Prostate Cancer and Prostatic Diseases最新文献

Background: Emerging evidence in cancer neuroscience indicates that the nervous system interacts directly or indirectly with cancer cells, promoting tumor progression. The prostate gland contains an extensive neural network essential for regulating key physiological functions of prostate cells, and the significant neural distribution observed in prostate cancer highlights its critical role in driving cancer pathogenesis. Unfortunately, Comprehensive reviews systematically summarizing progress in cancer neuroscience for prostate cancer are currently lacking.

Method: We synthesize existing research on interactions between the nervous system and prostate cancer cells, explore the neural distribution within the prostate, and evaluate the impact of neural innervation on prostate cancer development and progression. Additionally, we also assess the potential neural regulation mechanisms in neuroendocrine prostate cancer (NEPC).

Result: We found that neural interactions significantly influence prostate cancer development. Neural circuitry within the tumor microenvironment drives progression and contributes to the aggressiveness of lethal subtypes like NEPC. Targeting neuromodulation emerges as a promising therapeutic approach, potentially allowing the repurposing of established medications for treating advanced tumors.

Conclusion: Neuromodulation offers a promising therapeutic option for advanced prostate cancer, particularly NEPC, which faces limited treatment options. However, further research is necessary to fully understand the neural regulatory mechanisms involved in prostate cancer development and to identify new therapeutic targets and strategies for advanced stages.

Background: Oligometastatic hormone-sensitive prostate cancer (omHSPC) represents a favorable and potentially curable disease state in which metastasis-directed therapy (MDT) improves outcomes. The combination of MDT and systemic treatment is the next frontier of omHSPC.

Objective: To review and synthesize current evidence from prospective trials evaluating MDT alone or combined with systemic therapy in synchronous and metachronous omHSPC, and to highlight the evolving role of advanced imaging, genomics, and ongoing efforts in refining treatment strategies.

Methods: This review synthesizes data from prospective trials, meta-analyses, and ongoing studies assessing MDT in omHSPC. Key trials include STOMP, ORIOLE, EXTEND, RADIOSA, and the X-MET meta-analysis, with emphasis on clinical outcomes and biomarkers RESULTS: In metachronous omHSPC, STOMP and ORIOLE phase II trials demonstrated that MDT significantly improves progression-free survival (PFS) and delays androgen deprivation therapy (ADT) compared to observation. The EXTEND and RADIOSA trials suggest combining MDT with short-term ADT further improves outcomes. The X-MET meta-analysis confirmed benefits in PFS, radiographic PFS, and castration-resistance-free survival with MDT. No randomized trial has yet evaluated MDT with current standard of care ADT + androgen receptor pathway inhibitor (ARPI) therapy, though EXTEND did include a limited subset of patients receiving ARPI. Advanced imaging, especially PSMA-PET, is transforming MDT planning by enabling more accurate lesion detection than conventional imaging. In synchronous omHSPC, the role of MDT remains under investigation in ongoing trials such as TERPS, STAMPEDE2 and START-MET.

Conclusions: MDT offers clinical benefit in metachronous omHSPC, particularly when combined with systemic therapy. Advanced imaging and genomic profiling are critical tools for refining patient selection. Most data stem from phase II studies without ADT + ARPI control groups; larger randomized trials are needed to define the role of MDT in standard practice and optimize personalized care strategies.

Background: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is a widely accepted treatment option for metastatic castration-resistant prostate cancer (mCRPC). However, synthesized evidence regarding potential prognostic factors for oncologic outcomes in patients treated with PSMA-RLT is lacking. We aimed to synthesize prognosticators of oncologic outcomes in patients with mCRPC treated with PSMA-RLT.

