bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase II study of the efficacy of abirateron acetate with dutasteride for castration-resistant prostate cancer.
Authors: Matsuyama Hideyasu , Shiota Masaki , Tashiro Kojiro , Kanji Hiromi , Horiyama Shizuyo , Eto Masatoshi , Egawa Shin , Haginaka Jun , Inoue Ryo ,   Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan
Published: March 2021

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Background: Abiraterone (Abi) has been becoming a pivotal drug not only for metastatic castration resistant prostate cancer (mCRPC), but also for metastatic hormone sensitive prostate cancer (mHSPC). Abi is metabolized to delta-4 Abi (D4A), the strongest antitumor metabolite, by 3βHSD, and D4A is metabolized to 3-keto-5-α Abi, which acts as agonist to AR, by 5 α reductase. Reduction of 3-keto-5-α Abi by 5 α reductase inhibitor may increase the antitumor activity of Abi. Purpose of this study is to evaluate the efficacy and safety of the combination therapy of Abi and dutasteride (Duta), a 5 α reductase inhibitor, for the patients with CRPC. Methods: This is a non-randomized single-arm prospective phase II study. Patients with CRPC without any prior AR-targeting agent or docetaxel were recruited in this study with estimated enrollment of 20. Patients were treated with Abi (1,000 mg daily) and prednisone (5 mg daily) for 4 weeks, followed by the add-on of Duta (0.5 mg daily) for 12weeks. If PSA decline continued, combination treatment was allowed until progression. Abi and its metabolites including D4A and 3-keto-5-α Abi were measured by ESI-TOF-MS at baseline, 4, 6, 8, 12, 16, and 20 weeks, and the sample was collected at 2-4 hours after Abi administration. Primary endpoint was PSA decline >50%, and secondary endpoints were Time-to-treatment failure (TTF), and safety. Results: Totally 17 cases with CRPC (mean age: 78.4, initial PSA:92.6ng/ml, median Gleason score: 9) were recruited, and 14 were eligible for starting the combination therapy. Efficacy could be evaluated in 11 cases except 3 on-protocol treatment. Mean PSA decline of Abi/Duta combination therapy was significantly higher than that of monotherapy (p = 0.0143, 73 vs. 35 %). PSA decline>50% was noted in 36.4% for monotherapy, and 72.7% for combination therapy, respectively. Surprisingly, PSA decline>50% was significantly associated with lower Abi, D4A, and 3-keto 5 α Abi at 2 and 4 weeks after combination. Median TTF and progression (radiographic and/or PSA) was noted in 10.4 months (0.9-32), and 5 (45,4%), respectively with a median follow-up of 13.8 months. Progression was significantly associated with lower D4A, and 3-keto 5 a Abi at 4 and 8 weeks after combination therapy. Concerning safety, Grade 2 vertigo occurred in a case during Abi monotherapy period, while no adverse effect was found in combination therapy. Conclusions: Abi/Duta combination therapy seems to be theoretical to decrease AR-agonistic metabolite (3-keto 5 α Abi), and feasible for patients with first-line treatment of CRPC with lesser toxicity. Clinical trial information: UMIN000027795.
Evaluating the role of stereotactic body radiation therapy with respect to androgen receptor signaling inhibitors for metastatic prostate cancer.
Authors: Brennan Victoria , Spektor Alexander , Sweeney Christopher , Choudhury Atish Dipankar , Rathkopf Dana E. , Pomerantz Mark , Hertan Lauren Michelle , Martin Neil E. , Nguyen Paul L. , Balboni Tracy A. , Huynh Mai Anh , King Martin T.
Published: March 2021

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Background: Outcomes of stereotactic body radiation therapy (SBRT) with respect to androgen receptor signaling inhibitors (ARSI) have not been characterized for metastatic prostate cancer. Our purpose is to characterize prostate specific antigen (PSA) response and progression free survival (PFS) following SBRT among men who have received ARSI in castration sensitive and resistant settings. Methods: A single institution retrospective analysis was performed for men treated with SBRT and ARSI and categorized into 4 groups: 1) oligometastatic castration-sensitive prostate cancer (omCSPC), 2) ARSI-sensitive (ARSI-s) oligometastatic castration-resistant prostate cancer (omCRPC), 3) ARSI-resistant (ARSI-r) omCRPC, and 4) polymetastatic CRPC (pmCRPC). We calculated the PSA reduction greater than 50% (PSA50) and median PFS (PSA or radiographic progression) as determined by routine care. We also used Cox regression analysis to determine factors influencing PFS for ARSI-r disease. Results: 73 men with 126 lesions were treated with SBRT and followed for a median of 14.4 months. The percentages of men who achieved a PSA50 for omCSPC, ARSI-s omCRPC, ARSI-r omCRPC and pmCRPC were 100%, 90%, 62.9%, and 16.7%, respectively. Respective median PFS values were: not reached, 17.3, 9.0, and 1.6 months. For the 35 men with ARSI-r omCRPC, incomplete ablation (defined as the presence of untreated lesions after SBRT or prior palliative external beam radiation therapy (EBRT)) (HR 3.51 [1.36, 9.06]; p = 0.01) was associated with worse PFS on multivariable analysis. For the subgroup of 22 men with ARSI-r omCRPC without prior palliative EBRT or untreated metastases, the median PFS was 13.1 months. Conclusions: SBRT may augment the efficacy of ARSI, particularly among men with ARSI-r omCRPC, provided that all lesions received ablative radiation doses. Future prospective study of SBRT for men receiving ARSI is warranted.
Salvage chemotherapy with cisplatin, ifosfamide, and paclitaxel in metastatic castration-resistant prostate cancer.
Authors: Von Amsberg Gunhild , Zilles Mirjam , Gild Philipp , Alsdorf Winfried , Boeckelmann Lukas , Langebrake Claudia , Oh-Hohenhorst Su Jung , Tilki Derya , Graefen Markus , Dyshlovoy Sergey , Bokemeyer Carsten
Published: March 2021

