bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of PSMA PET staging on initial treatment in newly diagnosed prostate cancer: An emulated randomized controlled trial.
Authors: Miller Sean Ryan , Tucker Gonzalez Rachel , Jackson William C. , Caram Megan Veresh , Tsao Phoebe A. , Stensland Kristian , Shah Yashesh , Wale Daniel , Elliott David , Wong Ka Kit , Viglianti Benjamin , Caverly Tanner C. , Hofer Timothy , Saini Sameer D , Green Michael D , Schipper Matthew J. , Dess Robert Timothy , Bryant Alex K.
Published: February 2025

350

Background:
Prostate-specific membrane antigen (PSMA) PET/CT has become a common initial staging modality for localized prostate cancer due to its increased sensitivity and specificity over conventional staging. However, the causal impact of widespread PSMA staging on initial prostate cancer treatments has not been described.
Methods:
We used electronic medical record data from a national, diverse health system (Veterans Health Administration) to emulate a randomized controlled trial in which patients with newly diagnosed conventionally localized unfavorable intermediate, high, and very high-risk prostate cancer were allocated to either upfront PSMA staging or conventional imaging with technetium-99 bone scan and pelvic CT or MRI. Primary outcomes included the use of any androgen deprivation therapy (ADT), advanced androgen receptor pathway inhibitors (ARPIs), radiotherapy, and radical prostatectomy assessed in the year after diagnosis. We used the cloning, censoring, and weighting technique to estimate the causal effect of PSMA staging, controlling for potential confounders. In exploratory analyses, we extracted radiographic stage from PSMA reports using a natural language processing algorithm and assessed the influence of PSMA findings (N0M0, N1M0, or M1) on treatment patterns.
Results:
9,049 patients met criteria for inclusion in the emulated trial, of whom 35% underwent PSMA staging and 46% underwent bone scan. In the emulated trial, PSMA staging was associated with higher rates of any ADT usage relative to conventional staging (adjusted hazard ratio [aHR] 1.26, 95% confidence interval [CI] 1.19-1.44), higher ARPI usage (aHR 1.52, 95% CI 1.33-1.78), lower prostatectomy usage (aHR 0.69, 95% CI 0.56-0.83), and no effect on radiotherapy usage (aHR 1.10, 95% CI 0.99-1.25). Compared to patients with PSMA N0M0, ARPI usage was higher in patients with N1M0 (aHR 6.87, 95% CI 5.41-8.73) and M1 (aHR 10.13, 95% CI 8.16-1.2.58). Patients with N1M0 or M1 disease were less likely to undergo prostatectomy compared to N0M0. Similar patterns were seen in subgroup analyses within risk groups.
Conclusions:
In this emulated randomized trial, PSMA staging of localized prostate cancer was associated with increased rates of any ADT and ARPI use and lower rates of prostatectomy relative to conventional staging. The implications of these treatment changes on oncologic outcomes require further study.
Evaluating the spectrum of disease within Gleason grade group 3: Results from a large institutional cohort.
Authors: Shee Kevin , Cowan Janet E , Wang Lufan , Ding Chien-Kuang Cornelia , Washington Samuel L , Shinohara Katsuto , Nguyen Hao , Cooperberg Matthew R. , Carroll Peter
Published: February 2025

361

Background:
A biopsy diagnosis of Gleason Grade Group (GG) 3 prostate cancer (PCa), also known as Gleason 4+3, automatically risk stratifies patients into at least unfavorable intermediate-risk by major guidelines including the AUA and NCCN, for which definitive treatment such as surgery or radiation is warranted. We hypothesized that GG3 prostate cancers represent a spectrum of disease, and that there may be GG3 PCa patients with lower risk of disease that may benefit from more conservative management.
Methods:
The Urologic Outcomes Database (UODB) at the University of California San Francisco (UCSF) was queried for men with localized, non-metastatic PCa diagnosed after 2000 who underwent radical prostatectomy (RP). Pre-biopsy clinicodemographic factors and biopsy and surgical pathology data were obtained, and Cancer of the Prostate Risk Assessment (CAPRA) and post-surgical CAPRA (CAPRA-S) scores were calculated. Outcomes were recurrence after surgery, defined as either biochemical failure (two PSA ≥0.2 ng/ml) or second treatment, and development of new metastasis. Multivariable Cox proportional hazards regression models were used to calculate associations with risk of recurrence and development of metastases, adjusting for year of diagnosis, age at diagnosis, percentage of positive biopsy cores (PPC), PSA density (PSAD), PSA before RP, Gleason pattern 4 histology, genomic risk score, prostate MRI findings, with or without CAPRA-S.
Results:
5262 men from the UODB database who underwent RP were included in the study. Of these, 904 (17%) men were diagnosed with GG3 on diagnostic biopsy. The number of GG3 diagnoses over time increased from 8.5% between 2000-2004 to 27% between 2020-2023. Among patients with initial diagnoses of GG3, pathologic GG after RP showed an increasing proportion of patients with upgrade to ≥GG4 and a decreasing proportion of patients with downgrade to <GG3 over time. Post-RP CAPRA-S scores overall increased over time, but remained broadly distributed. On multivariable analysis, favorable biopsy Gleason pattern 4 histology was strongest pre-operative factor associated with decreased recurrence after RP (HR 0.54, 95% CI 0.35-0.85, p<0.01). Increased PPC was the only factor associated with risk of metastasis after RP (HR 1.13, 95% CI 1.00-1.27, p=0.04).
Conclusions:
Patients with GG3 on diagnostic biopsy are a heterogenous group, with post-surgical grade and risk scores both broadly distributed and increasing over time. These data suggest that certain GG3 patients, such as those with favorable biopsy histology and lower PPC, may not be as unfavorable as guidelines suggest and may benefit from more conservative management.
Phase II trial of image-guided oligometastatectomy and radiation therapy in recurrent prostate cancer (SOAR).
Authors: Sanchez Alejandro , Swami Umang , Schmidt Bogdana , Dechet Christopher B. , Boucher Kenneth M , Chapman Lisa , Davis Hillary , Linton Jeff , Farr Erica , Leonhart Samuel , Hawks Josiah , Johnson Skyler B , Tward Jonathan David , Odei Bismarck , Gupta Sumati , Agarwal Neeraj , ONeil Brock , Maughan Benjamin L.
Published: February 2025

