of serum albumin level has remained in dispute. The aim of this meta-analysis was to evaluate the role of pre-treatment albumin in predicting the prognosis of mRCC patients in the era of tyrosine kinase inhibitor (TKI) treatments.MethodsThe qualitative and quantitative synthesis was conducted of studies retrieved from PubMed, Embase, and Cochrane library from inception of these databases to July 19, 2020. The hazard ratio (HR) and its 95% confidence interval (CI) of overall survival (OS) and progression-free survival (PFS) were extracted from studies comparing different levels of pre-treatment serum albumin (as a dichotomous or continuous variable) in mRCC patients treated with TKI agents.ResultsWithin 5,638 primitive records, 16 were eligible and 14 had adequate data for quantitative analysis (N = 2,863 participants). Random-effects meta-analysis showed that lower albumin was related to poorer OS (dichotomous: HR = 2.01, 95% CI: 1.64-2.46, P < 0.001, I² = 28.8%; continuous: HR =0.93, 95% CI: 0.86-1.00, P = 0.040, I² = 67.5%) and PFS (dichotomous: HR = 1.45, 95% CI: 1.04-2.01, P = 0.029, I² = 57.4%; continuous: HR = 0.89, 95% CI: 0.80-0.98, P = 0.023, I² = 93.3%).ConclusionLower pre-treatment serum albumin level is an independent adverse predictor of prognosis of mRCC patients receiving TKI therapy.RegistrationPROSPERO ID: CRD42020196802 Sep. 2^nd, 2020     

Metastatic small cell carcinoma of the prostate: Population-based analysis of patient characteristics and treatment paradigms

IntroductionSmall cell carcinoma of the prostate is a rare malignancy comprising<1% of prostate cancers. Little is known about population-based treatment patterns for metastatic small cell carcinoma of the prostate. We evaluated clinical characteristics, treatment patterns, and survival outcomes.MethodsUsing the National Cancer Database, we identified patients between 1998 and 2011 diagnosed with pure small cell carcinoma of the prostate as their only malignancy who presented with nodal involvement or distant metastasis.ResultsTreatment information was available for 379 patients. Of them, 122 (32.5%) underwent chemotherapy (CT) alone, 25 (6.7%) received hormonal therapy (androgen-deprivation therapy) alone, 10 (2.7%) underwent radiation therapy alone, 3 (1%) underwent radical prostatectomy, and 167 (44.4%) underwent combination therapy. The 1- and 3-year survival rates were 35.3% and 4.4%, respectively. Those receiving any CT as part of their treatment had a median survival of 9.3 vs. 3.2 months for those not receiving it (P<0.001). Those receiving CT, androgen-deprivation therapy, and radiation had a median survival of 15.1 vs. 7 months for those receiving CT alone (P<0.001). On multivariable analysis (controlling for age, Charlson comorbidity index, extent of metastasis, prostate-specific antigen level, and type of treatment), older age (hazard ratio [HR] = 3.87; 95% CI: 1.41–9.34; P = 0.007) and distant metastatic disease (HR = 7.17; 95% CI: 1.62–31.8; P = 0.010) increased risk of death, whereas receipt of CT (HR = 0.15; 95% CI: 0.05–0.44; P = 0.001) decreased risk of death.ConclusionMen presenting with metastatic small cell carcinoma of the prostate have poor overall survival. Older patients and those presenting with distant metastases have an increased risk of death. It appears that patients receiving CT experience a modest survival benefit. The role of hormonal therapy in this population remains unclear.     

Long-term cancer control after radical prostatectomy and bilateral pelvic lymph node dissection for pT3bN0M0 prostate cancer in the prostate-specific antigen era

ObjectivesWe evaluated long-term cancer control outcomes of radical prostatectomy and bilateral pelvic lymph node dissection (RP) for pT3bN0M0 prostate cancer in the era of prostate-specific antigen (PSA) screening.Materials and methodsA retrospective analysis of prospectively collected data from the University of Southern California Prostate Cancer Database was performed. Between 1987 and 2008, 229 men underwent open RP for pT3bN0M0 prostate cancer. The cohort was divided into early (1987–1997) and contemporary (1998–2008) PSA eras. The Kaplan-Meier method and Cox proportional regression models were used to analyze clinical recurrence (CR) and biochemical recurrence (BCR).ResultsThe median follow-up duration was 14.5 years (range, 0.2–21.1 y). The predicted 10-year freedom from CR and BCR rates for men treated in the early and contemporary PSA eras were 73% and 95% (Log-rank P = 0.001) and 65% and 73% (Log-rank P = 0.055), respectively. Multivariable analysis showed that pathologic Gleason grade 8–10 (CR: hazard ratio [HR] = 5.11; 95% confidence interval [CI] = 1.72–15.20; P = 0.003; BCR: HR = 3.47; 95% CI = 1.60–7.48; P = 0.002) and contemporary PSA era (CR: HR = 0.15; 95% CI = 0.06–0.41; P<0.001; BCR: HR = 0.49; 95% CI = 0.28–0.86; P = 0.013) were independently associated with cancer control. Adjuvant radiation therapy and positive surgical margins were not independently associated with outcomes.ConclusionsRP conferred long-term cancer control in men with pT3bN0M0 prostate cancer treated in the PSA era. Pathologic Gleason grade 8–10 and treatment in the early PSA era were independently associated with poorer cancer control outcomes.     