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Background: Recent developments in the treatment of metastatic castration resistant prostate cancer (mCRPC) lead to a revival of platinum-based chemotherapy demonstrating increased activity in patients with aggressive variants of disease. Here, we report on the results of a combinational salvage therapy with cisplatin, ifosfamide and paclitaxel (TIP) in mCRPC. Methods: We retrospectively analyzed patients with mCRPC treated with TIP at the University Hospital Hamburg-Eppendorf between November 2013 and September 2020. Accompanying in vitro analyses were performed using human prostate carcinoma cell lines harboring different levels of drug resistance including the docetaxel-resistant sublines PC3-DR and DU45-DR. Results: In total, 17 mCRPC patients treated with TIP were eligible for efficacy analyses with a median age of 65 yrs. At baseline, liver metastases were present in 88%, metastases of other visceral sides (lung, adrenal gland, brain) in 47% and bone metastases in 76% of the patients. Median hemoglobin was 9.8mg/dl, LDH 903 U/l and AP 205 U/l. Median PSA value was 77 ng/ml covering a wide range including three patients with a PSA-value below 1ng/ml. NSE was evaluated in 83% of the patients (median 38,5 U/l). Patients were extensively pretreated with a median of three treatment lines before TIP (100% docetaxel, 82% abirateron and/or enzalutamide, 47% cabazitaxel, 41% others). A median of 3,5 cycles of TIP were applied with 29% of the patients receiving the maximum of 6 cycles. Four patients discontinued treatment due to side effects (PNP, infection, ifosfamide induced psychosis). At interim analyses, 59 % of the patients showed a radiological response or stable disease with only one patient progressing till the end of treatment. Median PFS was 2.5 months, median OS 6 months. A decrease of PSA > 30% and LDH > 50% was observed in 41% and 35% of the patients, respectively. In vitro experiments revealed additive effects of TIP in 22Rv1, LNCaP and DU45 cells and synergistic effects in neuroendocrine LASCPC-01 cells. In PC3 cells, TIP induced antagonistic effects at lower doses, whereas dose-independent additive effects were observed in docetaxel-resistant PC3-DR. Surprisingly, preliminary data of combined therapies with different drug pairs suggest an antagonistic effect of paclitaxel in the combination with both, cisplatin and ifosfamide. Conclusions: Combinational therapy with cisplatin, ifosfamide and paclitaxel showed promising activity in some patients with aggressive mCRPC. Preclinical data suggest that the drug combination of cisplatin and ifosfamide rule the efficacy of TIP in mCRPC.
Exploratory gene-by-gene analysis of olaparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): PROfound.
Authors: De Bono Johann S. , Matsubara Nobuaki , Penel Nicolas , Mehra Niven , Kolinsky Michael Paul , Bompas Emmanuelle , Feyerabend Susan , Gravis Gwenaelle , Joung Jae Young , Nishimura Kazuo , Gedye Craig , Mateo Joaquin , Saad Fred , Fizazi Karim , Shore Neal , Kang Jinyu , Desai Chintu , Burgents Joseph E. , Harrington Elizabeth , Hussain Maha H. A.
Published: March 2021

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Background: The Phase 3 PROfound trial (NCT02987543) met its primary endpoint and key secondary endpoints, including improved overall survival (OS) for olaparib in men with mCRPC with alterations in BRCA1, BRCA2, or ATM (Cohort A). We report gene-by-gene analysis of olaparib antitumor activity among the 15 prespecified homologous recombination repair (HRR) genes. Methods: Pts were randomized to olaparib (300 mg bid; n=256) or physician’s choice of enzalutamide or abiraterone (control; n=131). Exploratory analyses in pts with alterations in BRCA1 and/or BRCA2 (BRCA, regardless of co-occurring alterations with other HRR genes) or in single genes were conducted. Results: Evidence of olaparib antitumor activity was observed in subgroups with >10 pts (table). Data for pts with alterations in only BRCA1, BRCA2, PPP2R2A, RAD51B, RAD54L, PALB2, BRIP1, CHEK1, BARD1, and RAD51D will be reported (no FANCL or RAD51C enrolled). Conclusions: Small subgroups limit interpretation for some genes. Olaparib antitumor activity is greatest in pts with BRCA alterations, with a spectrum of clinical sensitivity to olaparib as defined by rPFS and OS across the broader population with alterations in other HRR genes. Clinical trial information: NCT02987543. [Table: see text]
Real-world comparison of abiraterone (A) versus enzalutamide (E) for first-line therapy of metastatic castration-resistant prostate cancer (mCRPC).
Authors: Briones Carvajal Juan Rodrigo , Naimi Mahdi Farzad , Zhang Liying , Emmenegger Urban
Published: March 2021