38

Background:
In a subset of patients with molecular-imaging defined recurrent oligometastatic prostate cancer (PCa), salvage oligometastatectomy with surgery and/or radiation may provide improved androgen deprivation therapy (ADT)-free survival.
Methods:
This is a phase II trial with oligorecurrent PCa after primary prostatectomy or radiation therapy detected on Axumin (n=11) or Prostate-Specific Membrane Antigen (PSMA) (n=9) positron emission tomography. Oligometastatic disease was defined as ≤ 10 total sites, either of lymph node (LN) only (Group A), bone only (Group B), or LN and bone (Group C). Surgical intervention for patients with LN disease included extended pelvic and/or retroperitoneal LN dissection, depending on the location of the LNs. Groups A and C received adjuvant IMRT without ADT if PSA response was ≥ 1/3 decrease but remained ≥ 0.2 ng/dL. The primary outcome was a reduction in PSA by ≥ 50% at 6 months. Secondary objectives included PSA progression free-survival (PSA-PFS), ADT-free survival, and safety.
Results:
We accrued a total of 20 patients. The median age was 65 years (IQR 61-70), 95% (19/20) had an ECOG of 0, and 10% (2/20) were Hispanic. All patients had a prior prostatectomy, after which 45% (9/20) received adjuvant/salvage RT, with 33% (3/9) including the pelvis/ prostate bed. 30% (6/20) had exposure to ADT before trial treatment. The median time from definitive prostate cancer treatment to trial treatment was 2.8 years (IQR: 0.9-6.0). Oligorecurrent disease occurred as lymph nodes only (18/20; 90%) or bony (2/20; 10%). Within Group A, one patient completed adjuvant RT. The average number of imaging-identified positive LNs was 1.8 (range 1-6). The primary endpoint of reduction in PSA by ≥ 50% at 6 months was 40% (95%CI 19-64%) (Table 1). The secondary endpoint of PSA-PFS at 12 months was 84.4% (95%CI 66.6-100%). ADT-free survival at 12-months was 71.4% (95% CI 52.7% - 96.6%). There were no Clavien Grade III-IV complications.
Conclusions:
Salvage treatment of oligometastatic disease after prostatectomy or radiation identified on molecular imaging is feasible and safe. Nearly half the cohort had a good response to salvage treatment, demonstrated by a ≥ 50% reduction in PSA at 6 months. Ongoing analyses include comparing imaging and pathology correlations, and comparing complete/ partial responders and treatment failure. Further research is needed to identify ideal candidates for salvage treatment. Clinical trial information:
NCT03796767
.

PSA progression-free survival at 6- and 12-months (PFS).

Time
Estimate
95% Confidence Interval

6 months
100%
---

12 months
84.4%
66.6-100%
Rates of acute GI and GU toxicities with dose-escalated intensity modulated proton therapy (IMPT) for the treatment of node-positive prostate cancer.
Authors: Zerey Mehmet Murat , Gal Omer , Rodrigues Maria-Amelia M. , Kaiser Adeel , Gutierrez Alonso , Mehta Minesh P. , Wohl Jessica , Fagundes Marcio
Published: February 2025

380

Background:
Node-positive prostate cancer (PCa) poses a unique treatment challenge since bowel radiation tolerance often limits the delivery of doses of 60-70Gy or more required to control gross nodal disease. IMPT is a novel therapeutic option which utilizes beam stopping properties to achieve dose sparing of normal organs with the ability to dose escalate (DE) with potentially greater safety. However, the safety of DE-IMPT in node positive PCa has not been well described.
Methods:
Data were reviewed for consecutive patients treated between 9/2018-4/2024 with DE-IMPT for radiographically detected node-positive PCa. Treatment to the prostate and seminal vesicles consisted of 78Gy/39fractions; elective nodal regions received 46-48.6Gy in 1.8-2Gy/fraction, as part of whole pelvis treatment, while positive nodes were DE to a mean equivalent dose at 2 Gy/fraction (EQD2) dose of 66Gy (54-77.1Gy) in 1.8-2.5Gy/fraction, based on respecting predefined surrounding organs at risk (OAR) tolerances. Acute toxicities were assessed at baseline, weekly during treatment, and up to 3 months post-IMPT using Common Terminology Criteria for Adverse Events (CTCAE version 5).
Results:
The study included 58 patients presenting with a mean of 3 positive nodes (1-12). Median follow up was 19.5 months (3-67 months). Median age was 73 years (49-86). Majority were high-risk: Gleason 8-10 (67.2%), T3a-b (50%), PSA > 20 (44.8%). Median prostate gland volume was 52cc (19-157). All pts received androgen deprivation therapy (ADT) with 97% completing at least 6 months; Androgen receptor pathway inhibitors were added in 26 pts (45%). Overall mean rectal V70, V60 and V50 were 6.7%, 11.2% and 16.5% while mean bladder V70, V60 and V50 were 12%, 17.3% and 24%, respectively. Mean small bowel dose to 1 cc volume D
1cc
was 50.7Gy (45.6-57Gy), while mean Dmax point dose to 0.03cc was 52.2Gy (47.8-61.8). Worst acute Genitourinary (GU) toxicities Grade 0 and 1 were 1.7% and 12%, respectively. During treatment, 18/58 patients (31%) were started on Alpha-blockers for increased urinary frequency, retention and urgency, consistent with GU Grade 2 toxicity of which 7(39%) had discontinued medication by 3 months post-treatment. Before treatment, 32/58 (55.1%) were already on Alpha-blockers. There were no GU Grade ≥ 3 toxicities observed. Acute gastrointestinal (GI) Grade 0 and 1 were 43.1% and 53.5%, respectively. Grade 2 GI toxicities were observed in 2 (3.4%) patients consisting of diarrhea and proctitis. One patient (1.7%) developed transient Grade 3 enteritis.
Conclusions:
This contemporary series demonstrates that DE-IMPT is a safe treatment option for node-positive PCa with acceptable rates of acute grade 1 or 2 toxicity. Acute grade 3 toxicity was rare, occurring in only one patient in this cohort.
Hypofractionated radiotherapy for prostate cancer (HYDRA): An individual patient data meta-analysis of randomized trials in the MARCAP consortium.
Authors: Kishan Amar Upadhyaya , Sun Yilun , Dearnaley David P. , Hall Emma , Tree Alison , Catton Charles , Lukka Himanshu , Lee William Robert , Sandler Howard M. , Incrocci Luca , Heemsbergen Wilma , Wong Jessica Karen , Horwitz Eric M. , Hoffman Karen E. , Hassanzadeh Comron , Kuban Deborah A. , Sanguineti Giuseppe , Arcangeli Stefano , Nikitas John , Spratt Daniel Eidelberg
Published: February 2025

