Poor Cancer-specific Survival Research Articles

Preoperative C-reactive protein to albumin ratio as a novel prognostic biomarker for the oncological outcomes of radical nephroureterectomy

PurposeThis study aimed to evaluate the prognostic impact of the preoperative C-reactive protein to albumin ratio (CAR) on progression-free survival (PFS) and cancer-specific survival (CSS) in patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). MethodsA retrospective analysis was conducted using data from a single-center nephroureterectomy registry between January 2011 and December 2017. Participants were categorized into high and low CAR groups based on the optimal CAR cut-off value determined using the Youden index. The primary endpoint was PFS, the time from RNU to metastasis or disease recurrence. The secondary endpoint was CSS, the time from RNU to UTUC-related death. Median PFS and CSS were compared between the high and low CAR groups using Kaplan–Meier analysis and log-rank test. Multivariable Cox proportional hazard regression analysis was performed to assess the prognostic significance of CAR, adjusting for known prognostic factors. ResultsWe included 491 patients with UTUC in the analysis. The optimal CAR cut-off value was determined to be 0.036, which resulted in classifying 49.3% (242/491) of patients into the high CAR group. The high CAR group had older patients (69.8 vs. 67.4, p-value = 0.01), advanced T and N stages (p-value<0.001), high-grade tumor (p-value = 0.03), and a higher incidence of preoperative hydronephrosis (p-value < 0.01) than the low CAR group. The high CAR group demonstrated significantly inferior median PFS (78.3 vs. 100.3 months, p-value < 0.01) and CSS (73.2 vs. 96.1 months, p-value < 0.01) than the low CAR group. Moreover, high CAR independently increased the risk of disease progression (hazard ratio [HR]: 1.80, 95% confidence interval [CI]: 1.23–2.64, p < 0.01) and UTUC-related mortality (HR: 1.79, 95% CI: 1.15, p < 0.01). ConclusionPre-operative CAR is independently associated with poor PFS and CSS in patients with UTUC undergoing RNU. Moreover, CAR may be an independent UTUC prognostic factor, offering a cost-effective and minimally invasive marker. However, further validation through large-scale, multi-center studies is necessary to confirm these findings and determine the optimal CAR cut-off value.

MicroRNA-299-3p inhibits cell proliferation, motility, invasion and angiogenesis via VEGFA in upper tract urothelial carcinoma.

Upper tract urothelial carcinoma (UTUC) is a rare tumor with extraordinarily different features between Eastern and Western countries. Vascular endothelial growth factor-A (VEGFA) was originally identified as a secreted signaling protein and regulator of vascular development and cancer progression. In this study, we aimed to elucidate the molecular mechanisms underlying the regulation of VEGFA by microRNA in UTUC. VEGFA expression was evaluated by immunohistochemistry in 140 human UTUC tissue samples. Next, we assessed the regulatory relationship between VEGFA and miR-299-3p by real-time PCR, western blotting, ELISA and dual-luciferase reporter assays using two UTUC cell lines. The role of miR-299-3p/VEGFA in cell proliferation, motility, invasion, and tube formation was analyzed in vitro. High VEGFA expression was significantly associated with tumor stage, grade, distant metastasis and cancer-related death and correlated with poor progression-free and cancer-specific survival. VEGFA knockdown repressed proliferation, migration, invasion and angiogenesis in UTUC cell lines. miR-299-3p significantly reduced VEGFA protein expression and miR-299-3p overexpression inhibited VEGFA mRNA and protein expression by directly targeting its 3'-UTR. Functional studies indicated that VEGFA overexpression reversed the miR-299-3p-mediated suppression of tumor cell proliferation, migration, invasion and angiogenesis. In addition, miR-299-3p/VEGFA suppressed cellular functions in UTUC by modulating the expression of P18 and cyclin E2. Our findings suggest that miR-299-3p possibly suppresses UTUC cell proliferation, motility, invasion and angiogenesis via VEGFA. VEGFA may act as a prognostic predictor, and both VEGFA and miR-299-3p could be potential therapeutic targets for UTUC.

