bluuebunny/crossref_metadata_2025 huggingface dataset:
Platinum-based chemotherapy in patients with castration-resistant prostate cancer and hepatic metastases.
Authors: Von Amsberg Gunhild , Lunger Lukas , Darr Christopher , Strewinsky Nadja , Busenbender Tobias , Kaune Moritz , Tennstedt Pierre , Steinhelfer Lisa , Retz Margitta , Sauer Markus , Karimzadeh Amir , Bartel Timo , Herrmann Ken , Hadaschik Boris A. , Grünwald Viktor , Fendler Wolfgang P.
Published: June 2023

e17063

Background: Patients with metastatic castration-resistant prostate cancer (mCRPC) and hepatic metastases face a dismal prognosis. In fact, the majority of phase 3 trials show no benefit of novel treatment modalities including Lutetium PSMA radioligand therapy (LuPSMA-RLT) in comparison with standard therapies for the subgroup of visceral metastases. In aggressive variant prostate cancer, the addition of platinum resulted in a clinically relevant improvement of progression free survival (PFS) and overall survival (OS). Whether adding platinum is also beneficial in unselected mCRPC patients with hepatic metastasis is unclear. Methods: We retrospectively analyzed mCRPC patients diagnosed with hepatic metastasis and treated with platinum-based chemotherapy or LuPSMA-RLT in three German centers (Hamburg, Essen, Munich). Patients with pure neuroendocrine prostate cancer were excluded. Survival rates and 95% confidence intervals (CI) were compared using the Kaplan Meier method and the logRank test. Results: A total of 84 mCRPC patients with hepatic metastasis who had received at least one platinum-based therapy and 32 patients treated with LuPSMA-RLT were evaluated. Median age at treatment initiation was 67 and 73 years. Patients had undergone a median of three treatment lines (83% ≥ 1 new hormonal agent (NHA); 87% ≥ 1 taxane based chemotherapy) before initiation of platinum based chemotherapy and a median of 4 treatment lines before LuPSMA-RLT. Median time to initiation of 1st platinum-based chemotherapy after diagnosis of liver metastases was 55 days. In total, 37% received carboplatin/cabazitaxel, 26% cisplatin or carboplatin/ etoposide, 11% carboplatin/docetaxel, and 26% other platinum-based combination therapies. In the platinum-treated group, 52.6% and 27% of the patients did not show progression at 3 and 6 months after treatment initiation as compared to 44.1% and 19.3% of the patients who received LuPSMA-RLT with a median PFS of 3.1 and 2.4 months, respectively. At 6 months 71.3% of the platinum-treated patients and 56.6% of the LuPSMA-RLT were alive. Overall, BRCA1/2 status was available for 53 of the platinum-treated patients, 15% of whom had a pathogenic alteration in either gene. This small subgroup was found to have a similar OS compared to the overall cohort. Conclusions: Platinum-based chemotherapy showed promising activity in mCRPC patients with hepatic metastasis. Given the high unmet medical need, platinum-based combination therapies should be further evaluated prospectively. [Table: see text]
Androgen receptor–specific CD8+ T cells with tumor cell cytotoxicity in patients with prostate cancer in Taiwan.
Authors: Huang Wilson , Lin Tzu-Ping , Huang William J. , Wu Chia-Jen
Published: June 2023

e17069

Background: Classical androgen receptor (AR) target is the new “tumor-specific” antigen for prostate cancer vaccine development to delay progression and castration-resistant disease. HLA-A2-restricted AR ligand-binding domain (LBD) has been demonstrated to stimulate cytotoxic T lymphocytes (CTL) in HLA-A2+ prostate cancer patients. Although the prevalence of HLA-A2 serotype and LBD-specific CD8+ T cells among Caucasians are known, their frequencies in the Taiwan patients have not been established. In this study, we performed HLA-A2 genotyping, HLA-A2+ LNCaP stimulation of autologous T cell, and CTL tumor cell cytotoxicity from 25 castration-sensitive prostate cancer patients using blood samples collected from a single hospital center. Methods: 20ml whole blood samples are collected in EDTA tube from non-metastatic, castration-sensitive prostate cancer patients. PBMCs are subjected to HLA-A2 allele sequencing, separated by CD3 magnetic bead column, and expanded and activated ex vivo using CD3/CD8 polymeric beads. Autologous T cells are then isolated by CD8 magnetic bead column, stimulated by HLA-A2+ lentivirus-transduced LNCaP (AR+), and targeted against transduced (HLA-A2+) and non-transduced (HLA-A2-) LNCaP (AR+) by Chromium-51 Release Assay. We identified and correlated their frequencies with patient’s age at diagnosis, Gleason grades, PSA level, and family history. Results: A total of 25 blood samples were tested and analyzed for HLA-A2 genotype with 44% (11/25) positive for the HLA-A2 [28% (7/25) heterozygotes, 16% (4/25) homozygotes]. Among the 11 HLA-A2+ patients, 72% (8/11) were HLA-A*02:07 allele, 100% (11/11) CD8+ T cells were successfully stimulated with HLA-A2+ transduced LNCaP (AR+) and 45% (5/11) patients demonstrated HLA-A2+ AR-specific CTL tumor cell lysis. No clinical association with patient age (54-86 y.o.), Gleason grades (6-9), PSA level (3.84-62.8 ng/ml), and family history (1/25). Conclusions: In this single hospital center study, we observed a similar prevalence of HLA-A2 alleles in Taiwan prostate cancer patient cohort with a predominant HLA-A2*02:07 allele, and higher frequencies of HLA-A2-restricted CD8+ T cell stimulation and HLA-A2+ AR-specific tumor cell cytotoxicity. Our findings support the application of AR LBD as tumor antigen for prostate cancer vaccine development for Taiwan prostate cancer patients.
Efficacy of bi-weekly docetaxel in hormone-sensitive metastatic prostate cancer (mHSPC).
Authors: Lombana Quinonez Milton Alberto , Torres Ana Milena , Gonzalez Guido
Published: June 2023