385

Background:
Trials comparing moderately hypofractionated radiotherapy (MHFRT) against conventionally-fractionated radiotherapy (CFRT) for prostate cancer have varied considerably in intent (non-inferiority vs. superiority) and MHFRT dose. Herein, we compare the efficacy and toxicity profiles of isodose MHFRT and dose-escalated MHFRT.
Methods:
Individual patient data were obtained from 7 phase III trials comparing MHFRT vs. CFRT: three (n=3454) with isodose and four (n=2426) with dose-escalated MHFRT. Meta-analyses were designed to compare progression-free survival (PFS), late grade ≥2 genitourinary (GU) and late grade ≥2 gastrointestinal (GI) physician-scored toxicity, and clinically-significant decrements in patient-reported urinary or bowel quality of life (QOL).
Results:
After a median follow-up of 5.4 years (interquartile range [IQR], 4.6-7.2) and 7.1 years (IQR 5.7-8.4) following isodose and dose-escalated MHFRT, there were no differences in PFS (hazard ratio [HR] 0.92, 95%CI 0.81-1.05 and HR 0.94, 95%CI 0.82-1.09, respectively). Neither isodose nor dose-escalated MHFRT were associated with increased odds of grade ≥2 GU toxicity (odds ratio [OR] 1.16 95CI% 0.86-1.57 and OR 1.20, 95%CI 0.95-1.51). The odds of grade ≥2 GI toxicity were higher with dose-escalated (OR 1.48, 95%CI 1.14-1.92) but not isodose MHFRT (OR 1.30, 95% 0.59-2.87). Isodose MHFRT did not show different odds of urinary (OR 1.03, 95%CI 0.51-2.09) and bowel (OR 0.76, 95%CI 0.40-1.43) QOL decrements, while dose-escalated MHFRT was associated with greater odds of bowel (OR 1.68, 95%CI 1.07-2.61), but not urinary (OR 1.57, 95%CI 0.87-2.85), QOL decrement.
Conclusions:
Isodose MHFRT and dose-escalated MHFRT both have similar efficacy compared with CFRT, but dose-escalated MHFRT is associated with higher physician-scored and patient-reported bowel and urinary toxicity. Isodose regimens, e.g. 60 Gy in 20 fractions, should be the standard MHFRT regimen for localized prostate cancer.
Clinical protocols to monitor efficacy of [
177
Lu]Lu-PSMA radiopharmaceutical therapy in metastatic castration-resistant prostate cancer.
Authors: Unterrainer Lena , De Leiris NIcolas , Unterrainer Marcus , Ilhan Harun , Delker Astrid , Hempel Linus , Ells Zachary , Zahner Joseph , Holzgreve Adrien , Zacherl Mathias J. , Casuscelli Jozefina , Kiraz Kevin , Leenhardt Julien , Jacquet Emmanuelle , Long Jerome , Laramas Mathieu , Paller Channing Judith , Solnes Lilja B , Gafita Andrei , Djaileb Loic
Published: February 2025

39

Background:
To assess the prognostic value of post-therapy [
177
Lu]Lu-PSMA (LuPSMA)-SPECT/CT by visual RECIP 1.0 during LuPSMA radioligand therapy and to develop an evidence-based clinical protocol to monitor efficacy to LuPSMA.
Methods:
Patients who received LuPSMA between April 2019 and November 2023 and who underwent at least two LuPSMA-SPECT/CT (SPECT) were included. Three independent readers interpreted pairs of baseline and interim LuPSMA-SPECT/CT after 2 cycles of therapy for visual Response Evaluation Criteria In PSMA-imaging (RECIP) 1.0. The primary outcome was the prognostic value of post-therapeutic SPECT by RECIP 1.0 for overall survival after LuPSMA. The secondary outcome was the agreement between SPECT and PSMA-PET/CT (PET) performed after 2 cycles of LuPSMA.
Results:
105 patients were included. In SPECT PD was associated with shorter OS compared to SD (HR=2.51;95%;CI:1.19-5.28;p=0.015) and to PR (HR=6.48;95%;CI:2.67-15.70;p<0.001). 73/105 (69.5%) had a PET after 2 cycles. 7/73 (10%), 30/73 41%), 22/73 (30%), and 30/73 (41%) patients had a tumor progression by SPECT, PET, SPECT+PSA, and PET+PSA, respectively. All 7/73 (10%) patients with PD by SPECT had PD by PET. The C-index for SPECT was inferior to the one of SPECT+PSA (0.54 vs 0.62; p=0.03) and PET (0.54 vs 0.66; p<0.001) while SPECT+PSA did not differ significantly from PET (0.62 vs 0.66; p=0.07).
Conclusions:
Post-therapeutic SPECT/CT by RECIP 1.0 after 2 cycles of LuPSMA therapy is prognostic for overall survival and can be used for treatment response evaluation purposes. PSMA-PET/CT identified significantly higher number of patients with progressive disease compared to LuPSMA-SPECT/CT. A composite classification system of LuPSMA-SPECT/CT+PSA was not significantly different from interim PSMA-PET/CT for response evaluation to LuPSMA.
Evaluating the efficacy and safety of pelvic lymph node dissection in high-risk prostate cancer patients undergoing radical prostatectomy: A systematic review and meta-analysis.
Authors: Wang Qihao , Ye Jianjun , Zheng Lei , Chen Kai , Wei Qiang , Bao Yige
Published: February 2025