Prognostic Impact of the Modified 5-Item Frailty Index After Radical Nephroureterectomy in Patients With Upper Tract Urothelial Carcinoma: A Multicenter Retrospective Study

IntroductionThe modified 5-item frailty index can be used to evaluate frailty using 5 routinely encountered clinical variables. This study aimed to assess the impact of the modified 5-item frailty index in patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma. Patients and MethodsIn this multicenter retrospective study, we calculated the modified 5-item frailty index scores of patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma between 2010 and 2022. Patients were categorized into the high (≥2) and low (≤1) modified 5-item frailty index score groups. To assess the prognostic influence of the preoperative modified 5-item frailty index, we conducted Cox proportional regression analyses concerning progression-free, overall, and cancer-specific survival. ResultsOf 434 patients, 82, and 352 were classified into the high and low modified 5-item frailty index score groups, respectively. The high modified 5-item frailty index score group had significantly higher rates of severe surgical complications (P = .038) and ≥30 days of hospitalization (P = .049) and significantly worse progression-free (P = .012) and overall survival (P = .002) than the low modified 5-item frailty index score group. The multivariable Cox proportional hazard analysis revealed that a high modified 5-item frailty index score was independently associated with poor progression-free (P = .044), overall (P = .017), and cancer-specific survival (P = .005). ConclusionThe modified 5-item frailty index emerged as a significant predictive indicator of severe surgical complications and postoperative survival outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.

Contemporary Incidence of Synchronous Multiple Primary Lung Cancers and Survival in the Era of Lung Cancer Screening.

Up to 15% of lung cancer patients have multiple suspicious nodules. While some of these nodules may represent metastatic lung cancer, others represent synchronous multiple primary lung cancer (SMPLC). The incidence of SMPLC ranges from 0.8% to 8.4% and appears to be increasing. Inconsistent identification of SMPLC can be detrimental for patients who are misdiagnosed as having intrapulmonary metastasis and not offered stage-based treatment. We sought to identify the contemporary incidence of SMPLC at a tertiary institution. From January 2018 to September 2019, patients who underwent lung cancer resection were retrospectively reviewed. Patients with SMPLC were identified using the modified Martini-Melamed criteria. During the 21-month period, 227 patients underwent lung cancer resection. There were 47 patients (20.7%) who had 119 pathologically confirmed SMPLC. Most patients had ipsilateral tumors (n = 24, 51.1%) with at least 1 adenocarcinoma (n = 40, 85.1%). Considering histologic subtyping, 38 (80.9%) had histologically distinct tumors. Overall and cancer-specific survival at 4 years was 86% and 90%, respectively. Only patients with 3 or more SMPLC had poor 4-year overall (P = 0.002) and cancer-specific survival (P = 0.043) compared with those with 2 SMPLC. Patient demographics, histology, tumor location, and highest pathologic staging did not affect survival outcomes. Using a strict inclusion criterion, the incidence of SMPLC is higher than previously reported. SMPLC patients have favorable survival outcomes, suggesting that they behave like primary lung cancer, not intrapulmonary metastasis. Awareness of SMPLC by thoracic surgeons is critical in optimizing outcomes in this patient population.

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

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

Advanced Age May Not Be an Absolute Contraindication for Radical Nephroureterectomy in Patients with Upper Tract Urothelial Carcinoma: A Single-Center Case Series and a Systematic Review with Meta-Analyses

Objective: This study aims to investigate whether advanced age is an absolute contraindication for radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) through a single-center case series and a systematic review with meta-analysis. Materials and methods: In the single-center case series, 588 UTUC patients who underwent RNU between May 2003 and June 2019 in West China Hospital were enrolled, and cancer-specific survival (CSS) was the primary outcome of interest. In the systematic review with meta-analysis, PubMed, Scopus, Embase, and Cochrane databases were systematically searched for related articles for further analysis. The endpoints for meta-analyses were overall survival (OS) and CSS. Results: The single-center case series included 57 (9.7%) octogenarians. The CSS of octogenarians after RNU was comparable to that of younger people. Advanced age (≥80) was not an independent risk factor for poor CSS (HR, 1.08; 95% CI, 0.48, 2.40). In a systematic review with meta-analysis, the cut-off value of advanced age is 70, and the results showed that advanced age was associated with inferior OS (pooled HR, 1.55; 95% CI, 1.29, 2.01) and CSS (pooled HR, 1.37; 95% CI, 1.08, 1.65). However, the subgroup analysis of countries found no positive correlation between advanced age and CSS (pooled HR, 1.33; 95% CI 0.92, 1.74) in Chinese. Conclusions: Advanced age may no longer be an absolute contraindication for RNU. RNU can be safely and effectively performed on UTUC patients of advanced age after a comprehensive presurgical evaluation.

Preoperative systemic immune-inflammation index as a prognostic indicator for patients with urothelial carcinoma.