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Background: Second generation androgen receptor signaling inhibitors such as A and E are commonly used first-line treatment options for mCRPC. While differences in the side effect profile of these agents are well documented, there are no predictive markers of response to A versus E, and there is a paucity of comparative outcome data. Methods: We conducted a retrospective exploratory analysis of 100 mCRPC patients (pts) treated at Odette Cancer Centre (Toronto, ON, Canada) between August 2012 and June 2020 with either A (n = 50) or E (n = 50). Pts undergoing first-line mCRPC therapy were randomly selected from a list of 327 A and 254 E patients. Following extraction of disease and pt characteristics, as well as outcome data, we applied the Wilcoxon rank-sum nonparametric test or the Fisher exact test for continuous or categorical variables, respectively, for between group comparisons. For time to event analyses, we created Kaplan-Meier (KM) curves with log-rank testing. Two-sided p-values < 0.05 were considered significant. Results: The A and E cohorts were comparable regarding diagnostic PSA, Gleason score categories, and treatments prior to presentation with mCRPC. The median time to CRPC in the A cohort was 23.3 (95%CI 15.6-29.9) months, compared to 24.1 (19.4-37.4) months in the E cohort (p = 0.942). At initiation of A or E therapy both the median (Q1,Q3) age (77(70,82) vs 76(69,81) years) and median Charlson Comorbidity Index (10(9,11) vs 10(9,11)) were similar (p = 0.469 and p = 0.736, respectively). The rate of diabetes was significantly lower in the A group (8% vs 38%; p < 0.001), but there were no significant differences in cardiovascular comorbidities. Pts starting A therapy had a higher rate of bone metastasis (92% vs 68%; p = 0.005); otherwise, the metastatic pattern did not differ. The median PSA at start of A was 46.75 (13.77,176.80), compared to 27.07 (8.64,136.20) in the E group (p = 0.218). Baseline ALP, hemoglobin and albumin were all comparable. Median follow-up was 13.7 (8.3,26.3) and 19.5 (9.8,34.0) months in the A and E groups (p = 0.091). 38% of A pts and 44% of E pts went on to further lines of systemic therapy upon progression (p = 0.685). The median time to next line of systemic therapy was 11.3 (95%CI 8.3-15.9) months for the A cohort and 12.7 (9.7-16.6) for the E cohort (p = 0.844). The actuarial median overall survival from KM estimations was 35.7 (20.4-52.5) months for the A group, and 34.0 (25.7-38.0) months for the E group. Conclusions: In men undergoing first-line A or E therapy for mCRPC, time to next line of systemic therapy and overall survival did not differ significantly, while baseline pt and disease characteristics were largely similar. A substantial number of pts do not receive ≥2 lines of therapy for mCRPC under real-world circumstances.
p2PSA-associated parameters are significant predictors of reclassification of first-year protocol biopsy on active surveillance for early-stage prostate cancer patients: From the PRIAS-JAPAN study.
Authors: Kato Takuma , Sugimoto Mikio , Kakehi Yoshiyuki , Shinohara Nobuo , Egawa Shin , Sasaki Hiroshi , Saito Toshihiro , Tanikawa Toshiki , Matsumura Masafumi , Hashine Katsuyoshi , Akamatsu Shusuke , Ogawa Osamu , Hara Isao
Published: March 2021

153

Background: 44 Japanese institutions have joined the Prostate Cancer Research International: Active Surveillance (PRIAS) study as PRIAS-JAPAN. As an side study, PRIAS-JAPAN investigates the usefulness of [-2] proPSA (p2PSA), a precursor of PSA, as a predictive marker for the reclassification during active surveillance patients. In this study, we aimed to evaluate the usefulness of p2PSA related parameters to predict the reclassification of first year protocol biopsy (1yr PBx). Methods: 19 institutions participated in this side study which started in January 2013. All participants were eligible for PRAIS inclusion criteria. These patients were required to receive blood sampling on every visit and protocol biopsy after inclusion. PSA and PSA isoforms (free-PSA, p2PSA) were measured in serum samples and parameters (%free-PSA, %p2PSA, phi) were also calculated. Mann-Whitney U test was used to compare continuous variables between reclassification and non-reclassification groups. Fisher's exact test and Chi-squared test with yates' continuity correction were used for categorical variables. Multivariable logistic regression models were used to predict the risk of reclassification. To assess the predictive power for reclassification, we plotted ROC curves and calculated the AUC. Decision curve analysis (DCA) was used to evaluate whether adding variables to the baseline (age, PSA, prostate volume) model would yield net clinical benefit. Results: From January 2013 to July 2017, this study enrolled 237patients. 99 patients were excluded for the reason of discontinuation of AS, non-adherence of protocol blood sampling and rejection of biopsy. 138patients were able to analyzed PSA, PSA isoforms and its parameters at the time of inclusion and 1yr PBx. Patients who showed reclassification were significantly higher level of %p2PSA at inclusion and %p2PSA and phi just before 1yr PBx. Multivariate analyses showed %p2PSA at inclusion (p= 0.04), %p2PSA (p= 0.01) and Phi (p= 0.008) before 1yr PBx were statistically significant predictors of reclassification at 1yr PBx. ROC analysis revealed that %p2PSA before 1yr PBx (AUC 0.674) and phi before 1yr PBx (AUC 0.669) were a significant discriminant factor in predicting reclassification. DCA analysis showed that phi before 1yr PBx had a highest net benefit in the range of clinically plausible risk threshold (10–40%). Conclusions: %p2PSA and Phi before 1yr PBx have good prediction power and phi is a most useful indicator of clinical decision making about active surveillance. Clinical trial information: UMIN 000009876.
Landscape of circulating tumor DNA (ctDNA) abnormalities in advanced prostate cancer (aPCa): Distinctions in African American (AA) versus Caucasian (Ca) patients.
Authors: Barata Pedro C. , Swami Umang , Kessel Adam , Jaeger Ellen , Wesolowski Sergiusz , Chipman Jonathan , Bilen Mehmet Asim , Heath Elisabeth I. , Nandagopal Lakshminarayanan , Vaena Daniel A. , Maughan Benjamin Louis , Nussenzveig Roberto , Yandell Mark , Kohli Manish , Agarwal Neeraj , Sartor Oliver A.
Published: March 2021

