bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between percentage of positive biopsy cores and risk of pelvic lymph node involvement in prostate cancer.
Authors: Yang David Dewei , Dee Edward Christopher , Arega Melaku A , Nguyen Paul L. , Orio Peter F. , King Martin T. , Kann Benjamin Harris , Yu James B. , Cook Kiri , Ma Ting Martin , Kishan Amar Upadhyaya , Muralidhar Vinayak 
Published: March 2021

205 Background: Commonly used tools for predicting the risk of pelvic lymph node involvement (LNI) in prostate cancer often do not incorporate information on the percentage of positive biopsy cores (PPB). To better inform the use of elective nodal irradiation in the definitive treatment of prostate cancer, we examined the association between PPB and risk of pathologic pelvic LNI in men with prostate cancer who underwent radical prostatectomy (RP). Methods: We identified 109,577 men from the National Cancer Database who were diagnosed in 2010-2015 with cN0M0 prostate cancer, had 6-24 cores sampled at biopsy, and underwent RP with pathologic nodal evaluation. Multivariable logistic regression was used to examine the association between PPB and the likelihood of having ≥1 positive pelvic lymph node, adjusting for other known clinicopathologic prognostic variables. Results: Overall, 4.0% (4,340) of the cohort was found to have pelvic LNI at the time of RP. Higher PPB was associated with an increased risk of pelvic LNI (adjusted odds ratio [AOR] 1.75 for 25.1-50.0% PPB, 2.63 for 50.1-75.0% PPB, and 4.49 for 75.1-100.0% PPB vs. ≤25.0% PPB, all P<0.001). Notably, men with Gleason 8 disease and ≤25.0% PPB only had a 3.6% risk of pelvic LNI, whereas men with Gleason 9-10 disease and 75.1-100.0% PPB had a 32.6% risk (Table). Other factors associated with the likelihood of pelvic LNI included a higher biopsy Gleason score (AOR 1.43 for Gleason 8 and 2.84 for Gleason 9-10 vs. Gleason 4+3, both P<0.001), more advanced clinical tumor stage (AOR 1.48 for cT2, 1.97 for cT3, and 3.87 for cT4 vs. cT1, all P<0.001), and a higher PSA (AOR 1.90 for 10.0-19.9 ng/mL, 2.40 for 20.0-39.9 ng/mL, and 2.60 for ≥40.0 ng/mL vs. <10.0 ng/mL, all P<0.001), but not more advanced age (AOR 0.98 for >62 years [median] vs. ≤62 years, P=0.59) or black vs. white race (AOR 0.99, P=0.92). Conclusions: There was a statistically significant and clinically relevant association between increasing PPB and a higher risk of pelvic LNI. As the ongoing RTOG 0924 randomized trial matures, clinicians should consider incorporating information on PPB in determining which patients with prostate cancer may benefit from receiving radiation therapy to the pelvic lymph nodes. [Table: see text]
Treatment decisions and outcomes for NCCN favorable intermediate-risk prostate cancer patients after receiving the 17-gene genomic prostate cancer score result.
