scholarly journals Population-Based analysis for newly diagnosed hepatocellular carcinoma with brain metastases

2020 ◽  
Author(s):  
Jincheng Feng ◽  
Georgios Polychronidis ◽  
Ulrike Heger ◽  
Arianeb Mehrabi ◽  
Katrin Hoffmann
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bone Metastasis ◽  
Brain Metastases ◽  
Cox Regression ◽  
Population Based ◽  
Rank Test ◽  
Newly Diagnosed ◽  
Cancer Specific Survival ◽  
Factors Associated ◽  
Increased Risk

Abstract Background: There is little population-based data on hepatocellular carcinoma (HCC) with brain metastases at initial diagnosis published. This study aimed to estimate incidence of brain metastases in initial metastatic HCC and its impact on prognosis.Methods: Newly diagnosed HCC cases from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were screened for the presence of brain metastases. Data were stratified by age and ethnicity. Multivariable logistic and Cox regression were used to identify factors associated with brain metastases and factors associated with overall survival (OS) and cancer-specific survival (CSS), respectively. Kaplan-Meier method and log-rank test were used for survival analysis.Results: 141 cases presenting with brain metastases were identified, accounting for 0.35% of all HCC cases and 2.37% of cases with metastatic HCC disease. The incidence rate was highest among cases with age 50-59 (2.74%), respectively. Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis. However, African American patients presented significantly lower disease-specific survival (median time: 1month; interquartile range (IQR):0-3.0 months). Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases (odds ratio (OR) 12.62, 95%CI 8.40-18.97), but not associated with worse OS and CSS among brain metastases cases. Conclusions: The study shows population-based incidence and survival of brain metastases at diagnosis of HCC. Brain metastases are most prevalent in initial metastatic HCC patients with lung or bone metastasis. The results may contribute to consider screening of the brain among HCC with initial lung or bone metastasis.

scholarly journals Population-Based analysis for newly diagnosed hepatocellular carcinoma with brain metastases

2019 ◽  
Author(s):  
Jincheng Feng ◽  
Georgios Polychronidis ◽  
Ulrike Heger ◽  
Arianeb Mehrabi ◽  
Katrin Hoffmann
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bone Metastasis ◽  
Brain Metastases ◽  
Cox Regression ◽  
Population Based ◽  
Rank Test ◽  
Newly Diagnosed ◽  
Cancer Specific Survival ◽  
Factors Associated ◽  
Increased Risk

Abstract Background: There is little population-based data on hepatocellular carcinoma (HCC) with brain metastases at initial diagnosis published. This study aimed to estimate incidence of brain metastases in initial metastatic HCC and its impact on prognosis. Methods: Newly diagnosed HCC cases from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were screened for the presence of brain metastases. Data were stratified by age and ethnicity. Multivariable logistic and Cox regression were used to identify factors associated with brain metastases and factors associated with overall survival (OS) and cancer-specific survival (CSS), respectively. Kaplan-Meier method and log-rank test were used for survival analysis. Results : 141 cases presenting with brain metastases were identified, accounting for 0.35% of all HCC cases and 2.37% of cases with metastatic HCC disease. The incidence rate was highest among cases with age 50-59 (2.74%), respectively. Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis. However, African American patients presented significantly lower disease-specific survival (median time: 1month; interquartile range (IQR):0-3.0 months). Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases (odds ratio (OR) 12.62, 95%CI 8.40-18.97), but not associated with worse OS and CSS among brain metastases cases. Conclusions: The study shows population-based incidence and survival of brain metastases at diagnosis of HCC. Brain metastases are most prevalent in initial metastatic HCC patients with lung or bone metastasis. The results may contribute to consider screening of the brain among HCC with initial lung or bone metastasis.

scholarly journals Elevated Expression of Glycerol-3-Phosphate Phosphatase as a Biomarker of Poor Prognosis and Aggressive Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1273
Author(s):  
Mohamed Amine Lounis ◽  
Veronique Ouellet ◽  
Benjamin Péant ◽  
Christine Caron ◽  
Zhenhong Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Biochemical Recurrence ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Specific Antigen ◽  
Metabolic Stress ◽  
Cancer Specific Survival ◽  
High Risk Prostate Cancer ◽  
Increased Risk