156

Background: AA have substantially higher prostate cancer incidence rates, are diagnosed at a younger age and with a more advanced stage as compared to Ca. However, after adjusting for known prognostic factors, AA have an increased overall survival. We hypothesized that these differences might be due to the underlying changes in the genomic landscape which can be revealed by liquid biopsy. Methods: Real world comprehensive genomic profiling of ctDNA from aPCa patients from two institutions. The first ctDNA results as reported by Guardant 360 panel (Redwood City, CA) were included. Association between genetic mutation and gene were tested using Barnard’s test. To account for multiple testing, we used Benjamini-Hochberg’s False Discovery Rate adjustment across all tests to determine thresholds for false discovery rates. Same analysis was performed using a Bayesian Network Machine learning approach. Results: Overall, 361 patients with aPCa (81 AA and 280 Ca) were included in the analysis. Pathogenic genomic alterations were found in 87.0% of the cases, more frequently TP53 (42.4%), AR (34.1%), PIK3CA (13.9%), BRAF (12.7%), NF1 (10.8%) and MYC (10.0%). Targetable alterations of interest included DNA repair genes [BRCA 2 (7.8%), BRCA 1 (4.4%), ATM (6.4%), CDK12 (2.2%)], PIK3CA/mTOR/AKT (19.1%), PTEN (3.3%) and NTRK (1.9%). MSI-high was found in 4 patients. AA as compared to Ca had a significantly higher prevalence of CDK12 (20.7% vs. 3.8%, p=0.016) and GNA11 mutations (3.7% vs. 0.4%, p=0.0225). BayesNet analysis also supported these results (table). Conclusions: In this dataset, liquid biopsy of ctDNA was useful for genetic characterization of aPCa and reveal differences in the molecular phenotype of AA and Ca in aPCa with potential clinical implications. These findings support ongoing research on the clinical utility of non-invasive genotyping and therapeutic response monitoring with a focus on AA population. [Table: see text]
Development and validation of circulating tumor cell (Epic Sciences) enumeration as a prognostic biomarker in men with metastatic castration-resistant prostate cancer.
Authors: Scher Howard I. , Armstrong Andrew J. , Schonhoft Joseph D. , Gill Audrey , Zhao Jimmy , Barnett Ethan , Carbone Emily , Lu James , Antonarakis Emmanuel S. , Luo Jun , Tagawa Scott T. , Yang Qian , George Daniel J. , Szmulewitz Russell Zelig , Danila Daniel Costin , Wenstrup Rick , Gonen Mithat , Halabi Susan
Published: March 2021

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Background: We evaluated the prognostic significance of circulating tumor cell (CTC) number as determined on the Epic Sciences platform in men with metastatic castration resistant prostate cancer (mCRPC) treated with an androgen receptor signaling inhibitor (ARSI). Methods: A pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a 1st, 2nd or 3rd line systemic therapy at Memorial Sloan Kettering Cancer Center (Discovery cohort, N=175) or as a 1st and 2nd line therapy as part of the multi-center PROPHECY trial (NCT02269982) (Validation cohort, N=107). Enumeration was performed on the Epic Sciences platform and associated with overall survival (OS) in the Discovery cohort, and progression-free survival (PFS) and OS in the Validation cohort. Matched blood samples from the Validation cohort were to CTC counts measured on the CellSearch Circulating Tumor Cell kit. Results: In the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous (< 3 CTCs/mL versus ≥ 3 CTCs/mL; HR = 1.8, (1.3-3.0, 95% CI)) and as a continuous variable when adjusting for line of therapy, presence of visceral metastases, PSA, lactate-dehydrogenase, and alkaline-phosphatase. The findings were validated in an independent dataset (PROPHECY trial) - (HR (95% CI) = 1.8, (1.1-3.0) for OS and 1.7 (1.1-2.9), for PFS). A strong correlation was observed between CTC counts determined in matched samples on the CellSearch and Epic platforms (r = 0.84). Conclusions: The findings validate the prognostic significance of pretreatment CTC number determined on the Epic Sciences platform for predicting OS in men with progressing mCRPC starting an ARSI.
Differences in the genomic landscape of advanced prostate cancer (aPC) patients (pts) with BRCA1 versus BRCA2 mutations as detected by machine learning analysis of the comprehensive genomic profile (CGP) of cell-free DNA (cfDNA).
Authors: Reisinger Raquel , Wesolowski Sergiusz , Swami Umang , Barata Pedro C. , Hernandez Edgar Javier , Nussenzveig Roberto , Lemmon Gordon , Peterson Bennet , Hensel Chuck , Bilen Mehmet Asim , Heath Elisabeth I. , Nandagopal Lakshminarayanan , Saylor Philip James , Babiker Hani M. , Kohli Manish , Pal Sumanta K. , Lilly Michael B. , Yandell Mark , Sartor A. Oliver , Agarwal Neeraj
Published: March 2021

162

Background: PARP inhibitors (PARPi) provide significant clinical benefit for men with aPC with BRCA 1 and BRCA 2 mutations. However, in clinical trials, pts with BRCA1 mutations appeared to derive less benefit than pts with BRCA2 (De Bono et al., 2020). Probabilistic Graphical Models (PGMs) are artificial intelligence (AI) algorithms that capture multivariate, multi-level dependencies in complex patterns in large datasets while retaining human interpretability. We hypothesize that PGMs can reveal variants in BRCA1 and 2 that co-segregate with other known pathogenic variants and may explain the difference in response to PARPi therapy. Methods: Multilevel gene interdependencies between BRCA1 or BRCA2 were assessed using a Bayesian Network (BN) machine learning approach and Fisher’s exact test. CGP was performed by a validated cfDNA NGS panel that sequenced 74 clinically relevant cancer genes (Guardant360, Redwood City, CA). Only variants of known significance and those of unknown significance with a pathogenic REVEL score were included in the analysis. Results: Of 4671 men with aPC undergoing cfDNA CGP, 1248 men with somatic mutations in BRCA1, BRCA2, ATM, or combinations of the three were included in the analysis. The Bayesian network analysis demonstrated positive interdependencies between pathogenic variants in BRCA1 and 7 other genes. A positive interdependency between BRCA2 and 2 genes was present (table). ATM displayed negative interdependency with both BRCA 1 and 2. Conclusions: Our results demonstrate a decreased association of BRCA2 versus BRCA1 with known or predicted pathogenic variants at other loci. This may explain increased sensitivity of aPC with BRCA2 mutations to PARPi due to fewer concurrent resistance pathways. For example, alteration of ERBB2, which segregates strongly with BRCA1, is known to induce tumor progression and invasion in aPC and is associated with castration-resistance. These hypothesis-generating data reveal differential genomic signatures associated with BRCA1 as compared to BRCA2 and may inform development of future combinatorial treatment regimens for these pts. [Table: see text]
The association between sexual orientation and screening of prevalent gender-specific cancers.
Authors: Herriges Michael Joseph , Pinkhasov Ruben , Lehavot Keren , Shapiro Oleg , Jacob Joseph M , Sanford Thomas , Liu Nick , Bratslavsky Gennady , Goldberg Hanan
Published: March 2021

