bluuebunny/crossref_metadata_2025 huggingface dataset:
CTC and AR-V7 analysis in the ECOG-ACRIN 8153 (CHAARTED2) randomized trial: Abiraterone (Abi) with or without cabazitaxel (Abi-Cabazi) in extensive mCRPC following docetaxel.
Authors: Kyriakopoulos Christos , Chen Yu-Hui , Jeraj Robert , Duan Fenghai , Tripathi Abhishek , Kosoff David , Garje Rohan , Pachynski Russell Kent , Parikh Rahul Atul , Harzstark Andrea , Adra Nabil , Maughan Benjamin L. , Zakharia Yousef , Corn Paul Gettys , Liu Glenn , Carducci Michael A , Luo Jun , Antonarakis Emmanuel S.
Published: February 2025

181

Background:
The CHAARTED2 trial showed improved PFS with Abi-Cabazi over Abi-alone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who previously received docetaxel for metastatic castration-sensitive disease. Here, we evaluated the prognostic and predictive impact of CTC and AR-V7 circulating biomarkers.
Methods:
The modified AdnaTest (Qiagen) was used to define CTC detection (+ vs –) and AR-V7 detection (+ vs –) at baseline, C5D1, as well as at the time of progression. We first assessed the prognostic value of baseline and C5D1 CTC and AR-V7 status in the two arms. We also assessed the predictive potential of baseline and C5D1 CTC and AR-V7 status to explore if these biomarkers may aid in treatment selection. Logrank test and Cox proportional hazards models were used to assess for associations between clinical outcomes and baseline biomarker status. Landmark analysis was performed to evaluate associations at C5D1.
Results:
A total of 223 pts were randomized between the two arms. CTC data were evaluable for 94/112 and 94/111 pts in the Abi-alone and Abi-Cabazi arms, respectively. Baseline CTC detection was prognostic for worse PFS in both the Abi-alone (7.1 vs 31.7 months, HR 3.64,
P
<0.001) and the Abi-Cabazi (9.6 vs 36.9 months, HR 4.13,
P
<0.001) arms. Likewise, baseline AR-V7 detection portended worse PFS in the Abi-alone (4.1 vs 12.8 months, HR 3.34,
P
<0.001) and the Abi-Cabazi (6.9 vs 15.1 months, HR 3.17,
P
<0.001) arms. At C5D1, there was a higher rate of CTC(-) conversion (60 vs 46%) and AR-V7(-) conversion (69 vs 58%) in the Abi-Cabazi arm. CTC(-) and AR-V7(-) status at C5D1 was prognostic of improved PFS in both arms (all
P
≤0.02). In terms of predictive impact, PFS was numerically but not statistically longer in the Abi-Cabazi arm in all biomarker groups; the greatest relative PFS benefit to Abi-Cabazi was in the baseline AR-V7(+) group (HR 0.68, 95%CI 0.36–1.3,
P
=0.2). Similarly, at C5D1, the greatest relative PFS benefit to Abi-Cabazi was in pts remaining AR-V7(+) (HR 0.57, 95%CI 0.15–2.16,
P
=0.4).
Conclusions:
Baseline CTC and AR-V7 detection were both prognostic for inferior PFS in both study arms. PFS outcomes were broadly longer in the Abi-Cabazi vs Abi-alone arm in all biomarker groups. The presence of AR-V7 at baseline and at C5D1 was the strongest relative predictor of Abi-Cabazi benefit, but did not meet statistical significance. Clinical trial information:
NCT03419234
.
Mature phase 1 follow up of alpha emitter 225Ac-J591 with 177Lu-PSMA-I&T in advanced prostate cancer.
Authors: Raab Gabriel , Okobi Tobechukwu Joseph , Holmes Aaron N. , Huicochea Castellanos Sandra , Avlonitis Vasilios , Patel Amie , Thomas Charlene , Nauseef Jones T. , Molina Ana M. , Davidson Zachary , Sternberg Cora N. , Nanus David M. , Osborne Joe Reginald , Bander Neil Harrison , Tagawa Scott T.
Published: February 2025

185

Background:
Targeted radionucleotide therapy (TRT) has become a standard of care. α-emitters have a higher energy transfer over a shorter range than β-emitters. PSMA-targeting antibodies have different biodistribution than small molecules and may improve intracellular retention based on pre-clinical models. Here, we present mature follow up of a phase 1 dose-escalation trial of 225Ac-J591 plus 177Lu-PSMA-I&T (aka PNT2002).
Methods:
Inclusion criteria:progressive mCRPC with ≥1 prior AR pathway inhibitor (ARPI), prior chemo (or unfit/refused), and with ≥1 lesion on PSMA PET where SUVmax >liver. 177Lu-PSMA-I&T (6.8 GBq) and 225Ac-J591 (30, 35, or 40 KBq/kg) given up to 2 doses 8 weeks apart. Primary outcome was dose-limiting limiting toxicity and recommended phase 2 dose (RP2D). Preliminary efficacy outcomes examined were overall survival (OS), progression-free survival (PFS), PSA response, and circulating tumor cell (CTC) changes.
Results:
18 patients (6 at each dose level) with median age 70, median PSA of 54.4 (2.43-9614). Previous therapies: 11 (61%) with >1 ARPI, 12 (67%) chemo, 5 (28%) sip-T, 3 (17%) radium-223. Baseline CTCs: 15 detectable, 9 unfavorable. The median SUVmax of the most avid lesion on PSMA-PET was 31.4 (95% CI 11-82.7). Metastatic sites: 13 bone, 9 lymph node, 4 visceral. 8 (44%) were Halabi high risk. Treatment emergent adverse events (AEs) included neutropenia in 3 patients (17%), all Grade <2; thrombocytopenia occurred in 12 (67%) (3 GR 3); anemia in 10 (56%, 3 GR 3); 12 (67%) xerostomia (one Gr2); one (6%) with acute renal failure. Other AEs: 10 (56%) pain flare (1 Gr3 in pt with cord compression), 11 (61%) nausea (all Gr 1), 9 (50%) fatigue (all Gr 1). The RP2D of 225Ac-J591 was 35 KGBq/kg. 17 (94%) patients experienced a decline in PSA levels, with 11 out of 17 (64%) achieving PSA50 response. 4/5 patients (80%) converted from unfavorable to favorable CTC count, 4/8 (50%) from detectable to undetectable, 1 of 2 (50%) remained undetectable. Median biochemical PFS was 7.3 months (95% CI 2.7-15.8), and median OS was 29.8 mo (95% CI 7.4-NR), with 10 patients still alive at time of submission. 5 were progression free at one year, including 3 of 6 treated at RP2D. With longer follow up, no new safety signals were identified.
Conclusions:
The combination of PSMA-targeted alpha (via antibody) plus beta (via small molecule) was feasible. High grade AEs were rare and no new safety signals emerged with longer term follow up. Nearly all patients had PSA decline, and 5 had durable disease control off therapy. Clinical trial information:
NCT04886986
.
Genomic features of prostate cancer patients with and without ductal adenocarcinoma (DA) based on liquid biopsy.
Authors: Zhu Qiyu , Zhao Jinge , Shi Yifu , Zeng Hao
Published: February 2025