The systemic immune-inflammation index (SII) is a cost-efficient indicator for carcinoma prognosis. However, its utility in urothelial carcinoma (UC) prognosis is disputed. This meta-analysis aims to assess SII's prognostic value in UC. A thorough search of databases including PubMed, Web of Science, Embase, Cochrane Library, and Scopus, was conducted to find studies until January 11, 2023. Eligibility criteria were applied to select studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted from selected studies and compiled in a meta-analysis to gauge SII's association with survival outcomes such as overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS). This analysis includes 19 studies with 12505 UC patients. It was found that high SII significantly correlated with worse OS in UC patients (HR 1.430, 95% CI 1.237-1.653, P<0.001). High SII values also linked with poorer CSS (HR 1.913, 95% CI 1.473-2.485, P<0.001), RFS (HR 1.240, 95% CI 1.097-1.403, P=0.001), and PFS (HR 1.844, 95% CI 1.488-2.284, P<0.001) compared to low SII values. Subgroup analysis revealed SII's consistent prognostic value in UC across races, carcinoma types, sample sizes, and SII cut-off values, suggesting its potential as a prognostic indicator in UC patients. Current evidence suggests SII as a promising, cost-efficient predictor in UC patients. This meta-analysis indicates SII's potential as a valuable prognostic tool in UC patients. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=307643, identifier CRD42022307643.

Geriatric nutritional risk index as a prognostic marker of first-line immune checkpoint inhibitor combination therapy in patients with renal cell carcinoma: a retrospective multi-center study

PurposeThis study aimed to investigate the effectiveness of the Geriatric Nutritional Risk Index (GNRI) in predicting the efficacy of first-line immune checkpoint inhibitor (ICI) combination therapy for metastatic or unresectable renal cell carcinoma (RCC) and associated patient prognosis.MethodsA retrospective study was conducted using data from 19 institutions. The GNRI was calculated using body mass index and serum albumin level, and patients were classified into two groups using the GNRI values, with 98 set as the cutoff point.ResultsIn all, 119 patients with clear cell RCC who received first-line drug therapy with ICIs were analyzed. Patients with GNRI ≥ 98 had significantly better overall survival (OS) (p = 0.008) and cancer-specific survival (CSS) (p = 0.001) rates than those with GNRI < 98; however, progression-free survival (PFS) did not differ significantly. Inverse probability of treatment weighting analysis showed that low GNRI scores were significantly associated with poor OS (p = 0.004) and CSS (p = 0.015). Multivariate analysis showed that the Karnofsky performance status (KPS) score was a better predictor of prognosis (OS; HR 5.17, p < 0.001, CSS; HR 4.82, p = 0.003) than GNRI (OS; HR 0.36, p = 0.066, CSS; HR 0.35, p = 0.072). In a subgroup analysis of patients with a good KPS and GNRI ≥ 98 vs < 98, the 2-year OS rates were 91.4% vs 66.9% (p = 0.068), 2-year CSS rates were 91.4% vs 70.1% (p = 0.073), and PFS rates were 39.7% vs 21.4 (p = 0.27), respectively.ConclusionThe prognostic efficiency of GNRI was inferior to that of the KPS score at the initiation of the first-line ICI combination therapy for clear cell RCC.

2 years is a reasonable age cut-off level for prognostic assessment of children with hepatoblastoma.

We aimed to elucidate the prognostic significance of age in hepatoblastoma patients. Data from 783 patients with hepatoblastoma were obtained from the Surveillance, Epidemiology and End Results database (2000-2018). The best age cut-off level was determined by X-tile, and the Kaplan-Meier method was used to estimate overall survival (OS) and cancer-specific survival (CSS). The results of the X-tile were verified by selecting the appropriate cut-off value to maximize the difference in survival outcomes at intervals of 1 year. The Cox regression model was used to determine the prognostic impact of risk factors and age. X-tile analysis determined that 2 years was the best cut-off age for OS and CSS. The overall prognosis in the ≥ 2 years group was worse than that in the < 2 years group (OS: p = 0.00017; CSS: p < 0.0001). In Cox univariate analysis, when 2 years was used as the standard group, the numbers of patients in the two groups were similar, with high hazard ratio (HR) value and narrow 95% confidence interval (CI) (OS: HR, 1.834; 95% CI, 1.329 - 2.532; p < 0.001; CSS: HR, 1.988; 95% CI, 1.410 - 2.801; p < 0.001), which was consistent with the age cut-off point determined by X-tile. Cox multivariate analysis showed that age ≥ 2 years, black ethnicity, no surgery, no chemotherapy, distant metastasis, and tumor size ≥ 5 cm were independent predictors of poor OS and CSS. On subgroup analysis, patients aged ≥ 2 years had worse survival if they were Caucasian, had elevated alpha-fetoprotein, tumor size ≥ 5 cm, or distant metastasis. Age is an important prognostic factor for hepatoblastoma. Age ≥ 2 years at diagnosis may predict poor prognosis and more active treatment measures can be implemented.