390

Background:
Pelvic lymph node dissection (PLND) is currently considered the gold standard for lymph node staging in prostate cancer patients. However, there is a paucity high-quality evidence demonstrating an oncological prognostic benefit of PLND in high-risk prostate cancer (PCa) populations, as defined by D'Amico risk classification.
Methods:
We conducted a comprehensive systematic literature review utilizing MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE databases. The search encompassed studies up to June 2024, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We identified original articles published in journals that reported survival analyses using Cox regression analysis and differences in hazard ratios (HRs) for the biochemical recurrence (BCR)-free survival (BRFS) (primary outcome) and metastasis-free survival (MFS), overall survival (OS) or cancer specific survival (CSS) (secondary outcomes). A meta-analysis of the effect of PLND on primary and secondary endpoints was performed using a random effects model.
Results:
Our analysis included seven studies, comprising one prospective and the rest retrospective. Pooled outcome data showed that PLND after radical prostatectomy did not independently predict BRFS (HR: 1.22; 95%CI: 0.99-1.50; p=0.006), MFS (HR: 1.21; 95%CI: 0.86-1.70; p=0.27), OS (HR: 0.91; 95%CI: 0.74-1.12; p=0.37), or CSS(HR: 1.02; 95%CI: 0.74-1.42; p=0.89) in high-risk prostate cancer patients. Heterogeneity was low to moderate.
Conclusions:
The available pooled analyses suggest that the therapeutic value of PLND is unclear. The high-risk PCa population should be carefully selected for lymph node dissection.
Cross resistance among novel androgen receptor axis-targeted agents in non-metastatic castration-resistant prostate cancer: A multi-institutional retrospective study.
Authors: Fujita Naoki , Yoneyama Fumiya , Kawashima Yohei , Tanaka Ryuma , Oishi Takuya , Miura Hikari , Okita Kazutaka , Ohyama Chikara , Hatakeyama Shingo
Published: February 2025

395

Background:
Previous studies reported a cross resistance among novel androgen receptor axis-targeted agents (ARATs) in patients with metastatic castration-resistant prostate cancer. However, the effects of sequential therapy with novel ARATs in non-metastatic castration-resistant prostate cancer (nmCRPC) remain unclear.
Methods:
This multi-institutional retrospective study included 56 patients with nmCRPC treated with second-novel ARATs after first-novel ARATs treatments, including apalutamide, enzalutamide, darolutamide, and abiraterone acetate between January 2014 and April 2024. The duration of novel ARATs treatment and PSA response were compared between first-use and second-use of novel ARATs.
Results:
The median age at nmCRPC diagnosis were 76 years. Of the 56 patients, 14 (25%), 16 (29%), 11 (20%), and 16 (29%) were treated with apalutamide, enzalutamide, darolutamide, and abiraterone acetate as second-novel ARATs. Median duration of novel ARATs treatment in second-use was significantly shorter than that in first-use (7.0 month vs. 14 month, respectively,
P
= 0.038). The rates of PSA decline ≥50% and ≥90% in second-use were significantly lower than those in first-use (25% vs. 73%,
P
< 0.001; 9.1% vs. 36%,
P
= 0.004; respectively). The rate of patients who did not achieve any PSA response in second-use was significantly higher than that in first-line use (45% vs. 11%,
P
< 0.001).
Conclusions:
A significant cross resistance among novel ARATs was observed in patients with nmCRPC. A further study is needed to evaluate the optimal candidates for sequential therapy with novel ARATs.
Using AI to identify optimal clinical, genomic, and radiographic prognostic features and novel risk classifiers compared to routinely available risk classifiers.
Authors: Tward Benjamin Victor , Johnson Skyler B , Tward Jonathan David
Published: February 2025

396

Background:
This study investigated the use of artificial intelligence (AI) and traditional statistical techniques to identify and validate clinical (Clin), MRI-report-derived (MRIr), and genomic classifier (GC) features important for prognostic biomarker development and staging systems for prostate cancer metastasis. AI models were compared with conventional risk classifiers for prognostic accuracy.
Methods:
Data from 576 patients in a prospectively collected research registry, including 35 Clin, 1 GC, and 7 MRIr features, were used. Random forest (RF) classification and artificial neural networks (ANNs) using Leave-One-Out Cross-Validation evaluated the key features predictive of metastasis. Models with 35, 9, 6, or 0 Clin features were compared to those ± MRIr or GC features. ANN prognosticators from each model were fed into competing-risk regressions and compared to other established risk classifiers (CAPRA, STARCAP, 22-gene genomic assay (Decipher), Cell-Cycle Progression (CCP, Prolaris) score, and Combined Clinical Cell-Cycle Risk (CCR, Prolaris)) by the 5-year AUC (AUC5) for prognostic accuracy.
Results:
AI-derived models combining Clin ±GC +MRIr features (AUC5 range 0.72-0.76) outperform models excluding MRIr features (AUC5 0.66-0.71). AI models perform similarly to contemporary risk classifiers like Prolaris, CAPRA, STARCAP (AUC5 of 0.79. 0.77, 0.76, respectively (Table)). Models with 6 Clin, 4 MRIr, and a GC (Clin: Age, BMI, PSA, cT, alcohol use, and primary Gleason score; MRIr: prostate volume, max tumor diameter, extracapsular spread, and lymphadenopathy suspicion; GC: CCP score) performed as well as conventional classifiers. The classifier with the best ability to prognosticate early metastasis was Prolaris (AUC5 0.79).
Conclusions:
The findings indicate that AI biomarker discovery pipelines, integrating Clin, MRIr, and GC features, can successfully identify new and previously identified prognostic factors. AI-derived models have similar accuracy in predicting metastasis compared to contemporary risk classifiers. Adding MRIr and GC features improves risk prediction of early metastasis in AI-trained models. Lifestyle factors may have an important role in metastasis.