191

Background:
Ductal adenocarcinoma (DA) is relatively rare and highly co-existed with prostate adenocarcinoma (AC). This study aims to investigate the distinctive genomic profiles of patients with DA compared to those without it.
Methods:
Blood samples were obtained from 144 patients (36 with DA and 108 without DA) who were diagnosed with prostate cancer from 2017 to 2023 at West China Hospital. We performed cell-free DNA sequencing to investigate the genomic differences between patients with DA (DA[+]) and those without (DA[-]), and explored the potential associations between their mutational status and prognosis. Pathogenic and likely pathogenic alterations were included for analysis.
Results:
We identified that AR pathway (16/36 [44.4%] vs 24/108 [22.2%], p=0.017) and WNT pathway (6/36 [16.7%] vs 5/108 [4.6%], p=0.029) mutations were significantly enriched in DA(+) compared to DA(-), with AR pathway featured by FOXA1 (9/36 [25%] vs 5/108 [4.6%], p=0.0012). DDR mutation rate and the HRD scores appeared to be comparable between DA(+) and DA(-). TP53 was associated with a deteriorating prognosis for both DA(+) and DA(-) in terms of castration-free survival (CFS).
Conclusions:
Our findings provide further genomic insights in prostate cancer with ductal morphology and are instructive for the diagnosis and treatment of DA.

Baseline characteristics of the DA (+) and DA (-) cohorts.

Variable

DA (-), N = 108
1

DA (+), N = 36
1

p-value
2

Treatment line

0.4

HSPC
34 (31%)
7 (19%)

CRPC
18 (17%)
6 (17%)

Treatment-naive
56 (52%)
23 (64%)

Metastasis at detection

0.6

M0
52 (48%)
19 (53%)

M1
56 (52%)
17 (47%)

Visceral metastasis
8 (7.4%)
8 (22%)
0.028

Bone metastasis

0.7

<5
12 (11%)
6 (17%)

≥5
38 (35%)
12 (33%)

0
55 (51%)
18 (50%)

Not available
3 (2.8%)
0 (0%)

ISUP

0.055

1
3 (2.8%)
0 (0%)

2
6 (5.6%)
3 (8.3%)

3
16 (15%)
11 (31%)

4
12 (11%)
7 (19%)

5
71 (66%)
15 (42%)

Age
68 (61, 73)
68 (61, 73)
>0.9

Baseline PSA

0.007

<50
41 (38%)
23 (64%)

≥50
67 (62%)
13 (36%)

1
n (%); Median (IQR).

2
Pearson's Chi-squared test; Fisher's exact test; Wilcoxon rank sum test.

DA: dutal adenocarcinoma of the prostate; HSPC: hormone-sensitive prostate cancer; CRPC: castration-resistant prostate cancer; ISUP: International Society of Urological Pathology grading; PSA: prostate-specific antigen.
NSD2 inhibition as a therapeutic approach for treatment-induced neuroendocrine prostate cancer.
Authors: Xu Lan , Flynt J Erin , Miskin Sanjana , Soares Luis Miguel Mendes , Corey Eva , Connolly Terry , Winograd Benjamin
Published: February 2025

198

Background:
Trans-differentiation from adenocarcinoma to neuroendocrine histology is a major treatment-induced resistance mechanism against androgen receptor pathway inhibitors (ARPI) in castration-resistant prostate cancer (CRPC). With increased use of ARPI in the clinic, neuroendocrine prostate cancer (NEPC) constitutes 15~20% of CRPC. The histone H3 K36 di-methyltransferase NSD2 has recently been shown to be a driver of the adeno-to-neuroendocrine trans-differentiation. The level of NSD2 expression is markedly increased in AR(-) NEPC compared to AR(+) CRPC and correlates with a poor disease outcome. Furthermore, genetic depletion of NSD2 has been shown to reverse AR(-) NEPC to an AR(+) adenocarcinoma phenotype and re-sensitize the prostate cancer cells to enzalutamide treatment.
Methods:
K36 Therapeutics has developed a selective NSD2 inhibitor KTX1001 that is currently undergoing clinical evaluation in multiple myeloma (NCT05651932). Dose proportional pharmacokinetics and on-target pharmacodynamics of KTX1001 have been observed as well as an excellent safety profile in patients. Here we have investigated whether pharmacological inhibition of NSD2 reverses AR(-) NEPC to AR(+) adenocarcinoma in preclinical models.
Results:
In the NEPC cell line NCI-H660, KTX1001 treatment led to a significant change in the epigenome landscape, resulting in reduced expression of neuroendocrine markers SYP, CHGA and FOXA2 and concomitant upregulation of the adenocarcinoma markers AR, NKX3.1 and KLK3. These observations are consistent with a lineage change from AR(-) NEPC to AR(+) adenocarcinoma. We further investigate this
in vivo
using a NEPC patient-derived xenograft model. Indeed, treatment with our selective NSD2 inhibitor resulted in pronounced upregulation of the Hallmark Androgen Response gene signature, suggesting restoration of the AR-signaling pathway. Moreover, Hallmark E2F and Myc signatures, which are known to be elevated in NEPC cells, were markedly downregulated after NSD2 inhibitor treatment. These observations suggest a significant change in NEPC lineage identity towards AR(+) adenocarcinoma.
Conclusions:
These data support our hypothesis that NSD2 inhibition can reverse NEPC to AR(+) adenocarcinoma lineage and restore sensitivity to standard-of-care ARPI. Given these mechanistic insights and the safety profile observed with our NSD2 inhibitor in the clinic, evaluation of NSD2 inhibition in NEPC patients is warranted.
Evaluation of ctDNA alterations in lethal mCRPC.
Authors: Huang Minqi , Habibian Nicholas , Nguyen Tivoli , Opeoluwa Akerele , Pocha Olivia , Bhandari Priya , Johnson Courtney , Lieberman Alexandra , Schwartz Jennifer , Layton Jodi Lyn , Lewis Brian E. , Sartor Alton Oliver , Ledet Elisa Marie
Published: February 2025