Authors: Margolis Eric , Bennett John , Pavlova Marina , Wong Kenny , Pieczonka Christopher Michael , Lowentritt Benjamin H. , Uchio Edward M. , Stoppler Melissa Conrad 
Published: March 2021

218 Background: Molecular assays are used to improve risk stratification in prostate cancer. This study determined how the 17-gene Genomic Prostate Score (GPS) assay guides treatment decisions in patients with NCCN favorable intermediate-risk prostate cancer. Methods: This retrospective study included 324 patients from 7 urology practices in the United States. All patients had NCCN favorable intermediate-risk prostate cancer, defined as <50% positive biopsy cores and only one of the following risk factors: grade group 2 (Gleason Score 3+4), clinical stage T2b-T2c, or PSA 10-20 ng/mL. All patients also had a GPS assay report dated May 2017 to April 2019. The GPS assay allows risk stratification into post-GPS very low-, low-, favorable intermediate-, unfavorable intermediate-, and high-risk groups, with higher GPS scores representing increased risk. Data were collected from patients' charts/electronic health records. The proportion of patients who selected active surveillance (AS) over immediate definitive treatment and AS, monotherapy, or multimodal therapy was calculated with 95% confidence intervals (CI) using the Clopper-Pearson method. Results: Patients comprised 79% with Gleason Score 3+4, 19% with PSA 10-20 ng/mL, and 2% with clinical stage T2b; median GPS result was 26. Post-GPS risk groups were 0%, 16%, 11%, 57%, and 16% very low-, low-, favorable intermediate-, unfavorable intermediate-, and high-risk groups respectively. Overall, 31% (95% CI 26%, 36%) of patients selected active surveillance (AS), with rate declining as post-GPS risk increased: 57% (95% CI 42%, 71%) selected AS in the post-GPS low-risk, 51% (95% CI 34%, 69%) in the post-GPS favorable intermediate-risk, 26% (95% CI 20%, 33%) in the post-GPS unfavorable intermediate-risk, and 6% (95% CI 1%, 16%) in the post-GPS high-risk group. Post-GPS unfavorable intermediate/high risk-patients were more likely to receive monotherapy than low/favorable intermediate-risk patients (high, 72%; unfavorable intermediate, 64%; favorable intermediate, 37%; and low, 37%); high-risk patients were more likely to receive multimodal therapy (high, 23%; unfavorable intermediate, 10%; favorable intermediate, 11%; and low, 6%). Median follow-up time was 18 months, and one prostate cancer-related metastasis and 2 deaths (neither prostate cancer-related) were reported. Complications (erectile dysfunction, urinary/bowel incontinence) were more common in treated than AS patients. AS persistence was 91% (95% CI 82%, 95%) at 12 months; patients discontinued AS due to disease progression (61%) or patient preference/unknown reasons (39%). Conclusions: The GPS result is associated with selection of AS and treatment intensity in this first examination of genomic classifiers in a cohort of prostate cancer patients with NCCN favorable intermediate-risk.
Adverse pathology as a predictor of distant metastasis and prostate cancer mortality with 20-year follow up.
Authors: Brooks Michael Austin , Thomas Lewis , Magi-Galluzi Cristina , Li Jianbo , Crager Michael , Lu Ruixiao , Abran John , Aboushwareb Tamer , Klein Eric A. 
Published: March 2021

219 Background: Adverse pathology (AP) at radical prostatectomy (RP) is often used as a proxy for long-term prostate cancer outcomes. The goal of this study was to assess the association of AP at RP, defined as high-grade (> Grade Group 3) and/or non-organ confined disease (pT3), with distant metastasis and prostate cancer death. Methods: A stratified cohort sample of 428 patients was used to evaluate the association of adverse pathology with the risk of distant metastases and prostate cancer-specific mortality over 20 years after prostatectomy in 2641 patients treated between 1987-2004. Cox regression of cause-specific hazards was used to estimate the absolute risk of both endpoints, with death from other causes treated as a competing risk. Subgroup analysis in patients with low/intermediate risk disease potentially eligible for active surveillance was performed. Results: Among the 428 patients, 343 had AUA Low or Intermediate risk disease and 85 had High risk disease. Median follow-up time was 15.5 years (IQR 14.6–16.6 years). Using the cohort sampling weights for estimation, at RP 29.8% of patients had high-grade disease, 42.3 % had non-organ confined disease, 19.3% had both, and thus 52.8% had AP. Adverse pathology was highly associated with metastasis and prostate cancer mortality in the overall cohort (HR 12.30, 95% CI 5.30-28.55, and 10.03, 95% CI 3.42-29.47, respectively, both p<0.001), and in the low/intermediate risk subgroup potentially eligible for active surveillance (HR 10.48, 95% CI 4.18-26.28, and 8.60, 95% CI 2.40-30.84, respectively, both p≤0.001). Conclusions: Adverse pathology at radical prostatectomy is highly associated with future development of metastasis and prostate cancer mortality and may be used as a short-term predictor of outcomes. [Table: see text]
Effectiveness of early diagnosis for prostate cancer based on PSA and multiparametric MRI: A simulation study.