Predictive factors for recurrence after complete metastasectomy in patients with metastatic renal cell carcinoma in the targeted therapy era

ObjectivesComplete metastasectomy is expected to improve the survival of patients with metastatic renal cell carcinoma (mRCC). However, many patients develop re-recurrence, despite achieving complete remission with surgery. We examined recurrence-free survival (RFS) and analyzed predictive factors for recurrence after complete metastasectomy.MethodsFifty-one patients with mRCC who underwent complete metastasectomy between 2008 and 2018 were included in this study. Multivariate Cox regression analyses were performed to identify the prognostic factors for RFS.ResultsOf 51 patients, 6 (12%) had multiple metastatic sites and 45 (88%) had solitary metastasis. The pathological subtype was clear cell in 42 (82%), papillary in 8 (17%), and other subtype in 1 (2%) patient. Sarcomatoid features were found in 2 (4%) patients. The Memorial Sloan Kettering Cancer Center risk category was favorable in 43%, intermediate in 53%, and poor in 4% of patients. The median duration from nephrectomy to metastasectomy was 32 months. Of the total cohort, 39 patients (74%) developed recurrence after complete metastasectomy. The median RFS was 22 months, and the 2- and 5-year RFS rates were 45% and 25%, respectively. Multivariate Cox regression revealed that ≥2 metastatic sites (vs. 1 site; HR = 4.52; P = 0.024) and sarcomatoid features (HR = 11.5; P = 0.0171) were independent predictive factors for recurrence. The 2- and 5-year cancer-specific survival rates were 98% and 82%, respectively.ConclusionThe number of metastatic sites and sarcomatoid features were associated with recurrence after complete metastasectomy, which suggests that careful observation is required for such patients, even after achieving complete remission with metastasectomy.     

PAK1 expression determines poor prognosis and immune evasion in metastatic renal cell carcinoma patients

BackgroundPrevious studies have shown the prognostic value of PAK1 expression in different tumor patients, including nonmetastatic renal cell carcinoma. In this study, we explored the prognostic and drug predictive value of PAK1 expression in metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs).Materials and MethodsWe retrospectively enrolled 138 mRCC patients treated with TKIs from a single institution from 2005 to 2014. Analyses were based on 111 patients who met our inclusion criteria. The validation set enrolled 538 RCC patients from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma cohort (TCGA KIRC) between 1998 and 2013 in North America. PAK1 expression was assessed by immunohistochemistry (IHC) on tissue microarrays.ResultsHigh PAK1 expression was associated with short overall survival (OS) (P < 0.001) and progression-free survival (PFS) (P = 0.008). Multivariate analyses further indicated that PAK1 expression was an independent prognostic factor for OS (hazard ratio 3.301 [95% confidence interval 2.579–10.899], P < 0.001) and PFS (hazard ratio 3.108 [95% confidence interval 1.795–5.381], P < 0.001). Subgroup analyses suggested that PAK1 was more significant in patients with the intermediate risk group of Heng risk criteria (OS, P = 0.004). Of note, patients treated with Sunitinib showed improved outcome in the low PAK1 subgroup (OS, P = 0.002; PFS, P = 0.013). Finally, relationship was found between PAK1 expression and natural killer cell-mediated cytotoxicity according to gene profile investigation.ConclusionsHigh PAK1 expression predicted dismal prognosis in mRCC patients treated with TKIs. Besides, PAK1 was a potential predictor for TKIs treatments.     

Expression of tyrosine kinase receptor AXL is associated with worse outcome of metastatic renal cell carcinomas treated with sunitinib

Background

Renal cell carcinoma (RCC) represents 2%–3% of all cancers of the Western countries. Currently, sunitinib, a receptor tyrosine kinase inhibitor, particularly of PDGF and VEGF receptors, is the first-line therapy for metastatic RCC (mRCC), with significant improvement in clinical outcome. However, there is a lack of predictive biomarkers of sunitinib response. Recently, others and our group suggested that the receptor tyrosine kinase AXL may modify the response to sunitinib.