Total # Features
Genomic Features
Radiographic Features
Clinical Features
Time-Dependent Competing Risk Regression

3-Year AUC
5-Year AUC

35 Clinical Feature AI Models (n=576)
43
1
7
35
0.70
0.72

42

7
35
0.69
0.72

36
1

35
0.64
0.66

35

35
0.62
0.65

11 Clinical Feature AI Models (n=576)
16
1
6
9
0.72
0.76

15

6
9
0.71
0.75

10
1

9
0.67
0.71

9

9
0.67
0.70

6 Clinical Feature AI Models (n=576)
11
1
4
6
0.73
0.75

10

4
6
0.73
0.75

7
1

6
0.61
0.64

6

6
0.62
0.65

0 clinical feature AI Models
7
1
6
0
0.66
0.68

6

6
0
0.65
0.67

Prolaris (n=570)
6
1

5
0.75
0.79

STARCAP (n=566)
5

5
0.72
0.77

CAPRA (n=570)
6

6
0.72
0.76

CCP score (n=576)
1
1

0.73
0.74

Decipher (n=25)
1
1

0.40
0.29
Feasibility of enriched amplicon circulating tumor DNA sequencing to detect minimal residual disease (MRD) after prostatectomy in localized prostate cancer.
Authors: Zang Peter D. , Lama Daniel , Huang Ziyi , Jaime-Casas Salvador , Contente-Cuomo Tania , Stampar Mojca , Marshall Adriana , Dinwiddie Devin , Berens Michael E. , Pond Stephanie , Trent Jeffrey M. , Yuh Bertram , Lau Clayton S. , Murtaza Muhammed , Li Yun Rose , Dorff Tanya B.
Published: February 2025

402

Background:
Nearly one third of men with prostate cancer experience relapse after radical prostatectomy, often despite achieving undetectable PSA nadir. An assay to detect minimal residual disease would be valuable to identify patients who could benefit from adjuvant therapy.
Methods:
Eligible patients had biopsy proven prostate cancer and planned to undergo prostatectomy for definitive therapy. Blood was drawn at pre-specified timepoints (TP) including prior to prostatectomy (TP1), on the day after surgery or at the 1-week post-op catheter removal visit (TP2), and at 1-month post-op with no interval treatment (TP3). We performed tumor-guided plasma DNA analysis using a novel method based on single-stranded adapter ligation, incorporation of unique molecular identifiers (UMIs), targeted PCR, normalization of amplicons using hybrid-capture, and targeted sequencing. Using tumor and germline exome sequencing, we designed and validated multiplexed assays to target somatic founder mutations. We prepared targeted sequencing libraries using a median of 6.7 ng input plasma DNA.
Results:
11 patients were enrolled after IRB approval. 1 (9.09%) had grade group 2, 1 (9.09%) grade group 3, 5 (45.45%) grade group 4, 4 (36.36%) grade group 5 disease. Median PSA pre-op was 9.3 ng/mL (range: 1.7 – 21.47). Tumor DNA sequencing was successful and targeted assays were generated for all patients (11/11). Median number of targets tested was 20 (range 4 to 88). We analyzed 31 plasma DNA samples obtained from 11 patients. Median on-target rate in plasma DNA was 90.5% (range 76.0% to 96.3%). Prior to surgery (TP1), 5/11 (45%) patients had detectable ctDNA at a median tumor fraction of 0.077% (range: 0.006% to 3.4%). At post-op TP (TP2), the ctDNA was detectable in 7/11 patients (64%) at a median tumor fraction of 0.024% (range: 0.004% to 3.1%). Detectable ctDNA was observed at 1 month (TP3) in 5/8 patients (62.5%) at a median tumor fraction of 0.022% (range 0.010% to 0.037%). For an exploratory analysis, we examined whether persistent ctDNA detection at the 1 month TP3 was associated with later relapse. Of the 5 patients with PSA relapse, 3 (60%) of patients had detectable residual ctDNA at TP3 with median follow up time of 61.75 months.
Conclusions:
Localized prostate cancer has been noted to have low tumor shed, limiting meaningful ctDNA detection rates with prior assays (Hennigan 2019). Our results show promising feasibility of a novel tumor-informed ctDNA assay in this setting. In addition, there was preliminary evidence of residual ctDNA detection predicting relapse.
Phenotypic and genetically predicted leukocyte telomere length and prostate cancer risk: Results from a large-scale longitudinal cohort study.
Authors: Liu Xiaoyang , Liu Shengzhuo , Yan Xin , Zhou Jing , Yu Yunfei , Dong Qiang
Published: February 2025

404

Background:
Previous studies on the correlation between leukocyte telomere length (LTL) and prostate cancer (PCa) have shown contradictory results. Our study aims to further explore the potential relationship between LTL and PCa.
Methods:
In this study, a total of 229,022 male individuals were enrolled from the UK Biobank to investigate this association . Both unadjusted and covariates-adjusted Cox proportional hazards regression models were employed. The primary outcome was defined as the diagnosis of incident prostate cancer using in-patient data and the death registry of the UKB cohort. To validate the reliability of the primary findings, secondary analyses, including Mendelian randomization (MR) were conducted.
Results:
The primary analysis demonstrated that longer LTL was substantially associated with higher risk of prostate cancer, with associations remaining robust after adjusting for potential covariates (HR: 1.444, 95% CI: 1.247-1.673, P < 0.001). Similar results were observed when LTL was analyzed as both a continuous and categorical variable, and the association were shown to be inversely U-shaped. At the genetic level, the association was further validated using MR across different prostate cancer databases, with results consistent with our primary analysis.
Conclusions:
Our findings offer compelling evidence that leukocyte telomere length is an important risk factor for prostate cancer.

Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between leukocyte telomere length (analyzed both as a continuous variable and by quartile categories) and prostate cancer risk in the UK Biobank study.

