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Purpose Quantification of PSMA expression via PSMA PET is well-established, however quantification of PSMA via immunohistochemistry (IHC) is not standardized. Our aim was to determine the most optimal PSMA IHC scoring system to quantify PSMA expression with PSMA PET as reference standard. Methods Primary intermediate- and high-risk prostate cancer patients received an [ 18 F]PSMA-1007 PET/MRI followed by radical prostatectomy. SUV max , SUV mean and K i of the prostate tumor was determined. Prostate tumors were stained with anti-PSMA antibodies and scored by 2 readers via 10 IHC scoring systems: histochemical score (H-score), immunoreactivity score predominant intensity (IRS predominant intensity ), IRS classification predominant intensity , IRS mean intensity , IRS classification mean intensity , Allred score, predominant expression pattern, Shannon diversity index (SDI), percentage negatively stained cells and total percentage positively stained cells. Spearman’s rank correlation coefficients (ρ) were calculated between PET parameters and IHC scoring systems. Interreader agreement for the IHC scoring systems was measured by the intraclass correlation coefficient (ICC). Results Fifty tumors in 46 patients were analysed. H-score had the best correlation with SUV max (ρ 0.615 p  < 0.0001) and SUV mean (ρ 0.570, p  < 0.0001) and the second best correlation with K i (ρ 0.411, p  = 0.0030). SDI had the best correlation with K i (ρ -0.440, p  = 0.0014) and the second best correlation with SUV max (ρ -0.516, p  = 0.0001) and SUV mean (ρ -0.490, p  = 0.0003). A moderate interreader agreement was observed for H-score (ICC 0.663, 95% CI 0.495–0.797) and SDI (ICC 0.546, 95% CI 0.354–0.725). Conclusion H-score had the best correlation with PSMA PET quantification and an acceptable interreader agreement. Therefore, we deem H-score the most optimal PSMA IHC scoring system.

ContextThere is an urgent need to develop novel treatment strategies in patients with unfavorable intermediate- and high-risk localized prostate cancer (PCa) to optimize the outcome of these patients. Androgen receptor signaling inhibitors (ARSI) have demonstrated a survival benefit in metastatic hormonesensitive and castration-resistant PCa. A similar benefit might be expected in the localized setting.ObjectiveTo perform a systematic review about the role of neoadjuvant ARSI in unfavorable intermediate and high-risk localized PCa.Evidence acquisitionWe performed a systematic review of the following databases: MEDLINE (PubMed), EMBASE, Cochrane Library and Web of Science. Publications of ASCO were consulted to identify meeting abstract with early results of ongoing trials. This systematic review was performed and reported in accordance with the PRISMA guidelines.Evidence synthesisPathological complete response (pCR) following neoadjuvant ARSI treatment was observed in 4%–13% of the patients. Minimal residual disease response ranged from 36% to 73.9% when defined as residual cancer burden < 0.25 cm3 at final pathology and from 8% to 20% when defined as the diameter of the remaining tumor < 5 mm. Despite intense neoadjuvant ARSI treatment, residual pT3 disease was observed in 48%–76% of the patients. In contrast, positive surgical margins (PSM) were present in only 5%–22%. Only one trial reported BCR following neoadjuvant ARSI therapy (44% BCR at a median follow-up of 4 years).ConclusionDespite intense neoadjuvant ARSI therapy, pCR is rarely attained and high proportions of pT3 disease are still observed at final pathology. In contrast, promising results are obtained in terms of PSMs. Long-term survival outcomes are eagerly awaited.