Oncological prognosis and morbidity of hepatectomy in elderly patients with hepatocellular carcinoma: a propensity score matching and multicentre study

PurposeWith increasing life expectancy, the number of elderly patients (≥ 65 years) with hepatocellular carcinoma (HCC) has steadily increased. Hepatectomy remains the first-line treatment for HCC patients. However, the prognosis of hepatectomy for elderly patients with HCC remains unclear.MethodsClinical and follow-up data from 1331 HCC patients who underwent surgery between 2008 and 2020 were retrospectively retrieved from a multicentre database. Patients were divided into elderly (≥ 65 years) and non-elderly (< 65 years) groups, and PSM was used to balance differences in the baseline characteristics. The postoperative major morbidity and cancer-specific survival (CSS) of the two groups were compared and the independent factors that were associated with the two study endpoints were identified by multivariable regression analysis.ResultsOf the 1331 HCC patients enrolled in this study, 363 (27.27%) were elderly, while 968 (72.73%) were not. After PSM, 334 matched samples were obtained. In the propensity score matching (PSM) cohort, a higher rate of major morbidity was found in elderly patients (P = 0.040) but the CSS was similar in the two groups (P = 0.087). Multivariate analysis revealed that elderly age was not an independent risk factor associated with high rates of major morbidity (P = 0.117) or poor CSS (P = 0.873). The 1-, 3- and 5-year CSS rates in the elderly and non-elderly groups were 91.0% versus 86.2%, 71.3% versus 68.8% and 55.9% versus 58.0%, respectively. Preoperative alpha fetoprotein (AFP) level, Child‒Pugh grade, intraoperative blood transfusion, extended hemi hepatectomy, and tumour diameter could affect the postoperative major morbidity and preoperative AFP level, cirrhosis, Child‒Pugh grade, macrovascular invasion, microvascular invasion (MVI), satellite nodules, and tumor diameter were independently and significantly associated with CSS.ConclusionAge itself had no significant effect on the prognosis of elderly patients with HCC after hepatectomy. Hepatectomy can be safely performed in elderly patients after cautious perioperative management.

Circulating Tumor Cells are an Independent Risk Factor for Poor Prognosis in Patients with Gallbladder Adenocarcinoma.

The study aimed to evaluate the prognostic impact of circulating tumor cells (CTCs) in patients with gallbladder adenocarcinoma after resection. Between January 2018 and January 2021, 101 consecutive patients with gallbladder adenocarcinoma were included. CTCs were detected and enumerated using the CanPatrol® technique. The follow-up period ended in January 2023. The cancer-specific survival (CSS) and disease-free survival (DFS) were calculated using log-rank and Cox regression analyses. CTCs were detected positively in 61.54% (8/13) of the patients in the non-operation group and 13.64% (12/88) in the operation group. In the operation group, the median CSS for CTCs-positive and CTCs-negative patients was 5.0 and 9.5 months (P < 0.001), respectively, and DFS was 2.8 and 5.0 months at stage III (P < 0.001), respectively. In the non-operation group, the median CSS for CTCs-positive and CTCs-negative patients was 3.5 and 6.5 months (P = 0.0031), respectively. The median CSS for CTCs-positive patients in the operation group was similar to that in the non-operation group (P = 0.67). Multivariate analyses showed that positive CTCs was an independent risk factor for poor CSS (HR 0.066, 95% CI 0.021-0.206, P < 0.001) as well as lymph infiltration (HR 0.320, 95% CI 0.110-0.930, P = 0.036), without R0 curative resection (HR 7.520, 95% CI 2.100-26.931, P = 0.002), and without adjuvant chemotherapy (HR 7.730, 95% CI 2.416-24.731, P < 0.001). Positive CTCs was an independent predictor of poor prognosis after resection in patients with gallbladder adenocarcinoma. Preoperative detection of CTCs may play an important guiding role in formulating treatment strategies for these patients.

Racial differences in survival for early stage (T1) penile cancer: Analysis from the SEER database.

