bluuebunny/crossref_metadata_2025 huggingface dataset:
Timely next-generation sequencing testing in patients with metastatic prostate cancer: A comparative analysis between Medicare Advantage and traditional Medicare.
Authors: Ji Jonathan Wenbin , Jafry Baqir , Lu Chuan Angel , 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

320

Background:
Next-Generation Sequencing (NGS) testing has become a cornerstone of personalized medicine in cancer care. With Medicare Advantage (MA) now covering nearly half of all beneficiaries, understanding differences in access to timely NGS testing between MA and Traditional Medicare (TM) is crucial, particularly given MA’s potential restrictions. This study aims to evaluate the effectiveness of MA plans on timely NGS testing in patients with metastatic prostate cancer (mPCa).
Methods:
This retrospective cohort study was based on the Flatiron Health deidentified Database, comprising electronic health record-derived data from ~280 cancer practices across the US. Our study included patients aged 65 or older, diagnosed with mPCa since 2018, and exclusively enrolled in TM or MA, either before or within 90 days following mPCa diagnosis. We compared the rates between TM and MA, using three timeframes—45-, 90-, and 180-days post-mPCa diagnosis. NGS testing was defined as any tissue or liquid genomic testing resulted within the time frame of interest. Multivariate logistic regression with inverse probability of treatment weighting was used, adjusting for demographics, year of mPCa diagnosis, practice setting, and baseline ECOG score.
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 higher 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, 8.8%, 14.5%, 18.8% of MA patients and 10%, 14.6%, 17.6% of TM patients received NGS testing at 45, 90 and 180 days, respectively. Notably, 63.4% and 60.8% of MA and TM patients, respectively, did not have any NGS testing. After adjusting for covariation, MA was associated with a 26.2% (OR=0.74, 95%CI 0.59-0.92), 16% (OR=0.84, 95%CI 0.7-1.01), 7.8% (OR=0.92, 95%CI 0.78-1.09) lower chance to receive timely NGS testing at 45 days, 90 days and 180 days, respectively.
Conclusions:
Patients with mPCa enrolled in MA are less likely to receive timely NGS testing compared to TM. The high rate of delayed or no testing underscores disparities in access, especially among MA patients. Policymakers should streamline approvals to ensure timely, high-quality care for all Medicare beneficiaries.
Evaluating the impact of a community-based prostate cancer screening program.
Authors: Leader Amy , Pham Kristine , Cianci Nicola , Doka Fatuma , Barron Suzanne , Bradley Katie , Kolesnikov Oleksandr , DeHoratius Jordan , Dahlgren Olivia , Robles Le'Ann , Giamboy Robert , Knapp Hannah , Gomella Leonard G.
Published: February 2025

324

Background:
One out of eight men in the U.S. will be diagnosed with prostate cancer during his lifetime. Early detection, often by routine screening, allows for more options for treatment and an increased chance of survival. Barriers to screening exist and may contribute to prostate cancer disparities, particularly among Black males and those who lack regular access to health care. Community based screening programs may be an effective way to overcome barriers to prostate cancer screening.
Methods:
An urban, NCI-designated cancer center collaborated with community partners and a national prostate cancer advocacy organization to provide free screening to males in our catchment area. Community partners identified the location of the screening and promoted the event. Participants completed a survey about their personal and family history of prostate cancer. A mobile screening team within the cancer center conducted the screenings, consisting of prostate specific antigen (PSA) tests. All participants received a letter with their PSA test results; males with an abnormal result (> 3 ng/mL) also received a phone call. Survey data was analyzed with descriptive statistics and bivariate analyses (ANOVA).
Results:
Two hundred and eighty-nine (n=289) males were screened at a community screening event. The mean age of males screened was 57.3 (SD=11.2) and the majority identified as Black (N=253, 84.9%). The mean PSA test value was 1.82 (SD= 2.70); 14% of males had an abnormal PSA test result. Black males had the highest PSA values of among all men who were screened.
Conclusions:
Disparities in prostate cancer, particularly among Black males, warrant interventions like community-based prostate screening events that reduce barriers of cost and access, bringing screening to those who would most benefit.

Mean PSA test results by patient characteristics.

N
Mean PSA Level
Sum of Squares, DF

Between Groups

Within Groups

F

p

Full Sample
298
1.82

Race/Ethnicity
3; 19.62
271; 1876.18
0.94
0.42

Black
246
1.85

Hispanic
18
0.80

White
9
1.48

Other
2
1.59

PSA in the last 3 years, # tests
3; 19.43
260; 1861.65
0.91
0.44

0
121
1.62

1-3
133
1.82

4-6
6
3.40

7+
4
2.08

Family history of PCa, # of relatives
2; 54.09
287; 2051.72
3.78
0.024*

0
215
1.78

1
63
1.50

2+
12
3.84

Family history of PCa genetic risk, # of relatives
2; 11.75
287; 2094.06
0.81
0.45

0
229
1.71

1
52
2.24

2+
10
1.96

Smoking status
4; 31.74
256; 1815.53
1.12
0.35

Current
26
2.19

Former, quit within 10 years
8
0.93

Former, quit within 11-19 years
8
1.46

Former, quit more than 20 years ago
20
2.75

Never
199
1.68

Diet, fat intake
2; 9.49
272; 1888.09
0.68
0.51

Low
60
1.65

Medium
186
1.71

High
29
2.29

Chemical Exposure
1; 2.80
257; 1824.87
0.39
0.53

Not exposed
210
1.72

Exposed
49
1.97

*Indicates significance (p <0.05).
PSMA-based PET imaging in newly diagnosed, high-risk localized prostate cancer, a National Cancer Institute (NCI) Cancer Moonshot trial.
Authors: Pramod Nikhil , Turkbey Baris , Choyke Peter , Lindenberg Liza , Mena Esther , Madan Ravi Amrit , Reed Michele , Eclarinal Philip , Merino Maria , Sowalsky Adam G. , Patel Krishnan R. , Citrin Deborah E. , Gulley James L , Figg William Douglas , Dahut William L. , Pinto Peter A. , Karzai Fatima
Published: February 2025