245

Background:
Circulating tumor DNA (ctDNA) can be used as a prognostic biomarker in mCRPC patients, with changes in ctDNA providing insight into patient survival. In this study, we evaluate the ctDNA landscape of patients with mCRPC prior to their death.
Methods:
A retrospective clinical data review, 2015-2024, was conducted at Tulane Cancer Center to identify mCRPC patients who underwent ctDNA testing prior to death. All ctDNA data were obtained through a multi-gene cancer panel via the Guardant 360 assay (70-83 genes). Lethal mCRPC was defined as patients who underwent ctDNA testing ≤3 months prior to death. A matched control group (CTRL) was defined as mCRPC patients with ctDNA collection ≥2 years prior to death or most recent follow-up. Statistical analyses were performed using Pearson Chi-Square Test or Fisher Exact Test whenever appropriate. Furthermore, survival analysis was conducted using the Kaplan-Meier method.
Results:
There were 70 patients in lethal mCRPC group and 157 patients in CTRL group. Compared to the CTRL group, in lethal mCRPC, somatic mutations and/or amplifications in BRAF(OR=2.1549, 95% C.I. [1.1136,4.1523], p=0.0298), CCND2 (OR=3.7925, 95% C.I.[1.1937,13.3380], p=0.03326), MYC (OR=2.6332, 95%C.I. [1.4158, 4.9120], p=0.0029), PDGFRA (OR=2.5235, 95% C.I. [1.1438, 5.5793], p=0.0291), and PIK3CA (OR=2.0328, 95% C.I. [1.1098, 3.7166], p=0.02846) were significantly more frequent. Additionally, lethal mCRPC patients were more likely to have missense (OR=4.3194, 95% C.I. [1.443456,19.3338], p=0.01687) and nonsense (OR=1.9364, 95% C.I. [1.06091,3.5250], p=0.04112) mutations at the end-of-life. Patients with a higher allelic fraction (≥0.6%) of TP53 alterations had a shorter median survival (p-value= 0.034).
Conclusions:
ctDNA mutations and/or amplifications in BRAF, CCND2, MYC, PDGFRA, and PIK3CA were more frequently detected in lethal mCRPC compared to matched CTRLs. Additionally, mCRPC patients with a lethal phenotype were more likely to have missense and nonsense mutations compared to the CTRL group. CtDNA assessment of copy number alterations was limited to amplifications only; additionally, with this assay, distinguishing between gene level and large scale chromosomal amplification is not assessable. Though this study is limited to a single-institution with retrospective analyses of clinical testing, understanding the somatic landscape of lethal mCRPC is critical for development of new biomarkers, strategies and ultimately druggable targets.
Evaluating the role of cancer-associated fibroblasts in T cell–mediated proinflammatory reprogramming of tumor associated macrophages in the prostate cancer tumor microenvironment.
Authors: Kosoff David , Heninger Erika , Breneman Matthew T , Recchia Emma , Maklakova Vilena , Lebeau Aaron
Published: February 2025

248

Background:
Tumor-associated macrophages (TAMs) have been implicated as a critical mediator of T cell exclusion and inhibition within the prostate TME. However, using a microscale cell culture platform, known as Stacks, we have previously demonstrated that while prostate tumor cells induce an immunosuppressive phenotype in TAMs, activated T cells can reprogram these macrophages towards a proinflammatory phenotype that augments tumor-directed T cell responses. To investigate how other cell populations within the TME impact T cell mediated macrophage reprogramming, we expanded our models to include cancer-associated fibroblasts (CAFs), which have been previously shown to have immunosuppressive effects that regulate macrophage function in the TME.
Methods:
Primary T cells and autologous monocyte-derived macrophages (MDMs) were derived from the peripheral blood samples of patients receiving care at the University of Wisconsin Carbone Cancer Center and with William S Middleton Memorial Veterans Hospital in Madison, WI. MDMs were cultured with prostate tumor (22Rv1) and CAF (hPrCSC-44) cells in mono-, co-, and tri-culture models for 72h in the Stacks microfluidic cell culture platform. Activated autologous T cells were then added to each condition for an additional 24h of culture. Models were analyzed for T cell migration and surface marker expression by confocal microscopy, secreted cytokine and chemokine profiles by protein bead array, and gene expression by qRT-PCR.
Results:
We found that MDM-mediated augmentation of CD4
+
and CD8+ T cell migration within the prostate TME models was abrogated in the presence of CAFs. Analysis of gene expression further demonstrated that the presence of CAFs in our quad culture models resulted in a decrease in expression of T cell recruitment chemokines by the MDMs, including CCL2, CCL5, CXCL9, CXCL10, and CXCL11, compared to MDM tri-culture with tumor cells and T cells. MDMs also expressed higher levels of IL-10 mRNA, a potent immune suppressive factor, when CAFs were present in the TME.
Conclusions:
Using microscale cell culture technologies, we provide the first direct evidence that CAFs inhibit T cell mediated proinflammatory reprogramming of MDMs in the prostate TME. Furthermore, we demonstrate that this inhibition of MDM reprogramming is associated with a decrease in tumor-directed T cell migration compared to MDM, tumor cell, and T cell tri-cultures. This data suggests that CAFs, through their effects on MDMs/TAMs, may be playing a vital role in the inhibition of tumor-directed T cell responses. The pathways that are mediating this effect therefore represent valuable therapeutic targets to augment immunotherapeutic efficacy in prostate cancer treatment.
Clinical significance of urotensin 2 plasma level in patients diagnosed with prostate cancer.
Authors: Dinckal Cigdem , Guc Zeynep Gulsum , Yilmaz Huriye Erbak , Dinckal Mustafa , Ozgul Semiha , Ozkan Gamze , Unal Sinan , Yildiz Yasar , Oflazoglu Utku , Salman Tarik , Alacacioglu Ahmet , Kucukzeybek Yuksel
Published: February 2025