Authors: Timsit Marc-Olivier , Baciarello Giulia , Hennequin Christophe , Kleinclauss Francois , Bazil Marie Laure , Bonnard Philippe , Pettre Segolene , Martin Blachier , Leleu Henri 
Published: March 2021

224 Background: Multiparametric magnetic resonance imaging (mpMRI) detects ISUP grade≥ 2 prostate cancer (PC) with a sensitivity over 90%. mpMRI can be used for early detection in patients with a risk of clinically significant PC (csPC) either in combination with systematic biopsy (SB) to increase the detection rate of csPC, or to reduce the number of biopsy procedures by performing biopsies only in positive mpMRI patients. Methods: We estimated the numbers of PC diagnosed, PC deaths averted, and biopsy procedures performed with early diagnosis in a simulated population of men beginning at age 50 using a microsimulation model. The model simulates the natural history of PC and the impact of early diagnosis using epidemiological data from a systematic review of literature. Early diagnosis started at age 55 years, with a PSA threshold of 4 ng/mL. The strategies included (S1) SB alone, (S2) SB combined with mpMRI-targeted biopsy (SB/mpMRI-TB), and (S3) SB/mpMRI-TB following selection of patients based on positive mpMRI (PIRAD3-5) or PSA density (PSAd) < 0.15. A sensitivity of 0.92 and specificity of 0.48 for detecting ISUP grade ≥ 2 PC was used for mpMRI. Results: Compared to no early diagnosis, early diagnosis with SB alone (S1) was estimated to avoid 647 PC-related deaths per 100,000 men over their lifetimes. Using mpMRI was estimated to result in an additional 126 and 118 fewer deaths per 100,000 if mpMRI was used in conjunction with SB (S2) or with SB following patient selection for biopsy by mpMRI or PSAd (S3). To avoid a PC-related death was estimated to require screening of 145 men with SB alone, 121 with SB/mpMRI-TB, and 122 with mpMRI or PSAd followed by SB/mpMRI-TB. Adding mpMRI to SB was also found to reduce the predicted number of biopsies performed (21,821 for SB alone versus 16,510 for SB/mpMRI-TB and 15,385 for SB/mpMRI-TB following selection with mpMRI or PSAd). Conclusions: The results indicate that using mpMRI as a detection method will improve the effectiveness of early diagnosis. Compared to SB alone, using mpMRI through the SB/mpMRI-TB approach, with or without prior patient selection based on mpMRI or PSAd assessments, would result in a reduction in PC-related mortality and in the number of biopsies performed. [Table: see text]
Impact of 5-ALPHA reductase inhibitor use on prostate cancer risk at the time of urology referral.
