bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating tumor DNA levels and related kinetics as prognostic biomarkers for clinical outcomes in mCRPC: A post hoc analysis of CM 7DX.
Authors: Fizazi Karim , Saad Fred , Alonso Gordoa Teresa , Barthelemy Philippe , Goh Jeffrey C. , Büchler Tomáš , Castellano Daniel , Lee Chung-Wei , Jiang Ding , Ray Pradipta , Paulucci David , Lako Ana , Gupta Saurabh , Campos Aranzazu , Subudhi Sumit Kumar , Van Kooten Losio Maximiliano A.G. , Cutuli Hernán Javier
Published: February 2025

252

Background:
Liquid biopsy assays in mCRPC are utilized for treatment eligibility of PARP inhibitors (HRR) and Pembrolizumab (MSI High). These ctDNA targeted gene panels provide translational data beyond gene mutations. Tumor Fraction (TF), the percentage of cfDNA from tumor, is a promising prognostic efficacy biomarker in pre-chemo mCRPC, and a potential predictive biomarker to post-chemo PSMA radioligand therapy.
Methods:
We analyzed ctDNA run with Illumina-TSO500 from the CA209-7DX Ph3 mCRPC trial (Nivo+chemo vs. Chemo in chemo-naïve mCRPC) to determine: TF at baseline or changes at Cycle6 Day1 (C6D1). TF at each timepoint was determined through the maximum somatic allelic frequency.
Results:
We present a combined analysis of treatment arms as both showed similar association between clinical outcomes and TF levels as well as clearance. Out of 1030 ITT patients TF data was available for 527 (51%) patients. Patients in the highest TF tertile had TF of ≥4.6% and TF<0.3% for the lowest tertile. Patients in the lowest TF tertile had 10 months longer overall survival (OS) to the highest TF tertile (p<0.001). Patients in the highest TF tertile demonstrated higher hazard ratio for OS (HR 3.42,[2.34-4.98] p<0.001) and rPFS (HR 1.95 [1.47-2.59], p<0001) over lowest tertile. This differential was maintained across arms and indicates that TF is a strong prognostic biomarker. High TF outperformed common stratification factors (prior exposure to chemo in CSPC or novel ARPIs) for poor prognostication in a multivariate analysis. TF high patients have higher rates of AR-Amp/AR-LBD mutations (72.6%) than TF low (28.8%). Patients with TF clearance, defined as TF < 1% at C6D1 had 8 months mOS advantage over patients with a TF >1% at baseline and on-treatment. TF clearance strongly correlated with OS (HR=0.42 [0.28-0.62], p<0.001), rPFS benefit (HR=0.24 [0.17-0.34], p<0.001) and PSA response (28% vs. 62%) regardless of treatment arm.
Conclusions:
This data advocates for plasma TF as a robust prognostic biomarker and as a potential stratification opportunity in mCRPC clinical trials. TF clearance may act as an early indicator of treatment response and hence can be an important monitoring tool for mCRPC patient management. Clinical trial information:
NCT04100018
.
Downregulation of E-selectin and contributions to immune restraining in prostate cancer.
Authors: Deichaite Ida , Elliott Andrew , Shabaik Ahmed , Sutton Leisa , Weaver Stephanie , Haraguchi Miki , Geynisman Daniel M. , Wei Shuanzeng , Ferrara Napoleone , Asimakopoulos Fotis , Tamayo Pablo
Published: February 2025

257

Background:
Immune surveillance in prostate cancer (PCa) relies on leukocyte trafficking into target tissues, a process mediated by endothelial adhesion molecules. This study investigates the role of E-selectin (SELE) in PCa immune evasion and patient outcomes.
Methods:
We analyzed transcriptomic data from 7,523 PCa samples (4,768 localized; 2,755 metastatic) molecularly profiled at Caris Life Sciences to assess SELE expression. Correlations between TNF and adhesion molecule expression were examined in normal prostate and PCa tissues. Survival analysis was performed based on SELE expression levels. Immunohistochemistry was conducted to evaluate SELE protein expression in tumor, benign prostatic hyperplasia (BPH), and stromal samples.
Results:
SELE was significantly upregulated in localized PCa samples compared to metastases (SELE: 0.83 vs 0.47 TPM, p<0.001), along with SELP (P-selectin) (3.15 vs 1.29 TPM, p<0.0001), ICAM1 (5.05 vs 3.70, P<0.0001) and VCAM1 (7.10 vs 5.41, P<0.001), while TNF expression was similar (0.48 vs 0.43 TPM, P<0.001). TNF positively correlated with SELE, with a stronger correlation observed in metastatic vs localized PCa samples, suggesting altered transcriptional regulation. High expression of SELE was associated with improved survival among patients with localized PCa (HR=0.61, p<0.0001), with no significant difference observed among those with metastatic PCa (HR=0.90, p=0.153). Among those with localized PCa, high expression of SELP was also associated with improved survival (HR=0.75, p<0.001), while worse overall survival was associated with high expression of ICAM1 (HR=1.58, p<0.0001), VCAM1 (HR=1.73, p<0.0001), and TNF (HR=1.23, p=0.004). Combined high SELE/low TNF demonstrated an enhanced survival effect compared to low SELE/high TNF (HR=0.44, p<0.001).
Conclusions:
Our findings suggest that downregulation of SELE in PCa contributes to tumor "coldness" by potentially reducing anti-tumor immune cell infiltration. This mechanism may explain the limited efficacy of immune checkpoint inhibitors in PCa. The strong association between SELE expression and improved survival highlights their potential for prognostic biomarker and therapeutic target in PCa.
Evaluating survival in aggressive variant prostate cancer patients undergoing PSMA radioligand therapy.
Authors: Moradpour Moein , Moradi Tuchayi Abuzar , Burger Irene , Pop Sabin George. , Aparicio Ana , de Kouchkovsky Ivan , Hope Thomas A.
Published: February 2025