249

Background:
Urotensin-II is a small somatostatin-like cyclic peptide characterized by its potent vasoconstrictor activity. Urotensin-II (UT-II) and its receptor (UTR) have been shown to play a role in the formation of different epithelial cancers. To date, many studies have been reported in prostate cancer that provide genetic contributions with diagnostic, prognostic and therapeutic potential for carcinogenesis. However, the role of urotensin-II in prostate carcinogenesis has not yet been elucidated. There are several limitations to using PSA as a biomarker in prostate cancer follow-up. More accurate and specific biomarkers are needed to improve diagnosis and monitoring of prostate cancer. Our study aimed to reveal the clinical importance of plasma UT-2 level in metastatic prostate cancer patients and to investigate its correlation and prognostic importance with clinical parameters such as PSA level and pathological parameters such as Gleason Score.
Methods:
Patients who applied to İzmir Katip Celebi University Atatürk Training and Research Hospital Medical Oncology Polyclinic in 2023 were included in our study. The demographic information of the patients was scanned from the oncology file system and recorded. Measurements of plasma ÜT-2 level were made by a biochemistry specialist at İzmir Katip Celebi University Atatürk Training and Research Hospital Biochemistry Laboratory. For the ELISA method, Urotensin 2 ELISA (Elabscience lot no: E-EL-2047) kit was used in the Biotek (ELx800, USA) semi-automatic ELISA device.
Results:
A total of 147 patients, 100 metastatic and 47 control groups, were included in our study. No statistically significant difference was observed between the groups in terms of additional diseases that may be related to UT-2 level: Diabetes Mellitus, hypertension, peripheral artery disease, coronary artery disease, chronic renal failure and smoking characteristics (p>0.05). When the PT-2 level was compared between the de-novo and non-de-novo metastasis groups and the control groups, both metastasis groups had a higher average than the control groups (p = 0.004). The cut-off value for UT-2 was determined as 1.269 ng/mL. UT-2 sensitivity, specificity, positive predictive value and negative predictive value were found to be 81%, 53%, 79% and 57%, respectively.
Conclusions:
Today, studies are continuing rapidly to increase the efficiency of PSA and to find new tumor markers. In our study, UT-2 levels in metastatic prostate cancer patients were found to be statistically higher than other groups. This is the first study in the literature to study the UT-2 plasma level in prostate cancer, and UT-2 may be an important biomarker in predicting prognosis in prostate cancer.
Ethnic disparities in clinical trials for FDA-approved drugs in prostate cancer: A post–COVID-19 era analysis (2020-2024).
Authors: Bastos Bruno R. , Schwartz Michael A. , Gligich Oleg , Barrientos Jacqueline Claudia , Ramirez-Ridelli Antonio , Borregales Leonardo , Nieder Alan , Bhandari Akshay , Linzer Debra , Kuritzky Nicolas , Cusnir Mike
Published: February 2025

25

Background:
It is known that ethnic and racial inequality in participation in oncology clinical trial is a contemporary problem. Efforts have been made by NCI and FDA to address cancer disparities as per new policies placed in 2017. Despite these efforts, there are still disparities in cancer treatment and clinical trial participation. There is paucity of data in participation of minorities in the post COVID-19 era of the FDA approved agents in Prostate Cancer.
Methods:
From 2020-2024, a total of 4,744 patients participated in the seven clinical trials (MAGNITUDE, TALAPRO-2, VISION, PROPEL, ARASENS, HERO, PROfound and TRITON3) that led to FDA approval of new agents or indications to treat patients with prostate cancer. All clinical trials were industry-sponsored. We assessed and tabulated the reporting of racial demographics within these trials employing chi-square statistics and machine learning algorithms to compare participation rates among White, Black, Asian and Hispanic patients against SEER data on prostate cancer incidence.
Results:
Among the eight trials, five (ARASENS, MAGNITUDE, PROPEL, TALAPRO, TRITON-3) reported racial data in White, Asian and Black participants, but only one reported data on Hispanics (MAGNITUDE). Our analysis revealed that in the five trials providing racial data, 68% were White indicating statistically significant overrepresentation (p<0.001), Black participation was only 3% signifying statistically significant underrepresentation with (p<0.0001). In the only trial with data in Hispanics, there was a 12.1% participation of Hispanics with no significant disparity observed (p=1).
Conclusions:
Lack of representation of minorities persist in post COVID area FDA approved drugs clinical trials in prostate cancer. Lack of a more comprehensive data in race have also been seen in recent trials. Further implementation of policies for better data capture and standardization in the nomenclature of ethnicity should be pursued. Additionally, in international collaboration trials, a separate data on US participants utilizing NCI SEER data ethnicity nomenclature should be considered.
Population-adjusted network meta-analyses (NMA) to evaluate the efficacy of treatment alternatives for metastatic hormone-sensitive prostate cancer (mHSPC).
Authors: Shore Neal D. , Morgans Alicia K. , Paracha Noman , Thom Howard , Keeney Edna , Orishaba Philip , Phillippo David , Aceituno David , Wallis Christopher J.D. , Boegemann Martin
Published: February 2025