327

Background:
Prospective randomized trials have suggested that prostate specific membrane antigen (PSMA)-based PET/CT may improve the detection of metastatic disease in patients with high-risk prostate cancer (HR-PCa) diagnosed by conventional imaging. Of patients with HR-PCa who undergo radical prostatectomy (RP), the majority will experience PSA recurrence within 5 years. PSMA-based PET/CT may improve patient selection for local therapy, suggesting that this imaging advancement may be integral to improving patient outcomes. Here, we present results from the NCI cohort of
NCT03976843,
which evaluated the use of 18F-DCFPyL PSMA- PET/CT in newly diagnosed HR-PCa prior to RP.
Methods:
Enrolled patients (pts) had HR-PCa (biopsy Gleason score [GS] ≥8, PSA >20, or ≥T3) with negative conventional imaging (CT & bone scan). Pts underwent 18F-DCFPyL PSMA PET/CT and prostate MRI prior to RP. The primary hypothesis was that the subgroup of patients with a negative pre-operative PET/CT would have improved progression-free survival (PFS) over historical controls. Progression was defined as a confirmed PSA ≥ 0.2 ng/mL and PET/CT at progression. Correlatives included IHC of RP specimens and expert NCI radiologic imaging review.
Results:
Forty patients enrolled, and 38 patients underwent RP. Of the 38, the median age was 68 years old (61-71 years old), median PSA was 8.15 ng/mL (5.75-16.25), median biopsy GS was 8 (8-9), and median RP GS was 7 (7-8). Pre-operative PET/CT demonstrated regional lymphadenopathy in 2 patients (5.3%), and the median SUVmax of the index lesion was 12.6 (6.6-17.1). At a median follow-up of 2.2 years, the 2- and 4-year PFS was 76% (63%-91%) and 45% (22%-95%), respectively. The median PFS was 3.2 years. Of the 11 pts who underwent progression restaging, 2 had recurrent pelvic nodal disease, and 9 had no visible disease. No AEs were observed.
Conclusions:
These results support 18F-DCFPyL PET/CT as a safe and effective pre-operative staging strategy with the potential to improve patient selection for local definitive therapy. Expert NCI radiologic review for this multisite study, with correlative molecular and genomic work, is ongoing. Clinical trial information:
NCT03976843
.
Optimizing the strategies to perform prostate biopsy in MRI-positive patients: A systematic review and network meta-analysis.
Authors: Wu Qiyou , Tu Xiang , Tang Bo , Bao Yige , Wei Qiang
Published: February 2025

340

Background:
Prostate cancer (PCa) is the most commonly diagnosed cancer in men, and early detection is crucial for better patient outcomes. This study aimed to thoroughly compare existing biopsy schemes for patients with suspicious lesions.
Methods:
This study conducted a systematic review and network meta-analysis following PRISMA guidelines, evaluating 13 biopsy schemes for detecting PCa in MRI-positive patients. Data from PubMed, Embase, and Cochrane databases were examined to assess the efficacy of biopsy schemes in detecting clinically significant (csPCa) and clinically insignificant (ciPCa) prostate cancer.
Results:
The analysis included 188 studies involving 64637 individuals. When compared with the combination of systematic biopsy (SB) and targeted biopsy (TB) (SB+TB), ipsilateral SB with TB (ips-SB+TB) and saturation TB (≥ 6 cores TB with or without perilesional cores) had comparable detection rate of csPCa (ips-SB+TB: RR 0.94, 95%CrI 0.87, 1.0; saturation TB: RR 0.94, 95%CrI 0.89, 1.0). While, saturation SB+TB and SB saturation (> 20 cores SB) detected slightly more csPCa than SB+TB (saturation SB+TB: RR 1.04, 95%CrI 0.97, 1.11; saturation TB: RR 1.09, 95%CrI 0.93, 1.29). And TB and SB alone detected significantly less csPCa than SB+TB (TB: RR 0.86, 95%CrI 0.84, 0.88; SB: RR 0.74, 95%CrI 0.72, 0.76). Saturation SB also did not show significant superiority in detecting csPCa. Additionally, saturation TB and ips-SB+TB also decrease the detection of ciPCa. (ips-SB+TB: RR 0.87, 95%CrI 0.73, 1.04; saturation TB: RR 0.81, 95%CrI 0.70, 0.94). The SUCRA results are detailed (Table).
Conclusions:
The network meta-analysis underscores that saturation SB+TB and SB+saturation TB can detect the most PCa. While, ips-SB+TB and saturation TB are effective biopsy strategies for MRI-positive PCa patients, offering a more targeted approach, improving diagnostic accuracy.

Ranking probability of different biopsy schemes.