259

Background:
Aggressive variant prostate cancer (AVPC) is a subtype of metastatic castrate-resistant prostate cancer (mCRPC) characterized by several high-risk features. AVPC is associated with poorer overall survival and has limited response to androgen receptor targeted therapy, although it often shows some responsiveness to chemotherapy. In this study, we evaluated the outcomes of AVPC patients who received Prostate-Specific Membrane Antigen (PSMA) radioligand therapy (RLT).
Methods:
This retrospective study included 201 mCRPC patients who received Lutetium-177, [
177
Lu]-PSMA RLT at two academic centers. Patients were classified as having AVPC based on the presence of at least one of the following eight criteria: exclusive visceral metastases (n=1), predominantly lytic bone metastasis (n=1), bulky lymphadenopathy or pelvic mass (≥5 cm) (n=4), low PSA (≤10 ng/mL) at initial presentation plus high-volume (≥20) bone metastases (n=0), serum CEA and/or LDH levels twice the upper limit of normal at the time of treatment (n=5), a short interval (≤6 months) to CRPC (n=7), small cell/neuroendocrine carcinoma morphology (n=5), and the presence of two or more genomic defects among TP53, RB1, and PTEN (n=13).
Results:
Of the 201 patients, 34 (16.9%) were classified as having AVPC (Table). The PSA50 response rate was 55% in the AVPC group and 60% in the non-AVPC group. The median overall survival (OS) (median time from the start of therapy to the last follow-up or death) was 171 days for the AVPC group and 282 days for the non-AVPC group. Although, the Kaplan-Meier plot only suggested a trend toward worse survival in AVPC patients compared to non-AVPC patients, the difference did not reach statistical significance (log-rank test p-value = 0.179).
Conclusions:
Our study suggests patients with AVPC may benefit from PSMA RLT and should be considered for this treatment if they are eligibly. Further studies are needed for a better understanding of this patient population.

Details of patients.

AVPC
Non AVPC

N=201
34
167

Age
1
(mean, year)

64.38
64.09

PSA
2
(mean, ng/mL)

331
251

PSA
3
(mean, ng/mL)

717
504

PSA50 (%)
55
60

OS/FU (median, day)
171
282

1
Age at the time of therapy.
2
Baseline PSA at diagnosis.
3
Most recent PSA prior to therapy.
Assessing the impact of PTEN loss on outcomes in high-/very high-risk, advanced hormone-sensitive prostate cancer patients: Institutional retrospective study.
Authors: Jamaspishvili Tamara , Patel Palak , Bennett Mackenzie , Bearden Jonathan , Bixby Amber , Desai Devashish , Nasr Michel R , Bratslavsky Gennady , Goldberg Hanan , Basnet Alina
Published: February 2025

260

Background:
Inactivation of tumor suppressor gene, PTEN (Phosphatase and tensin homolog) by deletion or mutation occurs in between 15-20% of localized prostate cancers and up to 50% of castration-resistant prostate cancers. The series of studies has shown a robust correlation between the genomic loss of
PTEN
and its protein as assessed by immunohistochemistry (IHC). Dysregulation of PI3K/AKT/mTOR signaling pathway has been linked with adverse pathological features and poor oncological outcomes such as the development of disease recurrence, metastasis, and castrate-resistant prostate cancer (CRPC). Here, we aim to study the prognostic and predictive role of PTEN in relation to treatment outcomes in a newly developed retrospective institutional research cohort.
Methods:
The cases with genomic
PTEN
loss (FoundationOne CDx, n=190) and protein loss by IHC (BenchMark Ultra, Roche Diagnostics, n=273) were pooled together. A total of 311 patients (PTEN loss=84, PTEN intact=227) that had available clinical and pathological information, including follow-up, were used for downstream statistical analysis. Kaplan-Meier analyses and univariate and multivariate Cox proportional hazard models were used to assess the benefit of RP over definitive RT with or without androgen deprivation therapy (ADT) for high-risk localized cohort as well as the benefit of primary ADT with or without intensification in the patients experiencing the loss of PTEN.
Results:
Patients with PTEN loss were more likely to present with advanced-stage disease (Stage IV: 33% vs. 19%) and more frequently received RT+ADT (43% vs. 34%) in high-risk patients. In contrast, those with intact PTEN were more likely to undergo radical prostatectomy (34% vs. 28%). Although overall survival (OS) did not differ significantly between all groups (log-rank p=0.51), mortality was higher in the PTEN loss group (32% vs. 22%). There was also a trend toward earlier development of castration-resistant prostate cancer (CRPC) in patients with PTEN loss (log-rank p=0.16).
Conclusions:
PTEN loss in prostate cancer is linked to more aggressive disease, higher mortality, and earlier CRPC development, consistent with existing literature. Our findings suggest that high-risk/very high patients with PTEN loss may benefit from definitive RT-based treatment over surgery. The study is limited by its retrospective, smaller sample size and single-institution design.
A novel predictive model using changes in clinical and serum biomarkers and automated quantitative imaging for mCRPC patients treated with AR-directed therapy.
Authors: Morris Michael J. , Flynn Jessica , Zhao Binsheng , Anand Aseem , Sjöstrand Karl , Larson Steven M. , Scher Howard I. , Regazzi Ashley M. , Borzillo Gary V. , Park Autumn , Schwartz Lawrence Howard , Heller Glenn
Published: February 2025

