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The testosterone (TT)/androgen receptor axis plays a crucial role in the initiation and progression of prostate cancer (PCa). We aimed to investigate the predictive value of serum TT levels on metastatic PCa progression. A total of 219 patients with metastatic PCa were included in this study. Analyses performed included Pearson’s correlation test, Wilcoxon rank test, Chi-square test, Cox regression, and Kaplan-Meier analysis. High serum TT levels (> 405 ng/dL) before ADT treatment, deep testosterone reduction (DTR) within the first year of ADT, rapid DTR within 3 months of ADT, and sustained DTR in the first year of ADT are associated with longer CRPC progression-free time. Low serum TT levels before abiraterone treatment are a risk factor for early PSA progression. We constructed a nomogram model based on the DTR within the first year of ADT. Calibration curve and decision curve analyses suggest the model has a high predictive ability for 1-, 1.5-, and 2-year CRPC progression and well clinical utility. Serum TT levels before and during ADT, as well as before abiraterone treatment, can predict metastatic PCa progression. Monitoring serum TT levels throughout the entire course of treatment is crucial for patient follow-up and prognosis.

Abiraterone (AA) and enzalutamide (ENZ) were introduced in Taiwan since 2012 for the treatment of patients with post-docetaxel metastatic castration-resistant prostate cancer (mCRPC). This study aims to retrospectively compare the efficacy of the two regimens. The study cohort consisted of 77 mCRPC patients previously treated with docetaxel and subsequently with AA (n=63, the AA group) or ENZ (n=13, the ENZ group), all treated in our hospital. Clinical parameters of the two groups were compared to determine differences between pre-treatment variables and treatment outcomes. Sixty-four patients received AA and 13 received ENZ, with a median 18.2 vs. 14.5 months follow-up (p=0.434). Prostate-specific antigen (PSA) response >50% was 31 (48.4%) in AA and 9 (69.2%) in ENZ (p=0.171), while PSA response >90% was 16 (25%) in AA and 5 (38.5%) in ENZ (p=0.32). The median progression-free survival (PFS) was 7.3 (95%CI=4.796-9.804) months in AA and 9.5 months (95%CI=5.743-13.257) in ENZ (p of log rank=0.766). The median overall survival (OS) from second-line hormone treatment was 30.2 months in AA group and 16.2 months in ENZ group (p of log rank=0.734). Neither the uni- nor the multi-variate COX-regression analysis distinguished any advantage of the two-drug regimen in terms of PFS or OS. Metastasis volume (HR=3.032, 95%CI=1.281-7.178, p=0.012) and nadir PSA (HR=1.000, 95%CI=1.000-1.001, p=0.010) were shown as independent risk factors for the survival of AA/ENZ-treated patients. AA and ENZ had a similar efficacy in treating post-docetaxel mCRPC patients. Metastatic volume and nadir PSA were independent risk factors of these patients in predicting their disease-specific survival and overall survival.

There is no definitive biomarker that predicts the effectiveness of abiraterone acetate. The objective of this study was to investigate whether dehydroepiandrosterone sulfate (DHEA-S) predicts the effectiveness of abiraterone acetate. This study included a total of 28 consecutive patients. The optimal cutoff value of DHEA-S for predicting the PSA response was calculated by receiver operating characteristic (ROC) analysis. The Cox proportional hazards model was performed to determine the predictive factors for the susceptibility to abiraterone acetate. Serum DHEA-S at baseline intercorrelated with the PSA response (correlation coefficient: -0.516). The optimal cutoff value of serum DHEA-S at baseline was 47.4 ug/dl in predicting >50% PSA decline. Serum PSA and serum DHEA-S at baseline were identified as significant factors for predicting PSA progression-free survival (p=0.010 and p=0.003, respectively). Serum DHEA-S at baseline may be a biomarker for predicting the prognosis of CRPC patients treated with abiraterone acetate.