267

Background:
Existing NMA in mHSPC compare treatments assuming homogeneity in treatment effect modifiers across study populations. However, evidence suggests that these effects vary in mHSPC. This study employs the recent methods of multilevel network meta-regression (ML-NMR) and network meta interpolation (NMI) to adjust for population differences and predict relative effect estimates for an ARASENS-like target population.
Methods:
We used a systematic literature review to identify studies for our NMA on overall survival (OS) in mHSPC. We applied ML-NMR to adjust for imbalances in treatment effect modifiers by integrating individual patient data (IPD) regression from the ARASENS trial across the covariate distributions of comparator studies. The IPD was reconstructed from Kaplan-Meier curves for aggregate data studies, incorporating covariates age, ECOG performance status, Gleason score, and disease volume. Utilizing the same set of variables, NMI was employed to analyze subgroup data from comparator studies using reported hazard ratios.
Results:
Twelve studies were identified for inclusion in our analyses. The ML-NMR demonstrated a significant benefit for the darolutamide (daro) triplet compared to enzalutamide + ADT, apalutamide + ADT, abiraterone + ADT, and the abiraterone triplet in the ARASENS-like population. However, in the NMI analysis, the daro triplet was significantly favored over abiraterone + ADT when compared to other commonly utilized alternatives (Table). A key strength of the ML-NMR over NMI is that it only requires baseline characteristics to be reported, rather than subgroups which were relatively poorly reported or not powered to detect statistically significant differences. The NMI method suffered due to incomplete subgroup data, with full data for effect modifiers available in 8/12 studies.
Conclusions:
Both ML-NMR and NMI analyses support triplet benefit with ADT + docetaxel + daro in improving OS for patients with mHSPC. The evidence from ML-NMR is particularly robust, benefiting from the better covariate data and the attendant decrease in uncertainty.

Hazard ratio from ML-NMR and NMI.

Daro + docetaxel + ADT versus
ML-NMR: OSHR (95% CrI)
NMI: OSHR (95% CrI)

SNA+ADT
0.28 (0.17, 0.46)*
0.36 (0.23, 0.56)*

ADT
0.43 (0.32, 0.60)*
0.51 (0.39, 0.65)*

Docetaxel + ADT
0.57 (0.42, 0.77)*
0.68 (0.57, 0.80)*

Enzalutamide + ADT
0.64 (0.44, 0.96)*
0.80 (0.57, 1.11)

Apalutamide + ADT
0.68 (0.46, 1.00)**
0.75 (0.55, 1.03)

Abiraterone + ADT
0.65 (0.45, 0.92)*
0.65 (0.52, 0.81)*

Abiraterone acetate + docetaxel + ADT
0.66 (0.47, 0.93)*
0.89 (0.59, 1.34)

CrI: credible interval, SNA: standard nonsteroidal antiandrogen, ADT: androgen deprivation therapy, *upper CrI did not cross the line of no effect, **rounding, upper CrI limit treated as below 1.00.
Beyond survival: Understanding the social dimensions of prostate cancer.
Authors: Jatwani Karan , Ma Philip , Miran Seyedeh Azadeh , Khosla Atulya Aman , Whalen Michael Joseph , Jain Maneesh Rajiv
Published: February 2025

28

Background:
Prostate cancer carries one of the highest burdens of racial disparities in outcomes in oncology. Understanding social determinants of health (SDOH), which measure inequities in healthcare, could give us insight into quality improvement strategies. We aimed to study the impact of key SDOH measures (everyday discrimination, supportive relationships, neighborhood characteristics, and food and housing security) on the perception of overall health in prostate cancer survivors using a publicly available database.
Methods:
A cross-sectional study was conducted using overall health and SDOH survey data collected by the National Institutes of Health All of Us Research Program from June 2017 to June 2022. Ordinal logistic regression was utilized to assess associations between overall perception of health and each specific SDOH survey domain. All statistical tests were two-sided, and a p-value less than 0.05 was statistically significant; multiplicity adjustments were not made. The Statistical package (0.13.5) of Python (Version 3.1) was used for all statistical analyses.
Results:
5,909 male participants with prostate cancer met the inclusion criteria. 2,280 (38.58%) had completed the SDOH surveys and were considered for analysis. Of those, 1,966 (86%) were White, 5.88% Black or African American, and 3.55% Hispanic in ethnicity. In the ordinal logistic regression models, for every unit increase in the SDOH neighborhood characteristics score, the odds of having a higher perception of general health increased by 3% (OR 1.03, 95% CI = [1.02, 1.04], p < 0.0001). For every unit increase in the SDOH day-to-day discrimination score, the odds of having a higher perception of general health increased by 3% (OR 1.03, 95% CI = [1.02, 1.04], p < 0.0001). For every unit increase in the score of the supportive relationships SDOH domain, participants were 4% (OR = 1.04, 95% CI = [1.035, 1.053]) more likely to have a higher perception of general health. Controlling for all other variables, Black race, Hispanic ethnicity, a history of mental health disorders, smokers, and age less than 65 years were independently significant for poor perception of overall health (p < 0.05).
Conclusions:
While SDOH have been linked with prostate cancer-specific mortality, this is one of the first studies evaluating the role of each component of SDOH on the perception of overall health. We highlighted that factors including neighborhood, discrimination, and supportive relationships have a quantifiable impact on health. Our study provides objective predictive changes in the overall perception of health. Using our variables as a model to predict the effect of changes in these determinants and tailor support to individual needs could ultimately improve quality of life.
Novel urine-enriched RNA panel (EPCAM, TTC3, H4C5) to detect prostate cancer and differentiate it from benign prostatic disease.
Authors: Perera Ranjan Joseph , Yuan Menglang , Moschovas Marcio , Perera Roshane , Amankwah Ernest , Lee Bongyong , Sonpavde Guru P. , Patel Vipul , Pavlovich Christian P. , Joshi Kandarp
Published: February 2025