Authors: Kearns James T , Matulay Justin T. , Anderson William E. , Hetherington Timothy C. , Grigg Claud , Zhu Jason , Gaston Kris E. , Riggs Stephen Boyd , Burgess Earle F , Clark Peter E 
Published: March 2021

226 Background: 5-alpha reductase inhibitors (5-ARIs) are commonly used medications for the treatment of lower urinary tract symptoms caused by benign prostatic hyperplasia. One of the consequences of 5-ARI use is a 50% drop in serum PSA without a concomitant reduction in prostate cancer (PCa) risk. Previous work has suggested that 5-ARI use is associated with worse PCa-specific outcomes. The objective of this study was to evaluate the impact of 5-ARI use on patients’ PCa risk at the time of referral from primary care to urology. Methods: This retrospective cohort study included all men ≥ 40 years who had a PSA resulted between 2018-2019 and were seen in an ambulatory setting. PSA testing was determined through laboratory data in the electronic health record (EHR). Clinical and demographic data were collected for all men. 5-ARI use was determined through orders in the EHR. Men were assigned PCa risk according to both the Prostate Biopsy Collaborative Group (PBCG) and Prostate Cancer Prevention Trial (PCPT) risk calculators. PSA values were doubled for 5-ARI users prior to calculating risk. Referral to urology for PCa risk was determined using the narrative reason for referral associated with the referral order. Results: Between 2018-2019, 91,368 men had a PSA test, including 2,939 5-ARI users, and 88,429 non-users. Uncorrected median PSA and the proportion of men referred to urology for PCa risk were similar between the two groups (p = 0.60 and p = 0.17, respectively). Of men referred to urology for PCa risk, 5-ARI users had similar uncorrected PSA to non-users (p=0.86) but higher risk for high grade PCa once PSA correction was performed, median (IQR) 48% (24%) vs 28% (18%) using the PBCG and 21% (17%) vs 10% (10%) using the PCPT (p < 0.01 for both) (Table). Conclusions: Men taking 5-ARIs have significantly higher risk for high-grade PCa at time of referral to urology than non-users in this cohort. As the unadjusted PSA at referral to urology for PCa risk was the same between 5-ARI users and non-users, this indicates that the effect of 5-ARI use on serum PSA levels is not routinely accounted for when assessing PCa risk. Further study on interventions to account for 5-ARI use when screening for PCa are warranted. [Table: see text]
Real-world prevalence of homologous recombination repair gene (BRCA1/2 and ATM) mutations (HRRm) in patients (pts) with advanced prostate cancer (aPC) as detected by comprehensive genomic profiling (CGP) of circulating cell-free DNA (cfDNA).
Authors: Sayegh Nicolas , Swami Umang , Barata Pedro C. , Lilly Michael B. , Nussenzveig Roberto , Hensel Chuck , Bryce Alan Haruo , Bilen Mehmet Asim , Heath Elisabeth I. , Nandagopal Lakshminarayanan , Garje Rohan , Saylor Philip James , Babiker Hani M. , Vaena Daniel A. , Kohli Manish , Pal Sumanta K. , Sartor A. Oliver , Agarwal Neeraj 
Published: March 2021

256 Background: PARP inhibitors, olaparib and rucaparib recently improved survival outcomes (in the Profound and Triton-2 trials) in pts with aPC harboring HRRm. Notably, ~35% of pts screened for the PROfound trial did not meet eligibility solely due to the lack of adequate quality/quantity of tumor tissue required for CGP (De Bono, NEJM, 2020). cfDNA analysis non-invasively assesses tumor-derived genomic alterations. We evaluated the prevalence of HRRm in a real-world aPC population, who had commercially available cfDNA assay results available. Methods: cfDNA based CGP (using a clinically-validated 73- to 74-gene panel i.e. Guardant360 or G360) from consecutive aPC pts between 11/2016–8/2020 were used for detection of HRRm. Frameshift and nonsense mutations were included as pathogenic. Variants of unknown significance were excluded. In this unmatched study, the prevalence of each HRRm was compared with those reported in literature using the chi square test. Results: cfDNA CGP from 7701 aPC pts were available for interrogation of BRCA1/BRCA2 mutations, & from 4671 aPC pts for ATM mutations. Prevalence of BRCA1 and 2 as detected by cfDNA was similar to historical CGP of primary tissue. Prevalence of BRCA1 was higher than historical CGP of metastatic tissue. Prevalence of ATM in cfDNA was higher than historic tumor tissue CGP but similar to prior reports from cfDNA testing (Table). Conclusions: In this large real-world population of pts with aPC undergoing routine cfDNA CGP by a CLIA certified lab, prevalence of HRRm was similar (or higher for BRCA1 and ATM) to what has been previously reported from the tumor tissue. These data provide the rationale for utilizing cfDNA CGP as a routine test for detection of HRRm in men with aPC to identify men who are candidates for PARPi. [Table: see text]
Lower risk of prostate cancer in patients with sedentary occupations presenting for a prostate biopsy: Analysis of a Veterans Affairs cohort.