264

Background:
In mCRPC, standard risk models use baseline clinical and blood-based biomarkers, excluding imaging. This study developed a new predictive model incorporating baseline and early on-treatment clinical, blood, and imaging biomarkers to inform overall survival (OS). The training set was derived from COU-AA-302 and validated using Alliance 031201 (A031201). Eligibility required patients to have at least two CT and bone scans within 6 months of randomization (COU-AA-302: n = 785; A031201: n = 582).
Methods:
Conventional biomarker data included PSA, albumin, alkaline phosphatase, hemoglobin, and ECOG status. Imaging data included > 1000 radiomic features and the automated Bone Scan Index (aBSI). Six-month biomarker trajectories were summarized using the intercept and slope from a random effects model, yielding over 2000 risk biomarkers. Due to the high dimensionality, an elastic net proportional hazards model was applied. Predictive concordance probability, which evaluates the ability to distinguish between long-term and short-term survivors, and R-square, a calibration measure that indicates how accurately the model predicts actual survival time were determined.
Results:
46 biomarkers were selected from over 2000, including 9 blood-based, 4 from aBSI, 1 tumor volume measure, and the remaining from radiomic features. In contrast, the non-imaging risk model contained 10 risk factors. Risk scores from these models were categorized into low, moderate, and high-risk groups. The median survival per group revealed significant separation, with a difference of over 30 months between low and high-risk groups. This separation was observed regardless of whether imaging was included in the model.
Conclusions:
This is the first model for mCRPC to integrate pre-treatment and early on-treatment serum, imaging, and clinical data from two large phase 3 trials, with external validation. While both imaging and non-imaging models showed good predictive accuracy, imaging did not significantly improve the discrimination of long-term from short-term survivors or enhance the precision of the model-based survival predictions.

Clinical + Serum biomarkers with imaging
Clinical + Serum biomarkers without imaging

Total # of risk factors
46
10

# of clinical/serum factors
9
10

# of radiomics factors
32
0

# of aBSI factors
4
0

# of tumor volume factors
1
0

Median Survival (mos)

Low risk group
55
54

Moderate risk group
38
39

High risk group
20
21

Predictive Concordance Probability
0.74
0.73

R-square Measure of Calibration
0.37
0.39
Feasibility of surgical orchiectomy in prostate cancer patients on long term luteinizing hormone-releasing hormone (LHRH) agonist therapy.
Authors: Lazarovich Alon Ya'aqov , Stadler Walter Michael , Eggener Scott , Page Ashley , Heiss Brian , Geynisman Daniel M. , Reizine Natalie Marie
Published: February 2025

265

Background:
Androgen deprivation, achieved through surgical or medical castration, is central to metastatic prostate cancer (PCa) treatment. Life-long castration is thought to be critical to the management of patients with metastatic disease. Orchiectomy offers an alternative, more convenient, and cheaper alternative for permanent castration, but is under-utilized, in part due to patient reluctance. We hypothesized that patients on long term medical castration therapy would be willing to accept surgical castration as an alternative to repeated LHRH agonist injections.
Methods:
Men ≥18 years with metastatic PCa, on LHRH agonists for ≥1 year and ≤2 prior systemic therapies, were eligible. Participants first provided consent for an educational session on orchiectomy, followed by the collection of demographic and disease characteristics. Those providing further consent completed the PROMIS sexual function and satisfaction measures v2.0 and the Hopwood body image surveys, with a urology consult offered. At 6 months, patients completed the same surveys, and those undergoing orchiectomy also completed the decision regret scale. 100 patients agreeing to the educational session were required to provide a 10% confidence interval on an estimated 30-50% of patients undergoing an orchiectomy.
Results:
Of the 130 patients approached, 101 signed the first consent form (education), 58 signed the second (surveys), and 27 agreed to meet with the urology team. Patients agreeing to the educational session had a median age of 71 years (IQR 65-75), 46% were Black and 48% White, 48% completed college or an advanced degree, 36% had annual income > $80K, 58% were married and 64% received systemic therapy other than LHRH agonists. Fourteen patients underwent bilateral orchiectomy (one subcapsular). No association was found between orchiectomy and race, education, annual income, or marital status. While ~75% of all patients were dissatisfied with their sexual life, the vast majority had no body image concerns. Decision regret was low, with 13/14 patients satisfied with their choice of orchiectomy. Pathology revealed testicular atrophy in all cases.
Conclusions:
Only 11% of patients approached, and 14% of patients who participated in an educational session on orchiectomy proceeded with the procedure, suggesting limited feasibility for surgical castration in patients on long-term LHRH agonists. Testicular atrophy suggests that discontinuing medical castration may be an alternative cost-effective strategy to maintain castration in prostate cancer patients with metastatic disease. Clinical trial information:
NCT04705038
.
Prostate cancer risk groups by PSMA-PET PROMISE (PPP): Results from an international multi-center registry study.
Authors: Fendler Wolfgang Peter , Karpinski Madeleine J. , Hoberück Sebastian , Rauscher Isabel , Unterrainer Lena , Rasul Sazan , Bjartell Anders , Lanfranchi Francesco , Di Giorgio Andrea , Pfob Christian Helmut , Soeterik Timo , Goffin Karolien , Kind Felix , Miksch Jonathan , Calais Jeremie , Hofman Michael S. , Hope Thomas A. , Herrmann Ken , Hadaschik Boris A. , Rahbar Kambiz ,   PROMISE Registry Group
Published: February 2025

