Abstract Background Oligometastatic prostate cancer (OMPC) is typically treated with systemic therapy, which may be complemented by radiotherapy (RT) of the prostate as part of primary directed therapy (PDT). This study retrospectively evaluated clinical outcomes following PDT in OMPC. Results Twenty-four consecutive patients who underwent PDT for OMPC between 2011 and 2023 were analyzed retrospectively. The primary endpoint was progression-free survival (PFS); secondary endpoints included biochemical PFS (bPFS), overall survival (OS), and treatment-related toxicity. Survival was estimated using Kaplan–Meier analysis, and prognostic factors for PFS were assessed using univariate log-rank tests and multivariate Cox regression. The median follow-up was 40 months. Median age was 75 years (range: 58–83), with a median of two metastases (range: 1–5). Nineteen patients (79%) were staged with PSMA-PET/CT; 20 had synchronous and 20 low-burden disease (CHAARTED criteria). The most common RT regimen was 60 Gy in 20 fractions. Twenty-three patients received androgen deprivation therapy (ADT), including six with an androgen receptor signaling inhibitor (median duration: 23 months). Additionally, 22 underwent metastasis-directed therapy (MDT), and five elective nodal RT. Median PFS and bPFS were 80 and 73 months, respectively; median OS was not reached. Three-year PFS, bPFS, and OS were 78%, 81%, and 84%. Low metastatic burden (p = 0.007) and synchronous metastases (p = 0.027) predicted longer PFS. No acute grade 3 toxicity occurred; late grade 3 gastrointestinal and genitourinary toxicity occurred in 8% each. Conclusions In this predominantly PSMA-PET/CT-staged cohort, PDT combined with MDT and ADT achieved promising long-term outcomes with acceptable toxicity, warranting confirmation in larger prospective studies.

Accurate clinical target volume (CTV) delineation is crucial for effective salvage radiotherapy (sRT) following radical prostatectomy. Current delineation guidelines are largely based on expert opinion and conventional imaging, with limited incorporation of prostate-specific membrane antigen (PSMA) PET/CT data. As PSMA PET/CT enables sensitive detection of local recurrences (LR), this study aims to evaluate the benefit of implementing PSMA PET/CT imaging into CTV delineation guidelines by evaluating spatial distribution of PSMA PET/CT-positive LR and their coverage by 5 commonly used guidelines. Methods: We retrospectively analyzed 77 postprostatectomy patients with 79 LR, staged with PSMA PET/CT and treated with sRT between 2014 and 2023. Planning CT scans on which the LR were delineated as gross tumor volume were further analyzed. The gross tumor volumes were mapped into a standard patient using a modified 3-dimensional prostate bed template according to the PSMA PET-guided hypofractionated salvage prostate bed radiotherapy of biochemical failure after radical prostatectomy for prostate cancer (PERYTON) guideline. Coverage of 5 commonly used CTV guidelines, namely, Groupe Francophone de Radiothérapie Urologique (GFRU), European Society for Radiotherapy and Oncology-Advisory Committee on Radiation Oncology Practice (ESTRO-ACROP), PERYTON, Faculty of Radiation Oncology Genito-Urinary Group (FROGG), and Radiation Therapy Oncology Group (RTOG) was assessed. Coverage was categorized as fully (100% coverage), partially (100% < coverage > 0%), or not covered (0% coverage). Results: Most LR occurred in the vesicourethral anastomotic region (52/79, 66%) and predominantly (73/79, 92%) posteriorly to the midline of the bladder. Full coverage of LR varied across guidelines: RTOG (44/79, 56%), PERYTON (41/79, 52%), ESTRO-ACROP (34/79, 43%), GFRU (31/79, 39%), and FROGG (30/79, 38%). Partial coverage accounted for the remaining cases, except for 1 lesion each missed entirely by FROGG, GFRU, and PERYTON. The posterior, posterolateral, and lateral borders were the most frequent sites where recurrences exceeded guideline-defined CTVs. Conclusion: Although current CTV guidelines achieve acceptable overall coverage, especially concerning the inferior, anterior, and superior border, recurrences tend to extend beyond posterior, lateral, and posterolateral borders, indicating potential areas for refinement. Incorporation of PSMA PET/CT data into CTV delineation may improve robustness and reduce the risk of geographic misses in sRT.