　

Model I
Model II
Model III

Cases

N

Median

HR

95%CI

HR

95%CI

HR

95%CI

10693
198830
0.810
1.505
1.301-1.741
1.454
1.256-1.683
1.444
1.247- 1.673

　
　
　
<0.001
　
<0.001
　
<0.001
　

2761
49708
0.683
ref
ref
ref

2782
49707
0.773
1.088
1.032 -1.147
1.087
1.031 - 1.145
1.084
1.029-1.143

2607
49707
0.849
1.090
1.033-1.151
1.086
1.029-1.146
1.084
1.028-1.144

2543
49708
0.960
1.187
1.124-1.253
1.174
1.112- 1.240
1.170
1.108-1.236

　
　
　
<0.001
　
<0.001
　
<0.001
　

Model I adjust for age; Model II adjust for demographic variables (age; ethnic background) and socioeconomic variables (socioeconomic status; education); Model III adjust for demographic variables (age class; ethnic background) socioeconomic variables (socioeconomic status; education) and lifestyle variables (alcohol intake frequency; smoking history; body mass index; duration of walks; sleep duration; blood pressure).
Application of canary histology classifier in prostate biopsies for risk stratification.
Authors: Ding Chien-Kuang Cornelia , Cowan Janet E , Greenland Nancy , Stohr Bradley A. , Sirohi Deepika , Cooperberg Matthew R. , Simko Jeff , Carroll Peter
Published: February 2025

412

Background:
Nguyen
et al
recently proposed an outcome-based radical prostatectomy (RP) histologic classifier (PMID 38828674, “Canary histology risk group”), combining all high-risk carcinoma histology patterns into “unfavorable histology,” versus absence as “favorable histology.” We examine whether this classifier, with additional stratification of favorable, is applicable to prostate biopsies for risk stratification.
Methods:
Archival databases of one single institution were searched for patients with long term clinical follow-up after RP and available prostate biopsy slides. Most recent biopsies underwent blinded re-review. Canary risk group was assigned based on highest risk patterns in any core. Unfavorable histology encompasses all Gleason pattern 5, large cribriform/intraductal carcinoma (>0.25 mm), anastomosing cords of carcinoma, grade 3 stromogenic carcinoma, and complex intraluminal papillary architecture. To capture patterns potentially predictive of unsampled unfavorable histology, “biopsy borderline” combines small cribriform/glomeruloid (≤0.25 mm), simple glomerulations, predominance of extensive poorly formed glands, equivocal small anastomosing cords, grade 2 stromal response, and epithelial complexity associated with mucin (beyond mucinous fibroplasia). “Biopsy favorable” is defined as void of any unfavorable or biopsy borderline histology. Biopsy and RP Gleason Grade Group (GG), pT stage, and pN stage were recorded from original reports. Biochemical recurrence (BCR) was defined as consecutive PSA of ≥0.2 ng/mL 8 weeks after RP or receipt of salvage treatment. RP stage and GG were analyzed using chi-square. BCR-free survival was analyzed using Kaplan-Meier curve.
Results:
360 patients were identified (median, IQR): Age at diagnosis 61 years (56, 66), PSA at diagnosis 5.38 ng/mL (4.2, 7.6), post-RP follow-up 9 years, (7, 12). The patients were classified as histologically unfavorable (n=63; 17.8%), biopsy borderline (n=92; 25.6%), and biopsy favorable (n=205; 56.9%). The three-tiered classification is significantly associated with earlier BCR (log-rank p-value <.01), RP GG (<.01), pT stage (<.01), and pN stage (<.01) (Table).
Conclusions:
Unfavorable histology on biopsy was associated with highest risk of BCR after RP, compared to “biopsy borderline” and “biopsy favorable” groups. This proof-of-principle study demonstrates the three-tiered histology-based classifier could be applicable in biopsies for risk stratification.

Canary Histology Risk Group
N (%)
GG3+ at RP
pT3a at RP
pT3b at RP
pN1
BCR event within 7 years of RP

Unfavorable
63 (18%)
46 (73%)
30 (48%)
11 (17%)
11 (17%)
53 (84%)

Biopsy Borderline
92 (26%)
21 (23%)
32 (35%)
5 (5%)
1 (1%)
60 (63%)

Biopsy Favorable
205 (57%)
22 (11%)
69 (34%)
3 (1%)
0 (0%)
110 (54%)

All patients
360 (100%)
89 (25%)
131 (36%)
19 (5%)
12 (3%)
223 (62%)
Relationship of spatial transcriptomic analyses with distance-associated transcriptomic spectrum and morphology-specific signatures of localized prostate cancer.
Authors: Raizenne Brendan , Song Hanbing , Greenland Nancy , Tsui Maggie , Khan Jared , Li Taiqi , Chang Chih-Hao , Cooperberg Matthew R. , Huang Franklin W.
Published: February 2025

422

Background:
Current clinical management and classification of prostate cancer is dependent upon specimen morphology assessment. Limited studies have focused on identifying and mapping transcriptomic signatures within morphological variants. Additionally, the impact of transcriptomic distance-relationship between benign and tumor glands has yet to be identified. In this analysis, we profiled and derived signature gene sets for morphological variants and assessed the spatial impact of distance from the adjacent tumor areas on surrounding benign tissues.
Methods:
Four (three African American and one European ancestry) formalin fixed paraffin embedded prostate cancer samples were obtained via radical prostatectomy and underwent the GeoMx DSP workflow with gene expression level counts. The four patients each had different dominant morphologic features on the slide used, with one patient with extensive foamy gland morphology, one with extensive atrophic morphology, one with extensive mucinous morphology, and one with extensive Gleason pattern 5 carcinoma. Other regions of interest (ROIs) were benign (including benign glands, benign stromal) or mixed tumor/benign. Transcriptomic analysis was performed on these ROIs to derive the morphology-specific gene signatures. Additionally, distance-based spectrum of proximity of benign ROIs to tumor ROIs was constructed to identify genes that are significantly associated with distance to the nearest tumor ROI.
Results:
96 ROIs from four patients (denoted by the dominant morphological tumor features) were annotated. In total, 95 ROIs and 8,102 genes passed quality control for analyses. A distance-based spectrum analysis revealed that benign ROIs that are closer to tumor ROIs were highly enriched in transcriptomic androgen signature and MYC signature and endothelial or club-like features were enriched in benign ROIs further from tumor ROIs. Moreover, distinct gene set signatures were established for each morphological feature.
Conclusions:
Benign ROIs closer to the tumor are more tumor-like and enriched in androgen receptor pathways and MYC signatures. We identified transcriptomic differences among the morphological tumor features that demonstrate inter-patient and intra-patient tumor heterogeneity.
Prospective monitoring of prostate specific membrane antigen (PSMA) –positive recurrent prostate cancer: Preliminary data from 6 months PSMA follow-up.
Authors: Madan Ravi Amrit , Abel Melissa Lauren , Mena Esther , Lindenberg Liza , Hausler Megan , Williams Monique , Hankin Amy , Aragon-Ching Jeanny B. , Sena Laura , Pachynski Russell Kent , Posadas Edwin Melencio , Moon Helen , Bilusic Marijo , Arlen Philip M. , Patel Krishnan R. , Jolissaint Deborah , Chesnut Gregory T , Figg William Douglas , Karzai Fatima , Choyke Peter L.
Published: February 2025