Penile cancer accounts for less than 1% of male cancers in the United States. Localized disease, particularly T1 tumors are potentially curable with local therapy. We present the racial differences in survival outcomes for T1, penile cancer from the SEER database. From 2004 to 2016 all men with T1, N0, M0 penile cancer in the SEER-18 database were included. Kaplan-Meier analysis and multivariable Cox-Regression analysis were conducted to investigate prognostic variables for cancer specific survival (CSS). A total of 4,406 men were identified with penile cancer; 1,941 men had T1 disease. The Kaplan-Meier (KM) analysis showed those with primary site surgery had better 5-year CSS compared to those without primary site surgery (P <.0001) and a significant difference in CSS based on race (P= 0.0078). On multivariable analysis, Hispanic individuals had worse CSS (HR 1.92; P = 0.0057) compared to the White men. Black men were also found to have a poor CSS however this was not statistically significant (HR 1.53, P = 0.118). Men with penile cancer who had either penectomy (HR 0.45; P = 0.006) or penile preservation surgery (HR 0.25; P< 0.001) had improved CSS. Racial disparities in CSS exist among men with in early-stage penile cancer. KM analysis showed significant differences in CSS by race and in those receiving primary site surgery. On multivariable analysis, the CSS is worse in Hispanic compared to White men. There is a trend towards worse CSS in Black men however this was not statistically significant.

Prognostic value of pretreatment Controlling Nutritional Status score in esophageal cancer: a meta-analysis.

Background and purpose: The association between the pretreatment Controlling Nutritional Status (CONUT) score and the prognosis of esophageal cancer patients remains unclear. The aim of this meta-analysis was to further elucidate the prognostic role of the pretreatment CONUT score in esophageal cancer based on current evidence. Methods: The PubMed, Embase, Web of Science and CNKI databases were searched up to 27 September 2022. The primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS)/cancer-specific survival (CSS), and the hazard ratio (HR) and 95% confidence interval (CI) were pooled for analysis. Results: A total of 11 retrospective studies involving 3,783 participants were included. The pooled results demonstrated that a higher pretreatment CONUT score was significantly related to poor OS (HR = 1.82, 95% CI: 1.31-2.54, p < 0.001), and subgroup analysis stratified by pathological type showed similar results. In addition, the pretreatment CONUT score was associated with poor PFS (HR = 1.19, 95% CI: 1.10-1.28, p < 0.001) and CSS (HR = 2.67, 95% CI: 1.77-4.02, p < 0.001). Conclusion: The pretreatment CONUT score was predictive of worse prognosis in esophageal cancer, and patients with a higher CONUT score showed worse survival.

Prognostic significance of pre-treatment albumin-bilirubin grade in metastatic urothelial carcinoma receiving pembrolizumab.

Pre-treatment albumin-bilirubin grade is a useful biomarker for predicting prognosis in patients receiving immune checkpoint inhibitors for advanced malignancies. We evaluated the prognostic impact of pre-treatment albumin-bilirubin grade in patients receiving pembrolizumab for metastatic urothelial carcinoma. In this multicenter retrospective study, we calculated pre-treatment albumin-bilirubin scores of 96 patients who received pembrolizumab for metastatic urothelial carcinoma between January 2018 and March 2022. Patients were classified according to albumin-bilirubin grade. Progression-free survival and cancer-specific survival were compared between the groups. To evaluate the prognostic impact of pre-treatment albumin-bilirubin grade, we also performed Cox proportional regression analyses for progression-free survival and cancer-specific survival. The median pre-treatment albumin bilirubin score was -2.52 (quartile: -2.76 to -2.10), and albumin-bilirubin grade was grade 1 in 37 patients (39%), grade 2a in 30 patients (31%), 2b in 22 patients (23%) and grade 3 in 7 patients (7%). The median progression-free survival and cancer-specific survival were 2 and 7months, respectively. Progression-free survival and cancer-specific survival were significantly different between the albumin-bilirubin grade groups (P<0.01 and P<0.01, respectively) and prognosis became poorer as albumin-bilirubin grade increased. High albumin-bilirubin grade was shown in multivariable Cox proportional analyses to be independently associated with both poor progression-free survival and poor cancer-specific survival. High pre-treatment albumin-bilirubin grade could be a significant independent predictor of poor prognosis in patients receiving pembrolizumab for advanced urothelial carcinoma.

Prognostic impact of the radiological infiltrative feature of primary renal tumor in metastatic renal cell carcinoma.