e17070

Background: In pts with mHSPC, docetaxel in a three-week schedule is associated with better overall survival (OS) vs androgen suppression alone, principally in pts with high tumor volume(HV). In pts with mCRPC stage, biweekly docetaxel demonstrated greater efficacy and a better toxicity profile. There are few published data about the use of bi-weekly docetaxel in pts with mHSPC. Methods: Pts with mHSPC and treated with bi-weekly docetaxel from January 2014 to December 2020 at The Comprehensive Cancer Center Clinica de Occidente in Cali-Colombia, were retrospectively identified. We collected relevant variables from electronic medical records. Our primary objective was to determine the efficacy in OS and the incidence of febrile neutropenia (FN). We performed Kaplan Meier, and cox regression analysis with relevant variables. Results: 69 pts were included, with a mean follow-up time of 45 months. Median age was 72y, 82% had ECOG PS 0/1, 74% grade group 4-5, 23% visceral metastases, and 93% de novo metastatic disease. The median OS was 51 months, and 39% at 5 years. In HV and de novo metastatic pts, the median OS was 49 months. The median time to development of mCRPC was 34 months. 35% of the patients had a PSA < 0.2ng/mL at month 6. In the univariate analysis, pts with HV (HR 10.49 95% CI 1.43-76.50, P = 0.0005), PSA > 0.2ng/mL (HR 4.43 95% CI 2.09-9.41, P = 0.0000), imagen objective response rate (ORR) (HR 1.47 95% CI 1.09-1.95, P = 0.0156) and PS ECOG > 0, (HR 3.3 CI95% 1.31-8.45, P = 0.003) had worse OS. Neither histologic grade 5 (HR 1.07, P = 0.8), visceral metastases (HR 1.2, P = 0.57), or de novo metastatic disease (HR 0.84, P = 0.74) were significantly associated. In the multivariate analysis, only PSA of > 0.2ng/mL at 6 months remained significantly [Table 1]. FN was detected in 3.2% of patients. Conclusions: We report the study with the largest number of patients and follow-up time (median 42.5 months) in patients with mCSPC who used biweekly docetaxel in addition to standard androgen suppression. The outcomes are similar, indirectly compared, to those reported in the CHAARTED study in OS, specifically in the de novo high-volume metastatic subgroup (CHAARTED 48 months, current study 49 months), better time to CRPC (20 months CHAARTED, 34 months current study), and with a lower incidence of FN (6% CHAARTED, 2% current study). None of the pts used primary granulocyte colony-stimulating factor prophylaxis. The use of biweekly docetaxel in this scenario offers high efficacy with less toxicity. Randomized studies are strongly recommended to confirm these results. [Table: see text]
Additional cycles of docetaxel in combination with androgen deprivation therapy (D-ADT) in metastatic hormone-sensitive prostate cancer (mHSPC): Efficacy and feasibility analysis.
Authors: Aydogdu Can , Urban Florian , Tamalunas Alexander , Berg Elena , Götz Melanie , Rodler Severin , Unterrainer Lena , Heinemann Volker , Stief Christian G. , Casuscelli Jozefina
Published: June 2023

e17074

Background: Several phase III trials have assessed efficacy and safety of 6 cycles of docetaxel combined to androgen deprivation therapy (D-ADT) in metastatic hormone-sensitive prostate cancer (mHSPC). This is the current standard of care for a subgroup of patients. We aimed to assess whether treatment beyond 6 cycles of docetaxel prove to be more effective than the standard of care. Methods: We retrospectively collected data from patients with histologically confirmed adenocarcinoma of the prostate and radiologically proven metastatic disease treated at a large tertiary care center. All patients with mHSPC were treated in first-line with D-ADT (75 mg/m2) intravenously on the first day of each 21-day cycle. A subset of patients was treated beyond the standard of 6 cycles. Clinical and pathological variables were examined, as were treatment-related toxicities; progression free survival on D-ADT (PFS1), progression free survival on subsequent therapy (PFS2) and overall survival (OS) were calculated from start of treatment to progression or death by log-rank test. Results: Between 2015-2023 a total of 108 mHSPC patients were treated and observed for a median time of 13.8 months. Mean age was 66.2 years (range 46.9-82.7), and 75.0% had GS≥8, 65.7% a CHAARTED high-volume and 69.4% LATITUDE high risk disease. 72 pts. were treated with ≤ 6 cycles (D-ADTstand) (4.2% 1-2 cycles; 95.8 % ≥3 cycles; mean 5.2 cycles) and 36 were treated with > 6 cycles docetaxel (D-ADTadd) (27.8% 7-8 cycles; 72.2% ≥9-10 cycles, mean 9.2 cycles). Frequency of toxicities did not differ in the groups. No significant differences were observed in median PFS1 (10.3 vs. 13.4 mos.) and PFS2 (6.3 vs. 6.6 mos.). Median OS in the D-ADTstand group was 39.8 mos., median OS in the D-ADTadd group was not yet reached. Conclusions: While more than 6 cycles of D-ADT in mHSPC proved to be feasible without significant additional toxicity, efficacy is not superior compared to the standard of 6 cycles. Overall survival data is not mature yet, but the benefit of more chemotherapy upfront is debatable and leverages further studies in light of the upcoming triplet combinations in mHSPC, that presumably will render doublet D-ADT obsolete in future. [Table: see text]
Prognosis stratification by a mutational signature in metastatic prostate cancer.
Authors: Zhang Gejun , Liu Huanhuan , Qin Jiayue , Cao Shanbo
Published: June 2023