PCa

csPCa

ciPCa

Biopsy schemes

Cumulative Probability

Biopsy schemes

Cumulative Probability

Biopsy schemes

Cumulative Probability

1
SB+saturation TB
0.936

SB+saturation TB
0.954

SB+saturation TB
0.958

2
saturation SB+TB
0.920

saturation SB+TB
0.922

saturation SB+TB
0.910

3
SB+TB
0.840

SB+TB
0.842

saturation SB
0.768

4
ips-SB+TB
0.621

ips-SB+TB
0.682

SB+TB
0.739

5
saturation SB
0.590

saturation TB
0.675

ips-SB+TB
0.520

6
saturation TB
0.536

non-targeted SB+TB
0.549

con-SB+TB
0.427

7
non-targeted SB+TB
0.524

saturation SB
0.489

non-targeted SB+TB
0.424

8
con-SB+TB
0.470

con-SB+TB
0.487

SB
0.392

9
TB
0.240

TB
0.401

saturation TB
0.381

10
SB
0.229

SB
0.250

ips-SB
0.306

11
ips-SB
0.096

ips-SB
0.143

con-SB
0.089

12
con-SB
0.000

adjacent sextant SB
0.108

TB
0.085

13

con-SB
0
Natural history and risk-stratification of biochemical recurrence in prostate cancer treated with definitive radiotherapy.
Authors: Riviere Paul , Morgan Kylie Margaret , Nelson Tyler , Sabater Minarim Daniel , Deshler Leah N. , Banegas Matthew P. , Stewart Tyler F. , McKay Rana R. , Javier-Desloges Juan , Parsons Kellogg , Rose Brent S
Published: February 2025

348

Background:
Biochemical recurrence (BCR) of prostate cancer following radiation therapy often does not result in clinically significant events, but a subset of patients may be at higher risk of developing metastatic disease or death. Identifying these patients is critical for clinical decision making, but unlike in the post-prostatectomy setting, no method has been externally validated for BCR after radiation therapy. This study characterized outcomes after post-radiation BCR and validated a proposed risk stratification heuristic.
Methods:
This was a retrospective, multicenter, nationwide cohort study of patients having post-radiation BCR treated in the United States Veterans Administration Health System. High-risk post-radiation BCR was defined as either Gleason score ≥8 or BCR occurring within 18 months of radiation therapy. BCR was defined as post-treatment PSA greater or equal to PSA nadir + 2 ng/ml, initiation of androgen deprivation therapy distinct from the initial treatment course, or development of metastatic disease, whichever occurred first.
Results:
Median time to BCR was 42.5 months (interquartile range 22.9-73.0). Among 7,126 patients who experienced BCR, 35.5% of patients developed metastatic disease and 17.4% died of prostate cancer at 10 years. 38.5% of patients had at least one qualifying high-risk feature of whom 23.3% had high-risk recurrence based on time to recurrence alone, 57.6% based on Gleason/Grade Group alone, and 19.1% based on both criteria. High-risk BCR resulted in higher 5-year rates of metastatic disease (42.0% versus 24.5%, hazard ratio (HR) 1.83, 95% confidence interval (CI) 1.69-1.98, p < 0.001), death from prostate-cancer (18.7% versus 8.78%, HR 1.82, 95% CI 1.63-2.03, p < 0.001), and death from all causes (37.1% versus 30.8% rates, HR 1.18, 95% CI 1.11-1.26, p < 0.001).
Conclusions:
A simple, two-element risk stratification tool using existing clinically data is the first validated tool for identifying patients at risk of metastases or PCSM following post-radiation BCR. Most patients experiencing BCR in this context do not develop metastases or lethal prostate cancer, making such stratification essential for treatment decision-making and refinement of patient populations for clinical trials. Further work remains on risk-adapted therapy intensification.
Evaluation of the impact on overall survival curves of patients with metastatic castration-sensitive prostate cancer staged with PET-PSMA and classified according to current prognostic criteria by volume and risk.
Authors: Sousa Isadora Martins de , Leite Luciana de Moura , Ribeiro André Marcondes Braga , Lima Eduardo Nobrega Pereira , Rinck José Augusto
Published: February 2025

36

Background:
The treatment of metastatic castration-sensitive prostate cancer (mCSPC) has evolved over the years. These therapies are guided by current volume (CHAARTED) and risk (LATITUDE) criteria, instituted based on conventional exams. The emergence of new imaging exams like PSMA PET, with its greater accuracy and early detection of metastatic disease, raises questions about the applicability of these criteria in this context.
Methods:
We conducted a retrospective, single-center study comparing patients staged with PSMA PET between August 2017 and February 2022 and classified as metastatic, after curative therapy or de novo metastatic. Patients with stage IVA, i.e., N1, were also included. Patients were stratified into high and low volume and risk, with the aim of comparing these prognostic factors with outcome of OS.
Results:
48 patients with a median age of 66 years at diagnosis were selected: 81.3% had Gleason scores between 8 to 10, 57% had T classification greater than or equal to T3 and 32% were N1 by conventional exams. According to PSMA PET, 40% were de novo metastatic, with disease sites being bones (M1b - 52%), non-pelvic lymph nodes (M1a - 21%), pelvic lymph nodes (N1 - 17%), and viscera (M1c - 10%). 71% of them were low volume and 75% were low risk. With a median follow-up of 37.5 months and 7 deaths, at 36 months we had 64.6% of the high-volume population alive versus 96.6% of low-volume patients (p=0.054), 77.8% of high-risk patients alive compared to 89.9% of low-risk ones (p=0.739). There was a 67% increase in distant metastasis detection. When correlated with bone scintigraphy (BS), there was a 78.9% discordance between the number and/or location of bone lesions, and in 53.3% of cases, PSMA PET was positive for bone disease with negative BS at the same time.
Conclusions:
PSMA PET appears to be prognostic when applied to volume curves, despite p=0.054, which does not happen for risk, in addition to increasing the detection of metastatic disease compared to conventional exams and being more accurate in the detection of bone disease when compared to BS.
Examining community social vulnerability domains and influence on treatment selection for men with prostate cancer.
Authors: Goodloe Jason Lloyd , Washington Samuel L , Wang Lufan , Cowan Janet E , Nguyen Hao , Carroll Peter , Chan June M. , Shariff-Marco Salma
Published: February 2025