31

Background:
Prostate Cancer (PCa) is one of the leading causes of cancer deaths among men worldwide. Although the Prostate-Specific Antigen (PSA) test is widely used for screening, several advisory groups recommend against PSA because of its non-specific and suboptimal performance. Hence, there is an urgent unmet need for novel and more accurate biomarker panels for PCa detection.
Methods:
To develop an alternate assay, we collected voided urine (50 ml) from 236 pre- and 198 matched post-prostatectomy men with PCa, 76 benign prostatic hyperplasia (BPH), 21 prostatitis and 107 normal healthy men between the years 40-80. We isolated RNA from exfoliated cells and debris shed into urine, subjected to deep-sequencing of 50 selected genes (adj
P
value < 0.05 and log FC > 2), and performed advanced machine-learning approaches to discover potential biomarkers in men with PCa.
Results:
From 50 RNAs initially tested in 20 pooled urine samples, 3 RNAs (EPCAM, TTC3, H4C5) were identified to detect men with PCa robustly (with higher specificity and sensitivity) and distinguished them between pre- and post-prostatectomy in PCa patients. The biomarkers, in combination, outperformed a known urinary RNA marker, PCA3 (area under the curve, 0.96, Figure 1 left). Immunohistochemistry and qPCR analysis in prostate FFPE tissues further confirmed that the origin of these three biomarkers is prostate-specific. In addition, the biomarker panel could separate PCa from benign prostatic disease (area under the curve, 0.89), where both diseases show a higher elevation of PSA. TTC3 and EpCAM gene silencing in PCa cells showed a tumor suppression
in vitro
and
in vivo
, suggesting its relevance to PCa development.
Conclusions:
The urine-based RNA biomarker panel (EPCAM, TTC3, H4C5) is a promising noninvasive diagnostic tool to separate PCa from BPH/prostatitis and healthy individuals; further prospective validation is warranted.
Racial differences in active surveillance intensity and overtreatment in men with prostate cancer.
Authors: Hill Dawson , Kaufman Samuel R , Guro Paula , Leick Sarah , Chachlani Preeti , Shay Addison , Oerline Mary , Dall Christopher , Hollenbeck Brent K. , Shahinian Vahakn B , Srivastava Arnav
Published: February 2025

316

Background:
Marginalized communities in cancer care are often characterized by lower healthcare utilization. In prostate cancer, however, utilization may have mixed effects on quality, particularly in the Medicare population where non-cancer health risks are more prevalent. In this context, we examined racial differences in active surveillance intensity (i.e. confirmatory testing) and potential overtreatment, two key measures of prostate cancer care quality.
Methods:
Using a 20% national sample of Traditional Medicare beneficiaries, we identified men with newly diagnosed prostate cancer from 2014 to 2019. We used multivariable logistic regression to evaluate the association between race (White, Black, or other) and receipt of a confirmatory test (prostate biopsy, magnetic resonance imaging, or genomic testing) within one year of diagnosis among men on active surveillance. We created a subset of patients with significant comorbidities to assess potential overtreatment (i.e., treatment among patients with >50% estimated non-cancer mortality in five years).
Results:
We identified 41,092 men meeting inclusion criteria. On adjusted analysis, Black men (OR=0.75; 95%CI: 0.62-0.92, p=0.01) had lower odds of receiving a confirmatory test compared to White men. Among men at risk of overtreatment, Black men (OR=0.86; 95%CI: 0.77-0.97, p=0.01) were less likely to receive treatment compared to White men. Further, all patients, regardless of race, had a predicted probability <50% of receiving a confirmatory test within one year of diagnosis (Table).
Conclusions:
Our study highlights racial differences in two measures of prostate cancer care, receipt of a confirmatory test and overtreatment. We demonstrated that Black men have lower odds of receiving a confirmatory test. This stands to disproportionately affect Black men, given that they present with higher risk tumors compared to other racial groups. Conversely, Black men have lower odds of being overtreated when compared with White men, suggesting that lower utilization may shield them from potential overtreatment and its related morbidity. As a result, policy efforts aiming to reduce disparities may be most impactful by prioritizing clinical contexts where utilization and access are tightly aligned with care quality.

Predicted probabilities for confirmatory testing and overtreatment.

White
Black
Other

Confirmatory Testing
43%
37%*
46%

Overtreatment
50%
43%*
46%*

Adjusted for socioeconomic status tertile, Charlson Comorbidity Index, age, rurality, and year of diagnosis.

*Indicates p<0.05.
Timely BRCA mutation testing in patients with metastatic prostate cancer: A comparative analysis between Medicare Advantage and traditional Medicare.
Authors: Ji Jonathan Wenbin , Lu Chuan Angel , Jafry Baqir , Bhanvadia Raj , Qin Qian , Vento Joseph , Courtney Kevin Dale , Wang Jue , Arafat Waddah , Yang Daniel X. , Cole Suzanne , Zhang Tian , Jiang Changchuan
Published: February 2025