Authors: Khadir Rimaz M. , Sayyid Rashid K. , Terris Martha K. 
Published: March 2021

257 Background: Sedentary behavior has been associated with increased serum prostate-specific antigen (PSA) levels. It is currently unknown whether this correlates with an increased risk of underlying prostate cancer (PCa). Our objective was to determine whether patients with sedentary occupations presenting for a prostate biopsy were at increased risk of PCa diagnosis. Methods: A prospectively collected registry of patients undergoing a prostate biopsy between July 1995 and June 2016 at the Veterans Affairs Medical Center in Augusta, GA was utilized. The occupation was classified as sedentary if it was associated with prolonged periods of sitting (i.e. >50% work hours). This was determined via patient reported history at time of biopsy. The associations between a sedentary lifestyle and risk of a positive prostate biopsy, high grade cancer (i.e. Gleason score 8 or higher), and high volume cancer (i.e. at least 50% of total cores were positive) were evaluated using multivariable logistic regression analyses, controlling for age, race, body mass index, PSA level, free PSA ratio, clinical stage, prostate volume, and family history of prostate cancer. Statistical significance was set at p<0.05. All statistical analyses were performed using R version 3.6.1. Results: Our cohort included 1,914 patients. 271 (14.2%) patients had sedentary jobs. Median patient age was 61.0 years (Interquartile range [IQR] 57.0 – 66.0). Median PSA at time of biopsy was 5.7 ng/ml (IQR 4.4 – 8.2). Of the 1,914 initial biopsies performed, 974 (50.9%) were positive for malignancy. Of patients diagnosed with PCa, 229 (23.5%) had high-grade disease and 316 (32.4%) had high volume disease. On multivariable analysis, patients with a sedentary job had a significantly decreased risk of PCa diagnosis (Odds ratio [OR] 0.43, 95% confidence interval [CI] 0.18-1.03, p= 0.058), but no difference in odds of high grade (OR 0.63, 95% CI 0.089-2.99, p= 0.60) or high volume disease (OR 1.07, 95% CI 0.93-1.21, p= 0.89). Conclusions: Patients with sedentary occupations presenting for a prostate biopsy are at a lower apparent risk for a positive prostate biopsy. These results suggest that the serum PSA levels in such patients may be artificially elevated secondary to increased recumbence with no corresponding increase in risk of malignancy. [Table: see text]
Effectiveness of first-line immune checkpoint inhibitors (ICI) in advanced non-clear cell renal cell carcinoma (ccRCC).
Authors: Graham Jeffrey , Wells Connor , Dudani Shaan , Gan Chun Loo , Donskov Frede , Lee Jae-Lyun , Kollmannsberger Christian K. , Pal Sumanta K. , Beuselinck Benoit , Hansen Aaron Richard , North Scott A. , Bjarnason Georg A. , Agarwal Neeraj , Kanesvaran Ravindran , Wood Lori , Hotte Sebastien J. , McKay Rana R. , Choueiri Toni K. , Heng Daniel Yick Chin 
Published: March 2021

316 Background: Immune checkpoint inhibitors (ICI) have demonstrated impressive activity in metastatic clear-cell renal cell carcinoma (ccRCC) and have become standard treatment options in this setting. Data supporting the effectiveness of ICI based therapy in non-clear cell RCC (nccRCC) is more limited. Methods: We performed a retrospective analysis using the International Metastatic RCC Database Consortium (IMDC). Patients with nccRCC were classified into 3 groups based on first-line therapy: ICI based therapy (in monotherapy or in combination), vascular endothelial growth factor targeted therapy (VEGF-TT) monotherapy, or mammalian target of rapamycin (mTOR) inhibitor monotherapy. Primary outcome was overall survival (OS). Secondary outcomes were time to treatment failure (TTF) and objective response rate (ORR). We used Kaplan-Meier method to compare OS and TTF between treatment groups and Cox proportional hazards models to adjust for prognostic covariates. Results: We identified 1181 patients with nccRCC. In first-line, 78.2% received VEGF-TT, 15.8% mTOR inhibitors, and 5.5% ICI based therapy, of which 41.5% in monotherapy, 30.8% doublet-ICIs and 27.7% an ICI combined with VEGF-TT. Median OS in the ICI group was 28.6 months, compared to 19.2 and 12.6 in the VEGF-TT and mTOR groups, respectively. Median TTF was 6.9 months vs. 5.1 and 3.9 and ORR was 25% vs. 17.8% and 5.8% in the ICI, VEGF-TT and mTOR groups, respectively. After adjusting for IMDC risk group, histological subtype, and age, the hazard ratio (HR) for OS was 0.58 (95% CI 0.35-0.94, p=0.03) for ICI vs. VEGF-TT and 0.48 (95% CI 0.29-0.80, p=0.005) for ICI vs. mTOR. Conclusions: In advanced nccRCC, first-line ICI based treatment appears to be associated with improved OS compared to VEGF and mTOR targeted therapy. These results need to be confirmed in prospective randomized trials. [Table: see text]
68Ga-PSMA expression changes on PET/CT for response assessment during taxane-based chemotherapy in metastatic prostate cancer patients.