Accurate prostate cancer (PCa) diagnosis remains difficult because of tumor heterogeneity and the challenge of integrating multimodal clinical information. We developed Prost-LM, a multimodal large language model that jointly embeds MRI-derived features, numerical PSA values, and free-text clinical reports into a unified semantic space to enable deep cross-modal reasoning. Trained and validated on a large multi-center cohort of 3940 patients, Prost-LM achieved strong diagnostic performance, with an internal validation AUC of 0.954 for distinguishing PCa from benign conditions, outperforming MRI-only models (AUC = 0.868, P < 0.001). For detecting clinically significant PCa (Gleason score ≥ 7), Prost-LM reached an AUC of 0.955. Additionally, the model provides interpretable diagnostic decisions to support clinical verification. These results suggest Prost-LM can improve automated PCa diagnosis and support precision oncology through multimodal AI.

Prostate cancer (PCa) remains a major cause of cancer-related mortality in men, largely due to therapy resistance and metastatic progression. Increasing evidence highlights the tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), as a critical determinant of disease behavior. CAFs constitute a heterogeneous population originating from fibroblasts, mesenchymal stem cells, endothelial cells, epithelial cells undergoing epithelial-mesenchymal transition (EMT), and adipose tissue. Through dynamic crosstalk with tumor, immune, endothelial, and adipocyte compartments, CAFs orchestrate oncogenic processes including tumor proliferation, invasion, immune evasion, extracellular matrix remodeling, angiogenesis, and metabolic reprogramming. This review comprehensively summarizes the cellular origins, phenotypic and functional heterogeneity, and spatial distribution of CAFs within the prostate TME. We further elucidate the molecular mechanisms by which CAFs regulate PCa progression and therapeutic resistance, and critically evaluate emerging strategies to therapeutically target CAF-mediated signaling, metabolic, and immune pathways. By integrating recent advances from single-cell and spatial transcriptomics (ST), our objective is to provide a holistic framework for understanding CAF biology and to highlight potential avenues for stromal reprogramming as an adjunct to current PCa therapies.

Recent advancements in imaging, particularly 18F-fluorodeoxyglucose positron-emission tomography–computed tomography (FDG-PET/CT), have improved the detection of involved lymph nodes, thus influencing staging accuracy and potentially treatment outcomes. This study is a post hoc analysis of the GAZAI trial data to evaluate the impact of FDG-PET/CT versus computed tomography (CT) alone on radiation target volumes for involved-site radiotherapy (IS-RT) in early-stage follicular lymphoma (FL). All patients in the GAZAI trial underwent pretherapeutic FDG-PET/CT examinations, which were subject to central quality control. Lymph nodes with pathological metabolism were assessed for CT morphology. Differential regional involvement and the impact on radiation target volume for IS-RT were compared between PET/CT-based to solely CT-based staging. In 54 patients with PET-positive lymph nodes after initial surgery, 170 involved lymph nodes were identified in total. FDG-PET/CT identified additionally involved lymph nodes not detected by CT in 61

Castration-resistant prostate cancer (CRPC) marks the advanced phase of prostate malignancy, manifested through two principal subtypes: castration-resistant adenocarcinoma (CRPC-adeno) and neuroendocrine prostate cancer (NEPC). This study aims to identify unique central regulatory genes, assess the immunological landscape, and explore potential therapeutic strategies specifically tailored to NEPC. We discovered 1444 differentially expressed genes (DEGs) distinguishing between the two cancer types and identified 12 critical hub genes. Notably, CHST1, MPPED2, and RIPPLY3 emerged as closely associated with the immune cell infiltration pattern, establishing them as top candidates. Prognostic analysis highlighted the potential critical roles of CHST1 and MPPED2 in prostate cancer development, findings corroborated through in vitro and in vivo assays. Moreover, we validated the functions and expression levels of CHST1, MPPED2, and RIPPLY3 in NEPC using cell lines, animal models and human tissues. In the final step, we found that imatinib might be the drug specific to NEPC, which was further confirmed by in vitro cell assay. Our results revealed the clinical characteristics, molecular features, immune cell infiltration pattern in CRPC-adeno and NEPC, and identified and confirmed CHST1, MPPED2, and RIPPLY3 as the critical genes in the development in prostate cancer and NEPC. We also predicted and validated imatinib as the potential specific drugs to NEPC.