e17079

Background: Metastatic prostate cancer (mPC) has a highly complex genomic landscape. With the recent development of novel treatments, accurate stratification strategies are needed. As cancer tissues are now frequently screened for specific sets of mutations, a large amount of samples has become available for analysis. Classification of patients with similar mutation profiles may help identifying subgroups of patients outcomes. However, classification based on somatic mutations is challenging due to the sparseness and heterogeneity of the data. Methods: A retrospective study was performed to identify the prognosis-related somatic mutations of mPC in 453 MSK-IMPACT, 1945 MSK-MET and 93 The Cancer Genome Atlas (TCGA) database. Cox regression were performed to screen out prognostic genes. Results: In the MSK-IMPAC cohort, a total of 35 genes were related with overall survival (OS). We selected genes mutated in at least 4 patients, leaving 6 genes (APC, ZFHX3, NCOR1, ASXL2, ARID1A, JAK1genes). We then recruited this mutation and formed a total number of 6-gene signature. Compared with the wildtype group, the OS of mutated signature was markedly lower, with p = 0.033. Similarly, the mutated signature harbored a lower OS than that in the wildtype group in the MSK-MET cohort (p = 0.001). In mutated signature cohorts, the five most frequently mutated genes were APC(45%), TP53 (42%), ZFHX3 27%), FOXA1(14%), and PTEN (13%). Dissimilarly, the five most frequently mutated genes were TP53 (43%), FOXA1 (10%), PTEN (9%), SPOP (7%), and CDK12 (7%) in wildtype cohorts. Furthermore, patients with mutated signature had higher WNT pathway (47.5% vs 14.8%), PI3K pathway (38.8% vs 12.0%), and NOTCH pathway (19.42% vs 6.0%) than those in the patients without mutated signature. Conclusions: These data underline the potential value of using somatic mutations to accurately stratify mPC patients into clinically actionable subgroups.
Real-world baseline characteristics and first-line (1L) treatment (Tx) in patients (pts) with de novo metastatic castration-sensitive prostate cancer (mCSPC) by disease volume.
Authors: Freedland Stephen J. , Hong Agnes , El-Chaar Nader N. , De Hoedt Amanda Marie , Kim Janet , Ramaswamy Krishnan , Gu Lin , Polascik Thomas
Published: June 2023

e17081

Background: Intensification of androgen deprivation therapy (ADT) using novel hormonal therapies (NHT) has been established as a new standard of care for pts with mCSPC. Tx intensification still remains suboptimal, and data in de novo mCSPC pts is limited. Moreover, prior studies utilized claims data and so could not assess the impact of disease burden on Tx intensification. This study assessed baseline characteristics and 1L Tx patterns in pts with high-volume (HV) vs low-volume (LV) de novo mCSPC. Methods: This retrospective study used the Veterans Affairs Informatics and Computing Infrastructure to identify adult men who had ≥1 ICD code for prostate cancer and de novo mCSPC diagnosed between February 2018 and June 2020 confirmed by clinical chart review and initiated either ADT alone, ADT + first-generation non-steroidal anti-androgens [NSAA], or ADT+NHT. Index date was defined as ADT initiation date. The volume of disease was defined as HV or LV per the CHAARTED trial criteria (presence of visceral metastasis and/or ≥4 bone metastases, with ≥1 metastasis beyond the pelvis and vertebral column). Clinical data was hand abstracted from the medical record. Baseline characteristics and 1L Tx were analyzed descriptively. Results: Of the 380 de novo mCSPC pts reviewed, 57% had HV and 43% had LV disease. Mean age of pts was similar between HV and LV cohorts, 74.5 vs 75.2 years, respectively. In addition, the proportion of Black vs White pts in the HV and LV cohorts was similar, 34% and 35% were Black, and 66% and 65% were White, respectively. At index date, HV pts had higher median prostate-specific antigen (153.1 ng/mL vs 73.8 ng/mL) and alkaline phosphatase (192.0 IU/L vs 106.0 IU/L) vs LV pts. HV pts were less likely to have diabetes and cardiovascular comorbidities than LV pts (Table); however, the distribution of Charlson Comorbidity Index score was similar between cohorts (mean [SD]: 4.4 [3.1] vs 4.2 [3.1]). Among the pts with bone metastases only, HV pts had higher proportion (65%) of “too numerous to count” bone metastases vs LV pts (9%). While ADT+NHT use was slightly more common among HV pts (35%) vs LV pts (27%), in both HV and LV cohorts, ADT±NSAA was the most common 1L Tx (Table). The median 1L Tx duration was shorter in the HV pts compared with the LV pts (286 vs 358 days). Conclusions: The results showed that Tx intensification was underutilized in de novo mCSPC pts, even among those with HV, pointing toward an unmet need among pts with de novo mCSPC regardless of disease burden. [Table: see text]
Survival of de novo metastatic hormone sensitive prostate cancer in US Veterans based on treatment and PSA at diagnosis.
Authors: Babar Arslan , Montgomery Robert Bruce , Riekhof Forest , Etzioni Ruth Douglas , Al masalmeh Nada , Knoche Eric Marshall , Sanfilippo Kristen Marie , Schoen Martin W.
Published: June 2023