Prognostic significance of indeterminate lung nodules in renal cell carcinoma

ObjectivesMany patients with renal cell carcinoma (RCC) are found to have lung nodules at the time of diagnosis. The significance of these nodules is unclear. This study sought to determine whether the presence of indeterminate lung nodules affects survival for patients with early-stage RCC.Methods and materialsA retrospective review was performed of patients with stages I to III RCC at an academic hospital who underwent nephrectomy between 2001 and 2006 and had baseline imaging available for review. Presence of lung nodule(s) was determined, along with patient and disease characteristics. The time from diagnosis to last known follow-up, metastasis, and death were determined. The study follow-up period extended to July 2012. Univariate and multivariate Cox proportional hazards models assessed disease-free and overall survival.ResultsOf 548 patients, 240 met the inclusion criteria. Lung nodules were absent in 148 and present in 92 cases. Disease-free survival was associated with the presence of nodules (hazard ratio [HR] = 1.90; 95% CI: 1.04–3.46; P = 0.0362), tumor stage (stage II—HR = 5.61; 95% CI: 2.69–11.72; P<0.001 and stage III—HR = 2.49; 95% CI: 1.21–5.10; P = 0.0129) and tumor grade (HR = 2.43 for grades 3 or 4; 95% CI: 1.31–4.53; P = 0.005). The number and size of nodules were not associated with survival. Overall survival was associated with Charlson comorbidity score (HR = 1.30; 95% CI: 1.15–1.47; P<0.0001) and primary tumor size (HR = 1.29; 95% CI: 1.14–1.46; P<0.0001) but not the presence of lung nodules (HR = 1.73; 95% CI: 0.83–3.60; P = 0.1454).ConclusionsThe presence of indeterminate lung nodules had a negative effect on disease-free survival. Stage and grade were also significant. These findings underscore the importance of baseline imaging and vigilant surveillance of patients in whom nodules are identified.     

Cachexia index in predicting outcomes among patients receiving immune checkpoint inhibitor treatment for metastatic renal cell carcinoma

IntroductionImmune checkpoint inhibitors (ICI) have transformed treatments for patients with metastatic renal cell carcinoma (mRCC). Although some patients benefit greatly from ICI treatments, an effective marker to determine which patients will benefit from these treatments is lacking. Moreover, chronic inflammation and sarcopenia have been associated with poor survival rates among cancer patients. Accordingly, in this study, we investigated how the cachexia index (CXI), used as a combined score for sarcopenia and chronic inflammation, affects the survival outcomes of patients with mRCC receiving ICI.MethodsWe retrospectively screened data from 52 mRCC patients who had followed up between October 2010 and October 2021 after receiving ICI as a second-line or later treatment. Patients’ respective basal CXI score were calculated according to the following formula, based on their L3 vertebral skeletal musculoskeletal area (SMI), neutrophil-lymphocyte ratio (NLR), and albumin (Alb) levels: CXI = (SMI x Alb) / NLR. Additionally, we analyzed how patients’ subcutaneous adipose tissue (SAT), body mass index (BMI), ECOG performance status, The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score, nephrectomy status, sites of metastasis, and histological subtypes affected survival outcomes.ResultsOur univariate analysis significantly associated CXI score, NLR, nephrectomy status, and patient age with overall survival (OS). However, only CXI scores’ significance was confirmed through multivariate analysis. The median OS (mOS) was 7 months for patients whose CXI score < the median value and 48 months for patients with a CXI score ≥ the median value. (HR 4.5, 95% CI [1.9-11], p = 0.001). Only CXI was significantly associated with progression-free survival (PFS) outcomes. The median progression-free survival (mPFS) was 4 months for patients whose CXI score < the median value and 17 months for patients with a CXI score ≥ the median value. (HR 2.6, 95% CI [1.3, 5.3], p = 0.007). Sarcopenia, sarcopenic obesity, and sarcopenia combined with NLR were not found to significantly affect OS.ConclusionOur findings suggest that CXI score, a combined indicator of sarcopenia and chronic inflammation parameters, may serve as a useful marker in predicting the outcomes of ICI-based treatments for mRCC patients.     

Outcomes of small bowel obstruction in patients with previous gynecologic malignancies

BackgroundFeatures predictive of malignant small bowel obstructions among patients with previous gynecologic malignancies remain undetermined.MethodsPredictors of malignancy and mortality among patients with gynecologic malignancies and bowel obstructions were identified through a retrospective review of records.ResultsMalignancy was noted among 69.8% of 189 patients included in the analysis. Advanced-stage cancer (P = .006, odds ratio [OR] = 6.62), ovarian malignancy (P = .001, OR = 25.64), and early-onset obstruction (P = .014) predicted malignant etiology, whereas chemotherapy (P < .001, OR = .02) or radiation therapy (P = .027, OR = .09) predicted benign obstruction. The average survival was 9 months versus 49 months for malignant and benign obstructions, respectively. Ovarian cancer (P = .009, hazard ratio [HR] = 4.45), anemia (P = .001, HR = 1.11), and renal dysfunction (P < .001, HR 1.81) impaired survival.ConclusionsPalliative care should be considered for patients with advanced-stage cancer, ovarian malignancy, and a shorter time interval between cancer diagnosis and bowel obstruction, especially in the setting of anemia and renal dysfunction.     