National guidelines offer little guidance on the use of PSA progression (PSA increase as defined below) as a clinical endpoint in metastatic castration-resistant prostate cancer (mCRPC). The aim of the study was to examine treatment patterns/outcomes with abiraterone (abi)/enzalutamide (enza) throughout PSA progression and near the end of life (EOL). Cases of mCRPC treated with abi or enza from the New York Veterans Affairs (VA) from 6/2011-8/2017 were reviewed. Regression analyses were conducted to identify factors associated with continuation of abi/enza treatment up to the EOL, and survival. Of 184 patients, 72 received abi alone, 28 received enza alone, and 84 received both. Treatment was changed for PSA progression alone in 39.1% (abi) and 25.7% (enza) of patients. A total of 37 patients (20%) received abi/enza within 1 month before death, 30% of whom were receiving hospice services. Older patients and black patients were less likely to receive abi/enza up to the EOL. Abi/enza are frequently discontinued for PSA progression alone and continued at EOL. The clinical benefit of these practices warrants additional study.

Purpose Compare the efficacy and tolerability of dutasteride in combination with bicalutamide to bicalutamide monotherapy in the treatment of locally advanced and metastatic prostate cancer (PCa). Methods One-hundred-fifty PCa patients with locally advanced or metastatic disease were prospectively enrolled and randomly assigned to receive either bicalutamide monotherapy 150 mg once daily (79 patients) or bicalutamide 150 mg plus dutasteride 0.5 mg once daily (71 patients). Treatment response was assessed by serum PSA level measurement, and standard procedures for diagnosis of clinical progression were used during follow-up. Patient-reported quality of life (QoL) was assessed using validated questionnaires (EORTC QLQ-C30 and QLQ-PR25). Results At 3 years follow-up, PSA progression was found in 52 patients [65.8 %; 95 % confidence interval (CI) 55.4–76.3] in the monotherapy group compared to 38 patients (53.5 %; 95 % CI 41.9–65.1) in the combined therapy group (p = 0.134). At the time of analysis 37 men (46.8 %; 95 % CI 35.8–57.8) in the monotherapy group had died versus 30 men (42.3 %; 95 % CI 30.8–53.7) in the combined therapy group. Median survival time was 5.4 and 5.8 years, respectively (p = 0.694). There was no statistically significant difference in the presentation frequency of adverse events between groups (p = 0.683). QoL was good and comparable between the two groups. Conclusions Both therapies were well tolerated with a good QoL. However, despite a trend toward higher efficacy of the combined therapy, progression-free survival and overall survival was not significantly different between the groups. Further research on this therapy should be performed.

Purpose The aim of the study was to correlate nuclear matrix (NM) protein expression profiles with the risk of PSA progression or death in early prostate cancer (PCa). Methods High-resolution two-dimensional gel electrophoresis (2D-PAGE) was used to identify tumor-associated NM proteins in the PCa specimens obtained from 94 patients. The association between the expression of each protein and the probability of PSA progression or death was studied through univariate analysis. Unsupervised hierarchical clustering analysis was then used to generate patient clusters showing comparable outcomes by including the proteins that were predictive at univariate analysis. PSA-free and overall survival curves relative to each cluster were constructed by means of the Kaplan–Meier method and curves compared by the log-rank test. Multi-parametric models were constructed according to Cox proportional hazard technique. Results After a median follow-up of 11.7 years (range, 6.5–16.2), 50 patients progressed and 22 died. Of the eight NM proteins identified through 2D-PAGE, proteins NM-6, NM-7 and NM-8 were confirmed to be individually associated with a higher risk of PSA progression at univariate analysis. Proteins NM-6 and NM-8 were also predictive of survival probability. Hierarchical clustering analysis of these proteins allowed to identify one cluster of tumors co-expressing the three proteins or proteins NM-6 and NM-8, characterized by a very poor outcome, suggesting a specific role for these proteins in PCa progression. The predictive value of this mini-signature in respect to PSA-free survival was confirmed by multivariate analysis. Conclusions Changes in NM scaffolding are strongly associated with the clinical outcome of patients following radical prostatectomy.