266

Background:
We previously established prognostic nomograms of PSMA-PET standardized by Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria in a large single-center cohort. Now, we reassess the PSMA-PET PROMISE (PPP) prognostic nomograms in a large international multi-center registry study with overall survival follow-up.
Methods:
We included patients with histologically proven prostate cancer who underwent PSMA-PET at 20 hospitals in Germany, Italy, Sweden, Netherlands, Belgium, Slovakia, Austria, United States and Australia between 2014 and 2021. PSMA-PET was standardized by molecular imaging TNM (miTNM). Total tumor volume in L, PSMA expression score and overall survival follow-up were obtained. The cohort was randomly split 2:1 into development and validation cohorts. In the development cohort we assessed PPP predictors and created visual and quantitative PPP nomograms based on Cox regression models with least absolute shrinkage and selection operator penalty for overall survival. Performance of both nomograms was measured in the validation cohort using Harrell´s C-index and calibration plots. Head-to-head comparison to the NCCN risk score was examined by ROC-curves.
Results:
We analyzed 6128 male patients (4075 development and 2053 validation) across all disease stages with 1915 (31.2%) reported deaths and median follow-up of 4.77 years [IQR 3.38-6.44]. Predictors in the visual PPP nomogram were distant metastases (extrapelvic nodal metastases [M1a], bone metastases [M1b; oligometastatic disease, disseminated or diffuse marrow involvement], and organ metastases [M1c]), PSMA expression score and total tumor lesion count. Predictors in the reassessed quantitative PPP nomogram were distant metastases (M1a, M1b, and M1c), tumor volume and PSMA expression score. C-indices (95% CI) in the validation cohort were 0.812 (0.794; 0.830) for the visual and 0.821 (0.805; 0.837) for the quantitative nomogram, respectively. For three-tier stratification (high, intermediate, low risk), accuracy of both PPP nomograms was superior when compared to the NCCN risk score (n=3638, visual: AUC 0.828 vs. 0.756; p<0.0001 and quantitative: AUC 0.837 vs. 0.756; p<0.0001).
Conclusions:
PSMA-PET PROMISE nomograms in an international multi-center study accurately stratify high vs. intermediate vs. low-risk groups for overall survival across all stages of prostate cancer and yield superior accuracy compared to the NCCN risk score. Follow-up continues in the PROMISE Registry (NCT06320223, promise-pet.org).
Androgen receptor alterations and survival in veterans who develop metastatic castrate resistant prostate cancer.
Authors: Pickett Carley , Karunanandaa Krishny , Doherty Jason M , Garraway Isla , Rettig Matthew , Maxwell Kara N. , Schoen Martin W.
Published: February 2025

269

Background:
Despite the increasing use of comprehensive genetic tumor profiling, molecular data has limited influence in determining treatment. However, with new therapies that target the androgen receptor in metastatic castration-resistant prostate cancer (mCRPC), molecular alterations in the androgen receptor signaling pathway have increasing importance. We sought to examine the association between androgen receptor (AR) alterations and overall survival in patients with metastatic hormone sensitive prostate cancer (mHSPC).
Methods:
In this retrospective study, we identified patients diagnosed with de novo mHSPC and treated with androgen deprivation therapy (ADT) between 2017 to 2021 within the Veterans Health Affairs. AR gene alterations were identified using National Precision Oncology testing from samples collected within 90 days before or after the mCRPC diagnosis date. Overall survival (OS) and time to mCRPC were compared between patients with and without AR alterations in patients whose samples were collected during mCRPC. Normally distributed variables were analyzed via t-test, nonnormal continuous variables via Kruskal-Wallis, and categorical variables via chi-square.
Results:
We identified 2431 patients with de novo metastatic prostate cancer who had somatic tumor testing (551 mCRPC samples and 1922 mHSPC samples). In samples collected in mCRPC, 40.8% (225) had AR alterations compared to 3.3% (65) in mHSPC patients (p<0.001). Of the mCRPC samples, 68.1% (375) were obtained via liquid biopsy, 74.2% (167) had a single AR alteration, and 25.8% (58) had two or more AR alterations (p<0.001). The most frequent AR alterations identified were amplification (n=135), T878A (n=48), L702H (n=40), H875Y (n=27), exon 4-8 rearrangement or deletions (n=23), W742L (n=11), and W742C (n=11). In patients with mCRPC samples, time to mCRPC was 31.3 months in patients with AR alterations compared to 34.7 months without AR alterations, HR 1.08 (95% CI: 0.91-1.28) (p=0.4). In mCRPC samples with AR alterations, the median overall survival was 56.8 months compared to 76.7 months in patients without AR alterations, HR 1.40 (95% CI: 1.15-1.70) (p<0.001).
Conclusions:
There are significantly more AR alterations in tissue samples collected from de novo metastatic prostate cancer patients who have progressed to mCRPC compared to samples collected at mHSPC. In patients tested during mCRPC, presence of AR alteration was associated with shorter overall survival compared to those without AR alterations. Genomic analysis of tumors at the time of disease progression may be an informative prognostic indicator and facilitate selection of therapy.

No AR alteration (n=326)
AR alteration present (n=225)
HR (95% CI)
p-value

Time to mCRPC (months)
34.7
31.3
1.08 (0.91-1.28)
0.4

Overall survival (months)
76.6
56.8
1.40 (1.15-1.70)
<0.001
Evaluating disparities in prostate cancer-related mortality among diabetic adults in the United States and Texas: A 21-year observational study (1999-2020).
Authors: Naz Sidra , Naz Hira , Ali Kashif , Hanif Muhammad , Patel Nirmit
Published: February 2025