Plasmacytoid urothelial carcinoma of the bladder: MRI features and their association with survival

ObjectivesPlasmacytoid urothelial carcinomas (PUC) of the bladder are rare variants known for diffuse and infiltrative spread, however their magnetic resonance imaging (MRI) features are not well established. We aimed to evaluate MRI features of PUC of the bladder and their association with survival.Methods and materialsThis retrospective single-center study included 41 patients with pathologically-proven bladder PUC of the bladder that underwent pre-treatment MRI between January 2000 and March 2020. Two radiologists reviewed MRIs independently followed by consensus with a third radiologist. On MRI, tumor extent, size, Vesical Imaging-Reporting and Data System (VI-RADS) scores (≥4, muscle-invasive; 5, extravesical extension [EVE]), pelvic peritoneal spread (PPS), hydronephrosis, pelvic adenopathy and clinicopathological factors of age, gender, pathological stage, and treatment type were extracted. Kaplan-Meier curves and Cox proportional-hazards models were used to evaluate association with survival.ResultsThirty-two men and 9 women (median age 70 years, IQR 64–76) were included. Most were muscle-invasive (n = 30 [73.2%]). On MRI, most tumors were diffuse (n = 28 [68.3%]), >5 cm (n = 30 [73.2%]), VI-RADS 4 to 5 (n = 36 [87.8%]) with features of EVE and (n = 31 [75.6%]) and PPS (n = 25 [61.0%]). Variables associated with survival were: Larger tumors (>5 cm; hazard ratio [HR] = 5.0; 95% confidence interval [CI] 1.6–15.5; P < 0.01), diffuse extent (HR = 4.0; 95% CI 1.4–11.2; P = 0.01), EVE (HR = 4.5; 95% CI 1.5–13.6; P < 0.01), PPS (HR = 3.0; 95% CI 1.2–7.4; P = 0.01), hydronephrosis (HR = 13.7; 95% CI 3.1–60.9; P < 0.01), pathologic stage (≥pT3 vs. pT1; HR = 5.6; 95% CI 1.3–22.0; P = 0.02), and margin positivity (HR = 4.4 [95% CI 1.2–16.4], P = 0.03).ConclusionPUCs of the bladder are commonly large, diffuse VI-RADS score 4 to 5 tumors with MRI features of EVE and PPS. These features and pathological stage were associated with survival.     

Effect of the time from the presentation of symptoms to medical consultation on primary tumor size and survival in patients with testicular cancer: Shift in the last 2 decades

ObjectivesTo clarify the effect of the time from the presentation of symptoms to medical consultation (time to consultation) on oncological outcomes in men with testicular cancer and to examine whether the recent improvement of delays in consultation has led to better outcomes.MethodsWe reviewed 175 consecutive patients registered for testicular cancer (124 men with seminoma and 51 men with nonseminoma) at a single institution between 1991 and 2010.ResultsMen with the time to consultation of>6 months (n = 56) had a poorer overall survival than those with the time to consultation of ≤6 months (log-rank test, P = 0.028), despite similar disease stage between them (P = 0.897) and less prevalent nonseminoma in the former (P = 0.032). Although the negative effect of consultation delay on overall survival was significant only in nonseminoma histology (log-rank test, P = 0.004), the time to consultation of>6 months was an independent risk factor associated with poorer overall survival (hazard ratio [HR] = 18.0, 95% confidence interval [CI]: 1.78–182, P = 0.014), in addition to nonseminoma histology (HR = 17.4, 95% CI: 1.38–219, P = 0.027) and stage II or higher disease (HR = 12.9, 95% CI: 1.36–123, P = 0.026) in all the patients. The time to consultation was positively correlated with the primary tumor size (P<0.001). The time to consultation was shorter and the primary tumor size was seemingly smaller in patients registered between 2001 and 2010 (n = 104) than in those registered between 1991 and 2000 (median 74 d vs. 109 d, P = 0.042 and 5.8±2.6 cm vs. 6.7±3.3 cm, P = 0.068, respectively), although disease stage and overall survival were not different between the 2 periods (P = 0.233 and log-rank test, P = 0.719, respectively).ConclusionsThe time to consultation and primary tumor size showed a strong positive correlation in men with testicular cancer. Delays in consultation had a negative effect on their survival, particularly in those with nonseminoma. The time to consultation significantly shortened and the primary tumor size was reduced with a borderline significance in men registered between 2001 and 2010 compared with those between 1991 and 2000, although stage migration or survival improvement in recent years was not observed.