45

Background:
PSMA imaging can identify recurrent prostate cancer after definitive surgery/radiation prior to detection on computed tomography (CT) or bone scan. Radiation to PSMA+ findings is common but lacks clear data demonstrating long term benefit. PSMA+ recurrent prostate cancer (PSMArpc) is often defined and treated as metastatic castration sensitive prostate cancer (mCSPC), yet PSMA imaging alone as an eligibility criteria was never studied in the mCSPC trials. PSMArpc requires better understanding to define at-risk patients (pts).
Methods:
NCT05588128 enrolls pts after definitive and possibly salvage therapies. Pts are required to be 1 year removed from definitive therapy with a PSA≥0.5 ng/ml, testosterone≥100 ng/dL, and negative CT/bone scans. Lymph nodes (LNs) up to 1.5 cm and prior therapies are permitted. At enrollment pts have a baseline PSMA, which is repeated every 6 months (mos) if positive. If negative PSMA is done annually. CT and bone scans are also repeated annually. Pts are allowed to have radiation therapy or systemic therapies for ≤6 mos and remain on-study. Up to 350 pts will be enrolled and followed for up to 5 years.
Results:
Over 100 pts have enrolled since 3/2023 and 73 pts were evaluable after the 6-month PSMA scan/follow-up. The pts had a median age of 71 years, PSA=2.8, PSA doubling time=11.1 mos (30% less than 6 mos). In an overlapping descriptive analysis 10 pts were PSMA- and 15 pts had only local disease. For PSMA+ LNs, 15 pts had 1 LN, 8 pts had 2-3 LNs+, 4 pts had 4 LNs+, and 16 pts had 5+ LNs. 6 pts had bone findings, but negative bone scan. 3 pts had PSMA+ serosal nodules. After baseline PSMA 3 pts had radiation to solitary LNs, only 1 resolved/PSA declined. 1 pt elected androgen deprivation and 1 pt had salvage radiation. 4 pts enrolled in a clinical study at the NCI without androgen deprivation. At 6 mos PSMA scan only 2 pts had metastatic disease, both with bone scan findings, no pts had LNs beyond eligibility size criteria, and no pts had new visceral findings.
Conclusions:
These preliminary data from an ongoing study suggest PSMArpc is an indolent disease process and pts are at limited risk for clinically relevant progression within 6 mos. This study continues to accrue at the NCI and will seek to better define high-risk PSMArpc. These preliminary data may better inform the risks/benefits of aggressive treatment of PSMArpc and clinical studies in PSMArpc. Clinical trial information:
NCT05588128
.
Clinicopathological characteristics of cancer of unknown primary (CUP) with renal profile using gene expression profiling (GEP) based cancer classification.
Authors: Allam Joelle , Ma Li , Zhao Jianping , Estrella Jeannelyn , Higbie Victoria , Willett Anneleis , Matamoros Aurelio , Lano Elizabeth A , Treuner Kai , Raghav Kanwal Pratap Singh , Huey Ryan W
Published: February 2025

456

Background:
CUP is a rare and heterogenous clinicopathologic syndrome with unidentifiable origin at time of diagnosis. Based on immunophenotyping, specifically PAX8 staining, CUP with Renal profile (RCUP) is emerging as a distinct clinical subset. In addition to clinical presentation and immunohistochemistry (IHC), molecular profiling for tissue of origin may aid defining CUP subsets. Precision in diagnosis impacts therapeutics given that cytotoxic chemotherapy options for CUP do not overlap with tyrosine kinase inhibitors or checkpoint inhibitors used for renal cell carcinoma.
Methods:
We retrospectively (2018-2022) evaluated patients with CUP composed of cases (renal profile, N=100, clear cell or papillary) or controls (non-renal, N=200) identified using the 92-gene assay (CancerTYPE ID), a validated classifier for predicting tissue of origin. Clinicopathologic data including IHC and molecular profiling results were collected using pathology specimens and reports.
Results:
Baseline characteristics (age, gender, tumor grade) of cases and controls were comparable, except for histology, wherein adenocarcinoma was less common with RCUP (27% vs 48%, p<0.001). Median number of IHC stains performed was 11 (range 0-30) vs 9 (0-29) (p=0.04) in RCUP vs non-renal cases, respectively. While PAX8 was tested in 64% vs 39% (p<0.001) of cases, it was found to be strongly or focally positive in 87.5% vs 21.8% (p<0.001), respectively. In contrast to non-renal CUP, RCUP patients were more likely to have bone biopsies (24% vs 11.5%, OR 2.4, p=0.007), less likely to have high-TMB (2.8% vs 28.2%, OR 0.07, p=0.001), and had a lower proportion of TP53 mutations (18.8% vs 89.2%, OR 0.028, p<0.001), KRAS mutations (13.3% vs 77.4%, OR 0.045, p<0.001) and BRAF mutations (0% vs 42%, OR 0, p=0.015).
Conclusions:
RCUP appears to be a distinct subset of CUP with variable diagnostic workup. Critical IHC markers may be omitted in a considerable number of cases and despite positivity, may still confer an uncertain diagnosis. Key molecular factors appear to be different and may require tailored therapeutic approaches. This study further supports the clinical utility of GEP-based cancer classification with the 92-gene assay to predict RCUP and may be an important adjunct to IHC to improve diagnostic accuracy for CUP and to guide treatment selection for better clinical outcomes.