e17091

Background: Combinations of androgen deprivation therapy (ADT) plus docetaxel (DOC) or androgen signaling agents (ASIs) (i.e. abiraterone, enzalutamide) improve survival in de novo metastatic hormone sensitive prostate cancer (mHSPC). In several trials, the benefit of combination therapy is greatest in patients with a high volume of disease. We sought to study the treatment and survival of US of veterans with mHSPC and stratify by PSA level at diagnosis during a time when different types of combination therapy was available. Methods: Veterans from 2018-2021 were identified with a pathologic diagnosis of prostate cancer with SEER stage ‘distant’. All veterans had ADT initiated within 1 month prior and 4 months after diagnosis. Combination therapy was determined if DOC or an ASI was initiated from 1 month prior to 4 months after ADT. Highest PSA level within 3 months of diagnosis was collected and patients with a PSA of ≥100ng/mL were included in PSA≥100. To avoid immortal time bias, all veterans had to survive 4 months after biopsy to be included. Baseline differences were compared using ANOVA and log-rank testing was used for time to event analyses. Results: 2,227 patients with de novo mHSPC were identified with mean age of 74.0 years (yrs), and 575 (25.8%) identified as Black race. From 2018 to 2021, ADT alone was used in 1,157 (52.0%) of veterans, DOC in 189 (8.4%) and ASIs in 881 (39.6%). Veterans treated with DOC were significantly younger (median 67.7 yrs, p < 0.001) compared to veterans treated with ASIs (72.9 yrs) or ADT alone (75.8 yrs). Veterans treated with combination therapies had longer median OS of 40.9 months (mos) compared to 32.9 mos for ADT alone (p < 0.001) with no difference within the combination treatment groups (p = 0.63). There was a trend for veterans with PSA≥100 to receive combination therapy (50.0% vs. 46.0%, p = 0.058). For 1,071 veterans with PSA≥100, median OS of veterans treated with combination therapy (n = 536, 37.4 mos) was longer than ADT alone (n = 535, 27.5 mos, p < 0.001). There was no differences in DOC combination treatment (n = 100, 37.9 mos) and ASI (n = 436, 36.6 mos) treatment groups (p = 0.37). Veterans with PSA≥100 had shorter OS compared to PSA < 100 (31.2 vs. 42.5 mos, p < 0.001). Conclusions: In veterans with de novo mHSPC, initial combination therapy was associated with longer survival than ADT alone. There were no differences in survival between DOC and ASI combinations observed in the entire population nor in veterans with PSA≥100. Further studies including tumor genetics or response to treatment may help guide treatment in mHSPC. [Table: see text]
A brief mind-body intervention to reduce pain and anxiety during prostate needle biopsy: A randomized, controlled trial with two-staged consent.
Authors: Gaffney Christopher , Vertosick Emily E. , Carlsson Sigrid V. , Lin Xin , Wolchasty Natalie , Hardbattle Robin , Vickers Andrew , Ehdaie Behfar
Published: June 2023

e17092

Background: Prostate biopsy is among the most common oncologic procedures performed annually. A substantial proportion of patients experience significant morbidity related to biopsy, including pain, anxiety, and discomfort which may discourage follow-up biopsy crucial for identifying progression or discourage enrollment in active surveillance programs that require serial biopsy. Guided meditation significantly reduces pain and anxiety during breast biopsy. We developed a brief mind-body intervention that could easily integrate into general practice for patients during prostate biopsy and compared patient-reported outcomes after biopsy with and without this intervention. Methods: We conducted a clinically-integrated randomized controlled trial (MSK IRB 18-089) of a brief mind-body intervention during prostate biopsy compared to usual care. All adult patients offered biopsy were eligible. Patients randomized to the intervention were offered both a pre-biopsy mind-body exercise and guided mindfulness meditation during biopsy via headphones. The primary outcome of interest was any severe patient-reported pain, anxiety, discomfort, or tolerability on a visual-analog scale (0-10). We compared the proportion of men in each arm reporting a severe score (7-10) on any of the four scales using Fisher’s exact test. The pre-specified clinically relevant improvement justifying integration into clinical practice was 15%. We compared means separately using ANCOVA with randomization stratum (first vs. prior biopsy) as a covariate. Results: 238 patients (119 per arm) enrolled. 102 in the intervention arm and 94 in the usual care arm proceeded to biopsy and completed the questionnaire. A total of 37/94 (39%) and 38/102 (37%) patients in the usual care and the intervention arms, respectively, reported severe scores in any of the four domains, a difference of 2.1% (95% confidence interval -13, 17%, p = 0.8). The upper bound of the confidence interval includes the pre-specified clinically relevant difference. There was no evidence of a difference in mean post-biopsy anxiety (p = 0.3), discomfort (p = 0.09), pain (p = 0.4) or tolerability scores (p = 0.2), Table. Conclusions: There was no difference in patient reported outcomes between a mind-body intervention and usual care for prostate biopsy. Though the upper bound of the 95% confidence interval included the clinically relevant difference in severe scores, the difference in means for each outcome suggests a clinically meaningful benefit for this brief mindfulness intervention is unlikely. [Table: see text]
Comparison of generic and specific anxiety in patients treated with apalutamide plus active surveillance vs active surveillance alone for low and intermediate risk prostate cancer.
Authors: Gravis Gwenaelle , Touzani Rajae , Walz Jochen , Ploussard Guillaume , Savoie Pierre-Henri , Durand Matthieu , Poinas Gregoire , Beauval Jean-Baptiste , Mathieu Romain , Ahallal Youness , Vincendeau Sebastien , Guerin Mathilde , Boudin Laurys , Crouzet Sebastien , Salem Naji , Vicier Cecile , Heux Pauline , Sfumato Patrick , Pignot Geraldine , Marino Patricia
Published: June 2023