198

Background: Data on heterogeneity in cancer screening and diagnosis rates among sexual minorities (SMs) is lacking. Recent studies have shown SMs are more likely to engage in risky health behavior and have decreased healthcare utilization. However, few studies have examined how sexual orientation impacts cancer screening and prevalence. We therefore investigated whether sexual orientation affects prevalent gender-specific cancer including prostate (PCa), breast (BC), and cervical cancer (CC). Methods: This was a cross-sectional survey-based US study, including men and women aged 18+ from the Health Information National Trends Survey (HINTS) database (part of the National Cancer Institute’s division of cancer control and population sciences) between 2017-2019. The primary endpoint was individual-reported PCa, BC, and CC screening and prevalence rates among heterosexuals and homosexuals/bisexuals. Multivariable logistic regression analyses assessed association of various covariates with undergoing screening and diagnosis of these cancers. Results: Overall, 4,441 and 6,333 heterosexual men and women, respectively, were compared to 225 and 213 homosexual/bisexual men and women, respectively. Homosexuals/bisexuals were younger and less likely to be screened for PCa (34.7% vs 41.3%, p=0.013), BC (54.5% vs 80.7%, p=<0.001), and CC (88.3% vs 95.4%, p=<0.001). While rates of PCa and BC diagnosis were similar, more than twice as many homosexual/bisexual women were diagnosed with CC (4.2% vs 1.9%, p=0.023). Multivariable logistic regression models (Table) showed homosexuals/bisexuals were less likely to be screened for cancer with ORs of 0.61 (95% CI 0.39-0.95) for PCa, 0.52 (95% CI 0.30-0.92) for BC, and 0.21 (95% CI 0.09-0.46) for CC. Homosexuals/bisexuals were more likely to be diagnosed with any cancer with ORs of 1.64 (95% CI 1.06-2.54) in women only and 1.50 (95% CI 1.11-2.03) in men and women combined. Conclusions: Homosexuals/bisexuals in the US may be less likely to undergo screening of gender-specific prevalent malignancies, including PCa, BC, and CC. The implementation of cancer screening among SMs should be improved. [Table: see text]
MRI-guided fusion biopsy of the prostate resection bed among post-radical prostatectomy patients with rising PSA.
Authors: Williams Cheyenne , Khondakar Nabila , Daneshvar Michael , O'Connor Luke P. , Egan Jillian , Yerram Nitin , Rompre-Brodeur Alexis , Owens-Walton Jeunice , Merino Maria , Choyke Peter L. , Wood Bradford , Turkbey Baris , Pinto Peter A.
Published: March 2021

208

Background: Following treatment of prostate cancer with radical prostatectomy (RP), biochemical recurrence (BCR) can be detected with elevated PSA. This may be attributed to either cancer recurrence or retained benign prostatic gland tissue. Options for detecting malignancy after RP currently entail diagnostic imaging and biopsy with transrectal ultrasound (TRUS). TRUS alone has limited accuracy in detecting recurrence in the prostate bed. MRI fusion-guided biopsy (Fbx) may be a more accurate method of detecting post-RP local recurrence. We hypothesize that Fbx for diagnosing benign versus malignant recurrence in the prostate bed is feasible and produces clinically meaningful results. Methods: Our institutional database was queried for patients who received RP and demonstrated BCR between February 2015 and July 2020. All patients with evidence of prostate bed recurrence on mpMRI were included in this analysis. Cancer detection via mpMRI-guided fusion biopsy using the UroNav platform was evaluated and patient variables including final Gleason Grade group (GG), margin involvement, PSA at BCR, and prostate bed lesion size were analyzed with univariate logistic regression. Results: 40 patients (median age = 68) with BCR underwent post-RP mpMRI. 25/40 (62.5%) patients had MRI-visible lesions, and among those, 17/25 (68%) patients underwent Fbx of the prostate bed. 15/17 (88.2%) Fbxs detected prostate tissue (either benign or cancer), 11/17 (64.7%) contained cancer, and 4/17 (23.5%) contained benign prostate glands. Median cores per biopsy was 4 (IQR 4-6). Among the 83 cores obtained, 57 (68.6%) cores contained prostate gland tissue and 26 (31.3%) contained fibromuscular tissue. Of those 57 with gland tissue, 33 (57.9%) cores contained cancer, and 24 (42.1%) contained benign prostate tissue. Among patients with benign biopsies, none had further evidence of metastasis at median follow-up of 13.5 months after Fbx and 182 months after RP. On final RP pathology, 4 patients had GG1 disease, 4 had GG2, 4 had GG3, 2 had GG4, and 3 had GG5. 6/17 (35%) patients had positive RP margins. Median prostate bed lesion size was 1.3 cm (IQR 0.9-1.5). Prostate bed lesion size (cm) was the only variable significantly associated with cancer on Fbx (OR = 2.20, 95% CI:1.29-3.76, p = 0.011). Conclusions: mpMRI-Fbx is a feasible method for reliably targeting prostate bed lesions. With this technique, we found improved accuracy for biopsy-proven recurrence in the prostate bed. This technique will help direct treatment planning of salvage therapies among patients with detectable PSA post-RP. [Table: see text]
Radical prostate radiotherapy and the use of androgen deprivation in the era of risk stratification: Does real-world practice follow the evidence?
Authors: Prentice Mark , Mpima Sheila , Nasuti Paola , Payne Heather Ann
Published: March 2021