Recent studies suggest that the radiological infiltrative feature (r-IF) of renal tumors is strongly correlated with poor oncologic outcomes in locally advanced renal cell carcinoma (RCC). This study investigated the prognostic impact of r-IF of primary renal tumors in metastatic RCC (mRCC) in comparison with International Metastatic RCC Database Consortium (IMDC) risk model. We retrospectively analyzed 91 patients with previously untreated mRCC. Dynamic computed tomography of the primary renal tumor was reviewed to assess r-IF, defined as a focally/extensively ill-defined tumor interface with normal renal parenchyma. The median age was 67 years, and 69 patients (76%) were men. Prior nephrectomy was performed in 47 patients (52%). The median size of the primary renal tumor was 6.7 cm, and 50 patients (55%) presented with cT3-4 stage. Overall, 25 (28%)/52 (57%)/14 (15%) patients were classified into IMDC favorable/intermediate/poor-risk groups, respectively. An image review identified r-IFs in the primary renal tumor in 40 patients (44%). The incidences of r-IFs were 28%/46%/64% in IMDC favorable/intermediate/poor-risk groups, respectively. During a median follow-up of 2.6 years, 31 patients (34%) died of RCC. On multivariable analysis, r-IF and IMDC intermediate-poor risks were independently associated with poor cancer-specific survival (CSS). Two-year CSS were 64%/87% in patients with/without r-IF, respectively. C-index was improved from 0.73 to 0.81 by adding r-IF to the IMDC risk factors. R-IF of the primary renal tumor was an independent risk factor for poor CSS in patients with mRCC, which may improve the prognostic accuracy when combined with the IMDC risk model.

Clinicopathological characteristics and survival outcomes for testicular choriocarcinoma and non-testicular choriocarcinoma: A SEER database analysis.

e17026 Background: Primary Choriocarcinoma (CC) is a rare germ cell tumor that can occur in males. The most common primary site in men is the testis. It can occur in extragonadal sites such as the mediastinum, retroperitoneum, lungs or brain. The clinical and prognostic differences between testicular CC and non-testicular CC are unclear. We aim to study the differences in clinical features, prognostic factors, and outcomes between the two subtypes of CC. Methods: We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with pure CC between 2000 and 2018. Patients with a previous history of cancer or with other concurrent malignancies were excluded. These patients were divided into two groups: testicular and non-testicular CC. The clinicopathological features of each group were compared using chi-square tests. Kaplan-Meier estimator, log-rank tests, and Cox proportional hazard regression were used to identify prognostic factors over overall survival (OS) and cancer-specific survival (CSS). Results: The study included 363 patients, with 270 (74.4%) patients classified as having testicular CC and 93 (25.6%) as having non-testicular CC. The results showed that testicular CC was more likely to occur in white patients, be bilateral in distribution, have a smaller size, and be in more advanced SEER stages compared to non-testicular CC. Additionally, testicular CC patients were more likely to undergo surgical treatment, but not radiation. Testicular CC patients had a better OS and CSS (HR = 0.52, 95% CI: 0.38-0.71 and HR = 0.52, 95% CI: 0.37-0.71, respectively) compared with non-testicular CC. Our Cox multivariate analyses for OS and CSS identified the following independent prognostic factors for testicular CC: localized stage, surgery, tumor size ≥ 4cm, radiotherapy, and chemotherapy. Interestingly, the use of radiotherapy was actually associated with poor OS and CSS (HR = 1.8, 95% CI: 1.17-2.85 and HR = 1.7, 95% CI: 1.05-2.73, respectively). For non-testicular CC, the independent prognostic factors for OS and CSS were age ≥ 30 years, non-paired site, regional stage, surgery, and chemotherapy. Conclusions: Our study provides important insights into the differences between testicular and non-testicular CC. The use of radiotherapy is generally not recommended in testicular CC which might explain its bad prognostic effect as these patients might be naturally at higher risk of dying. However, the bad poor prognosis of patients using radiotherapy persisted even after controlling for other important prognostic factors. Further studies with larger sample sizes are needed to validate and build upon these findings, but our results provide a starting point for a better understanding of such rare cancer.

Can Peripheral Blood Systemic Immune Response Parameters Predict Oncological Outcomes in Patients with Non-Muscle-Invasive Bladder Cancer?