e17093

Background: Active surveillance (AS) is a standard of care for low-risk prostate cancer (PCa). However, it is not yet clear whether AS may be a source of anxiety in patients (pts) compared to pts receiving treatment. The objective of this study is to compare anxiety in pts receiving apalutamide monotherapy plus AS versus AS alone in pts with low and intermediate-risk PCa. Methods: The study was conducted, in pts enrolled in a multicenter randomized phase 2 trial comparing AS with apalutamide (240 mg) 6 months versus AS alone. Participants completed questionnaires at baseline, 3, 6, and 12 months after diagnosis. We assessed anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and prostate-specific anxiety using the Memorial Anxiety Scale for Prostate Cancer (MAX-PC). Results: Patients were randomized to AS alone (n = 40) or AS + apalutamide (n = 51). Anxiety questionnaire, response rates, were 98%, 88%, 92%, and 82%, respectively, at baseline, 3 months, 6 months, and 12 months. HADS scores were similar between treatment groups (p > 0.05 at each assessment point) and did not change significantly over time (p > 0.05 for each comparison over time). By analyzing the general MAX-PC anxiety score, we observed that for pts on treatment, anxiety decreased significantly at 3 months compared to baseline (p = 0.01), then remained stable between 3 and 6 months. For pts on AS, anxiety remained stable during the first 3 months and decreased significantly after 3 months (p = 0.018). At the end of treatment (6 months), anxiety increased significantly in pts in the apalutamide arm (p = 0.05) while it remained stable for pts on AS alone. One year after inclusion, the MAX-PC general anxiety levels returned to baseline for both groups of pts. However, for the prostate cancer anxiety subscale, scores decreased significantly from baseline to 12 months in the AS alone group (p = 0.031). Conclusions: Anxiety was reduced in the apalutamide arm after the start of treatment, but this effect was transient and disappeared at the end of treatment. The decrease in anxiety appears to be delayed over time for AS patients, but after a few months, these patients experience a decrease in anxiety levels, suggesting that patients have become accustomed to not being treated. Better detection of PCa specific anxiety was observed, with disease-specific tools such as MAX-PC compared with generic anxiety detection with HADS. Clinical trial information: NCT03088124 .
Maintenance of castration with concomitant relugolix and apalutamide (Apa) in patients with high-risk localized prostate cancer (HR-LPC): 1 year update.
Authors: Brown Gordon , Belkoff Laurence , Hafron Jason , Aggarwal Pankaj , Potdar Rushikesh , Bhaumik Amitabha , Phillips Jennifer , McGowan Tracy , Shore Neal D.
Published: June 2023

e17094

Background: Androgen deprivation therapy (ADT) is a mainstay in the management of prostate cancer (PC). We assessed the efficacy of achieving and maintaining castrate testosterone (T) levels when combining relugolix, an oral gonadotropin-releasing hormone antagonist, concomitantly with Apa, an androgen receptor inhibitor. The single-arm, open-label, multicenter, phase 2 Apa-RP study evaluates the biochemical recurrence-free rate in patients with HR-LPC following radical prostatectomy (RP) who received 12 months of adjuvant Apa and ADT (main study). A substudy was added to assess whether the approved maintenance dose of relugolix with concomitant Apa maintained castration. Study results of the 28-day coadministration of relugolix + Apa showed that all evaluable patients achieved and maintained castration at standard relugolix dose and were transitioned into the main study (Brown et al. Target Oncol. 2022). Herein, we report longer term data of T levels and safety findings in the substudy patients who received relugolix + Apa for 1 year. Methods: Patients (n = 12) with HR-LPC (PSA ≥20 ng/mL or Gleason score ≥8) received a loading dose of relugolix (360 mg) at substudy initiation (Day -14) followed by the standard, approved relugolix dose (120 mg/d) for 13 days. Starting on Day 1, patients received relugolix + Apa (240 mg/d) for 28 days, with substudy completion on Day 28. These patients transitioned to the main study and received relugolix + Apa for a total of 1 year. T levels (castrate level defined as < 50 ng/dL) were measured at baseline (Day -14), Day 1, Day 28, and then every 3 months. Results: Of the 12 patients who continued onto the main study, 1 withdrew and another was noncompliant with therapy and subsequently withdrew but maintained castration while on therapy. Of the 10 patients who successfully completed therapy, 100% maintained castration during 1 year of concomitant therapy with relugolix + Apa . No patient required dose modification of relugolix. Median T level was 10.0 ng/dL after 1 year of treatment. One month after treatment discontinuation, 8/10 (80%) patients saw recovery of their T (T ≥50 ng/dL). Treatment-emergent adverse events (TEAEs) occurred in all 12 patients (100%). TEAEs were consistent with known safety profiles for each drug administered separately. Conclusions: During the 12 months of concomitant relugolix + Apa administration, all patients who completed therapy maintained castrate T levels without relugolix dose modification. All but 2 patients had T recovery within 30 days of therapy discontinuation. These data support long-term T suppression with relugolix + Apa at standard doses. Subsequent T levels will be reported upon final analysis of the main study. Clinical trial information: NCT04523207 .
A novel, AI-generated morphologic biomarker to predict prostate cancer recurrence in patients with intermediate risk of progression.
Authors: Nair Sujit , Muhammad Hassan , Jain Parag , Xie Chensu , Pavlova Ina , Brody Rachel , Huang Wei , Nakadar Maria , Zhang Xiangfu , Basu Hirak S , Wilding George , Chakravarty Dimple , Roy Rajat , Tewari Ashutosh K.
Published: June 2023