363

Background:
For men with clinically localized PCa, treatment selection guided by patient age, comorbidities, and tumor characteristics can offer improved outcomes. While informative, these observations remain difficult to translate into local, state, and federal policy change to eliminate health disparities for communities at greater risk. We sought to examine how community SVI influences primary treatment, a key determinant of cancer outcomes, for men with clinically localized PCa treated primarily in a community setting.
Methods:
Men diagnosed and managed in CaPSURE practices after 1998 with clinically localized disease (no cM+ or cT4) and who underwent primary management within six months of diagnosis were identified. Community social vulnerability, as defined by census tract-level rankings from 0 to 1 with >90
th
percentile deemed high, was appended to participants’ geocoded baseline addresses. SVI encompasses four domains (socioeconomic status, household characteristics, racial and ethnic minority status, and housing type and transportation). Prostate cancer treatment included prostatectomy, radiation, active surveillance/watchful waiting (AS/WW), primary androgen deprivation therapy (pADT). Multivariate multinomial logistic regression analyses examined associations between SVI and treatment selection, adjusted for patient, clinical, and tumor characteristics with sensitivity analyses using each SVI domain. Odds ratios and confidence intervals were reported with a two-sided p-value < 0.05 considered significant. Analysis was performed with SAS 9.4 for Windows.
Results:
9,023 men diagnosed with low (43%) or intermediate (42%) risk disease and treated at community urology practices (90%) were included. Half (52%) underwent prostatectomy, 26% radiation, 13% ADT, and 9% AS/WW. Median SVI was 0.37 (IQR 0.17-0.59) and varied by theme: socioeconomic status (median 0.35, IQR 0.18-0.57), household characteristics (median 0.41, IQR 0.22-0.64), racial and ethnic minority status (median 0.37, IQR 0.17-0.63), and housing type and transportation (median 0.44, IQR 0.21-0.70). Correlations between SVI themes varied broadly (r = 0.21-0.63, p < 0.001). Having high SVI was associated with increased odds of non-invasive treatment compared to RP: RT (OR 1.56, 95% CI 1.39-1.77), AS/WW (OR 1.21, 95% CI 1.0-1.45), or pADT (OR 1.51, 95% CI 1.27-1.79). Individuals with high SVI by household characteristics had significantly greater likelihood of pADT (OR 1.61, 95% 1.34-1.94) compared to RP.
Conclusions:
Community social vulnerability independently increases the likelihood of non-surgical and potentially non-curative management of prostate cancer. SVI domains can provide specificity into which community characteristics may drive vulnerability and aid in identifying communities for targeted, policy-focused interventions.
Impact of COVID-19 pandemic on the treatment of prostate cancer in Brazilian public health system, comparing pre and post pandemic data.
Authors: Carvalhal Gustavo Franco , Zulli Guilherme Augusto , Morbeck Igor Alexandre Protzner , Herchenhorn Daniel , Sasse Andre Deeke , McKay Rana R. , Rose Brent S , Maluf Fernando Cotait , Monteiro Fernando Sabino Marques , Souza Vinicius Carrera , Soares Andrey , Jardim Denis L. , Bastos Diogo Assed , Lages Dr. Paulo Sergio , Firminiano Elcio , Valverde Douglas Andreas , James Nicholas David
Published: February 2025

373

Background:
During the COVID-19 pandemic resources from the Brazilian Public Health System (BPHS) were directed to the treatment of COVID-19. The impact of the pandemic on the treatment of prostate cancer in Brazil has not yet been rigorously evaluated.
Methods:
We compared the number of radical prostatectomies (RP), radiotherapy (RT), and hormonal (HT) and chemotherapy (CT) treatments from March 1st, 2020 to February 29th, 2022, with that of the two pre-pandemic years (March 1st, 2018, to February 28th, 2020). Additionally, we evaluated the post-pandemic period from March 1st, 2022 to February 28th, 2024. A large proprietary healthcare data science platform offered by TECHTRIALS was surveyed.
Results:
In the pandemic, 15,364RPs were performed in the BPHS, (U$14,271,297); there was a 23.3% reduction in the number of surgeries compared with the pre-pandemic years: 19,778RPs, (U$18,056,470). In the post-pandemic years 18,716 RPs were performed (U$ 18,373,781.92), an increase of 21.8% in those treated by surgery. In the pandemic, 34,922 men received RT (U$39,616,736), a 18.7% reduction in the number of patients as compared with the two pre-pandemic years, when 42,614 men were treated (U$44,148,190). In the post-pandemic years, 43,142 men received RT, an increase of 19% compared to the pandemic years (U$48,870,739.03). Regarding HT, 116,490 men were treated during the pandemic (U$74,834,615); in the pre-pandemic, 115,949 patients received HT (U$75,179,674). In the post-pandemic years, 127,602 men were treated with HT (U$80,078,824), an increment of 6.5% in cost and 10% in the number of patients treated compared to the pandemic years. As to CT for hormone-resistant disease, in the pandemic period 14,946 men were treated (U$23,402,947) compared with 12,695 men treated in the two pre-pandemic years (U$19,239,099). In the post-pandemic years 18,850 men were treated (U$33.571.073,40) an increment of 48.4% in number of patients treated and with an increase of 74% in costs compared to the pandemic period.
Conclusions:
During the pandemic years, there was a significant reduction of potentially curative treatments for prostate cancer in the BPHS. The number of systemic therapies increased, probably reflecting the policy of maintaining systemic therapies active during the pandemic. In the post-pandemic years, there was an increase in the number of systemic treatments, while RT and RP returned to a state very close to their pre-pandemic numbers. The impact of the COVID-19 pandemic on prostate cancer mortality in Brazil remains speculative.
Fifteen-year outcomes of external radiation with or without 6 months of neoadjuvant deprivation therapy for intermediate risk prostate cancer.
Authors: Goy Barry , Yao Janis
Published: February 2025