The limitations of the biomarker prostate-specific antigen (PSA) necessitate the pursuit of biomarkers capable of better identifying high-risk prostate cancer (PC) patients in order to improve their therapeutic management and outcomes. Aggressive prostate tumors characteristically exhibit high rates of glycolysis and lipogenesis. Glycerol 3-phosphate phosphatase (G3PP), also known as phosphoglycolate phosphatase (PGP), is a recently identified mammalian enzyme, shown to play a role in the regulation of glucose metabolism, lipogenesis, lipolysis, and cellular nutrient-excess detoxification. We hypothesized that G3PP may relieve metabolic stress in cancer cells and assessed the association of its expression with PC patient prognosis. Using immunohistochemical staining, we assessed the epithelial expression of G3PP in two different radical prostatectomy (RP) cohorts with a total of 1797 patients, for whom information on biochemical recurrence (BCR), metastasis, and mortality was available. The association between biomarker expression, biochemical recurrence (BCR), bone metastasis, and prostate cancer-specific survival was established using log-rank and multivariable Cox regression analyses. High expression of G3PP in PC epithelial cells is associated with an increased risk of BCR, bone metastasis, and PC-specific mortality. Multivariate analysis revealed high G3PP expression in tumors as an independent predictor of BCR and bone metastasis development. High G3PP expression in tumors from patients eligible for prostatectomies is a new and independent prognostic biomarker of poor prognosis and aggressive PC for recurrence, bone metastasis, and mortality.

scholarly journals Impact of pre-existing cardiovascular disease on treatment patterns and survival outcomes in patients with lung cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Atul Batra ◽  
Dropen Sheka ◽  
Shiying Kong ◽  
Winson Y. Cheung
Keyword(s):  
Lung Cancer ◽  
Cardiovascular Disease ◽  
Cox Regression ◽  
Population Based ◽  
Treatment Patterns ◽  
Competing Risk ◽  
Survival Outcomes ◽  
Multistate Model ◽  
Cancer Specific Survival ◽  
Increased Risk

Abstract Background Baseline cardiovascular disease (CVD) can impact the patterns of treatment and hence the outcomes of patients with lung cancer. This study aimed to characterize treatment trends and survival outcomes of patients with pre-existing CVD prior to their diagnosis of lung cancer. Methods We conducted a retrospective, population-based cohort study of patients with lung cancer diagnosed from 2004 to 2015 in a large Canadian province. Multivariable logistic regression and Cox regression models were constructed to determine the associations between CVD and treatment patterns, and its impact on overall (OS) and cancer-specific survival (CSS), respectively. A competing risk multistate model was developed to determine the excess mortality risk of patients with pre-existing CVD. Results A total of 20,689 patients with lung cancer were eligible for the current analysis. Men comprised 55%, and the median age at diagnosis was 70 years. One-third had at least one CVD, with the most common being congestive heart failure in 15% of patients. Pre-existing CVD was associated with a lower likelihood of receiving chemotherapy (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.48–0.58; P < .0001), radiotherapy (OR, 0.76; 95% CI, 0.7–0.82; P < .0001), and surgery (OR, 0.56; 95% CI, 0.44–0.7; P < .0001). Adjusting for measured confounders, the presence of pre-existing CVD predicted for inferior OS (hazard ratio [HR], 1.1; 95% CI, 1.1–1.2; P < .0001) and CSS (HR, 1.1; 95% CI, 1.1–1.1; P < .0001). However, in the competing risk multistate model that adjusted for baseline characteristics, prior CVD was associated with increased risk of non-cancer related death (HR, 1.48; 95% CI, 1.33–1.64; P < 0.0001) but not cancer related death (HR, 0.98; 95% CI, 0.94–1.03; P = 0.460). Conclusions Patients with lung cancer and pre-existing CVD are less likely to receive any modality of cancer treatment and are at a higher risk of non-cancer related deaths. As effective therapies such as immuno-oncology drugs are introduced, early cardio-oncology consultation may optimize management of lung cancer.