Background and purpose:Daily cone-beam computed tomography (CBCT) in image-guided radiotherapy administers radiation exposure and subjects patients to secondary cancer risk. Reducing imaging dose remains challenging as image quality deteriorates. We investigated three imaging dose levels by reducing projections and correcting images using two deep learning algorithms, aiming at identifying the lowest achievable imaging dose.Materials and methods:CBCTs were reconstructed with 100%, 25%, 15% and 10% projections. Models were trained (30), validated (3) and tested (8) with prostate cancer patient datasets. We optimized and compared the performance of 1) a cycle generative adversarial network (cycleGAN) with residual connection and 2) a contrastive unpaired translation network (CUT) to generate synthetic computed tomography (sCT) from reduced imaging dose CBCTs. Volumetric modulated arc therapy plans were optimized on a reference intensity-corrected full dose CBCTcor and recalculated on sCTs. Hounsfield unit (HU) and positioning accuracy were evaluated. Bladder and rectum were manually delineated to determine anatomical fidelity.Results:All sCTs achieved average mean absolute mean absolute error/structural similarity index measure/peak signal-to-noise ratio of ⩽59HU/⩾0.94/⩾33dB. All dose-volume histogram parameter differences were within 2Gy or 2%. Positioning differences were ⩽0.30 mm or 0.30°. cycleGAN with Dice similarity coefficients (DSC) for bladder/rectum of ⩾0.85/⩾0.81 performed better than CUT (⩾0.83/⩾0.76). A significantly lower DSC accuracy was observed for 15% and 10% sCTs. cycleGAN performed better than CUT for contouring, however both yielded comparable outcomes in other evaluations.Conclusion:sCTs based on different CBCT doses using cycleGAN and CUT were investigated. Based on segmentation accuracy, 25% is the minimum imaging dose.

Infra-fraction motion of the prostate was recorded during 2.385 fractions of image guided radiotherapy (IGRT) in 126 patients, 14 of which were treated by intensity modulated radiation therapy (IMRT), and 112 of which were treated by volumetric arc therapy (VMAT). The prostate was imaged by three-dimensional and time-resolved transperineal ultrasound (4D-US) of type Clarity by Elekta, Stockholm, Sweden. The prostate volume was registered and the prostate position (center of volume) was recorded at a frequency of 2.0 samples per second. This raw data set contains a total of 1.138.024 prostate and patient couch positions over a time span of 158 hours, 25 minutes and 50 seconds of life radiotherapy as exported by the instrument software. This data set has been used for the validation of models of prostate intra-fraction motion and for the estimation of the dosimetric impact of actual intra-fraction motion on treatment quality and side effects. We hope that this data set may be reused by other groups for similar purposes.