388

Background:
Our aim is to retrospectively compare survival outcomes in intermediate-risk prostate cancer (IRPC) treated with external-beam radiation therapy (EBRT) with or without neoadjuvant-deprivation-therapy (NADT).
Methods:
Retrospective analysis was performed on 566 IRPC treated with EBRT from 2004-2007. NADT was given to 336 patients, while 230 underwent EBRT alone. Median duration of NADT was 6 months. Median dose of radiation was 75.6 Gy to isocenter. Freedom-from-biochemical-failure (FFBF) was defined by the PSA nadir+2.0. Multi-variable analysis and Kaplan-Meier estimates were performed.
Results:
Median follow-up was 11.5 years in the NADT+EBRT vs 12.0 years in the EBRT alone group, with up to 19.8 years of follow-up. NADT+EBRT had more adverse factors of clinical stage (p=0.02), iPSA (p<0.01), Gleason group (p=0.02), %cores>50% (p<0.01). 15-year FFBF, metastases-free-survival (MFS), prostate-cancer-specific-survival (PCSS), and overall survival (OS) for NADT+EBRT vs EBRT alone was 52% vs 49% (p=0.41), 85% vs 83% (p=0.59), 91% vs 91% (p=0.67), 53% vs 51% (p=0.82).
Conclusions:
After 15 years of follow-up, IRPC treated with EBRT with or without 6 months of NADT experienced a high PCSS of 91%, despite a very high PSA failure rate of about 49-52% of the patients. It’s unclear if 6 months NADT in addition to EBRT can improve PCSS or overall survival for IRPC, or just merely delay PSA progression.
Prognostic significance of tumor immune microenvironment dynamics in prostate cancer induced by androgen deprivation therapy.
Authors: Yanai Yoshinori , Kosaka Takeo , Mikami Shuji , Arai Masashi , Baba Yuto , Watanabe Keitaro , Takeda Toshikazu , Matsumoto Kazuhiro , Yamashita Makiko , Kitano Shigehisa , Oya Mototsugu
Published: February 2025

398

Background:
The dynamics of the prostate cancer microenvironment through androgen regulation are unclear. In this study, we analyzed the relationship between the dynamics of the immune microenvironment and prognosis after androgen deprivation therapy.
Methods:
We retrospectively reviewed the patients who underwent radical prostatectomy at our institution. Among them, 104 patients received prostate needle biopsy and neoadjuvant androgen deprivation therapy at the same institution. These cases were compared before and after androgen deprivation therapy. Immune cell infiltration in the cancer areas was assessed using multiplex fluorescent immunohistochemistry. Transcriptome analysis and gene panel analysis by next-generation sequencing were used to systematically and comprehensively analyze the expression and mechanisms of the immune microenvironment.
Results:
Few immune cells were detected in the needle biopsies before androgen deprivation therapy. After androgen deprivation therapy, prostatectomy specimens showed a significant change in various immune cells, including CD4
+
T cells, CD8
+
T cells, Foxp3
+
regulatory T cells, CD204
+
macrophages, and CD20
+
B cells (P< 0.001). In particular, CD8
+
T cells and CD20
+
B cells were significantly increased compared to patients who did not receive androgen deprivation therapy followed by total prostatectomy (P<0.001). Clustering analysis allowed stratification into three groups: One group had a predominant increase in CD8
+
T cells after androgen deprivation therapy, another group had a predominant increase in CD20
+
B cells, and the third group had no significant increase. The group with increased CD8
+
T cells had a significantly higher 5-year biochemical recurrence rate of 56 % (P=0.045). Differences in the mechanisms of androgen metabolism were observed among these cases.
Conclusions:
Differences in immune induction after androgen deprivation therapy have an impact on the prognosis of prostate cancer.
The impact of neoadjuvant therapy on the formation of tertiary lymphatic structures and the distinct prognosis in prostate cancer.
Authors: Liu Shengzhuo , Zhou Jing , Yan Xin , Yu Yunfei , Liu Xiaoyang , Dong Qiang
Published: February 2025