30

Background:
The prostate cancer (PCa) mortality risk with diabetes is poorly understood and understudied. We aim to study the annual trends and sociodemographic factors in prostate cancer-related mortality among diabetic individuals in the United States and its state of Texas from 1999 to 2020 to evaluate public health initiatives and offer insights for improving patient outcomes.
Methods:
Mortality trends in PCa among diabetic adults aged ≥25 years were analyzed using the CDC WONDER database, identifying through ICD-10 codes C61 “Prostate Malignant neoplasms” and E14 “Diabetes Mellitus”. Crude and age-adjusted mortality rates (AAMRs) per 100,000 people were extracted. Annual percent changes (APCs) in AAMRs, with 95% confidence intervals, were determined using joint point regression analysis across various demographic (sex, race/ethnicity, age) and geographic (state, urban-rural, regional) subgroups.
Results:
Between 1999 and 2020, 4477954 documented deaths were attributed to PCa associated with diabetes. The overall AAMR for PCa-related mortality in diabetic adults decreased in the US from an adjusted rate (AR) 109.8 in 1999 to (79.1) in 2018 (APC: -1.84%; 95% CI: -2.22% to -1.58%), then it increased to 100.4 in 2020 (APC: 10.4%; 95% CI: 2.97% to 13.4%). In Texas, AAMR for PCa among diabetic adults decreased from AR 125.5 in 1999 to 93.9 in 2018 (APC: -1.71%; 95% CI: -2.25% to -1.26%), after which it increased to 126.6 in 2020 (APC: 14.3%; 95% CI: 4.83% to 18.9%). The AAMR in U.S. men decreased from 166.8 in 1999 to 119.1 in 2018 (APC: -1.96%; 95%CI: -2.34% to -1.68%) and then increased to 147.7 in 2020 (APC: 9.66%; 95% CI: 2.66% to 12.7%). The non-Hispanic (NH) Black or African American (AA) population has the greatest AAMR (191.6), followed by the NH American Indian or Alaska Native (166.2) and the Hispanic or Latino population with AAMR (117.8). The lower-risk population was NH White with AAMR (87.2) and NH Asian or Pacific Islander (59.1). AAMR also varied by region (South: 116.5; Midwest: 101.2; Northeast: 95.5; West: 75.9), and non-metropolitan areas had higher AAMR (small metro: 100.6; micropolitan: 119.9; non-core areas: 124.3) than metropolitan areas (large central metropolitan: 102.2; large fringe areas: 84.8). The states in the upper 90th percentile of AAMRs were Oklahoma, Louisiana, Mississippi, Kentucky, Ohio, West Virginia, Maryland exhibited an approximately two-fold increase in AAMRs, compared to states falling in the lower 10th percentile i.e Nevada, Kansas, Arizona, Florida, MA, Wyoming, and Colorado.
Conclusions:
Mortality rates from prostate cancer among diabetic adults have risen in the United States and Texas over the past two decades. However, NH Black or AA, NH American Indian or Alaska Native, Hispanic or Latino men are at more risk than NH White and NH Asian or Pacific Islander.
Validation of navigator-assisted hypofractionation (NAVAH) program surveys in African-American prostate cancer patients.
Authors: Fleming Hall Erica , Burnette Ursula , Smith Tamika , Sanchez Feliciano Abizairie , Stephens Maya J , Onyewadume Louisa , Cheatham Chesley , Spratt Daniel Eidelberg , Jia Angela Y , McClelland Shearwood
Published: February 2025

313

Background:
Prostate cancer is a leading cause of malignancy and death in men. African-Americans have the highest overall cancer death rate and shortest survival time of any racial or ethnic group in the United States, with African-American prostate cancer patients having a morality rate 80% higher than White patients. The disparities in access to radiation therapy (RT), mortality rates, and treatment outcomes among African-American prostate cancer patients compared to other populations highlight the urgent need for targeted interventions. The Navigator-Assisted Hypofractionation (NAVAH) program, with its innovative patient navigation approach and culturally sensitive survey, aims to better identify the specific barriers faced by African-American patients with prostate cancer. This study is a report of the NAVAH program experience piloting a culturally sensitive survey in African -American prostate cancer patients.
Methods:
African-American patients with established prostate cancer having seen a Radiation Oncologist and consented to receive RT were recruited to participate in our ongoing Phase I trial (clinicaltrials.gov, NCT05978232); those enrolling on trial were administered surveys prior to receipt of RT. Survey information was assessed by topic category and survey responses were combined into a representative score for each category (outstanding, excellent, good, average, below average). Survey categories include availability (access to a medical center, coordinating care, and overall quality of care), accessibility (transportation, distance to care, and healthcare literacy), affordability (financial considerations, employment, and level of education), accommodation (access to internet, navigating transportation), acceptability (comfort and prejudice among interactions with the system), and cancer screening/cancer treatment.
Results:
Mean scores noted good availability (32 responses), excellent accessibility (20 responses), excellent affordability (22 responses), excellent accommodation (18 responses), average acceptability (44 responses), and average cancer screening/cancer treatment (40 responses). Patients noted neutral to positive interactions with doctors and nurses, but distrust of following the advice given to them at hospitals, and that the time interval from their first abnormal test to being informed of a cancer diagnosis was too long.
Conclusions:
Our findings indicate that this novel survey design is feasible in the African-American prostate cancer population. As more patients enroll in our ongoing Phase I trial, implementation of this survey will provide more definitive and comprehensive answers regarding additional topics, including financial challenges during treatment, access to accommodations, and perception of treatment during cancer care.
The Man Van phase 2 results: Mobile targeted case finding for prostate cancer.
Authors: Moghul Masood , Croft Fionnuala , Mutch Fiona , Westaway Elisabeth , Bradshaw Kathyrn , Kierkegaard Patrick , Kinsella Netty , Cahill Declan , James Nicholas David
Published: February 2025