Purpose: This study aims to address therapy-related toxicities and quality of life in prostate cancer patients undergoing transperineal ultrasound (TPUS) guided radiotherapy (RT). Methods: Acute and late gastrointestinal (GI) and genitourinary (GU) toxicities were assessed by physicians using CTCAE v5.0. Patient-reported quality of life outcomes were evaluated using EORTC QLQ-C30,-PR25 and IPSS. We utilized Volumetric Modulated Arc Therapy (VMAT) or intensity modulated radiation therapy (IMRT) as the RT technique for this study. The assessments were carried out before RT, at RT end, 3 months after RT and subsequently at 1-year intervals. Prostate- specific antigen (PSA) was also evaluated at each follow-up. Results: In this study, a total of 164 patients were enrolled, while among them, 112 patients delivered quality-of-life data in a prospective evaluation. The median pretreatment PSA was 7.9 ng/mL (range: 1.8-169 ng/ml). At the median follow-up of 19 months (3-82 months), the median PSA decreased to 0.22 ng/ml. Acute grade II GI and GU toxicities occurred in 8.6 % and 21.5 % patients at RT end. Regarding late toxicities, 2.2 % patients experienced grade II GI toxicities at 27 months and only one patient at 51 months, whereas no grade II GU late toxicities were reported at these time points. Quality of life scores also indicated a well-tolerated treatment. Patients mainly experienced acute clinically relevant symptoms of fatigue, pain, as well as deterioration in bowel and urinary symptoms. However, most symptoms normalized at 3 months and remained stable thereafter. Overall functioning showed a similar decline at RT end but improved over time. Conclusion: The outcomes of TPUS-guided RT demonstrated promising results in terms of minimal physician-reported toxicities and satisfactory patient-reported QoL.

Bone metastases are very common in advanced prostate cancer and can sensitively be detected utilizing PSMA-PET/CT. Therefore, our goal was to evaluate the suitability of PSMA-PET/CT-guided metastasis-directed external beam radiotherapy (MDT) as treatment option for patients with biochemical recurrence and oligometastatic bone lesions. We retrospectively examined 32 prostate cancer patients with biochemical recurrence and PSMA-positive oligometastatic disease limited to the bone (n = 1–3). A total of 49 bone lesions were treated with MDT. All patients received a post-radiotherapy PSMA-PET/CT-Scan. Changes in SUVmax, PSMA-positive tumor volume per lesion and PSA, as well as the correlation between the PET/CT-interval and SUVmax response were calculated. MDT lead to a SUVmax decrease in 46/49 (94

Fatty acid (FA) reprogramming has a significant role in liver cancer. However, the contribution of FA metabolism reprogramming to the heterogeneity of hepatocellular carcinoma (HCC) has not been established. Bioinformatics analysis using single-cell sequencing, a non-negative matrix factorization (NMF) algorithm, and survival analyses were used to investigate FA metabolism reprogramming in HCC patients. Molecular targets and the progress of drug discovery were also analyzed and discussed. Among 13 types of HCC cells, epithelial cells exhibited the highest score for FA metabolic aberrance, while certain lymphocytes, such as B cells, CD8Tcm cells, and Treg cells, exhibited the lowest score. Furthermore, epithelial cells displayed significant diversity in FA metabolism with a wide distribution range (−0.2 to 0.8). Additionally, a low level of FA metabolism was associated with poor prognosis in HCC patients (log-rank test, P =0.0089). Higher oxidase expression was correlated with a lower risk of oncogenesis and higher overall survival. However, enzymes involved in synthesis, oxidation, storage, and release exhibited considerable phenotypic diversity in HCC. FA metabolism reprograming was shown to be significantly correlated with the heterogeneity of HCC, which is characterized by a diversity of cancerous cells and enzymes.