411

Background:
This study aims to investigate the characteristics and prognostic predictive efficiency of tertiary lymphoid structures (TLS) in prostate cancer (PCA). We also perform experiments to explore the effects of neoadjuvant hormone therapy (NHT) on TLS formation and immune infiltration in PCA.
Methods:
We retrospectively collected paraffin-embedded tumor tissue samples from 27 patients who didn`t receive NHT and underwent radical prostatectomy for PCa, and these patients were categorized as Cohort 1. We Additionally retrospectively collected 28 PCa tumor samples, from 14 NHT treated and 14 NHT naive patients, which are categorized as Cohort 2. We prospectively collected prostate biopsy tissue samples, as well as corresponding radical prostatectomy tumor specimens, from 21 patients who all received NHT and are categorized as Cohort 3. We performed HE staining and Multiplex immunohistochemical (mIHC) staining for ki67, panCK, CD21, CD4, CD8, and CD20 to evaluate TLS characteristics and immune infiltration level in different cohorts. We enrolled two GEO cohorts to evaluate the difference of TLS signature between NHT treated PCA and NHT-Naive PCA patients, and between pre-NHT and post-NHT tumor paired samples. We developed an immunocompetent orthotopic prostate cancer mouse model based on CRISPR-Cas9 gene editing technology. In in vivo experiments, we utilized flow cytometry to investigate the difference of CD4 and CD8 immune cell infiltration level in tumor tissues of mice treated or not with androgen deprivation treatment.
Results:
We found most of the NHT-naive PCa tissues were TLS positive (93%), and the majority of TLSs are located within the tumor region. Patients with positive mature TLSs, SFL-TLSs and higher intra-tumor TLSs density had significantly longer PFS duration. Compared with that in patients received no NHT, TLSs maturity grade and density were higher in NHT treated patients. A matched analysis using biopsy and paired post-NHT tumor samples revealed that NHT significantly increased the positive detection rate of tertiary lymphoid structures (TLSs) within the tumor, the maturity grade of TLSs, and the level of CD8+ T cell infiltration within the TLSs. Transcriptome analysis revealed elevated TLSs signature expression and CD8+ T cell infiltration in NHT treated tumor samples. In vivo experiments also show elevated CD3+ and CD8+ T cells infiltration level after NHT treatment.
Conclusions:
This study comprehensively characterizes TLSs in PCa and highlights the heterogeneity among patients. Our clinical cohort data, transcriptome sequencing analysis, and in-vivo experiment data confirm that neoadjuvant hormone therapy promotes immune cell infiltration, as well as the formation and maturation of TLSs within PCa tissues. Combining endocrine therapy with immunotherapy is a potential treatment approach for promoting prostate cancer prognosis.
Utilizing ChatGPT for assessing disease volume in patients (pts) with metastatic prostate cancer (mPC).
Authors: Garg Diya , Ostrowski Micah , Srivastava Ayana , Chigarira Beverly , Jo Yeonjung , Ozay Zeynep Irem , Hage Chehade Chadi , Gebrael Georges , Sayegh Nicolas , Fortuna Gliceida Galarza , Mathew Thomas Vinay , Maughan Benjamin L. , Swami Umang , Agarwal Neeraj , Li Haoran
Published: February 2025

42

Background:
Artificial intelligence (AI) has transformed many aspects of healthcare, particularly in medical imaging analysis. In mPC, accurate identification of bone metastases is crucial in guiding pt management. This proof-of-concept study explores the application of ChatGPT-4o, a multimodal, generative pre-trained transformer (large language model) with emerging image recognition capabilities, in diagnosing bone metastases from bone scans and determining disease volume in pts with mPC.
Methods:
In this IRB-approved, retrospective study, pts with newly diagnosed mPC and bone-predominant disease were randomly selected. Those who had previously received bone-protecting agents, chemotherapy, hormone therapy, or radiation therapy prior to the bone scan were excluded. Using CHAARTED criteria, high-volume versus low-volume bone disease was classified based on radiologist reports. The bone scan images were then uploaded to ChatGPT, which was instructed to act as a radiologist and asked to classify the disease volume. ChatGPT's classifications were compared to the radiologists’ findings by using Cohen’s Kappa test. Confusion’s matrix was used to represent the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of ChatGPT.
Results:
A total of 110 pts were selected, with a median age of 67 years (range: 44 to 89). The majority were Caucasian (98.2%). The median Gleason score was 9, and 77.3% of pts had de novo metastatic disease. The median PSA value at diagnosis was 35.2 ng/ml (range: 1-5843). High-volume disease was present in 52% of pts. ChatGPT's overall concordance with radiologists was 74% (Cohen's Kappa = 0.65). For high-volume disease, ChatGPT demonstrated a high sensitivity of 92.3% (48/52). However, it misclassified 45.8% of low-volume cases as high-volume (specificity: 54.2%). The PPV and NPV of ChatGPT were 68.6% and 86.7%, respectively. Interestingly, ChatGPT’s accuracy was significantly higher when each case was analyzed individually (77.7%) compared to when cases were grouped in a single conversation (43.5%, p<0.001).
Conclusions:
This hypothesis-driven research demonstrated that ChatGPT-4o has the potential to read medical images independently and apply existing knowledge, such as the CHAARTED criteria, to assist in content generation. However, its reliability remains a significant challenge for broader use in healthcare. Notably, it exhibited "information fatigue," where accuracy significantly declined when similar or repetitive information accumulated within a single conversation.
Domain-specific large language model for predicting prostate cancer treatment plan.
Authors: Ghaffar Umar , Tariq Amara , Choudry Mouneeb , Briggs Logan , Channar Aneeta , Banerjee Imon , Luo Man , Riaz Irbaz Bin , Abdul-Muhsin Haidar
Published: February 2025

428

Background:
Prostate cancer management presents a significant healthcare burden, with the need to efficiently triage patients for treatment. Our objective is to leverage large language models to predict physician-recommended treatment plans from unstructured clinical notes. By accurately predicting treatment plans, we aim to risk stratify and triage patients effectively, thereby optimizing the allocation of physician resources.
Methods:
448 unstructured initial urology consultation patient notes following first positive prostate cancer biopsy were identified. The recommended and final treatments received were manually annotated to establish ground truth labels (Table 1). The dataset was split 80:20 for training and testing, preprocessed to remove plan sections and formatted into question-answer (QA) format. A domain-specific large language model (LLM) inspired by GPT and a specialized tokenizer (PCa- LLM) for prostate cancer terminology were developed. QA models were built using the PCa-LLM and compared with those using GPT-2 as the backbone to predict recommended and final treatments.
Results:
For the physician-recommended treatment plans, our LLM (PCa-LLM) showed superior performance with higher AUROC scores for curative vs. non-curative treatments (0.78 vs. 0.65), chemo-hormonal vs. other non-curative treatments (0.89 vs. 0.65), and surveillance vs. all other treatments (0.72 vs. 0.70), while both models achieved the same high AUROC of 0.99 for chemo-hormonal vs. all other treatments. For final treatments, PCa-LLM demonstrated better AUROC for curative vs. non-curative treatments (0.77 vs. 0.74) and chemo-hormonal vs. other non-curative treatments (0.71 vs. 0.66), while GPT2 outperformed PCa-LLM for surveillance vs. all other treatments (0.78 vs. 0.70). Both models achieved an AUROC of 0.99 for chemo-hormonal vs. all other treatments.
Conclusions:
PCa-LLM accurately predicted most treatment categories better than GPT2, with higher AUROC scores, and can be utilized to triage prostate cancer patients using initial consultation notes.