e17097

Background: About half of the prostate cancer (PCa) patients within an intermediate-risk group return to the clinic with disease progression after the first line of therapy. While these patients can be stratified into Gleason Grades (GG) 3+4 and 4+3, studies indicate that high-risk patients can still be found in both groups. Using our AI platform, we have developed a morphometric biomarker by analyzing digitized H&E slide images (WSIs), which can accurately predict early biochemical recurrence (within 36 months post-surgery) and the risk of metastatic disease more accurately than GG, TNM staging, and genomic tools. Methods: 125 intermediate-risk (n = 67, 3+4; n = 58, 4+3) samples were collected from the Icahn School of Medicine at Mount Sinai (ISSMS) to form a held-out test set. Seventy-eight patients within the test set had an associated genomic score. A series of deep learning models trained using data from ISMMS, the University of Wisconsin-Madison, and TCGA generated a high dimensional vector for each WSI to provide a numerical representation of observed morphologies, which is then converted into a single score to predict biochemical recurrence within 36 months (BCR) and rank risk of metastasis (MET). Area-under-the-receiver operating characteristic (AROC) was used to measure the accuracy of BCR, and the concordance index (CI) was used to measure the performance of MET. The high and low-risk groups' hazard ratios (HR) for patients within grades 3+4 and 4+3 show that our model can further stratify GG. Results: Our method was significantly better at predicting BCR (AROC: 0.801) and ranking MET (CI: 0.764) relative to GG, TNM, and genomic tool (Table 1). We further sub-stratified the patients into GG 3+4 and 4+3 and identified high-risk patients within each GG. Patients in GG 3+4 with high PATHOMIQ scores had a significantly higher risk of BCR (HR 3.3; 95% CI 1.44 – 7.56; p < 0.005) compared to the low PATHOMIQ score patients. A similar trend was seen in the GG 4+3 group (HR 3.0; 95% CI 1.32 – 6.83; p < 0.01). Conclusions: Our histopathology-based prognostic biomarker significantly improves over standard clinical markers in stratifying patients with intermediate-risk PCa for BCR and MET. Our method overcomes several limitations of genomic testing: We only need digitized WSIs. Our method is non-destructive and preserves the tissue for further interrogation. Moreover, our turn-around time is a few hours. Thus, the PATHOMIQ scoring method may strongly impact the management of intermediate-risk PCa patients and clinical trial patient selection for the successful development of new therapies for early-stage PCa. [Table: see text]
Validation of AI-based postoperative nomograms for biochemical recurrence in prostate adenocarcinoma.
Authors: Lee JaeHeon , Kwak Tae-Yeong , Cho Joonyoung , Kim Sun Woo , Chang Hyeyoon , Ha Hong Koo
Published: June 2023

e17104

Background: After radical prostatectomy (RP), a steep increase in PSA level is an early sign of the disease progression in prostate cancer, which is known as biochemical recurrence (BCR). The risk of BCR can be evaluated based on a combination of clinicopathological factors, and the patient’s Gleason score plays a significant role. However, this scoring system may have lower consistency due to interobserver reproducibility in classifying Gleason Patterns (GP) as well as in quantifying the amount of each GP. We developed AI-based nomograms, with the aim of investigating their prognostic efficacy. Methods: In this study, digitized whole-slide images (WSIs) of H&E-stained prostatectomy specimens and clinical follow-up information were obtained from two sources: Pusan National University Hospital (PNUH, n = 967, event = 342) from 2010 to 2021 with the median follow-up being 3.7 years, and The Cancer Genome Atlas (TCGA, n = 352, event = 79) from 2000 to 2013 with the median follow-up 2.6 years. We used the DeepDx Prostate - RP, an AI-based prostate cancer Gleason grading model, to compute a pixel-wise probability map of each GP in WSIs. Then, a weighted sum of the probabilities and GPs was calculated for each pixel. The proposed slide-level score (AI score) was then determined by averaging them across all pixels in WSI, resulting in a value ranging from 3 to 5. Also, patients were divided into five groups using AI score thresholds (3.1, 3.5, 3.9, and 4.1), and five binary variables (AI score group 1-5) were generated, where a value of 1 indicates a patient’s categorization into a group. To evaluate predictability we created new nomograms incorporating AI scores based on existing nomograms: MSKCC and CAPRA-S. Unlike the original nomograms, the proposed nomograms do not include the Grade Group (GG) made by pathologists. Then, we fitted a Cox regression model on one of two datasets using the original and newly formed nomograms, and validated on the other dataset reporting the concordance index (c-index). Confidence intervals for the c-index were generated via the non-parametric bootstrap resampling with 9,999 samples. Results: The table shows the prognostic performance of sets of clinicopathological factors and demonstrates that the proposed AI score improved the predictive power. The nomograms with AI score group 1-5 outperformed the original nomograms, as shown in (d). Conclusions: In conclusion, we developed the AI-based nomograms which can improve the accuracy of predicting the biochemical recurrence in prostate cancer compared to the existing nomograms. [Table: see text]
Impact of obesity on admissions for COVID-19 with concurrent prostate cancer.
Authors: Verma Renuka , Ramphul Kamleshun , Dandwani Mehndi , Sharma Shivani , Chennapragada Suma Sri , Pagidipally Alekhya , Sombans Shaheen , Sanikommu Sailaja , Ramphul Yogeshwaree , Mejias Stephanie G , Pekyi-Boateng Prince Kwabla , Arti Fnu , Dhillon Balkiranjit Kaur , Kumar Vijay , Lohana Petras
Published: June 2023

