bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and genomic factors associated with tumor mutational burden (TMB) in prostate cancer.
Authors: Hougen Helen Y , Graf Ryon , C. F. Quintanilha Julia C. F. , Li Gerald , Punnen Sanoj , Mahal Brandon A 
Published: March 2023

240 Background: TMB is an emerging biomarker to predict clinical benefit from immune checkpoint inhibitors (ICI). Although high TMB in prostate cancer is rare, and we sought to evaluate independent associations of TMB by clinical factors, prior treatment, and genomics. Methods: This study used the US-based nationwide de-identified Flatiron Health-Foundation Medicine prostate cancer clinico-genomic database. The de-identified data originated from approximately 280 US cancer clinics (~800 sites) between January 2011-March 2022. Multivariable linear regression model was used to assess independent prediction of TMB levels, which were log2+1 transformed to better normalize distribution. Data are expressed as (estimate, [95% CI], p-value). Results: The study included 2,748 tissue specimens: 51.7% were from the prostate, 10.3% from bone, and 14.6% from lymph nodes. Specimens from white patients comprised 61.2% of samples, with another 7.5% from Black, 1.1% from Asian, and 30% from other or unknown race patients. Of our cohort, 58.5%, 15.5%, and 26.0% were from patients who received 0, 1-24 months, and >24 months of androgen deprivation therapy (ADT), respectively. Also 19.7%, 1.8%, 11.4%, and 0.4% had any exposure to novel hormonal therapies (NHT), Radium-223, taxanes, and ICI, respectively. Higher TMB was independently associated with ADT use >24 months (0.16, [0.05-0.27], p=0.005) and Asian race (0.36, [0.03-0.69], p=0.034). Prior treatment with NHT, taxanes, or radium was not associated with higher TMB. Compared to prostate, bladder (0.22, [0.03-0.41], p=0.023), liver (0.27, [0.13-0.42], p<0.001), and other (0.29, [0.15-0.43], p<0.001) biopsy sites were associated with high TMB, but lymph node biopsy was not. MSI-high (2.30, [1.96-2.64], p<0.001), MSI-intermediate (0.51, [0.14-0.88], p=0.007), and MSI-unknown (0.84, [0.60-1.09], p<0.001) were associated with increased TMB. Individually altered genes associated with increased TMB included MLH1 (0.77, [0.31-1.24], p=0.001), MSH2 (1.09, [0.74-1.45], p<0.001), MSH3 (0.64, [0.018-1.11], p=0.006), MSH6 (0.94, [0.61-1.26], p<0.001), BRCA2 (0.56, [0.43-0.69], p<0.001), CDK12 (0.38, [0.24-0.53], p<0.001), FANCA (0.42, [0.07-0.77], p=0.02), MRE11 (0.87, [0.11-1.62], p=0.025), and PALB2 (0.83, [0.48-1.18], p<0.001). No individual gene was independently associated with lower TMB. Conclusions: TMB associates with MSI status and MMR genes. However, aside from associating with long term ADT use, TMB does not have strong association with prior systemic treatment. Certain biopsy specimen sites including bladder and liver have increased TMB but overall, the association is relatively weak in comparison to MMR genes and MSI status. This study allows better understanding of how prior treatments, clinical and genomic factors affect TMB status, which may add value to MSI status in predicting treatment response in advanced prostate cancer.
Biology and usefulness of [-2]proPSA as a prognostic marker in CRPC patients.
Authors: Miyazawa Yoshiyuki , Tsuji Yusuke , Arai Seiji , Sekine Yoshitaka , Suzuki Kazuhiro 
Published: March 2023