319

Background:
BRCA mutations have emerged as critical biomarkers for guiding the use of PARP inhibitors in metastatic prostate cancer. Timely access to BRCA testing remains a challenge, especially for those enrolled in Medicare Advantage (MA) plans, which cover more than half of Medicare beneficiaries but often impose greater restrictions than Traditional Medicare (TM). This study compares the timeliness of BRCA testing in patients with metastatic prostate cancer (mPCa) across these two insurance types.
Methods:
A retrospective cohort study was conducted using the Flatiron Health deidentified Database, including electronic health record-derived data from ~280 cancer practices across the US. Our study population consisted of patients aged 65 or older, diagnosed with mPCa since 2018, and enrolled in either TM or MA. TM and MA were defined as patients enrolled in TM or MA health plans, respectively, either prior to or within 90 days following their mPCa diagnosis. BRCA testing was defined as either germline or somatic testing. We compared the rates of BRCA testing within 45, 90, and 180 days of diagnosis between TM and MA. Given the lack of clinical consensus, we defined timely BRCA testing using three-time windows—45-, 90-, and 180-days post-mPCa diagnosis. Multivariate logistic regression with inverse probability of treatment weighting was used, adjusting for demographics, year of mPCa diagnosis, practice setting, and baseline ECOG performance status.
Results:
Among the 1,582 MA patients (mean age: 75.9 ± 5.8) and 2,749 TM patients (mean age: 75.4 ± 5.8), significant proportions were from community practice (MA: 78%, TM: 80%) and were characterized by being White (MA: 59%, TM: 65%), aged 75 to 85 (MA: 54%, TM: 57%), having better socioeconomic status (SES 4 or 5: MA: 40.3%, TM: 47.5%), presenting with de-novo mPCa (MA: 53%, TM: 54%), and having better baseline functional performance (ECOG 0 or 1: MA: 70%, TM: 69%). Since 2018, 25.0%, 29.4%, 33.2% of MA patients and 25.9%, 29.1%, 31.9% of TM patients received BRCA testing at 45, 90 and 180 days, respectively. After adjusting for covariates, MA was associated with a 15.2% (OR=0.84, 95%CI 0.73-0.98), 11% (OR=0.89, 95%CI 0.77-1.02), 7.9% (OR=0.92 95%CI 0.80-1.06) lower chance to receive timely BRCA testing within 45 days, 90 days and 180 days, respectively.
Conclusions:
This study suggests that, compared to TM, mPCa patients enrolled in MA are less likely to receive timely BRCA testing. These findings highlight the needs for further investigation into how Medicare Advantage plans impact cancer care delivery and patient outcomes.
Exploring social vulnerability in prostate cancer management: Insights into utilization of watchful waiting and active surveillance from 1998 to 2017.
Authors: Shakhnazaryan Nana , Winebaum Jenna , Wang Lufan , Jhandi Angad , Nguyen Nathan , Cowan Janet E , Carroll Peter , Chan June M. , Shariff-Marco Salma , Washington Samuel L
Published: February 2025

322

Background:
Active surveillance (AS) and watchful waiting (WW) represent different conservative management strategies for prostate cancer (PCa), with AS being the preferred strategy. The Social Vulnerability Index (SVI) is enhancing our understanding of healthcare treatment disparities and social risk factors in the cancer care, but its impact in prostate cancer care remains unclear. We examine how social vulnerability influences the choice of WW vs AS in managing men with low and intermediate risk prostate cancer.
Methods:
The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database was used to identify men diagnosed with localized, low, and intermediate-risk prostate cancer (i.e., those potentially eligible for active surveillance) from 1998 to 2017. Participants' data were geocoded and de-identified, then combined with Social Vulnerability Index (SVI) data, which is based on four themes: socioeconomic status, household composition, minority status, and housing & transportation. We used multinomial logistic regression to examine the association between SVI and conservative management strategies of WW and AS.
Results:
Among 681 low-risk and intermediate-risk prostate cancer patients diagnosed from 1998 to 2017, 135 were assigned to watchful waiting (WW) and 546 to active surveillance (AS), reflecting a trend toward AS. The mean Social Vulnerability Index (SVI) was higher in the WW group (0.30) than in the AS group (0.21). Significant differences were noted by Socioeconomic Status (0.33 vs 0.15, p = 0.02).
Conclusions:
For patients with low and intermediate risk localized prostate cancer higher SVI, particularly in communities with greater socioeconomic challenges and higher proportion of racial while the overall proportion of AS increased over time. Our findings underscore how patients with higher SVI may experience considerable undertreatment, even with the concomitant increase in AS utilization over time. Identifying these communities remains a crucial step in addressing local drivers of treatment disparities in PCa care.
Implementation of a digital multimedia tool for prostate cancer patient consultation.
Authors: Walker Kristin , Samadi Samira , Chen Joe , Showalter Timothy N , Luminais Christopher
Published: February 2025

345

Background:
MyCareGorithm, is a digital health tool designed to improve the cancer consultation experience for patients, companions, and physicians. This tool provides audiovisual guides for cancer related evaluation and management. This study aims to evaluate the effectiveness of this tool for both the patient and physician.
Methods:
In a prospective, IRB-approved, pilot study, 31 patients with prostate cancer and 12 companions from a single institution underwent an initial consult using this digital multimedia tool. They completed a survey of 6 “yes” or “no” questions to evaluate their understanding of their disease and treatment options. Two physicians completed a 7-question survey to evaluate their experience with this tool. Descriptive statistics were used to analyze the data.
Results:
Over 90% of patients reported this tool helped them better understand their cancer diagnosis, treatment options, and felt their understating of their medical situation and the quality of the consult was enhanced. 100% would recommend this to other patients. Their companions agreed and answered “yes” over 90% of the time in all categories. Comments from patients include phrase “very helpful” multiple times. Physicians agreed 97% of the time that this helped communicating difficult information and enhanced the quality of the consult. Physicians agreed that the patient had a greater understanding of their cancer, treatment, and that they would use this tool again 100% of the time. 94% of physicians agreed this tool improved efficiency and provided a more effective consult. Physician comments described the infographics as “helpful” in several instances. Survey questions and results are shown (Table).
Conclusions:
Implementing the MyCareGorithm digital health tool resulted in high levels patient satisfaction, comprehension, and enhanced the overall consult experience. Physicians also report high patient satisfaction and comprehension, enhancements to the overall consult, and improved clinical efficiency. The recurring comment from both physicians and patients was “helpful.” The positive results show the value of this digital communication tool. Further studies with a larger cohort and other disease sites should be assessed.

Patient, companion, and physician survey questions and results.