e17110

Background: Obesity is a significant risk factor for prostate cancer and its associated mortality. Recent studies have shown that a five-point rise in BMI can lead to a 10% rise in death among these patients. Since the pandemic of COVID-19, obesity has also been associated with poorer outcomes among the general population. As there is a paucity of data on the impact of obesity among prostate cancer admissions with COVID-19, we conducted a retrospective study to provide a novel perspective. Methods: Patients with a diagnosis of COVID-19 were used for our study from the 2020 National Inpatient Sample. We included cases between April 2020 to December 2020. Hospitalization records with prostate cancer and obesity were also identified via their respective ICD-10 codes. The differences in outcomes, including non-invasive ventilation, use of mechanical ventilation, pulmonary embolism, events of Acute Kidney Injury(AKI) and in-hospital mortality were compared between obese and non-obese patients with a history of prostate cancer, admitted for COVID-19. We also compared the mean lengths of stay, mean ages between the two groups, and their overall mean hospitalization charge. Results: A total of 7165 prostate cancer patients were hospitalized with COVID-19 between 1st April 2020 to 31st December 2020 in the United States. 1065 (14.9%) were obese. Prostate cancer patients admitted with COVID-19 who were obese were also younger (mean age 71.75 years) than those who were not obese (77.50 years) and recorded a more extended stay (mean LOS 9.68 days vs. 7.93 days). Obese patients also recorded a higher adjusted odds ratio for needing non-invasive ventilation (aOR 1.736, 95% CI 1.331-2.263, p < 0.01), mechanical ventilation (aOR 1.894, 95% CI 1.533-2.340, p < 0.01), events of acute kidney injury (aOR 1.328, 95% CI 1.137-1.550, p < 0.01), and in-hospital mortality (aOR 1.246, 95% CI 1.033-1.502, p = 0.021). While more patients with obesity developed pulmonary embolism (4.2% vs. 3.6%) after adjusting for confounders, the result was not statistically significant (aOR 1.258, 95% CI 0.879-1.800, p = 0.209). Obese patients also recorded a higher mean hospital charge compared to non-obese cases ($117200.50 vs. $81028.15). Conclusions: Obesity in prostate cancer patients admitted with COVID-19 is linked with several poor outcomes and complications, including AKI, mechanical ventilation, non-invasive ventilation, and mortality. Thus, physicians must identify such cases as higher-risk and encourage closer monitoring during their hospitalizations.
Late-stage prostate cancer and associated socioeconomic and demographic factors: A National Cancer Database Study.
Authors: Abodunrin Faith , Adeoye Oluwatayo , Masih Durva , Nelson Nick , Silberstein Peter T. , Tupper Connor
Published: June 2023

e17115

Background: Prostate cancer accounts for 29% of all cancer diagnoses in men in the United States. A 3% annual increase in the incidence of prostate cancer was reported between 2014 to 2019. The stage at initial presentation significantly impacts the overall mortality of prostate cancer. Current 5-year survival estimates ranged from 99% in early-stage disease to <31% in distant disease. Given this enormous difference in survival rates, we studied the socioeconomic and demographic factors impacting the stage of prostate cancer at diagnosis. We also explored the time trends in the staging of prostate cancer. Methods: Using the National Cancer Database, we identified 1,880,352 patients diagnosed with prostate cancer between 2004 and 2019. We used variables including age at diagnosis, race, insurance status, and year of diagnosis. We used Chi-square tests to determine the association of a variable with staging at diagnosis. Multivariable logistic regression analyses determined the impact of our selected variables on the likelihood of early or late staging at diagnosis. All statistical analyses were performed using SPSS. All tests were performed with a significance level of a = 0.05. Results: In this study, we found that the relative percentage of late-stage diagnoses for blacks 21.5%, Hispanics 24.6% and Asians 25.3% were greater than for Whites 20.7%. Hispanics (OR 1.016) and Asians (OR 1.137) in particular, were more likely to be diagnosed at late stage compared to their white counterparts. Blacks were less likely to be diagnosed at a late stage compared to whites (OR 0.947). Men older than 70 years were more likely to be diagnosed at a late stage than men younger than 60 years (OR 1.149). Insurance status showed the greatest number of late-stage diagnoses in the uninsured 32.4% and Medicaid 31.6% populations while private 19.2% and Medicare 21.9% coverage had lower percentage of late-stage diagnoses. Finally, the year of diagnosis showed large differences in relative percentage of late-stage diagnoses with the 2004-2007 group diagnosing of cases 13.8% at late stage while the 2016-2019 group diagnosed 31.0% at late stage. The probability of having a late-stage diagnosis was higher between 2016-2019 than 2004-2007 (OR 2.724). These results were statistically significant (p<0.001). Conclusions: Old age is associated with late-stage diagnosis. This might be explained by the change in guidelines regarding screening against routine PSA screening in men older than 70 years of age. Since the change in 2008, we have seen a steady increase in the number of late diagnoses. In blacks, there have been some positive strides in late-stage diagnoses as they are less likely to be diagnosed later than whites. However, it is crucial to also pay attention to other groups like Hispanics and Asians that are not considered at increased risk for prostate cancer and hence typically screened less frequently.
Difference in management of patients with prostate cancer and spinal cord compression in teaching vs non-teaching hospitals in the United States.
Authors: Yazdanpanah Omid , Sharma Aditi , Rezazadeh Arash
Published: June 2023