scholarly journals Liver Metastases in Newly Diagnosed Pancreatic Ductal Adenocarcinoma: A Population Based Analysis

2020 ◽  
Author(s):  
Guoyi Wu ◽  
Xiaoben Pan ◽  
Baohua Wang ◽  
Xiaolei Zhu ◽  
Jing Wu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Metastases ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Size ◽  
Cox Regression ◽  
Population Based ◽  
The Body ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Factors Associated

Abstract Background Estimates of the incidence and prognosis of developing liver metastases at the pancreatic ductal adenocarcinoma (PDAC) diagnosis are lacking.Methods In this study, we analyzed the association of liver metastases and the PDAC patients outcome. The risk factors associated with liver metastases in PDAC patients were analyzed using multivariable logistic regression analysis. The overall survival (OS) was estimated using Kaplan-Meier curves and log-rank test. Cox regression was performed to identify factors associated with OS.Results Patients with primary PDAC in the tail of the pancreas had a higher incidence of liver metastases (62.2%) than those with PDAC in the head (28.6%). Female gender, younger age, primary PDAC in the body or tail of the pancreas, and larger primary PDAC tumor size were positively associated with the occurrence of liver metastases. The median survival of patients with liver metastases was significantly shorter than that of patients without liver metastases. Older age, unmarried status, primary PDAC in the tail of the pancreas, and tumor size ≥4 cm were risk factors for OS in the liver metastases cohort.Conclusions Population-based estimates of the incidence and prognosis of PDAC with liver metastases may help decide whether diffusion-weighted magnetic resonance imaging should be performed in patients with primary PDAC in the tail or body of the pancreas. The location of primary PDAC should be considered during the diagnosis and treatment of primary PDAC.

scholarly journals Survival and prognostic factor analyses in malignant giant cell tumour of bone

2020 ◽  
Author(s):  
Jin Zhang ◽  
Xin Wang ◽  
Feng Lin ◽  
Guijun Xu ◽  
Haixiao Wu ◽  
...  
Keyword(s):  
Giant Cell ◽  
Cox Regression ◽  
Giant Cell Tumour ◽  
Large Population ◽  
Survival Rates ◽  
Population Based ◽  
Cell Tumour ◽  
Rank Test ◽  
Seer Database ◽  
Increased Risk

Abstract Background: The characteristics and survival of patients with malignant giant cell tumour of bone (GCTB) have not been investigated thoroughly due to the rarity of the disease. We evaluated these factors in a large cohort in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database.Methods: Data from patients who were diagnosed with malignant GCTB from 1975 to 2016 were extracted from the SEER database. The overall survival (OS) was calculated by Kaplan–Meier analysis, and intergroup differences were tested by the log-rank test. Univariate and multivariate Cox proportional hazard regression analyses were conducted to identify the independent survival factors.Results: A total of 325 patients with malignant GCTB were included. The overall 1-, 5-, and 10-year survival rates were 94.3% (95% CI: 91.7-96.8), 82.3% (95% CI: 77.9-86.6), and 80.1% (95% CI: 75.4-84.7), respectively. A potential non-linear J-shaped dose–response relationship between the age or diagnosis year and survival were found. Multivariate Cox regression showed poor survival in patients with age from 35 to 60 years (hazard ratio (HR) =9.99, 95% CI: 1.34-74.80, P=0.025), age older than 60 years (HR=62.03, 95% CI: 7.94-484.38, P<0.001), with stage T2 disease (HR=4.85, 95% CI: 1.52-15.47, P=0.008), with stage T3 disease (HR=6.09, 95% CI: 1.03-36.23, P=0.047), and with distant tumours (HR=2.76, 95% CI: 1.14-6.65, P=0.024), and extraskeletal sites (HR=3.33, 95% CI: 1.02-10.85, P=0.046).Conclusions: This large population-based series described the clinical characteristics of malignant GCTB. Patients with stage T2/3disease, distant disease and extra-skeletal sites had more odds to be with worse survival. The elder age than 34 years had a gradually increased risk for survival.