RCUP (N=100)
Non-renal CUP (N=200)

IHC

Cases Tested (%)
 

Cases Positive (%)
 

Cases Tested (%)

Cases Positive (%)
 

CK7 
83 
47 
81
75*

CK20 
75 
11
77
24*

PAX8 
64* 
88*
39
22

Napsin 
29 
28*
25
8

RCC
26*
31
4
13

Vimentin 
17 
94
5.5
73

*Significantly (p<0.05) greater proportion of cases.
Clinical and radiographic trends in patients with renal angiomyolipomas (AML).
Authors: Choudry Mouneeb
Published: February 2025

458

Background:
Renal angiomyolipoma (AML) is a common benign solid tumor of the kidney, typically found incidentally through imaging. These tumors can also present with symptoms like flank pain, hematuria, or retroperitoneal bleeding. AMLs are usually monitored and treated when they reach sizes between 4 and 6 cm based on clinical judgment, although the timing for intervention remains debated. This study aimed to investigate growth rates, assess radiographic features, and evaluate trends in clinical presentation.
Methods:
This multicenter, single-institution retrospective study reviewed patients diagnosed with renal AML at three Mayo Clinic locations (Rochester, Arizona, Jacksonville) from 1997 to 2021. Eligible patients had at least three abdominal scans over a minimum of two years and 36 months of follow-up. We reviewed radiologic reports, images, and charts to record demographics, tumor characteristics, imaging modalities, intervention rates, tumor sizes, and growth rates. The Mann-Whitney and Fisher exact tests were used for comparisons.
Results:
Among 839 patients, most were female (81.6%), with a median age of 58.55 years. Bleeding patients had significantly larger initial tumors (median 6.50 cm) compared to non-bleeding patients (median 1.20 cm), p < 0.001. Treatment with everolimus was more common in bleeding patients (12.2% vs. 2.1%), and the prevalence of tuberous sclerosis was higher in the bleeding group (19.5% vs. 6.3%). All bleeding patients underwent intervention, while 22.3% of the overall cohort received treatment. Follow-up duration and total scans did not differ significantly between groups. Over 12 months, non-bleeding patients had a median growth change of 0.00 cm [IQR: 0.00, 0.30], whereas bleeding patients showed a median growth change of 0.40 cm [IQR: 0.15, 1.00], p = 0.002.
Conclusions:
This study reveals significant differences in characteristics and growth patterns of renal angiomyolipomas between bleeding and non-bleeding patients. Bleeding patients had larger initial tumors and greater growth changes over time. Further studies on radiographic features may help identify lesions needing earlier intervention.

Demographic and clinical characteristics of patients with renal AML: Comparison bleeding vs non-bleeding groups.

Overall
Non-bleeding
Bleeding
P-Value

N
839
798
41

Gender (%)

Female

685 (81.6)
650 (81.5)
35 (85.4)
0.793

Male

152 (18.1)
146 (18.3)
6 (14.6)

Unknown

2 (0.2)
2 (0.3)
0 (0.0)

Age (median [IQR])
58.55 [47.04, 66.95]
58.72 [47.32, 67.19]
53.84 [42.88, 60.82]
0.015

Follow up (months) (median [IQR])
45.30 [37.12, 89.15]
46.45 [36.32, 89.52]
39.70 [36.30, 61.63]
0.233

Total scans (median [IQR])
3.00 [3.00, 5.00]
4.00 [3.00, 5.00]
3.00 [3.00, 4.00]
0.282

Initial size (cm) (median [IQR])
1.30 [0.80, 2.70]
1.20 [0.70, 2.50]
6.50 [3.00, 9.30]
<0.001

Everolimus (%)

Yes

22 (2.6)
17 (2.1)
5 (12.2)
0.001

Tuberous sclerosis (%)

Yes

58 (6.9)
50 (6.3)
8 (19.5)
0.003

Intervention (%)

Yes

187 (22.3)
147 (18.4)
41 (100)
<0.001
First preliminary results of artificial intelligence-generated, explainable treatment recommendations for renal cell cancer based on multidisciplinary cancer conferences.
Authors: Duwe Gregor , Mercier Dominique , Kauth Verena , Moench Kerstin , Junker Markus , Dengel Andreas , Haferkamp Axel , Höfner Thomas
Published: February 2025

465

Background:
The expert panel in multidisciplinary cancer conferences (MCC) decides on the best available treatment for the individual cancer patient. To support these complex evidence-based decisions, an artificial intelligence (AI) was developed to generate treatment recommendations for renal cell cancer (RCC) patients to support decision-making in MCC.
Methods:
We have transformed comprehensive patient data (99 individual machine-readable features) of 880 MCC recommendations for RCC from the years 2015 - 2022 into representations that can be used in software development. We developed a two-step process in order to train classifiers to mimic MMC recommendations. First, we identified superordinate categories of the recommendations. Afterwards, we specified the detailed recommendation. For this purpose, we used different machine learning (CatBoost, XGBoost, Random Forest) and deep learning (SoftOrdering-1d-CNN) approaches with 787 training cases and 93 test set cases. Accuracy weights are determined by F1-Score.
Results:
The KITTU-AI is able to generate fully automated treatment recommendations for patients with histologically confirmed RCC in MCC. First, the AI can decide which kind of superordinate recommendation should be applied, e.g. surgery or anticancer-drugs (Table). Second, our AI system is able to suggest the specific surgical treatment as well as the correct drugs (Table). The AI-generated recommendation is presented explainable based on the clinical features and their importance score.
Conclusions:
To our knowledge, we present the first time data for fully automated AI-based treatment recommendations for MMC in RCC with promising accuracy rates.Our selected AI architecture is able to learn and to generate medically comprehensible and explainable treatment recommendations. Small numbers of recommended therapies hamper AI training but this will improve with increasing numbers over time. Next, clinical trial data will be implemented to enable a higher level of explainability. Meanwhile, the first prospective validation is ongoing.

Accuracy rates for AI-generated treatment recommendations of renal cell cancer based on F1-scores (test set of 93 cases).

Task (number)
F1-Score ↑
#Classes
Class (number)
F1-Score

High Level Prediction (93)
0.76 (CatBoost)
5
Surgery (10)Medication (45)Aftercare (22)Best supportive care (4)Radiotherapy (12)
0.450.920.880.000.47

Low Level Surgical Prediction (10)
0.81(Soft Ordering)
3
Primary tumor resection (4)Resection of recurrent tumor (1)Metastases resection (5)
0.670.000.73

Low LevelDrug Prediction (45)
0.73 (XGBoost)
8
Sunitinib (8)Nivolumab (7)Cabozantinib (6)Pembrolizumab/Axitinib (5)Nivolumab/Ipilimumab (4)Pazopanib (3)Pembrolizumab (3)Other (9)
0.520.780.400.890.601.001.000.67