317

Background:
Early intervention is potentially lifesaving in prostate cancer and is a major limitation of cancer outcomes with ethnicity and deprivation being determinants of inequalities that impact outcomes. The Man Van is designed to address health inequalities and barriers to accessing healthcare that affect prostate cancer with novel community-based targeting of high-risk groups using a mobile clinical unit. These inequalities are particularly relevant for men from ethnic minorities and lower socio-economic groups.
Methods:
A bespoke nurse-led mobile clinical unit was moved to community-based locations in areas of high deprivation indices in London (UK) with targeted invitations to high-risk men. Men were offered prostate-specific antigen (PSA) tests and a general health check including: blood pressure, body mass index and an HbA1c test for diabetes.
Results:
Between January 2023 and January 2024, 3379 men attended a Man Van clinic (non-attendance rate 15.1%). The median age of attendees was 59 years (range 39-97). 36.4% of attendees were non-White including 16.7% of men who were Black. The median IMD rank was within the 6
th
lowest decile. 310 men were referred for prostate cancer investigations, 262 had prostate MRI scans. 139 (53.1%) of MRIs were PIRADS 1/2, 35 (13.4%) PIRADS 3, 85 (32.4%) were PIRADS 4/5. 3 (1.1%) scans could not be scored. 127 patients underwent a prostate biopsy (48.5% of men having an MRI scan), with 94 prostate cancers diagnosed (74.0% of biopsies). 81 (86.2%) of these were cancers with clinically significant disease, being grade group 2 (i.e. Gleason 7) or higher (all with >5% pattern 4 Gleason scores). The overall diagnostic rate of clinically significant disease was 2.8%. No prostate cancers were metastatic at presentation, with only one being T4. Of the men diagnosed with prostate cancer (N=94), 25 (26.6%) were managed with active surveillance, 2 (2.1%) were managed with cryotherapy, 2 (2.1%) were managed with low dose-rate brachytherapy, 39 (41.5%) underwent robotic prostatectomy and 26 (27.7%) underwent radiotherapy. 59 patients were referred on two week wait pathways for haematuria (visible or persistent non-visible). One bladder cancer (TCC) was diagnosed (G3pT1bN0M1). 43 patients (2%) were diagnosed with diabetes, 207 patients (11%) with pre-diabetes.
Conclusions:
The Man Van initiative is a novel method of linking primary and secondary care for a range of health checks, including PSA. With a streamlined and more efficient service we have maintained high uptakes for health checks a willingness to engage with health improvement measures from deprived and ethnic minority groups. As well as comparatively high levels of prostate cancers diagnosed at early stages, high levels of other health conditions were found; improving the economic value of the service. Clinical trial information:
NCT06357416
.
Impact of liquid biopsies on early detection, monitoring, and prognostication in prostate cancer: A meta-analysis of emerging evidence.
Authors: Saddique Muhammad Nabeel , Sarwar Atif Hussain , Hashim Hashim Talib , Alhatemi Ahmed Qasim Mohammed , Shamoon Sheena
Published: February 2025

32

Background:
Prostate cancer remains a leading cause of cancer-related morbidity and mortality among men worldwide. Traditional diagnostic and monitoring techniques often lack sensitivity and specificity, particularly in early stages. Liquid biopsies, which analyze circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) from blood samples, have emerged as a promising non-invasive alternative for early detection, monitoring disease progression, and prognostication in prostate cancer.
Methods:
The PubMed, Embase, Scopus and Cochrane databases were systematically searched from inception until June 2024 using relevant keywords. We analyzed the pooled data as untransformed proportions with 95% confidence intervals (CI) using Random Effects model in OpenMeta (version 5.3). The I
2
and X
2
statistics were used to evaluate inter-study heterogeneity. An I
2
value of >50% was considered significant heterogeneity. Subgroup analyses were performed to assess the diagnostic accuracy, prognostic value, and clinical utility of CTCs and ctDNA.
Results:
A total of 30 studies involving 5,200 prostate cancer patients were included in the meta-analysis. Liquid biopsies demonstrated a pooled sensitivity of 85% (95% CI: 80%-90%) and a specificity of 88% (95% CI: 83%-92%) for early detection of prostate cancer. CTCs and ctDNA levels were significantly correlated with tumor burden, Gleason score, and metastatic potential. Furthermore, elevated levels of CTCs and ctDNA were associated with poorer overall survival and progression-free survival, underscoring their prognostic value.
Conclusions:
Liquid biopsies offer a robust, non-invasive method for the early detection, monitoring, and prognostication of prostate cancer. This meta-analysis highlights their potential to improve clinical outcomes through timely and accurate disease management. Future research should focus on standardizing methodologies and integrating liquid biopsies into routine clinical practice.
An online clustering algorithm predicting model for prostate cancer based on PHI-related variables and PI-RADS in different PSA populations.
Authors: Zhang Gejun , Hu Jiyuan
Published: February 2025

328

Background:
Prostate cancer is the most common male malignancy. Current diagnostic methods using single TPSA and PHI lack specificity. Some researches have created nomograms for predicting risk, but these are not easily visualized. Our study aims to find the best negative predictive value (NPV) for PHI, then build a clustering model to display prostate cancer risk categories, particularly useful for patients with PSA>20 and be actually applied in clinical work.
Methods:
We collected 708 patients in the training cohort and 143 in the validation cohort, divided into three groups based on their PSA levels. Next, we determined optimal and customized PHI cut-off values, calculated NPV and PPV, and selected logistic regression as the best method among several machine-learning algorithms. Subsequently, the significant variables were identified, and then a clustering algorithm was constructed. Finally, the model was validated and made available online for further clinical application.
Results:
The Optimal PHI cut-off lower limits for PSA>4, PSA4-20, PSA>20 subgroups were 23.85, 24.35, and 40.75, with upper limits of 142.9, 143, and 135.6, respectively. The clustering model of the optimal cohort for PSA>4 and PSA 4-20 sub-groups showed a superior Silhouette coefficients of 0.433 and 0.526 than that of the customized PHI cohort (0.432, 0.452). The PSA>20 subgroup owned the highest Silhouette coefficient of 0.572. The validation cohort showed AUC values of 0.761, 0.823, 0.833 for these 3 sub-groups, with accuracy rates of 88.81%, 90.38%, and 82.05%.
Conclusions:
In conclusion, our clustering model effectively categorizes patients into distinct risk groups with clear visualization and has demonstrated stability and reliability in the validation cohort, potentially aiding in early diagnosis of prostate cancer in clinical practice.
Interpretable machine learning for prostate biopsy: Cohort study.
Authors: Dai Jindong , Zhao Jinge , Shen Pengfei , Zeng Hao
Published: February 2025