e17116

Background: Spinal Cord Compression (SCC) secondary to metastatic prostate cancer is a complication that can lead to irreversible loss of neurologic function. Many factors including age, comorbidities, severity of the compression, and neurological deficit can affect the treatment from conservative management to radiation and surgery. We aimed to study the difference in practice patterns and their outcomes in teaching hospitals (TH) vs non-teaching hospitals (NTH) in the United States. Methods: Utilizing the National Inpatient Sample Database (NIS), we conducted a retrospective cohort study on hospitalizations with prostate cancer and SCC between 2016 and 2020 across the US. Patients were divided into two groups of TH and NTH. Demographics, comorbidities, treatment modality, length of hospitalization, costs, and mortality were compared between the two groups. We also studied patients’ characteristics and outcomes in TH and NTH according to their treatment strategy. Results: We identified 11,380 metastatic prostate cancer patients with SCC admitted to the hospitals with a 7-day median length of stay. While 27.4% underwent surgical procedure and 11.5% received inpatient radiation, 61.2% were treated conservatively. The median cost of hospitalization was $21,922 in TH and $15,141 in NTH ( P< 0.001). Although the median age and Charlson Comorbidity Index did not differ between two groups ( P =0.12 & 0.66 respectively), patients in TH were more likely to receive intervention (either radiation or surgery) compared to NTH (Surgery: 28.2% in TH vs 23.0% in NTH; P <0.01 & Radiation: 12.1% in TH vs 8.2% in NTH; P <0.01). Mortality rate was lower in TH than NTH (4.5% vs 7.9%; P < 0.01). In both TH and NTH, patients with private insurance were more likely to undergo surgery (TH: Surgery 25.1% vs Radiation 18.8%; P< 0.05 & NTH: Surgery 27.0% vs 6.9% P< 0.05). Among different races, black patients were more likely to receive radiation than surgery in TH (34.2% vs 26.8%; P <0.05). With no difference in comorbidities between surgery and radiation group in TH ( P =0.16), all-cause mortality was higher for those who received radiation than for surgery (4.4% vs 1.9%; P <0.05) . Conclusions: This study indicated that practice pattern for the management of SCC in prostate cancer is different in teaching and non-teaching hospitals. In addition to more surgery being performed in teaching hospitals, the mortality rate was also lower. There was an association between race and insurance type with different treatment modalities. We also revealed that all-cause mortality was higher with radiation therapy compared to surgery in teaching hospitals.
Fully automated prostate cancer identification using multiplex fluorescence immunohistochemistry to assess prognosis markers on a single tissue section.
Authors: Blessin Niclas C. , Mandelkow Tim , Bady Elena , Mueller Jan H. , Simon Ronald , Lennartz Maximilian , Sauter Guido , Heinzer Hans , Graefen Markus , Steurer Stefan
Published: June 2023

e17118

Background: Most prostate cancers diagnosed are low to intermediate risk and face the decision on whether active surveillance or active treatment represents the optimal treatment option. To incorporate a reproduceable parameter in treatment planning, prognostic marker assessment using multi-gene panels has been frequently proposed. However, the fluctuating tumor purity can reduce the predictive value of such tests. A more accurate prognostication would be the quantification of prognosis markers exclusively on cancer cells. Methods: To enable automated prognosis marker quantification, a framework for automated prostate cancer detection that comprises three different artificial intelligence analysis steps and an algorithm for cell-distance analysis have been developed and validated using 8 marker BLEACH&STAIN mfIHC (i.e., panCK, p63, PSA, PSMA, INSM1, AR, Ki-67, CD56) in a tissue microarray and prostate biopsy cohort of 10’234 prostate cancers. Results: The approach for automated prostate cancer detection mimics the way pathologists use for identification of cancer cells and identified epithelial cells (CKpan positive) that were non-adjacent to basal cells (p63 positive). Validation experiments revealed that the optimal distance between p63+ basal cells and benign panCK+ cells was 23 µm to exclude benign glands from the prognosis marker analysis. A distance of 23µm as threshold for automated cancer detection showed a 39% higher accuracy compared to the cutoff value 5 µm. To compare this automated mfIHC-based prognosis marker assessment with the frequently used bright field IHC-based QuPath software package, and the manual prostate identification by pathologists, a cohort of 30 biopsies from routine clinical practice was assessed. An excellent agreement between the mfIHC-based automated cancer detection and manual cancer identification by pathologists was found (intraclass correlation [ICC]: 0.94 [95% CI 0.87 – 0.97]), while the QuPath-based model showed a 20 % deviation from the gold standard (manual assessment by pathologists). Accordingly, the automated mfIHC-based approach was used to search for a prognosis marker panel for routine clinical practice. 5 out of 6 analyzed prognosis markers (PSA, PSMA, INSM1, AR, Ki-67) were significantly liked to biochemical recurrence in univariate analysis (p ≤ 0.021) and 2 of 6 parameters (AR, Ki-67) were independent in multivariate analysis (each p≤ 0.0078). Several prognosis scores of different marker combinations were found that showed strong prognostic relevance in univariate analysis (p < 0.001) and were independent from Gleason groups, pT, pN, serum PSA and R-Status (p = 0.001). Conclusions: Automated prostate cancer identification enables fully automated prognosis marker assessment in routine clinical practice using deep learning and mfIHC.