216

Background: Prostate cancer is a common condition with varied pathologies based on stage, grade and presenting PSA allowing non-metastatic cases to be risk stratified at presentation. There is an evidence base for the use of Androgen Deprivation Therapy (ADT) combined with radical radiation showing a survival benefit but with an increase in patient morbidity. Prostate cancer risk stratification can be used to guide ADT therapy duration to reduce toxicity but it is unknown how closely these guidelines are followed internationally. Methods: A cross sectional survey collecting data on 15,255 patients with prostate cancer was conducted across 5 European countries and Japan. Data was interrogated to provide real-world evidence for ADT prescribing in combination with radical radiotherapy treatment and compared against the available evidence base and international best practice guidelines. Results: 3,393 patients were included in data analysis; 53% were high risk, 35% intermediate, and 12% low risk cases. 48% of patients were ages 71-80yrs with 10% being aged over 80. Data, including proposed length of hormone treatment was available for 2,832 patients. Concordance to the evidence base was good for high- and low-risk prostate cancer patients (64% and 96% respectively) but there was more disparity in the intermediate risk group with a concordance rate of only 28%. Conclusions: The data was robust enough to be interrogated and produce meaningful results. Concordance to the evidence base was high in both high and low risk disease although there was a tendency towards over-treatment in both these groups in some of the countries included. There was significant disparity in the intermediate risk group with evidence of both over- and potential under-treatment across all countries. Any potential over treatment with ADT needs to take account of the known evidence base and the potential for bone and metabolic toxicities. The data suggests that guidelines offering greater clarity on the role of ADT in intermediate risk prostate cancer may be beneficial.
Impact of inflammatory bowel disease on radical prostatectomy outcomes and costs of care.
Authors: Goldberg Ilana , Chang Steven Lee , Kundu Shilajit , Chung Benjamin I. , Singer Eric A.
Published: March 2021

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Background: Recent studies suggest an association between prostate cancer and inflammatory bowel disease (IBD). Our objectives were to investigate clinical and financial impacts of IBD on radical prostatectomy (RP), and to determine the impact of surgical approach on our findings. Methods: The Premier Hospital Database was queried for patients who underwent RP from 2003 to 2017. Multivariable logistic regression models were used to determine the independent impact of IBD on complications and readmission rates. We determined 90-day readmissions and examined 90-day hospital costs adjusted to 2019 US dollars with multivariable quantile regression models. Results: Our study population included 262,189 men with prostate cancer, including 3,408 (1.3%) with IBD. There were higher odds for any complication for IBD patients compared to non-IBD controls for RP (15.64% vs. 10.66%). IBD patients had overall complication rates of 14.1% ( P < 0.05) for open surgery and 17.2% for MIS ( P < 0.01). Between 2013-2017, the IBD cohort had significantly more complications (OR: 2; 95% CI: 1.5 to 2.67; P < 0.0001), was more likely to have surgical costs in the top quartile (OR: 1.6; 95% CI: 1.23 to 2.1; P < 0.01), and had higher readmission rates (OR: 1.51; 95% CI: 1.1 to 2.06; P = 0.01). Conclusions: The IBD cohort who underwent MIS had the highest complication rates. Hospital readmissions and surgical costs were significantly higher for the IBD cohort who underwent RP between 2013-2017, when a minimally invasive approach was more prevalent than an open approach. These findings may be important when deciding which surgical approach to take when performing RP on men with IBD. [Table: see text]
Association between travel distance and use of postoperative radiation therapy among men with organ-confined prostate cancer: Does geography influence treatment decisions?
Authors: Arega Melaku A , Yang David , Royce Trevor Joseph , Mahal Brandon Arvin Virgil , Dee Edward Christopher , Butler Santino , Sha Sybil , Mouw Kent William , Nguyen Paul L. , Muralidhar Vinayak
Published: March 2021

24

Background: Following radical prostatectomy, men with adverse pathologic features or a persistent post-operative detectable PSA are candidates for postoperative radiation therapy (PORT). Previous data have suggested disparities in receipt of adjuvant radiation therapy for adverse pathologic features according to travel distance. Among patients without adverse pathologic features (pT2 disease and negative margins), the main indication for PORT is a persistent post-operative detectable PSA. However, it remains unknown whether the rate of receipt of PORT in this cohort of men with persistently detectable PSA is related to travel distance from the treating facility. Methods: Using the National Cancer Database, we identified 287,274 men with prostate cancer diagnosed in 2004-2015 managed with upfront surgery who were found to have pT2 disease with negative surgical margins. Multivariable logistic regression defined adjusted odds ratios (AORs) with 95% confidence intervals (95CI) of receiving PORT as the primary dependent variable and distance ( < 5, 5-10, 10-20, > 20 miles from the treatment facility) as the primary independent variable. Results: Within our cohort, progressively farther distance from the treatment facility was associated with lower rates of PORT. In patients living < 5 miles, 5-10 miles, 10-20 miles, and > 20 miles from the treating facility, rates of PORT were 1.52% (referent), 1.23% (AOR 0.86, 95CI 0.78-0.96), 1.11% (AOR 0.81, 95CI 0.73-0.90), and 0.65% (AOR 0.43, 95CI 0.38-0.47), respectively (p < 0.005 in pairwise comparisons). Conclusions: For men with localized prostate cancer without adverse pathologic features managed with surgery, increasing distance from treatment facility was associated with lower receipt of PORT. Given that the rate of a persistent post-operative detectable PSA is unlikely to depend on the distance to the treatment facility, these findings raise the possibility that the geographic availability of radiation treatment facilities influences the decision to undergo PORT for patients with persistent post-operative detectable PSA.
Early surrogate measures for ablative therapies for intermediate-risk prostate cancer patients.
Authors: Glicksman Rachel , Kishan Amar Upadhyaya , Katz Alan W. , Mantz Constantine Anastasios , Collins Sean P. , Fuller Donald B. , Zhang Liying , Loblaw Andrew
Published: March 2021