Methods: PubMed®, Web of Science™, and Embase® databases were systemically searched in March 2025 for studies. Eligible studies investigated pretreatment clinical, hematologic, or radiographical prognostic factors for oncologic outcomes, such as progression-free (PFS) or overall survivals (OS) in patients with mCRPC treated with PSMA-RLT. Only parameters assessed through multivariable analysis adjusting for potential confounders were synthesized. (CRD42024598718) RESULTS: A total of 39 studies (n = 4819) were included in the systematic review and 32 studies (n = 3038) were included in the meta-analysis. Prior chemotherapy (pooled HR: 1.43, 95%CI: 1.10-1.85), visceral metastases (pooled HR: 1.41, 95%CI: 1.05-1.89), and liver metastasis (pooled HR: 1.75, 95%CI: 1.37-2.25) were associated with worse PFS. Poor performance status (PS) (pooled HR: 1.99, 95%CI: 1.45-2.74), prior chemotherapy (pooled HR: 1.39, 95%CI: 1.19-1.63), visceral metastasis (pooled HR: 1.65, 95%CI: 1.33-2.05), bone metastasis (pooled HR: 2.09, 95%CI: 1.39-3.13), liver metastasis (pooled HR: 2.15, 95%CI: 1.84-2.50), and lower pretreatment hemoglobin levels (pooled HR: 1.25, 95%CI: 1.09-1.43) were associated with poorer OS. Higher pretreatment SUV_mean was associated with improved OS benefit (pooled HR: 0.91, 95%CI: 0.85-0.97). PSA decline after treatment initiation, particularly ≥50%, was associated with improved PFS and OS.

Conclusions: Prior chemotherapy use and location of metastases influence the prognosis of patients with mCRPC treated with PSMA-RLT. A higher pre-treatment SUV_mean is predictive of better PSMA-RLT efficacy, and a greater PSA 'response is associated with improved survival outcomes. These findings may help guide clinical decision-making regarding PSMA-RLT and support prognostication of its oncological benefits.

Background: Life expectancy (LE) is essential for triage between aggressive and conservative management for all prostate cancer risk subtypes. We sought to investigate differences in how Black and Hispanic men interpret LE in treatment decision-making.

Methods: We used targeted crowdsourcing to sample a cohort reflecting sociodemographics of a US prostate cancer population. Subjects completed a conjoint analysis exercise where they iteratively chose between aggressive treatment versus conservative management across levels of 4 tradeoffs-tumor risk (lives saved by aggressive treatment at 5/10/20 year); erectile dysfunction; urinary incontinence; and irritative urinary symptoms-while considering their LE as calculated by the Prostate Cancer Comorbidity Index. Multinomial conditional logistic regression compared odds of choosing aggressive vs. conservative treatment across LEs ranging from 0 to 20 years overall and across racial/ethnic subgroups.

Results: Of 2046 men, 435 (22%) were Black and 230 (11%) were Hispanic. Across all men, the odds of aggressive treatment choice increased by 17% for every 5 years of additional LE (OR = 1.17, 95%CI = 1.12-1.22, p < 0.001). Men were significantly more likely to choose aggressive treatment at LE > 13 y and non-aggressive treatment at LE ≤ 10 y. Among Black men, LE was not associated with treatment choice, as they consistently preferred aggressive treatment across all LE categories. Among Hispanic men, increased LE was associated with a higher likelihood of choosing aggressive treatment, with significant preference for aggressive treatment observed only when LE > 10 years. These patterns remained consistent when further stratified by tumor risk.

Conclusions: LE had no impact on treatment decisions in Black men, in contrast to other races and ethnicities. Future research is needed to identify reasons for this phenomenon and to inform culturally relevant approaches to communicating competing mortality risks.

Background: The combination of multiparametric magnetic resonance imaging (MP-MRI) and ultrasound-guided fusion biopsy is increasingly recognized as a valuable tool for diagnosing prostate cancer. However, up to 80% of PI-RADS 3 lesions and 50% of PI-RADS 4 lesions are benign. This study evaluates whether lesion echogenicity observed during MRI-ultrasound fusion biopsy is associated with detecting clinically significant prostate cancer (csPCa).