Authors: Shagera Qaid , Artigas Carlos , Flamen Patrick 
Published: March 2021

35 Background: Imaging-based response to systemic therapies in metastatic prostate cancer is still challenging. The aim of this study was to retrospectively investigate the association between Prostate-Specific Membrane Antigen (PSMA) expression changes on 68Ga PSMA PET/CT and the response to treatment following the start of taxane-based chemotherapies (docetaxel or cabazitaxel) in both metastatic hormonosensitive (mHSPC) and castration-resistant prostate cancer (mCRPC) patients. Methods: We retrospectively reviewed all 68Ga-PSMA-11 PET/CT scans performed at our institution from November 2014 to June 2020. We included mHSPC and mCRPC patients with a baseline 68Ga-PSMA PET/CT performed < 2 months before, and a second 68Ga-PSMA PET/CT performed < 3 months after docetaxel or cabazitaxel (with no modification in therapy between scans). The biological data was used to distinguish PSA-non-responders (increasing PSA or decreasing PSA by < 50% from pretherapy level) and PSA-responders (decreasing PSA > 50% following the start of therapy or the peak thereafter). The PSMA PET/CT response was assessed visually by two independent nuclear medicine physicians blinded to clinical data and patient outcomes. Patients were classified as PSMA-non-responders (≥1 new PSMA-expressing metastases, majority of PSMA-expressing metastases increasing in intensity, or stable PSMA-expression of the disease) or PSMA-responders (complete disappearance of pathologic PSMA uptake, or majority of PSMA-expressing metastases decreasing in intensity). Majority of lesions was defined as > 50% of registered lesions. Descriptive statistics and measures of associations (two-sided Fisher’s exact test and Phi coefficient) were calculated. Results: A total of 37 patients were included (8 mHSPC and 29 mCRPC), 21 patients under docetaxel and 16 cabazitaxel. All patients received at least 3 cycles [median 6 (range 3-10)]. The mean time (±standard deviation) between the first 68Ga-PSMA PET/CT and the start of therapy was 22±16 days. The mean time between the the last cycleand the second 68Ga-PSMA PET/CT was 36±27 days. PSA-response and PSMA-response were concordant in 95% of cases with 18 patients PSA/PSMA-non-responders and 17 PSA/PSMA-responders (Phi = 0.90, p = 0.0001). Two discordant patients presented with PSMA-response but PSA-non-response. No isolated PSMA flare was observed, as PSA-response was always associated with a decrease in PSMA-expression on the second PET/CT. Conclusions: This retrospective study suggests PSMA expression changes on PET/CT at least after 3 cycles of chemotherapy (docetaxel or cabazitaxel) are strongly associated with PSA response. No flare phenomenon was found at this evaluation. Prospective studies are needed to better define the potential role of PSMA-PET/CT in response assessment.