242 Background: Prostate health index (phi) using -2proPSA (p2PSA), which is a precursor of PSA, has been reported to be useful as a marker for predicting the presence of cancer in the gray zone with a PSA value of 4-10 ng/ml. There is no detailed report on the biology of p2PSA in castration resistant prostate cancer (CRPC) patients and it is unknown. We retrospectively investigated the biology of p2PSA and its usefulness as a marker using CRPC patient's samples. Methods: The study was performed using samples from a prospective study of CRPC patients treated with enzalutamide. We examined 98 pre-enzalutamide treatment serum samples that can measure p2PSA. The samples were collectively measured by Beckman Coulter (Tokyo, Japan). We also examined the correlation between the measurement results of p2PSA and the prognosis of phi and CRPC patients calculated accordingly. This study was approved by the IRB of Gunma University Hospital (IRB 2021-092, 1983). Results: The study population of 98 patients had a median age of 73 years. The median PSA before administration of enzalutamide was 23.8 ng/ml, the median p2PSA was 208.8 pg/ml, and the median phi was 188.0. The median values of each parameter were divided into two groups, and the PSA progression free survival (PSA-PFS) and overall survival (OS) rate were compared by the Kaplan-Meier method. In the study of PSA-PFS, PSA, p2PSA, and phi could not be significant markers. In the OS study, the median OS of the PSA low group was NYR (not yet reached), the high group was 26.8 months, the p2PSA low group was NYR, the high group was 26.8 months, the phi low group was NYR, and the high group was 26.8 months. The OS was significantly better in the low- value group for each parameter (p-values 0.024, 0.034, 0.018, respectively). Conclusions: The biology of p2PSA in CRPC patients has been clarified. Although we couldn't find a clear advantage over PSA, we would like to add a study based on the data of this study.
Genomic alterations in patients with prostate cancer with liver metastases.
Authors: Casado Crystal , Caputo Sydney , Jaeger Ellen B. , Jang Albert , Sweeney Patrick L , Lanka Sree M , Gupta Kanika , Pocha Olivia , Hawkins Maddie , Huang Minqi , Lieberman Alexandra , Schwartz Jennifer , Miller Patrick , Barata Pedro C. , Layton Jodi Lyn , Lewis Brian E. , Ledet Elisa M. , Sartor A. Oliver 
Published: March 2023

248 Background: mCRPC patients with liver metastases have a poor prognosis and often progress rapidly on a variety of treatments. Previously, preliminary ctDNA analyses of mCRPC patients with liver metastases showed a range of commonly altered genes in patients with liver metastases (Ranasinghe et al; 2019). In this follow-up, we evaluated ctDNA alterations in an expanded cohort of mCRPC patients with liver metastases. Methods: From Tulane Cancer Center, retrospective review of mCRPC patients was used to identify patients with confirmed liver metastasis. All liver metastases were confirmed based on imaging data. All patients included had ctDNA evaluated with a multi-gene cancer panel via Guardant 360 assay (Guardant Health, Inc). Additional clinical annotation including family history, germline testing, staging, imaging, and laboratory values. Statistical analyses were performed with Fisher’s Exact and Wilcoxon Rank Sum tests. Results: 158 mCRPC patients with appropriate diagnostic imaging as well as ctDNA testing. From this group, 8% (n= 12) had confirmed liver metastases. Among the patients with liver metastasis, the most common alterations detected were in AR (50%; 6/12) and PIK3CA (25%; 3/12). Patients with liver metastasis were more likely to have amplifications in FGFR1 detected in their ctDNA (OR= 14.40; 95% C.I. (1.83, 113.22); p= 0.03). In addition to ctDNA, germline data was assessed, and it was found that patients with liver metastasis were more likely to have a pathogenic germline mutation (OR= 7.61; 95% C.I. (2.85, 20.31); p<.0001). The most common germline mutations detected in patients with liver metastasis were in BRCA2 (n= 3) and TP53 (n= 2). Conclusions: Though liver metastasis are less common in prostate cancer, it often occurs following extensive treatment and results in a poor prognosis for patients. In patients with liver metastasis, FGFR1 amplification was more often detected in ctDNA. Importantly, patients with liver metastasis were significantly more likely to have a pathogenic germline alteration.
Survival patterns based on site-specific visceral metastasis in patients with metastatic prostate cancer: Are outcomes of visceral metastases the same?
Authors: Ahmed Mohamed E. , Andrews Jack R. , Mahmoud Ahmed , Lee Matthew , Childs Daniel S , Kendi Ayse T. , Johnson Geoffrey , Tollefson Matthew K. , Boorjian Stephen A. , Karnes R. Jeffrey , Kwon Eugene D. 
Published: March 2023