Task
Physician -Recommended Treatment Plan
Final Treatment Received

Curative

Prostatectomy/Radiation
228
230

Non-Curative

Focal Therapy
22
15

Active Surveillance
40
45

Chemo-hormonal
30
30

Model Predictions (AUROC)

GPT2

PCa-LLM

GPT2

PCa-LLM

Curative vs. non-curative
0.65
0.78
0.74
0.77

Chemohormonal vs. other non-curative
0.65
0.89
0.66
0.71

Chemohormonal vs. all other
0.99
0.99
0.99
0.99

Surveillance vs. other non-curative
0.64
0.60
0.67
0.59

Surveillance vs. all other
0.70
0.72
0.78
0.70
Ethnic disparities in clinical trials for FDA-approved drugs in renal cell carcinoma: An analysis in the post-COVID-19-era (2020-2024).
Authors: Bastos Bruno R. , Schwartz Michael A. , Gligich Oleg , Barrientos Jacqueline Claudia , Ramirez-Ridelli Antonio , Borregales Leonardo , Bhandari Akshay , Nieder Alan , Kuritzky Nicolas , Linzer Debra , Cusnir Mike
Published: February 2025

452

Background:
Ethnic and racial disparities in oncology clinical trial participation remain a pressing challenge. Despite initiatives by the NCI and FDA since 2017 aimed at addressing these disparities, significant gaps persist in cancer treatment access and clinical trial involvement for minority populations. Notably, data on minority participation in clinical trials for FDA-approved renal cell carcinoma treatments during the post-COVID-19 era is limited.
Methods:
From 2020 to 2024, we analyzed data from 2,940 patients enrolled in five clinical trials (CheckMate 9ER, CLEAR, KEYNOTE 564, LITESPARK 005, TIVO-3) that resulted in FDA approval of new agents or indications for renal cell carcinoma. All 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 compared participation rates among White, Black, Asian and Hispanic patients against SEER data on renal cell carcinoma incidence.
Results:
Among the five trials, three (KEYNOTE 564, LITESPARK-005, and TIVO-3) reported racial data, but only two (KEYNOTE 564 and LITESPARK-005) provided information beyond White participants, including Black and Asian populations. No data on Hispanic participation was reported. Our analysis revealed that in the three trails providing racial data, 88% of participants were White indicating statically significant overrepresentation (p<0.0001). In the two trials with broader racial data, Black participation was only 1.2% signifying substantial underrepresentation (p<0.0001), while Asian representation was 11.6% with no significant disparity observed (p=0.05).
Conclusions:
The underrepresentation of minority groups (particularly Blacks and Hispanics) in FDA-approved clinical trials for renal cell carcinoma remains a significant concern in the post-COVID-19 landscape. Addressing these disparities necessitated the implementation of policies that enhance data collection and standardize ethnic classification. Additionally, international collaborative trials should prioritize distinct data reporting for U.S. participants, utilizing NCI SEER nomenclature for consistency.
Inclusion of patients with reduced performance status (ECOG 2 or higher) in FDA registrational trials for renal cell carcinoma (RCC).
Authors: Juthani Ronit , Parab Panah , Seetharaman Kala
Published: February 2025

453

Background:
Clinical trials often use performance status indicators to include only those participants with good baseline functional status. The Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) and the Karnofsky Performance Scale (KPS) are two such scales that determine a cancer patient’s ability to perform common tasks. As a result, the study population does not accurately represent the real-world population. We evaluated the inclusion of patients with ECOG 2 or greater/ KPS less than 70 in RCC clinical trials leading to FDA approvals between 2014 and 2024.
Methods:
The US Food and Drug Administration (FDA) approvals for drugs approved in RCC and associated clinical evidence were collected from the FDA website from 2014-2024. Data from each registrational trial was searched in public databases using drug name, trial name, and registration number. The total number and percentage of participants in each ECOG/KPS category were recorded and analyzed.
Results:
The FDA approved 13 drugs and combinations for the treatment of RCC from 2014 - 2024. A cumulative total of 8731 participants were included in these trials, with only 24 (0.3%) participants with ECOG PS 2 or greater (KPS <70). Only 3 of the 13 trials included participants with ECOG 2 (KPS <70) with 2 trials having <1% ECOG 2 participants. Only CABOSUN trial had >10% enrolment of ECOG 2 participants. There was no participation of ECOG 3 in any of the trials. Of the total participants, over 70% belonged to ECOG score 0 or KPS 90-100 (excluding CheckMate 214 for which PS distribution data was unavailable).
Conclusions:
There is poor enrollment of participants with ECOG 2 and greater in registrational clinical trials for RCC. This limits the therapeutic options available for patients with poor PS and is not representative of the real-world population. Greater inclusion of poor PS patients is needed in future trials.

Percentage enrollment of patients with reduced PS in registrational trials for RCC.