241

Background: Stereotactic body radiotherapy (SBRT) is increasingly used to treat patients with intermediate-risk prostate cancer (IR-PCa), but there is a lack of early surrogate measures in this patient population treated with SBRT to guide clinicians and patients. We aim to explore the outcomes of IR-PCa patients treated with SBRT and to assess the role of PSA response at 4 years (4yPSARR) as an early surrogate measure given its encouraging results in patients treated with brachytherapy. Methods: Individual patient data from 6 institutions for 820 patients with IR-PCa treated with SBRT between 2006 and 2014 were analyzed. Cumulative incidence of biochemical recurrence (defined by Phoenix criteria) was calculated using Nelson-Aalen estimates, and metastases-free survival and overall survival were calculated using the Kaplan-Meier method. Biochemical recurrence-free survival was analyzed according to 4yPSARR with groups dichotomized based on PSA < 0.4 ng/mL or >0.4 ng/mL and compared using Log-rank test. Results: 820 patients were included, including 549 (67%) with favorable intermediate and 271 (33%) with unfavorable intermediate risk disease defined by NCCN risk group classification. Median age at time of treatment was 70 years. The most common dose, fractionation and treatment schedule was 36.25 Gy in 5 fractions prescribed to the planning target volume delivered every other day. Androgen deprivation therapy was used in combination with SBRT in 9.2% of patients for a median duration of 3 months. Median follow-up was 5.9 years. The cumulative incidence of biochemical recurrence was 7.9% at 5 years. Metastases-free survival and overall survival rates at 5 years were 99.4% and 94.6%, respectively. Median 4yPSARR (n = 504) was 0.2 ng/mL. Biochemical recurrence-free survival in patients with 4yPSARR < 0.4 ng/mL (n = 387) was 99.2%, and in patients with 4yPSARR >0.4 ng/mL (n = 117) was 81.5% at 5 years (p < 0.0001). Conclusions: Prostate SBRT is an effective treatment modality in men with IR-PCa with at least comparable rates of biochemical failure and metastases compared to other standard treatment modalities in patients with IR-PCa. 4yPSARR may represent an early surrogate measure for use in this patient population treated with SBRT and should be included for further study in prospective SBRT trials.
Neoadjuvant versus concurrent androgen deprivation therapy plus radiotherapy for unfavorable intermediate-risk and high-risk prostate cancer with low PSA.
Authors: Andruska Neal , Agabalogun Temitope , Fischer-Valuck Benjamin Walker , Brenneman Randall , Gay Hiram Alberto , Michalski Jeff M. , Baumann Brian Christopher
Published: March 2021

243

Background: Dose-escalated radiotherapy (RT) with androgen-deprivation therapy (ADT) is a standard definitive treatment for localized prostate cancer (LPCa), but the optimal sequencing of hormone therapy with RT is unclear, with most patients treated with neoadjuvant ADT. Clinical trials addressing this question have not yielded definitive results. During COVID-19, there has been greater interest in neoadjuvant ADT as a way to delay initiation of RT to reduce risk of COVID transmission from daily RT visits with recent analysis from the NCDB showing that RT can be delayed for up to 6 months after neoadjuvant ADT. It is unclear if neoadjuvant ADT is appropriate for all patients or if select cohorts may benefit from concurrent ADT and upfront RT, such as patients with higher grade disease and low PSA who may have less hormone-responsive disease. Methods: Using the NCDB, we identified men diagnosed from 2004 to 2015 with NCCN unfavorable intermediate risk or high-risk adenocarcinoma of the prostate with a presenting PSA ≤ 5 ng/mL treated with definitive RT and either ADT initiated 2-4 months prior to RT (neoadjuvant ADT) or ADT started within 7 days of RT (concurrent ADT). OS was the primary endpoint. OS was estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards analyses was performed using age, facility type, Charlson-Deyo comorbidity score, clinical T stage, and Gleason score. Results: 2393 patients were identified, with 2103 receiving neoadjuvant ADT and 290 receiving concurrent ADT. Multivariable analysis (MVA) showed that concurrent ADT was associated with a lower risk of death relative to patients receiving neoadjuvant ADT {hazard ratio (HR): 0.58 [95% confidence interval: 0.36-0.94], p = 0.02}. The number of days from diagnosis to the start of RT was not associated with worse OS (HR:[0.99-1.01], p = 0.61) on MVA. Age (HR = 1.03 [1.01-1.05], p = 0.002) and treatment at an academic center (HR: 0.71 [0.53-0.94], p = 0.02) were also significantly associated with OS on MVA. The benefit of concurrent ADT relative to neoadjuvant ADT was greatest in patients with Gleason 4 and Gleason 5 disease (HR: 0.31 [0.14-0.71], p = 0.005). Conclusions: For patients with unfavorable intermediate-risk or high-risk prostate cancer and a PSA ≤ 5 ng/mL, concurrent ADT and upfront RT was associated with improved OS compared to neoadjuvant ADT and RT. The associated benefit appeared to be more pronounced for Gleason Score ≥ 8. Results are hypothesis generating and require validation in a randomized trial.
Normal tissue complication probabilities (NTCP) of urethral stricture following salvage SBRT or HDR for periurethral recurrences following prior definitive radiation therapy.
Authors: Injerd Russell , Burnham Kristen , Walb Matthew , Hershatter Bruce , Patel Sagar A , Fischer-Valuck Benjamin Walker
Published: March 2021