Adverse Prognostic Factors for Testicular Cancer–Specific Survival: A Population-Based Study of 27,948 Patients

2011 ◽  
Vol 29 (8) ◽  
pp. 963-970 ◽  
Author(s):  
Sophie D. Fosså ◽  
Milada Cvancarova ◽  
Linlin Chen ◽  
Annie L. Allan ◽  
Jan Oldenburg ◽  
...  
Keyword(s):  
Testicular Cancer ◽  
Marital Status ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Fold Increase ◽  
Population Based ◽  
Retroperitoneal Lymph Node Dissection ◽  
Cancer Specific Survival ◽  
Increased Risk ◽  
Specific Mortality

Purpose The prognostic significance of age at testicular cancer (TC) diagnosis, socioeconomic status (SES), race, and marital status on TC-specific mortality is not well-characterized. In a cancer that is so curable, it is important to identify any influence that confers an increased risk of TC-specific mortality. Patients and Methods Using multivariate cause-specific Cox regression models that accounted for competing risks, hazard ratios (HRs) were calculated for 10-year TC-specific mortality among 27,948 patients with TC reported to the Surveillance, Epidemiology and End Results program (1978 to 2006). Independent predictors were age at diagnosis, SES, race, marital status, extent of disease (EOD), calendar year of diagnosis, radiotherapy, and retroperitoneal lymph node dissection (RPLND). Results Compared with younger patients, diagnostic age 40+ was associated with increased mortality (seminoma, HR, 2.00, P < .001; nonseminoma, HR, 2.09; P < .001; most evident in metastatic disease, HR, 8.62; P < .001; HR, 6.35; P < .001, respectively). Unmarried men had two-to three-fold excess mortality compared to married men (HR, 2.97; P < .001; HR, 1.54; P < .001, respectively). Among nonseminoma patients, decreasing SES (P trend < .001) and nonwhite race (HR, 2.11; P < .001) increased mortality. Diagnosis after 1987 resulted in reduced mortality compared to earlier calendar years (HR, 0.58; P = .001; HR, 0.74; P = .001, respectively). Lack of RPLND was associated with seven-fold increase in death (P < .001). Conclusion TC-specific mortality is doubled among US patients diagnosed with seminoma or nonseminoma after age 40, even when initial treatment and EOD are taken into account. Among men with nonseminoma, nonwhite race and lower SES also significantly increase TC-specific mortality. Additional research is needed, enabling the development of interventional strategies and preventive approaches, as applicable.

Maternal Hypothyroidism during Pregnancy and the Risk of Pediatric Endocrine Morbidity in the Offspring

2018 ◽  
Vol 36 (09) ◽  
pp. 975-980 ◽  
Author(s):  
Tamar Eshkoli ◽  
Tamar Wainstock ◽  
Eyal Sheiner ◽  
Ofer Beharier ◽  
Merav Fraenkel ◽  
...  
Keyword(s):  
Cox Regression ◽  
Survival Curve ◽  
Mode Of Delivery ◽  
Cumulative Risk ◽  
Maternal Diabetes ◽  
Population Based ◽  
Rank Test ◽  
Increased Risk

Objective Previous studies suggested maternal hypothyroidism during pregnancy to be associated with cognitive impairment of the offspring. Scarce data exist regarding long-term endocrine health of the offspring. This study was aimed to assess whether children born to mothers with hypothyroidism during pregnancy are at an increased risk for long-term endocrine morbidity. Study Design A retrospective population-based cohort study compared long-term endocrine morbidity of children born between the years 1991 and 2014 to mothers with and without hypothyroidism. Multiple gestations, fetuses with congenital malformations, and women lacking prenatal care were excluded. Hospitalizations of the offspring up to the age of 18 years involving endocrine morbidity were evaluated according to a predefined set of ICD-9 codes. Kaplan–Meier's survival curves were used to compare the cumulative risk and a Cox multivariable model was used to adjust for confounders. Results During the study period, 217,910 deliveries met the inclusion criteria; 1.1% of which were with maternal hypothyroidism (n = 2,403). During the follow-up period, the cumulative incidence of endocrine morbidity among children born to mothers with hypothyroidism was 27 per 1,000 person-years and 0.47 per 1,000 person-years in the comparison group (relative risk: 2.14; 95% confidence interval [CI]: 1.21–3.79). The Kaplan–Meier's survival curve demonstrated a significantly higher cumulative endocrine morbidity in children born to mothers with hypothyroidism (log-rank test, p = 0.007). In the Cox regression model controlled for maternal age, birth weight, preterm birth, maternal diabetes, hypertensive disorders of pregnancy, induction of labor, and mode of delivery, maternal hypothyroidism was found to be independently associated with pediatric endocrine morbidity in the offspring (adjusted hazard ratio = 1.92, 95% CI: 1.08–3.4, p = 0.025). Conclusion Maternal hypothyroidism appears to be independently associated with long-term pediatric endocrine morbidity of the offspring.