269 Background: Metastatic visceral involvement in prostate cancer patients conveys a poor prognosis. Survival patterns of site-specific visceral metastasis are poorly understood. Here, we sought to investigate survival patterns in prostate cancer patients according to their first detected site of visceral metastasis. Methods: Retrospectively, we identified 200 patients with visceral metastatic prostate cancer. Patients were divided into three groups according to first site detected with visceral metastases; first-site lung metastases, first-site brain metastases, and first-site liver metastases. Visceral metastases were detected on either conventional imaging (CT/MRI), metabolic imaging (C-11 choline), or PSMA PET-CT scan. Follow up duration of our study was 80 months. Results: Clinicopathological variables are shown. The K-M curve of overall survival of the entire cohort suggests better survival patterns in patients with first-site lung metastases compared to patients with first-site brain or liver metastases (p<0.0001). In subset analysis of patients with CRPC, the K-M curve of overall survival, which demonstrates better survival outcomes in patients with first-site lung metastases in comparison with patients with first-site brain or liver metastases (p<0.0001). Conclusions: Our data suggests that prostate cancer patients with visceral metastatic disease have different survival patterns according to the first site detected with visceral metastasis. In our cohort, patients with first-site lung metastasis demonstrated better survival outcomes than patients with first-site brain or liver metastasis. Further studies are warranted. [Table: see text]
The profile study: Prostate cancer screening in men of Black African and African Caribbean ancestry—Early results.
Authors: Kinsella Netty , McHugh Jana Kathlyn , McGrowder Eva , James Denzil , Saunders Ed , Bancroft Elizabeth , Kote-Jarai Zsofia , Eeles Ros A. 
Published: March 2023

306 Background: Heritable risk factors account for a significant proportion of prostate cancer (PrCa) risk, of which only a minority are high risk Mendelian traits. Men of Black African and African Caribbean ancestry are at higher risk of developing PrCa in their lifetime (1 in 4) compared with the general population in the United Kingdom (1 in 8). PROFILE is a multi-cohort study of targeted screening for groups of men at higher risk of developing PrCa: 1) men of European ancestry with family history of PrCa, 2) men of black African and African Caribbean ancestry regardless of family history and 3) men with known rarer higher risk gene mutations for PrCa. This abstract concentrates on group 2. The aim is to investigate the role of targeted PrCa screening in men at higher genetic risk and its association with specific genetic profiles and biomarkers. Methods: Healthy men aged 40-69 are invited to participate. Inclusion Criteria: Both parents and all four grandparents must be of either black African or African Caribbean ancestry. Arm 1: PSA only – once PSA is below an age-related threshold (aged 40-49 and PSA ≥0ng/ml, aged 50-69 PSA >/= 2ng/ml) they continue on the study with annual PSA, only triggering a prostate MRI and Biopsy if the PSA is above the threshold. Arm 2: Regardless of PSA men opt for prostate mpMRI and biopsy. Polygenic risk score (PRS) calculated based on 230 SNPs including latest AA specific variants. Results: Arm 1: 121 enrolled PSA only (this has triggered 8 biopsies with 3 cancers). Arm 2: 58 enrolled MRI and biopsy, 58 MRIs and 36 biopsies carried out, PrCa detected in 15 men (42%). 22% are Gleason score ≥7. Association between PRS and MRI/Biopsy results will be presented. Conclusions: We will continue to perform MRI and biopsies on men, we will also carry out polygenic risk scores on these men to verify whether a genetic PRS can help guide enhanced screening for certain men in the population. Although data are early, a significant proportion of biopsies are positive for PrCa that needs radical treatment. Clinical trial information: NCT02543905 .
Geometry of hydrogel rectal spacer placement and risk of MRI-identified rectal wall infiltration.
Authors: Lischalk Jonathan W. , Haas Jonathan A. , Santos Vianca F. , Mendez Christopher , Sanchez Astrid , Doshi Ankur , Akerman Meredith , Kaminetsky Jed , Carpenter Todd , Sadowsky David , Katz Aaron , Lepor Herbert , Tong Angela 
Published: March 2023