Patients with high-risk prostate cancer treated with curative intent are at an increased risk of biochemical recurrence, metastatic progression and cancer-related death compared with patients treated for low-risk or intermediate-risk disease. Thus, these patients often need multimodal therapy to achieve complete disease control. Over the past two decades, multiple studies on the use of neoadjuvant treatment have been performed using conventional androgen deprivation therapy, which comprises luteinizing hormone-releasing hormone agonists or antagonists and/or first-line anti-androgens. However, despite results from these studies demonstrating a reduction in positive surgical margins and tumour volume, no benefit has been observed in hard oncological end points, such as cancer-related death. The introduction of potent androgen receptor signalling inhibitors (ARSIs), such as abiraterone, apalutamide, enzalutamide and darolutamide, has led to a renewed interest in using neoadjuvant hormonal treatment in high-risk prostate cancer. The addition of ARSIs to androgen deprivation therapy has demonstrated substantial survival benefits in the metastatic castration-resistant, non-metastatic castration-resistant and metastatic hormone-sensitive settings. Intuitively, a similar survival effect can be expected when applying ARSIs as a neoadjuvant strategy in high-risk prostate cancer. Most studies on neoadjuvant ARSIs use a pathological end point as a surrogate for long-term oncological outcome. However, no consensus yet exists regarding the ideal definition of pathological response following neoadjuvant hormonal therapy and pathologists might encounter difficulties in determining pathological response in hormonally treated prostate specimens. The neoadjuvant setting also provides opportunities to gain insight into resistance mechanisms against neoadjuvant hormonal therapy and, consequently, to guide personalized therapy.Cancer recurrence after radical prostatectomy for high-risk prostate cancer is common. The addition of neoadjuvant hormonal therapy with the introduction of potent androgen receptor signalling inhibitors has gained interest in the oncological community. However, conclusions of a survival benefit with this therapy cannot currently be made and results of several phase II trials are much anticipated.

For patients presenting with limited metastatic disease burden, known as the oligometastatic state of disease, a more aggressive treatment approach targeting the new or progressive metastatic lesions might improve patient outcome, with no or only limited toxicity to be expected from the treatment. This review provides an overview of the existing evidence and on-going trials on oligometastatic disease and metastasis-directed therapy in the field of renal, bladder and prostate cancer.

[...]although reasonably high numbers of high-risk PCa patients (according to EAU risk grouping system) were included in the development and PCBaSe cohorts (22.4% and 15.1% ISUP grade group 4–5 PCa, respectively; 14.5% and 16% stage T3–4, respectively), it is unclear how well the model performs in actively treated high-risk and very-high-risk PCa patients. Today, international PCa guidelines strongly recommend against the use of ADT monotherapy in newly diagnosed, non-metastatic PCa patients [2]. [...]the model is less useful in optimizing the therapy decision in this high-risk population. [...]the tool does not take into account recent changes in PCa management, such as the implementation of MRI prior to prostate biopsy or the use of targeted biopsies.

Accurately identifying motives to gamble is crucial in the functional analysis of gambling behavior. In this study, a data-driven approach was followed to clarify the factor structure underlying a pool of motives for gambling, selected from the Gambling Motives Questionnaire-Financial (GMQ-F), and the Reasons for Gambling Questionnaire (RGQ), in a sample of regular problem and non-problem gamblers. Additionally, the role of gambling motives in the relationship between root behavioral activation/inhibition systems (BIS/BAS) and gambling severity, frequency, and preferences was explored using structural equation modelling (SEM). The present study identified Social, Financial, and Fun/thrill-related gambling motives factors, but also a fourth factor in which some positive and negative reinforcement-based motives were grouped into a single and broader Affect regulation factor. This Affect regulation factor shared variance both with BIS and BAS-related measures, and was the only direct predictor of disordered gambling symptoms. The Fun/thrill factor was directly related to frequency of participation in high-arousal, skill-based games, and all factors were related to participation in lower-arousal, chance games (with Social motives negatively predicting both participation in the latter and total severity). In the SEM model, measures of BIS/BAS sensitivity were connected to gambling behavior only through gambling motives. Based on measures of items' specificity, a shortened Spanish scale (the brief Gambling Motives Inventory, bGMI) is proposed to assess gambling motives in accordance with the observed 4-factor structure.

The long-term outcomes of the first prospective, multi-institutional, single-arm study of patients with prostate cancer treated with salvage radical prostatectomy after disease recurrence following radiotherapy have recently been published. Durable oncological control was reported, possibly because most patients had low-risk or intermediate-risk prostate cancer at initial diagnosis and the biochemical progression-free survival interval was long.

Prostate cancer is an androgen-driven tumor. Different prostate cancer therapies consequently focus on blocking the androgen receptor pathway. Clinical studies reported tumor resistance mechanisms by reactivating and bypassing the androgen pathway. Preclinical models allowed the identification, confirmation, and thorough study of these pathways. This review looks into the current and future role of preclinical models to understand resistance to androgen receptor-targeted therapies. Increasing knowledge on this resistance will greatly improve insights into tumor pathophysiology and future treatment strategies in prostate cancer.