Der Anstieg des prostataspezifischen Antigens nach radikaler Prostatektomie (RP) oder nach kurativer Strahlentherapie (RT) ist das frühe Zeichen einer Tumorprogression. Die aktuelle Definition nach RP ist 0,4 ng/ml und weiter steigend, die nach RT Nadir + 2 ng/ml. Die Prognose dieser Patienten ist heterogen. Die wesentlichen Prognoseparameter sind Gleason-Score, Zeit bis zum Auftreten der PSA-Progression und PSA-Verdopplungszeit (PSA-DT). Bildgebende Verfahren spielen in der frühen Phase (PSA<0,5 ng/ml) nach radikaler Prostatektomie, in der die Entscheidung für eine Salvage-RT getroffen werden muss, keine wesentliche Rolle. Nach kurativer Strahlentherapie ist für die Entscheidung zur lokalen Salvagetherapie (Prostatektomie, Kryotherapie, HIFU) eine Biopsie indiziert. Nach radikaler Prostatektomie erreichen im Langzeitverlauf ohne Therapie nur ca. 30% der Patienten das Stadium der klinischen Metastasierung, nach kurativer Strahlentherapie häufiger (bis 75%). Dies ist bei der Indikationsstellung zur Hormontherapie zu bedenken. Bei fehlenden aussagekräftigen prospektiven Studien sind der optimale Zeitpunkt und die Art der Hormontherapie derzeit nicht definiert.

Objective: To assess the influence of biochemical recurrence (BCR) risk groups and PSA kinetics on the outcomes of radioguided surgery against prostate-specific membrane antigen (PSMA-RGS). Currently, neither BCR risk group nor PSA doubling time (PSA-DT), or PSA velocity (PSA-V) are actively assigned or relevant for counseling prior to PSMA-RGS. Methods: We retrospectively analyzed PSMA-RGS cases for oligorecurrent prostate cancer between 2014 and 2023. BCR risk groups, PSA-DT, and PSA-V were analyzed as predictors for complete biochemical response (cBR, PSA < 0.2 ng/mL), BCR-free, and therapy-free survival (BCRFS, TFS). Results: Of 374 included patients, only 21/374 (6%) and 201/374 (54%) were classified as low- and high-risk BCR (no group assignment possible in 152/374, 41%). A total of 13/21 (62%) patients with low- and 120/201 (60%) with high-risk BCR achieved cBR (p = 1.0). BCR classification was no predictor for BCRFS (HR:1.61, CI: 0.70–3.71, p = 0.3) or subsequent TFS (HR:1.07, CI: 0.46–2.47, p = 0.9). A total of 47/76 (62%) patients with PSA-DT ≤ 6 mo and 50/84 (60%) with PSA-DT > 6 mo achieved cBR (p = 0.4). PSA-DT was not associated with cBR (OR: 0.99, CI: 0.95–1.03, p = 0.5), BCRFS (HR: 1.00, CI: 0.97–1.03, p = 0.9), or TFS (HR: 1.02, CI: 0.99–1.04, p = 0.2). Consistent negative findings were recorded for PSA-V. Conclusions: The BCR risk groups and PSA kinetics do not predict the oncological success of PSMA-RGS performed at low absolute PSA values. Indolent low-risk BCR is rarely treated by PSMA-RGS.

Methionine addiction is a general and fundamental hallmark of cancer due to the excess use of methionine for transmethylation reactions, termed the \"Hoffman Effect\". Methionine addiction has been shown to be a highly-effective target for cancer therapy by methionine restriction with oral recombinant methioninase (o-rMETase) in preclinical studies, including patient- derived orthotopic xenograft (PDOX) mouse models of cancer. A clinical study of o-rMETase as a supplement showed a 70% reduction of PSA levels in a patient with bone-metastatic prostate cancer. In the present study, two advanced prostate-cancer patients took o-rMETase as a supplement for approximately one month. One of the patients taking o-rMETase showed a 38% reduction of PSA levels and the second patient showed a 20% PSA reduction. o-rMETase shows promise for treating patients with advanced prostate cancer.