333

Background:
The objective of this study is to develop prediction models and provide diagnostic results for prostate biopsy among patients.
Methods:
This paper presents an improved tree model, called the Light gradient boosting machine model, for building a prostate cancer (PCa) risk prediction model. The research data used in this study (Waves 2008-2022) are obtained from 1987 patients who underwent transperineal biopsy at West China Hospital. All patients had biopsy indications (high levels of prostate specific antigen (PSA), suspect lesions in magnetic resonance imaging (MRI) suspect lesions). A total of 13 baseline variables were considered as candidate features, and eight machine learning models were compared in the experiment. Shapley additive explanations (SHAP) was used for explaining the prediction model.
Results:
The Light gradient boosting machine model demonstrated the best performance, achieving an area under the receiver operating characteristic (ROC) curve of 0.76 (CatBoost=0.71, KNN=0.65, LDA=0.61, CART=0.67, SVM=0.64, NB=0.55, XGBoost=0.71). According to the interpretable analysis, the apparent diffusion coefficient (ADC) of MRI was identified as the most important feature in the prediction model. Other important features included prostate volume, red blood cell count, neutrophil count, and platelet count.
Conclusions:
This study suggests that optimal models show promise in screening out patients at high risk for PCa in prostate biopsies. The decisions regarding prostate biopsies should specifically focus on the ADC of MRI, prostate volume, and blood routine indices such as RBC count, platelet count, and neutrophil count.

Baseline characteristic of all patients.

Mean (SD)
Pca (n=1001)
Non-Pca (n=986)
P

Age (years)
68.68(9.29)
67.99(9.32)
0.901

Blood routine

RBC (10
12
/L)

4.66(0.62)
4.65(0.61)
0.56

Hemoglobin (g/L)
141.46(19.72)
141.84(17.21)
0.149

Platelet (10
9
/L)

188.49(64.65)
193.46(69.12)
0.02

WBC (10
9
/L)

6.76(6.36)
6.6(1.95)
0.56

Neutrophil count (10
9
/L)

4.15(1.52)
4.19(1.71)
0.026

Lymphocyte count (10
9
/L)

1.89(5.73)
1.75(0.76)
0.405

Monocyte count (10
9
/L)

0.48(0.16)
0.47(0.17)
0.626

Eosinophil count (10
9
/L)

0.16(0.16)
0.15(0.16)
0.781

Basophil Cell Count (10
9
/L)

0.25(1.21)
0.36(1.47)
<0.001

PSA (ng/ml)
65.02(346.16)
11.32(23.01)
<0.001

Prostate volume (ml)
43.96(27.66)
51.24(26.85)
0.007

PSAD (ng/ml
2
)

1.82(12.88)
0.28(0.544)
0.001

ADC
733.13(172.09)
756.93(181.31)
0.004
Influence of MRIs performed in a 6-week interval on the histopathological detection of prostate cancer with different PIRADS classifications: A real-world data analysis.
Authors: Nestler Tim , Schoch Justine , Düring Viola , Wiedmann Michael , Overhoff Daniel , Dillinger Daniel , Waldeck Stephan , Schmelz Hans
Published: February 2025

334

Background:
In the early phases of MRI-guided prostate biopsies, it was often necessary to perform an additional in-house multiparametric MRI after an external MRI to accurately assess lesions for biopsy. This study aims to evaluate the consistency of lesion identification and the associated clinical and histological outcomes at a high-volume tertiary care center performing over 500 biopsies annually.
Methods:
This analysis included real-world data from 111 patients treated between 2018 and 2022. Each patient underwent two multiparametric MRI scans of the prostate at different institutions, with a median interval of 42 days [32–52] between scans. An MRI-fused biopsy followed 7 days [4–10] after the second MRI. Data were analyzed using the Chi-square test.
Results:
The PIRADS scores for index lesions on the in-house MRI were as follows: PIRADS V in 33.3% (n=37), PIRADS IV in 49.5% (n=55), PIRADS III in 12.6% (n=14), and PIRADS II in 4.5% (n=5) (Table 1). Most lesions were located in the peripheral zone of the prostate (68.8%, n=75). Cancer detection rates for randomized and/or targeted biopsies were 91.9% (n=34) for PIRADS V, 65.5% (n=36) for PIRADS IV, 21.4% (n=3) for PIRADS III, and 20% (n=1) for PIRADS II. Clinically significant prostate cancer (ISUP > 1) was detected in 91.9% (n=34) of PIRADS V, 60% (n=33) of PIRADS IV, and 21.4% (n=3) of PIRADS III lesions. Overall, malignant histology was found in 64.9% (n=72) of targeted lesions and 59.5% (n=66) of randomized biopsies. A median of 7 [5.5–8.5] biopsies were taken per lesion, with an additional 13 [11–15] randomized biopsies. In the initial external MRI, 18% (n=20) of patients were assigned a higher PIRADS category, while 10.8% (n=12) were had a lower score (p<0.001). The biopsy plan was adjusted for 57 patients (51.4%) based on the findings of the second MRI. However, given the cancer detection rates in both targeted and randomized biopsies, it is likely that all cancers would have been detected regardless of these adjustments.
Conclusions:
Although PIRADS classifications varied slightly between the two MRI scans performed six weeks apart, and biopsy plans were adjusted in about half of the cases, all cancers would likely have been identified. The six-week interval between MRI scans does not appear to significantly affect biopsy accuracy.

PIRADS classification comparison of internal and external MRI.