312 Background: The use of rectal spacers in the management of localized prostate cancer treated with definitive radiotherapy has become ubiquitous in recent years. However, pre-treatment MRIs often identify varying degrees of hydrogel involvement within the rectal wall. In the present study, we evaluate the geometry of spacer placement and its association with radiological rectal wall infiltration. Methods: We identified all patients who underwent hydrogel rectal spacer placement in preparation for 5-fraction prostate SBRT from 1/2020 to 9/2021. Two specialty trained body radiologists evaluated all MRIs independently. Scans were evaluated for the following spacer parameters: spacer thickness, prostate-rectal distance, symmetry, and degree of rectal wall infiltration. Prostate-rectal distance was measured at the level of the prostatic apex, midgland, and base. Symmetry of the rectal spacer was measured using right or left lateralization from midgland. Degree of rectal wall invasion was categorized as follows: none, muscularis, submucosal, and intraluminal. Results: A total of 336 patients underwent MRI following hydrogel rectal spacer placement from 1/2020 to 9/2021. Patients were excluded from MRI if they had AICD/pacemaker, foreign body, or patient refusal. In those patients with any rectal wall invasion, gel thickness as measured at the base (11 vs. 10 mm, p = 0.02), midgland (14 vs. 10 mm, p < 0.001), and apex (12 vs. 8 mm, P < 0.001) was significantly larger than those patients without invasion. This translated into significantly larger distances between the posterior aspect of the prostate and anterior aspect of the rectum at the level of the apex (12 vs. 8 mm, p < 0.001) and midgland (13 vs. 11, p < 0.001), but not at the base (14 vs. 14 mm, p = 0.5). There was no association seen with asymmetrical spacer placement and rectal wall invasion (p = 0.7). Subgroup analysis of patients with more extensive invasion into the muscularis or submucosa confirmed significantly larger gel thickness at all prostate levels, as well as a larger prostate-rectal distance at the level of the apex and midgland. Significant associations remained consistent with both independent radiological evaluations. Conclusions: Hydrogel spacer rectal wall infiltration was associated with increased axial gel thickness, specifically at the level of the prostatic midgland and apex. Rectal wall infiltration was not associated with lateralization of gel. Rectal infiltration may be a result of surplus hydrogel placed particularly in the region where the potential space between the prostate and the rectum is limited.
Patient experiences with tissue-based genomic testing during active surveillance for prostate cancer.
Authors: Leapman Michael , Sutherland Ryan Andrew , Gross Cary Philip , Ma Xiaomei , Jeong Farah , Seibert Tyler M , Cooperberg Matthew R. , Catalona William , Loeb Stacy , Schulman-Green Dena 
Published: March 2023

333 Background: Tissue-based gene expression (genomic) tests improve estimates of prostate cancer aggressiveness and are increasingly used for patients considering or engaged in active surveillance; however, little is known about patient experiences with genomic testing and its role in decision-making for active surveillance. Methods: We performed a qualitative descriptive study consisting of in-depth, semi-structured interviews of patients with low- or favorable-intermediate-risk prostate cancer managed with active surveillance. The interview guide focused on experiences with biopsy-based genomic testing during their decision-making for prostate cancer management. We used purposive sampling to include patients who received genomic testing as part of routine clinical care and we over-sampled Black and Latino men. We continued interviews until thematic saturation was reached, iteratively created a code key and used conventional content data analysis. Results: The mean age was 68 years (range 51-79; n=20). At initial biopsy, 17 (85%) had a Gleason grade group 1, and 3 (15%) had a grade group 2 tumor. Fourteen (70%) participants identified their race/ethnicity as White, 5 (25%) as Black, and 2 (10%) as Latino. The decision to undergo genomic testing was driven by both participants and physicians’ recommendations; however, some participants were unaware that testing had occurred. Overall, participants understood the role of genomic testing in estimating their prostate cancer risk, and the test results increased their confidence in the decision for active surveillance. However, participants did not understand the difference between tissue-based gene expression tests and germline genetic tests, and commonly believed that tissue-based tests measured hereditary cancer risk. While some participants expressed satisfaction with the explanations provided by their physicians, others felt that communication was inaccessible and lacked sufficient detail. Conclusions: Patients interact with and are influenced by the results of biopsy-based genomic testing during active surveillance for prostate cancer, however testing may increase informational needs. Our findings indicate areas for improvement in patient counseling that can be used to increase patient knowledge and comfort with genomic testing.
Trends in the use of local intervention and its impact on oncological outcomes for metastatic castration-sensitive prostate cancer: A multicenter retrospective study.
Authors: Hatakeyama Shingo , Narita Shintaro , Tanaka Toshikazu , Sakurai Toshihiko , Ito Akihiro , Tsuchiya Norihiko , Habuchi Tomonori , Ohyama Chikara 
Published: March 2023