Clinical trial
Year
Reduced PS% (ECOG 2 or higher/KPS <70)

CABOSUN
2017
12.7%

S-TRAC
2017
0.2%

CheckMate 025
2015
0.4%

LITESPARK-005, KEYNOTE-564, TIVO-3, CLEAR, CHECKMATE-9ER, JAVELIN Renal 101, KEYNOTE-426, CheckMate 214, METEOR, Lenvatinib+Everolimus
2016-2023
0.0%
18
F-PSMA-1007 PET/CT for response assessment in patients with metastatic renal cell carcinoma undergoing first line tyrosine kinase or checkpoint inhibitor therapy.
Authors: Staehler Michael D. , Kunte Sophie , Holzgreve Adrien , Unterrainer Marcus , Blajan Iulia , Stief Christian G. , Bartenstein Peter , Casuscelli Jozefina , Unterrainer Lena
Published: February 2025

455

Background:
Evaluating the effectiveness of systemic therapy in patients with metastatic renal cell carcinoma (mRCC) is crucial for timely treatment adjustments. In an earlier preliminary study on a subset of mRCC patients, we compared responses to systemic therapy using [¹⁸F]PSMA-1007 PET and conventional imaging methods. In this research, our aim was to compare response assessments using PSMA PET versus CT scans in a larger cohort of mRCC patients undergoing systemic therapy. Additionally, we investigated the potential of using PSMA-PET-derived responses to predict outcomes.
Methods:
We performed a retrospective single-center analysis of patients with mRCC who underwent [¹⁸F]PSMA-1007 PET/CT in the context of tyrosine kinase or checkpoint inhibition and had at least one PET avid metastatic RCC lesion at baseline. All patients were treated with IO combination therapy either in combination with a TKI or ICI. Early treatment response at a mean of 9.5 weeks after the start of systemic therapy was compared to baseline scans. PET responses and measurements were correlated with CT results, progression-free (PFS) and overall survival (OS). Survival data were analyzed using log rank testing and Kaplan-Meier analysis.
Results:
25 patients with mRCC were enrolled. Median age was 65.2 years (range 24-87). Median PFS was 16.6 months (range 1.38 -58.69) and median OS 28.8 months (range 3.6 - 65.16). Median SUV, TTV, CT or PET response were not correlated with PFS or OS. Patients with a 10% reduction in SUVmax had a significant longer PFS with 23.1 months (95% CI 13.8-32.3) vs 3.6 (95% CI 1.4 – 5.9) months and OS of 36.2 months (95% CI 17.5 – 70.6) vs 11.1 months (95% CI 5.604 – 16.8) than patients without SUVmax response. SUVmax response was independent of administration of tyrosine kinase inhibitors or checkpoint inhibitors.
Conclusions:
Reduction of PSMA uptake on PET scans may be an independent biomarker beyond CT findings and warrants further investigation in mRCC. PSMA PET could be used for a better understanding of drug efficacy. Changes in PSMA PET are independent of the mechanism of action of systemic therapy in early prediction of therapy response and therefore might be considered a clinical biomarker.
Safety and efficacy of immune checkpoint inhibitor rechallenge in metastatic fumarate hydratase-deficient renal cell carcinoma: A retrospective study.
Authors: Tang Yanfeng , Wang Minghao , Liang Jiayu , Zeng Hao
Published: February 2025

500

Background:
Fumarate hydratase–deficient renal cell carcinoma (FH-deficient RCC) is a rare subtype of kidney cancer characterized by FH-inactivating alterations. Studies have revealed highly immunogenic features in this lethal disease, providing molecular evidence for implement of immune checkpoint inhibitor (ICI). Due to the lethal nature of FH-deficient RCC, a significant proportion of patients continue to have disease progression after receiving ICI combination therapy (ICI plus tyrosine kinase inhibitors, TKI). Herein, we aim to evaluate the safety and efficacy of immune checkpoint inhibitor rechallenge in metastatic fumarate hydratase-deficient renal cell carcinoma in real-world settings.
Methods:
A multicenter database of patients diagnosed with FH-deficient RCC, identified through IHC evidence of negative FH and/or positive 2SC, was explored. The study enrolled patients with metastatic FH-deficient RCC who received ICI combination therapy within three months of discontinuing prior ICI treatments between January 2018 and July 2023.
Results:
A total of 18 patients, each receiving at least two lines of ICI combination therapy, were included in the study. The majority of patients (n=15) experienced disease progression following prior-line immunotherapy. Among these, with 66.7% (10/15) showed progression in the original lesions, while 33.3% (5/15) developed new metastatic lesions. Three patients transitioned to later-line immunotherapy due to immune-related adverse events (irAEs) of grade 3 or higher. The incidence of grade 1-2 irAEs was comparable between prior and later-line therapies (28.15% vs. 27.30%, p=0.8932), as was the incidence of grade 3 or higher irAEs (0.86% vs. 0.29%, p=0.594). For the entire cohort, the median progression-free survival (mPFS) for prior-line ICI combination therapy was 16.2 months (95% CI: 5.565-26.835 months), and the mPFS for later-line ICI combination therapy was 15.2 months (95% CI: 3.915-26.485 months). The objective response rate (ORR) and disease control rate (DCR) for later-line therapy were 17% and 78%, respectively, compared to an ORR of 28% and a DCR of 67% for prior-line therapy.
Conclusions:
This cohort study demonstrated that ICI rechallenge achieved mPFS of 15.2 months and DCR of 78%, with a favorable safety profile in patients with FH-deficient RCC. Therefore, the resumption of ICI combination therapy may be a viable option for managing this lethal subtype of RCC.