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Background: SBRT and HDR brachytherapy have emerged as definitive salvage re-irradiation options for men with locally recurrent prostate cancer after prior radiation therapy (RT). Toxicity with re-irradiation remains a concern in this setting, particularly for salvage of periurethral recurrences. We calculated the normal tissue complication probability (NTCP) of urethral stricture following salvage re-irradiation (HDR and SBRT) after previous definitive RT (external beam or HDR) for periurethral recurrences. Methods: Two upfront definitive treatment plans were generated for 5 men with localized prostate cancer: External Beam RT (EBRT1) to a dose of 79.2 Gy in 1.8 Gy fractions and HDR monotherapy (HDR1), 13.5 Gy x 2 implants. Periurethral recurrences were virtually created on diagnostic MRI scans for each of the five men and defined as a recurrent dominant intraprostatic lesion (DIL). Three salvage RT plans were generated for each patient (constraints in Table): HDR salvage (10 Gy whole gland; 13.5 Gy to DIL; 2 implants), SBRTr with maximal rectal sparing (constraints designed for salvage following prior EBRT; 30 Gy in 5 fractions whole gland; 40 Gy in 5 fractions to DIL), and SBRTu with maximal urethral sparing (constraints designed for patients with prior HDR monotherapy; same Rx). DVH data was collected for each plan (previous RT and each salvage approach) and the equivalent uniform dose (EUD) was calculated. NTCP for the urethral stricture in the summed plans (prior definitive treatment + each salvage plan) was calculated by the Lyman-Kutcher-Burman model using the following parameters: (α/β = 5Gy; TD50= 116.7; m = 0.23; n = 0.3). Results: Prescription coverage of 90% of the DIL volume was achieved for each plan. The mean NTCP of urethral stricture for EBRT1 + HDR salvage was 55.2% (range, 52.2-59.1%) and for HDR1 + HDR salvage was 49.2% (42.9-57.5%). For EBRT1 + SBRTr and EBRT1 + SBRTu the NTCP for urethral stricture was 54.0% (50.4-61.0%) and 43.2% (39.4-48.4%), respectively. The NTCP of urethral stricture for HDR1 + SBRTr was 48.1% (41.0-57.2%) and for HDR1 + SBRTu was 37.6% (30.9-44.6%). Conclusions: In this modeling analysis of salvage RT for periurethral recurrences following previous RT (EBRT or HDR monotherapy), the NTCP for urethral stricture was numerically lowest for salvage SBRT using maximum urethral sparing dose constraints in comparison to salvage SBRT with maximum rectal sparing constraints or salvage HDR brachytherapy. This type of analysis lends insight into personalized treatment planning based on previous RT modality and previous dose to organs at risk. Expanded analysis is underway. [Table: see text]
Impact of early hypothalamic-pituitary-gonadal axis maturation on prostate cancer:Cross-sectional analysis of a Veterans Affairs cohort.
Authors: Khadir Rimaz M. , Sayyid Rashid K. , Terris Martha K.
Published: March 2021

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Background: Early onset of puberty, resulting in more prolonged exposure to higher androgen levels, has been hypothesized to be a risk factor for more aggressive prostate cancer (PCa) later in life. We sought to determine whether earlier age of first shave and height, as surrogates of pubertal onset, were associated with worsening PCa characteristics. Methods: A prospectively collected registry of patients presenting for a prostate biopsy at the Charlie Norwood Veterans Affairs Medical Center in Augusta, GA between July 1995 and June 2016 was utilized. Age of first shave and height were compared to the risk of cancer on prostate biopsy, high grade cancer (i.e. Gleason score 8 or higher), and high volume disease (i.e. at least 50% of total cores were positive) using univariable and multivariable logistic regression analysis, controlling for patient age, race, prostate specific antigen, percent free prostate specific antigen, clinical stage, prostate volume, body mass index, family history. Statistical significance was set at p < 0.05 and all statistical analyses were performed using R version 3.6.1. Results: Of the 1,176 patients analyzed, 599 (50.9%) had a cancer on prostate biopsy, of which 141 (23.5%) and 194 (32.4%) had high grade and volume disease, respectively. Median age of first shave was 17.0 years (interquartile range 16.0-19.0) and height was 177.8 cm (172.7-182.9). On multivariable analysis, later age of first shave was significantly associated with increased odds of a positive prostate biopsy (odds ratio for > 18 years versus < 16 years: 5.36, p = 0.03) and taller patients had significantly increased odds of high-grade cancer (odds ratio for 175-180 cm versus < 175 cm 7.41, p = 0.038). Conclusions: Among patients presenting for a prostate biopsy, those with a later age of first shave and taller height had an increased risk of a positive prostate biopsy and high-grade PCa, respectively. This suggests that patients with later age of puberty, and thus later testosterone surges, are at increased risk of overall and high-grade PCa. [Table: see text]
The comparison of cytoreductive nephrectomy (CN) with tyrosine kinase inhibitor therapy alone in patients with primary metastatic renal cell carcinoma (mRCC).
Authors: Hatakeyama Shingo , Naito Sei , Numakura Kazuyuki , Kato Renpei , Koguchi Tomoyuki , Kojima Takahiro , Kawasaki Yoshihide , Kandori Kandori , Tsushima Eiki , Nishiyama Hiroyuki , Ito Akihiro , Kojima Yoshiyuki , Habuchi Tomonori , Obara Wataru , Tsuchiya Norihiko , Ohyama Chikara
Published: March 2021

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Background: We aimed to compare overall survival (OS) between patients with metastatic renal cell carcinoma (mRCC) treated by cytoreductive nephrectomy (CN) and those not treated by CN. Methods: We retrospectively evaluated 278 patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs) between January 2008 and November 2019. Patients were divided into two groups, CN group (immediate or deferred CN) and systemic TKI therapies alone without CN (Ctrl group). The OS was compared in all patients between the Ctrl and CN groups, between the Ctrl and immediate CN groups, between the Ctrl and deferred CN groups, and between the deferred CN and immediate CN groups. Analyses were weighted using the propensity score–based inverse probability of treatment weighting (IPTW) method to adjust for group imbalances. Results: The median age of the patients was 65 (range 59–73) years. Of the 278 patients, 132 and 146 were in the Ctrl and CN (immediate: 107 and deferred: 39) groups, respectively. A significant difference was noted between the Ctrl and CN groups in age, clinical stage, IMDC risk factors, and the number of metastatic sites. An IPTW-adjusted Cox regression analysis revealed a significant difference in OS between the Ctrl and CN groups and between the Ctrl and immediate or deferred CN groups. However, there was no significant difference in OS between immediate and deferred CN groups. Conclusions: The OS in CN group was significantly longer than that in Ctrl group even after the adjustment of potential selection biases.