354 Background: The role of local intervention in addition to the standard of care for metastatic castration-sensitive prostate cancer (mCSPC) is unknown. Therefore, this study evaluated the trends of local intervention and their impact on oncological outcomes in patients with mCSPC in real-world practice. Methods: This multicenter retrospective study included 760 patients treated with either androgen deprivation therapy (ADT) without local treatment (no castration-resistant prostate cancer [CRPC] progression within 12 months, control group) or ADT plus local intervention (intervention group) between January 2005 and March 2022. The primary outcome was trends in the use of local intervention in patients with mCSPC. The secondary outcomes included evaluations of factors associated with CRPC-free survival in the intervention group. Results: The use of local intervention gradually increased in combination with upfront treatment for the duration of our study. The number of patients with local intervention combined with upfront treatment was significantly higher in patients with high tumor burden disease than in those with low tumor burden disease. Of the 108 patients who received local intervention comprising radiation therapy targeted to the prostate, a duration of >7 months of initial therapy before local intervention and a level of prostate-specific antigen <0.20 ng/mL at the time of local intervention were significantly associated with prolonged CRPC-free survival. Conclusions: Regardless of the tumor burden, the use of local intervention in combination with upfront therapy to treat mCSPC increased for the duration of our study. Local intervention in addition to the standard of care for mCSPC may be a feasible treatment option for selected patients, taking into consideration the duration of and response to initial treatment.
Length and Gleason pattern at positive surgical margin after radical prostatectomy to assess risk of postoperative recurrence in localized prostate cancer.
Authors: Kato Masashi , Tsuzuki Toyonori 
Published: March 2023

359 Background: The prostatic apex is most popular location of positive surgical margin (PSM) at radical prostatectomy (RP) and the frequency of apex is reported to be about 20-40% of all positive cases. Prostatic apex is also reported to lack a well-defined capsule. Some recommendation suggest that reporting require location of a PSM, as well as length of PSM, though there are also reports that these classifications is inadequate in some patients. In addition, there is a lack of tumor grade at PSM in these recommendations. This study aims to investigate the impact of location, number, length, and tumor grade at PSM on biochemical recurrence (BCR) after RP. Methods: We retrospectively evaluated 1013 patients with prostate cancer who underwent radical prostatectomy without neoadjuvant or adjuvant therapy at the hospitals that the authors were affiliated with between 2005 and 2013. All prostatectomy specimen slides were reviewed by a single genitourinary pathologist according to ISUP 2019 criteria. PSM were subcategorized according to the length of PSM (≤ 5mm or > 5mm), Gleason pattern (GP3 vs. GP4 or 5) at PSM, the number (single or multiple), and the location (apex-only or others). Results: The median patient age was 67 (range, 45–80) years. The median initial PSA was 6.8 ng/ml (0.4–82 ng/ml). The median follow-up period was 69 (0.7–135) months. Pathological T stage was in 73% of pT2 (n=733), 22% of pT3a (n=229), and 4% of pT3b (n=41). PSM was found in 377 cases. Length of margin is total and 5mm in median. PSM was found at apex-only in 187 cases (50%), and others showed other single location or multiple PSM. Single PSM is found in 293 cases (78%). GP3 at PSM was found in 130 cases, GP4 in 214, and GP5 in 33. GP3 at PSM tended to be more common in apex-only PSM. GP5, extra prostatic extension (EPE), seminal vesicle invasion, IDC-P, and PSM were significant in all the patients to predict BCR. Among the patients with PSM, multivariate analysis showed that length and GP at PSM were significantly strong factors and were stronger than location and number of PSM. The prognosis in pT2 patients with PSM were significantly subcategorized into 3 groups according to the length and GP at PSM (P<0.001). Conclusions: We proposed the recurrence risk classification based on the length and the GP at PSM to predict BCR after radical prostatectomy. It is useful for prognosis prediction and high-risk group should be considered for adjuvant radiation and/or hormonal therapy in postoperative care.