Methods: In this retrospective analysis (March 2017-February 2022), we reviewed patients who underwent both standard 12-core random biopsies and targeted MP-MRI/US fusion-guided biopsies at our institution. Lesions were categorized as strongly hypoechoic, weakly hypoechoic, or non-hypoechoic based on ultrasound echogenicity. CsPCa was defined as a Gleason score ≥7.

Results: Among 222 biopsy patients, 59.3% were diagnosed with PCa, and 68% had csPCa. Of 420 lesions, 19.1% were strongly hypoechoic (45% csPCa), 29.5% were weakly hypoechoic (25% csPCa), and 51.4% were non-hypoechoic (11.8% csPCa) (p < 0.001). Echogenicity improved csPCa detection for PI-RADS ≤ 3 lesions from 7.5% (non-hypoechoic) to 27.5% (strongly hypoechoic), for PI-RADS 4 from 13.1% to 35.1%, and for PI-RADS 5 from 42% to 63.5%. The ROC analysis demonstrated AUCs of 0.6958 for PI-RADS, 0.6929 for echogenicity, and 0.7434 for their combination (all p < 0.001).

Conclusion: Lesion echogenicity observed during MRI-ultrasound fusion biopsy enhances csPCa detection and complements PI-RADS scoring. Incorporating echogenicity into risk assessment may improve biopsy decision-making and diagnostic accuracy.

Background: Despite advancements in treatment, metastatic prostate cancer remains a lethal disease. As prostate cancer becomes resistant to standard of care treatments like androgen receptor pathway inhibitors (ARPIs) and chemotherapy, cell surface tumor antigens and receptors become increasingly heterogeneous and diverse, dependent on androgen receptor dependency with relevance for both diagnostic positron emission tomography (PET) imaging and cell surface targeting therapeutics. Our review aims to describe emerging theranostic targets and agents in cell surface imaging and therapies.

Methods: A literature search was carried out in March 2025, on Pubmed, as well as Clinicaltrials.gov to determine cell surface targets with viable trials for imaging and/or therapeutic agents. Keyword searches included "Prostate Cancer" AND "CRPC" AND "Cell Surface Targets."

Results: Among the literature, 13 novel targets with robust supporting literature were found. Targets were subsequently divided into targets of interest in AR-positive and AR-negative (NEPC and/or double negative) mCRPC. Ongoing and completed trials for imaging and/or therapeutics leveraging these targets was described.

Conclusion: Numerous prostate cancer cell surface markers are emerging as theranostic targets. For patients ineligible for or developing progression following PSMA-targeting therapies, extending cell surface targeting therapeutics, whether they are ADCs, cellular therapies, or RPTs, is increasingly vital.

Background: Pelvic lymph node dissection (PLND) is integral to prostate cancer staging, but its therapeutic value remains debated. PSMA PET/CT has shown high accuracy in detecting lymph node metastasis (LNM). This study evaluates the feasibility of performing PLND based on PSMA PET/CT findings during robotic-assisted radical prostatectomy (RARP).

Methods: In this prospective, randomized study, biopsy-confirmed prostate cancer (PCa) patients with intermediate or high risk were enrolled. Patients with distant metastasis or prior endocrine therapy were excluded. All underwent 18F-PSMA PET/CT imaging, and those with LNM were assigned to Group A. Patients without LNM were randomized in a 1:1 ratio into Groups B and C. All patients underwent RARP and Groups A and B with PLND while Group C without. The primary outcomes were PSMA PET/CT accuracy in detecting LNM and oncological results. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2200063256).

Results: Between September 2022 and August 2023, 120 PCa patients were enrolled. The sensitivity, specificity, accuracy, positive predictive value (PPV), and NPV of PSMA PET/CT were 76.5%, 86.8%, 65.0%, 92.0%, and 84.3%. There were no significant differences in clinical parameters, progression-free survival (PFS) or PSA persistence between Groups B and C. However, PLND patients had longer surgical times, hospital stays, and higher complication rates.

Conclusions: PSMA PET/CT offers high specificity and NPV in detecting LNM.LND may be unnecessary for node-negative patients identified by PSMA PET/CT, with close follow-up recommended for those not undergoing LND.