External MRI

PIRADS II

PIRADS III

PIRADS IV

PIRADS V

All

Internal MRI

PIRADS II

0
40% (2)
40% (2)
20% (1)
5

PIRADS III
0
28.6% (4)
57.1% (8)
14.3% (2)
14

PIRADS IV
0
9.1% (5)
81.8% (45)
9.1% (5)
55

PIRADS V
0
2.7% (1)
16.2% (6)
81.1% (30)
37

All
0
12
60
39
Prostate Cancer Supportive Care (PCSC) program: An alternative to consolidated framework for implementation research (CFIR) model.
Authors: Higano Celestia S. , Ho Rosalie , Sare Daniella , Shih Judy , Hwang Angela , Sundar Monita
Published: February 2025

346

Background:
The CFIR model is one approach to implementing supportive care services. It requires extensive resources, staff training, and reliance on infrastructure. In contrast, the PCSC Program grew organically based on knowledge of patient-expressed needs. Rather than tailoring services to individuals, the PCSC Program offers a menu of services that the patient can choose from with the help of a program coordinator.
Methods:
We compared the implementation considerations for CFIR (1) to those of the PCSC Program.
Results:
Patient Needs Assessment & Staffing: CFIR assesses needs at diagnosis using specific tools in the EHR and recommends a care plan formulated by a multidisciplinary team. In contrast, PCSC empowers patients to self-select services from eight modules (see table below) based on their needs after registration, whether at diagnosis or beyond. This flexibility allows the program to operate efficiently, freeing up clinician time for delivering group education sessions and clinic appointments. Resource Management and follow-up: CFIR identifies community resources with a multidisciplinary team. This may require referrals and clinic-specific communication. This approach may lead to inconsistencies and variation in patient experience. In contrast, PCSC provides all services at a single site that is familiar to many patients as it is across from the urology clinic. Clinic visits are in person or virtual, allowing access to all patients across the province. This model eliminates the need for extensive documentation, and the quality of the services is controlled centrally. Since there is transparency on available services from the outset, patients may return as needed, negating the need for individualized formal follow-up assessments. Sustainability and Impact: While CFIR is process-driven, PCSC’s model has supported over 5,288 patients and their families, free of charge, with $3.25 million in philanthropic support over 11 years in addition to grants and government funding, underscoring the community's trust in the program's efficacy and value.
Conclusions:
CFIR is a structured and resource-intensive approach that focuses on the individual patient. The PCSC Program presents patients with a menu of services known to be of importance to this population and offers a flexible, patient-driven approach. The longevity of the PCSC Program and the patient satisfaction responses suggest that this is an alternative model for delivering supportive care. 1. Stout et al JCO Oncol Pract 20:1173-1181.

Attendance for 5288 registrants from 2013 to 09/2024.

Modules
Attendees 2013-9/2024, n

Introduction to PC and Primary Treatment Options
1994

Managing Sexual Function and Intimacy
2461

Management of side effects of ADT
809

Pelvic Floor Physiotherapy for Incontinence
1890

Counselling
852

Metastatic Disease Management
162

Nutrition
1527

Exercise
1336
Management strategies and patient outcomes among LPC patients with persistently positive PSA after RP.
Authors: Malone Shawn , Wallis Christopher J.D. , 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. , Chan Katherine , Zardan Anousheh , Shayegan Bobby
Published: February 2025

353

Background:
Patients (pts) with localized high-risk/very high-risk prostate cancer (PCa) have an elevated risk of metastases and Prostate Cancer (PC)-specific death following local therapy. This risk is significantly higher for patients with a persistently elevated PSA (pPSA) after Radical Prostatectomy (RP) We aim to better understand the current management strategies for this population using real world data.
Methods:
We performed a retrospective population-based cohort study using province-wide linked administrative data from 2010-2022, in Ontario, Canada. Patterns of patient management in the intermediate (IR)/High-/very high risk (h/vHR) LPC patients who underwent RP with persistently elevated PSA≥0.1 ng/ml were analyzed.
Results:
In this retrospective cohort between 2010-2021, 31,571 patients diagnosed with LPC were identified. Cohorts were stratified by IR (58.2%, n=18,365) and H/vHR (41.8%, n=13,206). Overall, 13493 pts with IH/HvHR received RP as their treatment for LPC, from which 314 pts (Intermediate Risk=127; High-Very high risk=187) had a persistently positive PSA after RP. 46.8% (n=147) of pts with pPSA received RT, 40.4% (n=127) ADT and 21.7% (n=68) RT+ADT as their next line of treatment (p=<.0001; SD=0.880). PSA value after RP and immediately preceding start of next line of therapy was 0.6 ng/ml (Median IQR: 0.2-1.5 ng/ml) in the RT subgroup and 5.8 ng/ml (Median IQR 2.9-10.5 ng/ml) and 0.9 ng/ml in ADT and ADT+RT groups respectively (Median IQR 0.2-4.3 ng/ml; p=<.0001). Median (IQR) time to CRPC was 9 years (7-11.3) in pts without a pPSA and 7.4 years (5.2-10) in patients with a persistent PSA (P=<.0001).
Conclusions:
Patients who do not achieve a PSA<0.1 ng/ml after radical prostatectomy have a worse prognosis. LPC patients should be monitored closely after RP to identify the sub-population with persistent PSA that could benefit from additional therapies intensified systemic therapies including Androgen Receptor Pathway Inhibitors (ARPIs).

Time to progression to CRPC, PC event, and mortality by persistent PSA status among patients with RP.

Persistent PSA

Label

Total

No

Yes

P Value

Variable

(Sample size)

N=14,084
N=13,770
N=314

Time to CRPC

n (%)

186 (1.3%)
148 (1.1%)
38 (12.1%)
<.0001

Median (IQR), Years
9.1 (7-11.3)
9 (7-11.3)
7.4 (5.2-10)
<.0001

Time to PC event

n (%)

6,001 (42.6%)
5,744 (41.7%)
257 (81.8%)
<.0001

Median (IQR), Years
6.7 (1.9-3.6)
6.8 (1.5-10)
0.8 (0.4-4)
<.0001

PSA value before RP (PSA test closest to RP)

Median (IQR),
(1)
ng/ml

6.7 (5.1-9.6)
6.7 (5.0-9.6)
9.0 (5.9-12.8)
<.0001