scholarly journals CMET-39. DISPARITIES IN STEREOTACTIC RADIOSURGERY USE AND OUTCOMES FOR MELANOMA BRAIN METASTASES – AN AUSTRALIAN POPULATION-BASED STUDY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi60-vi60
Author(s):  
Wee Loon Ong ◽  
Morikatsu Wada ◽  
Farshad Foroudi
Keyword(s):  
Logistic Regression ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Cox Regression ◽  
Population Based ◽  
Mortality Data ◽  
Multivariate Logistic Regression ◽  
Factors Associated ◽  
Significant Difference ◽  
Melanoma Brain Metastases

Abstract INTRODUCTION We aim to evaluate the use of stereotactic radiosurgery (SRS) among patients who received radiotherapy for melanoma brain metastases (MBM), and the associated outcomes. METHODS This is a population-based cohort of patients who received radiotherapy for MBM between 2013 and 2016, as captured in the Victorian Radiotherapy Minimum Dataset. Brain radiotherapy was classified as SRS (including multi-fraction stereotactic radiotherapy) and non-SRS. Mortality data was obtained through linkage with the Victorian Cancer Registry. The primary outcomes were: proportion of patients who had SRS for MBM, and overall survival (OS) following radiotherapy. Multivariate logistic regression was used to evaluate factors associated with SRS use, Kaplan Meier method for estimation of OS, and multivariate Cox regression for evaluation of factors associated with OS. RESULTS 294 patients received 551 courses of radiotherapy for MBM in this study, of which 39% (116/294) patients received SRS. Patients from higher socioeconomic status were more likely to have SRS – 49% in top quintile vs. 22% in lowest quintile (P< 0.009). Patients treated in regional centres were less likely to have SRS compared to metropolitan centres (3% vs. 48%,P< 0.001). In multivariate logistic regression, treatment in regional centres was the only factor independently associated with lower likelihood of receiving SRS (OR=0.04;95%CI=0.01–0.18;P< 0.001). The median follow-up of the cohort was 3.8 months (range: 0.1–42 months). There were 227 death observed, with 12-month OS of 23%. There was significant difference in 12-month OS between patients who received SRS compared to those who did not receive SRS (43% vs. 11%; P< 0.001). In multivariate Cox regression, the use of SRS was the only factor independently associated with OS (HR=0.38;95%CI=0.28–0.51;P< 0.001). CONCLUSION We observed sociodemographic and institutional disparities in SRS use for MBM. The observed impact of SRS use on OS is most likely confounded by patient selections for SRS.

scholarly journals CMET-42. USE OF STEREOTACTIC RADIOSURGERY AND OUTCOMES FOLLOWING RADIOTHERAPY FOR BRAIN METASTASES IN PATIENTS WITH PRIMARY LUNG CANCER – AN AUSTRALIAN POPULATION-BASED STUDY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi60-vi61
Author(s):  
Wee Loon Ong ◽  
Morikatsu Wada ◽  
Farshad Foroudi
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Cox Regression ◽  
Primary Lung Cancer ◽  
Population Based ◽  
Mortality Data ◽  
Factors Associated ◽  
Geographical Variations ◽  
The Impact