Many studies have investigated most cancer types - associations with systemic inflammatory response (SIR) parameters. Aim: This study investigated predictive values of SIR parameters in oncological outcomes and survival - to primary non-muscle-invasive bladder cancer (NMIBC) patients. We analyzed 74 primary NMIBC patients. Clinical features, laboratory results, and tumor characteristics were recorded. In addition, the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), serum C-reactive protein, albumin-to-globulin ratio (AGR), and modified Glasgow prognostic scores (mGPS) were calculated. The - mean age of the patients was - 67.41 ± 11.31 years, and the follow-up duration was 38.77 ± 19.53 months. We - found no significant NLR, CRP, and AGR - correlations with tumor characteristics and oncological outcomes. There were significant - correlations between MLR and pathological-T-stage and the PLR, pathological-T-stage, and tumor count. Carcinoma in situ was associated with a high mGPS. Multivariate analysis revealed no significant - correlations between systemic inflammatory response parameters and oncological outcomes. Patients with a high mGPS had poor cancer-specific survival. Increased NLR was associated with reduced overall survival. This study revealed no significant correlation between SIR parameters and oncological outcomes. Therefore, we need more reliable indicators than SIR parameters in NMIBC patients in clinical practice.

Knockdown of kinesin family member 4A inhibits cell proliferation, migration, and invasion while promoting apoptosis of urothelial bladder carcinoma cells.

Kinesin family member 4A (KIF4A) is upregulated in a variety of cancers. However, its expression and potential downstream targets in urothelial bladder carcinoma (UBC) remain unclear. Expression data of KIF4A in UBC and noncancerous tissues were downloaded from the GEPIA database. Cell proliferation, migration, invasion, and apoptosis of T24 and 5637 UBC cells were examined using wound healing, transwell, colony formation, CCK-8, and flow cytometry assays. KIF4A and potential downstream genes were analyzed using qRT-PCR, western blot analysis, and immunohistochemistry. In UBC samples, KIF4A expression was significantly higher than in corresponding noncancerous samples. UBC patients with high KIF4A expression had poor cancer-specific survival and overall survival. Knockdown of KIF4A significantly inhibited proliferation and promoted apoptosis of UBC cells, accompanied by dephosphorylation of AKT and increased the protein level of proapoptotic factors. Additionally, knockdown of KIF4A reduced migration and invasion of UBC cells whereas overexpression of KIF4A exhibited opposite effects, along with altered protein level in epithelial-mesenchymal transition-related genes. Furthermore, overexpression of YAP1 promoted KIF4A expression whereas knockdown of YAP1 suppressed KIF4A expression in UBC cells. Alternatively, KIF4A knockdown reduced YAP1 nuclear protein level whereas KIF4A overexpression suppressed YAP1 phosphorylation and facilitated YAP1 nuclear translocation. KIF4A upregulation correlates with poor prognosis of UBC. Knockdown of KIF4A inhibits proliferation, migration, and invasion of UBC cells while inducing apoptosis possibly through dephosphorylation of AKT, changes in EMT-related genes, and interaction with YAP1.

Abstract 1238: Loss of HSPD1 induces cellular plasticity in triple-negative breast cancer cells

Abstract Abstract Background Unlike Breast cancer (BRCA) luminal subtypes, Triple negative breast cancer (TNBC) subtype lacks expression of estrogen receptor-α (ERα/ESR1), progesterone receptor (PGR) and/or epidermal growth factor (EGF) family receptor HER2/ERBB2 where patients do not benefit from endocrine and HER2 based therapies in addition to its poor differentiation that results in greater aggressiveness and poorer prognosis. The 60 KD Heat shock protein (HSP60) is a Mitochondrial protein that plays a role in stabilizing and refolding proteins and is regulated by HSPD1 gene. In normal cells, HSPD1 gene expression is controlled, however in TNBC, HSPD1 overexpression is common and is associated with poor cancer-specific survival. This study aims to understand downstream signaling pathways dependent on the function of HSPD1 in TNBC. Method To understand downstream signaling pathways dependent on the function of HSPD1, we analyzed the transcriptomic profiles of metastatic MDA-MB-231-WT and HSPD1-KD cells. Results Bioinformatics data analysis shows that HSPD1 is overexpressed in TNBC, particularly in basal subtype. High expression of HSPD1 related to low survival in breast cancer patients. HSPD1 KD in MDA-MB-231 cells identified several differentially regulated genes (DEG) as compared to WT MDA-MB-231 cells by RNA-seq analysis. Pathway analysis of DEG showed downregulation of mitochondrial respiration, thermogenesis, citric acid cycle, PD-1 signaling while upregulation of estrogen dependent gene expression, estrogen mediated signaling, nuclear receptor transcription pathway. These suggests that HSP60 overexpression in TNBC promotes basal type phenotype. Downregulation of HSP60 expression upregulated hormone receptors, particularly estrogen receptor (ESR1) and androgen receptor (AR) expression, thus inducing basal to luminal switch in MDA-MB-231 cells. These findings suggest that loss of HSPD1 significantly Induces plasticity in TNBC. Conclusion Our results suggest that loss of HSPDI in the context TNBC cells may promotes oncogenic transformation to an intermediary luminal progenitor phenotype that gains differentiation plasticity based on the upregulation of Estrogen-receptors signaling pathways. Ongoing analyses will be performed to identify the possible links between loss of HSPD1 and key transcription factors that define mammary epithelial cell differentiation. Citation Format: Muhammad G. Khodary, Alehegne W. Yirsaw, Temesgen Samuel, Clayton Yates, Deepa Bedi. Loss of HSPD1 induces cellular plasticity in triple-negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1238.