Survey Questions
% Patients Agreed
% Companions Agreed
% Physicians Agreed

Helped patient greater understand their prostate cancer
97%
100%
100%

Helped patient greater understand treatment
90%
100%
100%

Enhanced the quality of the consultation
97%
100%
97%

Helped patient greater understand their medical situation
100%
100%
-

Would recommend this tool to other patients
100%
100%
100%

Would review the information after consult
84%
92%*
-

Improved efficiency of the consultation
-
-
94%

Helped physician provide more effective consult
-
-
94%

Helped ease communication of complex information
-
-
97%
Prognostic significance of PSA in the outcomes of patients with high risk localized prostate cancer.
Authors: Ganiyani Mohammad Arfat , Khosla Atulya Aman , Prabhakar Pushan , Pon Avudaiappan Arjun , Jatwani Karan , Ahluwalia Manmeet Singh , Manoharan Murugesan , Garje Rohan
Published: February 2025

347

Background:
Patients diagnosed with localized high-risk prostate adenocarcinoma (LHRPC) with high Gleason scores (8-10) and prostate-specific antigen (PSA) levels ≤ 4 may experience an altered clinical course. In these patients, low PSA levels may reflect cellular dedifferentiation, indicating more aggressive tumor behavior despite appearing to have a low disease burden. We aim to investigate the impact of PSA levels in patients with LHRPC to better understand prognosis and optimize treatment strategies.
Methods:
We included patients diagnosed with LHRPC based on TNM stage (T1-T4, N0, M0) and Gleason 8–10 from 2004 to 2020, using data from the National Cancer Database. We stratified patients based on PSA levels (≤4 and >4 ng/dl) and treatment approaches. We utilized Kaplan-Meier analysis and Cox proportional hazard model to study survival outcomes in patients with LHRPC.
Results:
We included 160,971 patients diagnosed with LHRPC, of which 86.69% (139,546) had PSA >4 ng/dl, while only 13.31% (21,425) had PSA ≤4 ng/dl. Our cohort had 69.55% (111,953) patients aged ≥ 65 years and 30.45% (49,018) aged < 65 years. Regarding race, the cohort was predominantly white, comprising 81.69% (131,497), followed by black at 14.47% (23,292), and other racial categories at 3.84% (6,182). In our cohort 34.43% (55,425) underwent surgery only (S), 9.62% (15,484) received radiation therapy only (RT), 46.81% (75,350) had radiation therapy combined with androgen deprivation therapy (RT + ADT), and 9.14% (14,712) received androgen deprivation therapy only (ADT). In our multivariate cox proportional hazard analysis, LHRPC patients with PSA >4 ng/dL had a 7% (HR 0.93, 95% CI: 0.90–0.95; p<0.001) decreased risk of death compared to those with PSA ≤4 ng/dL.
Conclusions:
In our study, LHRPC patients with PSA ≤4 ng/dL had poorer survival outcomes after adjusting for the treatment approach, race, age category, income, insurance status, facility type, and location. Further research is required to explore potential biological differences in patients with low PSA-secreting LHRPC.

Cox proportional hazard analysis in patients with LHRPC, GS 8-10.

Categories
Hazard Ratio (95% CI)
P-value

Treatment type: Surgery only

reference

RT only
2.27 (2.19, 2.36)
<0.001

RT + ADT
2.37 (2.30, 2.44)
<0.001

ADT only
5.68 (5.49, 5.87)
<0.001

Charlson Deyson score : 0

reference

>=1
1.43 (1.40, 1.46)
<0.001

Facility type : Academic

reference

Non-Academic
1.20 (1.17, 1.23)
<0.001

PSA ≤ 4 ng/dl

reference

PSA > 4 ng/dl
0.93 (0.90, 0.95)
<0.001
Population-based assessment of treatment patterns for high-risk localized prostate cancer.
Authors: Wallis Christopher J.D. , Malone Shawn , Cagiannos Ilias , Hamilton Robert James , Basappa Naveen S. , Ferrario Cristiano , Gotto Geoffrey , Fernandes Ricardo , Niazi Tamim , Morash Chris , Rendon Ricardo A. , Saad Fred , Hotte Sebastien J , Osborne Brendan J.W. , Zardan Anousheh , Shayegan Bobby
Published: February 2025

349

Background:
Patients diagnosed with high- or very high risk (H/vHR) prostate cancer (PCa) are at substantial risk of disease recurrence, metastasis, and death after treatment. Historically, treatment paradigms for these patients have been similar to those with intermediate-risk (IR) disease [radiotherapy (RT) with androgen deprivation therapy (ADT) and radical prostatectomy (RP)] though there is a growing body of evidence supporting intensified systemic therapy in this group. To contextualize this emerging trial data, we characterized real world treatment patterns for these patients.
Methods:
We performed a retrospective population-based cohort study using province-wide linked administrative data in Ontario, Canada. We descriptively characterized initial treatment patterns (within 1 year of diagnosis) for men with H/vHR PCa and compared them to a concurrent cohort of patients with IR disease to assess differences in management.
Results:
We identified 13,206 patients diagnosed with H/vHR PCa from 2010-2021 who were compared to 18,365 with IR disease. Most patients received active treatment, though rates were statistically significantly higher in the H/vHR (n=12,606, 95.5%) than IR cohort (n=14,995, 81.6%; p<0.001; standardized diff 0.44). 6207 (47%) of patients in the H/vHR cohort and 7286 (40%) of patients in the IR cohort underwent RP (p<0.001; standardized difference 0.148). Median time to RP was 98 days in the HR cohort and 105 days in the IR cohort (Median time (Q1-Q3); p<0.003; standardized difference 0.11). 6321 (47.9%) of those with H/vHR disease and 7427 (40.4%) of those with IR disease underwent radiotherapy (p<0.001; standardized difference 0.150). Very few patients received intensified systemic therapy: 77 patients (0.2%) received chemotherapy and 49 (0.2%) received androgen receptor pathway inhibitors. While treatment patterns were similar, patients with H/vHR disease were more likely to progress to metastasis (46% vs 30%, p<0.001) and more rapidly (2.6 vs 4.3 years, p<0.001), with similar patterns observed for CRPC, mCRPC treatment, prostate cancer events, and death.
Conclusions:
Despite higher rates of treatment, patients with H/vHR localized disease experience significantly worse clinical outcomes than those with IR. These data highlight the need for therapies which can improve clinical outcomes in this patient population, such as the potential use of intensified systemic therapies including Androgen Receptor Pathway Inhibitors (ARPIs).