Abstract INTRODUCTION We aim to evaluate the use of stereotactic radiosurgery (SRS) among lung cancer (LC) patients who received radiotherapy (RT) for brain metastases (BM), and the associated outcomes. METHODS This is a population-based cohort of LC patients who received RT for BM between 2013 and 2016, as captured in the Victorian Radiotherapy Minimum Dataset. Brain RT was classified as SRS (including multi-fraction stereotactic RT) and non-SRS. Mortality data was captured through data linkage with the Victorian Cancer Registry (VCR). The primary outcomes were: proportion of patients who had SRS for BM, and overall survival (OS) following brain RT. Multivariable logistic regression was used to evaluate factors associated with SRS use. Kaplan-Meier method was used to estimate OS. Multivariable Cox regression was used to evaluate factors associated with OS. RESULTS 1,002 LC patients were included in the study. 1,395 courses of RT for BM were delivered, of which one quarter (362/1,395) were SRS. Almost all SRS were delivered in metropolitan centres (347/362), and two-third in public institutions (235/362). In multivariate logistic regressions, increasing age (OR=0.91;95%CI=0.82–0.99;P=0.04) and treatment in regional centres (OR=0.13;95%CI=0.06–0.28;P< 0.001) were independently associated with lower likelihood of SRS use. Median follow-up was 3.3 months (IQR=1.3–7.8 months). 876 deaths were observed with 12-month OS of 16%. The 12-month OS for patients who had SRS were 38% vs. 12% in patient did not have SRS (P< 0.001). In multivariable Cox regressions, the use of SRS (HR=0.44,95%CI=0.37–0.54;P< 0.001) and female (HR=0.76;95%CI=0.67–0.87;P< 0.001) were associated with improved OS, while increasing age was associated with worse OS (HR=1.02;95%CI=1.01–1.03;P< 0.001). CONCLUSION This is the largest Australian study reporting on SRS use for BM in LC patients. We observed geographical variations in SRS use. We believe the impact of SRS use on OS is most likely due to patient selection for SRS.

scholarly journals Prognostic Impact of Different Gleason Patterns on Biopsy Within Grade Group 4 Prostate Cancer

2021 ◽  
Author(s):  
Keiichiro Mori ◽  
Vidit Sharma ◽  
Eva M. Comperat ◽  
Shun Sato ◽  
Ekaterina Laukhtina ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Rank Test ◽  
Prognostic Impact ◽  
Grade Group ◽  
Cancer Specific Survival ◽  
Kaplan Meier ◽  
Pathologic Features ◽  
Increased Risk

Abstract Background Grade group (GG) 4 prostate cancer (PC) is considered a single entity; however, there are questions regarding prognostic heterogeneity. This study assessed the prognostic differences among various Gleason scores (GSs) classified as GG 4 PC on biopsy before radical prostatectomy (RP). Methods We conducted a multicenter retrospective study, and a total of 1791 patients (GS 3 + 5: 190; GS 4 + 4: 1557; and GS 5 + 3: 44) with biopsy GG 4 were included for analysis. Biochemical recurrence (BCR)-free survival, cancer-specific survival, and overall survival were analyzed using the Kaplan–Meier method and the log-rank test. Logistic regression analysis was performed to identify factors associated with high-risk surgical pathologic features. Cox regression models were used to analyze time-dependent oncologic endpoints. Results Over a median follow-up of 75 months, 750 patients (41.9%) experienced BCR, 146 (8.2%) died of any causes, and 57 (3.2%) died of PC. Biopsy GS 5 + 3 was associated with significantly higher rates of GS upgrading in RP specimens than GS 3 + 5 and GS 4 + 4. On multivariable analysis adjusted for clinicopathologic features, different GSs within GG 4 were significantly associated with BCR (p = 0.03) but not PC-specific or all-cause mortality. Study limitations include the lack of central pathological specimen evaluation. Conclusions Patients with GG 4 at biopsy exhibited some limited biological and clinical heterogeneity. Specifically, GS 5 + 3 had an increased risk of GS upgrading. This can help individualize patients’ counseling and encourage further study to refine biopsy specimen-based GG classification.

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