MP29-20 FACTORS ASSOCIATED WITH POOR SURVIVAL OUTCOMES IN PROSTATE CANCER (PCA) PATIENTS WITH RADIOGRAPHIC DISEASE PROGRESSION IN THE SETTING OF LOW PSA

You have accessJournal of UrologyCME1 Apr 2023MP29-20 FACTORS ASSOCIATED WITH POOR SURVIVAL OUTCOMES IN PROSTATE CANCER (PCA) PATIENTS WITH RADIOGRAPHIC DISEASE PROGRESSION IN THE SETTING OF LOW PSA Mohamed Ahmed, Jack Andrews, Ahmed Mahmoud, Matthew Lee, Elizabeth Bearrick, Daniel Childs, A. Tuba Kendi, Matthew Tollefson, Stephen Boorjian, R. Jeff Karnes, and Eugene Kwon Mohamed AhmedMohamed Ahmed More articles by this author , Jack AndrewsJack Andrews More articles by this author , Ahmed MahmoudAhmed Mahmoud More articles by this author , Matthew LeeMatthew Lee More articles by this author , Elizabeth BearrickElizabeth Bearrick More articles by this author , Daniel ChildsDaniel Childs More articles by this author , A. Tuba KendiA. Tuba Kendi More articles by this author , Matthew TollefsonMatthew Tollefson More articles by this author , Stephen BoorjianStephen Boorjian More articles by this author , R. Jeff KarnesR. Jeff Karnes More articles by this author , and Eugene KwonEugene Kwon More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003257.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recent studies, including a post-hoc analysis of the ARCHES trial, highlight radiographic disease progression (rDP) occurring without concordant rise in prostate specific antigen (PSA). In a previous study by our group, we reported that almost 40% of patients on 2nd generation hormone therapy experience rDP with non-rising PSA and have poor survival outcomes. The current analysis more specifically focuses on the subgroup of patients with rDP occurring at low PSA (<0.5 ng/dL) and describes factors associated with poorer survival outcomes in this patient population. METHODS: In a single institution study, we reviewed the prospectively maintained Mayo Clinic C-11 Choline PET registry for patients treated between 2011 and 2021, who experienced rDP at low PSA (value < 0.5 ng/mL). Disease progression on C-11 choline PET was confirmed by either tissue biopsy or subsequent response to therapy. We investigated factors associated with poor cancer-specific survival outcomes in univariable and multivariable cox regression analyses. RESULTS: In total, 220 (16%) patients experiencing rDP at low PSA were identified. Median (IQR) age at rDP was 67.91 (61.10 – 73.87) yrs., median (IQR) primary Gleason score was 9 (7-9), and median (IQR) PSA was 0.17 (0 – 0.32) ng/ml. 75% of the patients (n=166) had CRPC disease status at time of rDP. Prior systemic treatments included 2nd generation HT in 18% (n= 40) and chemotherapy in 31% (n=70). Sites of rDP were divided into 7% local (n=16), 42% lymph nodes (n=91), 43% bone (n=95), and 8% visceral metastases (n=18). Over a median follow-up duration of 55 months, 46% of patients (n=100) reported death. Factors associated with poor survival outcomes are demonstrated in table-1 and include age at rDP, CRPC status, and disease location (P-value <0.05). CONCLUSIONS: We found that radiographic disease progression commonly occurs at low PSA (<0.5 ng/mL). CRPC-disease status and the development of visceral metastases are associated with particularly poor survival outcomes. To identify early progression, monitoring with imaging may be warranted, even in the patients with low PSA. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e390 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohamed Ahmed More articles by this author Jack Andrews More articles by this author Ahmed Mahmoud More articles by this author Matthew Lee More articles by this author Elizabeth Bearrick More articles by this author Daniel Childs More articles by this author A. Tuba Kendi More articles by this author Matthew Tollefson More articles by this author Stephen Boorjian More articles by this author R. Jeff Karnes More articles by this author Eugene Kwon More articles by this author Expand All Advertisement PDF downloadLoading ...