Ethnopharmacological relevance: Polygoni Multiflori Radix Praeparata (Zhiheshouwu) has been a Wudang Taoist medicine for tonifying the liver and kidney, resolving turbidity and reducing lipid. Emodin is one of the active anthraquinones in Zhiheshouwu. Our previous studies showed that emodin (EM) and the other anthraquinones in Zhiheshouwu extract (HSWE) exerted similar inhibitory effects on liver cancer cells in vitro. However, it is still unknown if the other anthraquinones enhance pharmacokinetics (PK) of EM in HSWE in vivo.Aim of the study: In this study, we compared the PK characteristics of EM alone with that in Zhiheshouwu aiming to explore which anthraquinones in HSWE contribute to the changed PK of EM in rats.Materials and methods: Quality control of HSWE was determined using high performance liquid chromatography (HPLC). The ratios of emodin to other anthraquinones, physcion (PH), chrysophanol (CH), rhein (RH), aloe-emodin (AE), emodin-8-O-beta-D-glycoside (EMG), physcion-1-O-beta-D-glycoside (PHG) and chrysophanol-8-O-beta-D-glycoside (CHG) in HSWE were determined and analyzed using UPLC combined with tandem mass spectrometry (UPLC/MS). The PK parameters and intestinal tissue concentration of EM alone, EM in HSWE, or with other anthraquinones in SD rats were analyzed using UPLC/MS.Results: The quality of the Zhiheshouwu samples met the quality standard of the Chinese Pharmacopoeia (Version 2020). The PK results showed that compared with EM alone, Cmax (239.90 +/- 146.71 vs. 898.46 +/- 291.62, P < 0.001), Tmax (0.26 +/- 0.15 vs. 12.55 +/- 1.33, P < 0.001), AUC0-t (1575.09 +/- 570.46 vs. 12154.96 +/- 5394.25, P < 0.001), and AUC0-infinity (4742.51 +/- 1837.62 vs. 37131.34 +/- 21647.39, P < 0.001) of EM in HSWE were decreased due to PH and EMG, while the values of Vd (380.75 +/- 217.74 vs. 11.75 +/- 7.35, P < 0.001), T1/2 (10.81 +/- 1.99 vs. 6.65 +/- 2.76, P < 0.05) and CL (19.30 +/- 7.82 vs. 2.78 +/- 1.88, P < 0.001) of EM in HSWE were increased due to PH and AE. In addition, the intestinal tissue concentration of emodin in HSWE was decreased compared with that of EM alone in 20 and 780 min (25.37 +/- 5.98 vs. 43.29 +/- 4.16 and 26.72 +/- 4.03 vs. 43.40 +/- 14.19, respectively. P < 0.05) dominantly due to RH and PH.Conclusion: In conclusion, compared with treatment of EM alone, the AUC0-t value of EM in HSWE was decreased with different ways in rats. PH shortened Tmax, and increased Vd and CL. While AE prolonged T1/2 of EM. This indicated that the other anthraquinones in HSWE changed the PK of EM in rats and participated in the complex effects of EM on liver cancer. Besides the other anthraquinones, other components (e.g., 2,3,5,4 '-tetrahydrox-ystilbene-2-O-/3-D-glucoside) in Zhiheshouwu may contribute in the pharmacokinetic and pharmacodynamic interactions with EM for anti-liver cancer.

PURPOSE:To develop a CT-based radiomic signature to predict biochemical recurrence (BCR) in prostate cancer patients after sRT guided by positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET). MATERIAL AND METHODS:Consecutive patients, who underwent 68Ga-PSMA11-PET/CT-guided sRT from three high-volume centers in Germany, were included in this retrospective multicenter study. Patients had PET-positive local recurrences and were treated with intensity-modulated sRT. Radiomic features were extracted from volumes of interests on CT guided by focal PSMA-PET uptakes. After preprocessing, clinical, radiomics, and combined clinical-radiomic models were developed combining different feature reduction techniques and Cox proportional hazard models within a nested cross validation approach. RESULTS:Among 99 patients, median interval until BCR was the radiomic models outperformed clinical models and combined clinical-radiomic models for prediction of BCR with a C-index of 0.71 compared to 0.53 and 0.63 in the test sets, respectively. In contrast to the other models, the radiomic model achieved significantly improved patient stratification in Kaplan-Meier analysis. The radiomic and clinical-radiomic model achieved a significantly better time-dependent net reclassification improvement index (0.392 and 0.762, respectively) compared to the clinical model. Decision curve analysis demonstrated a clinical net benefit for both models. Mean intensity was the most predictive radiomic feature. CONCLUSION:This is the first study to develop a PSMA-PET-guided CT-based radiomic model to predict BCR after sRT. The radiomic models outperformed clinical models and might contribute to guide personalized treatment decisions.

Purpose: In prostate cancer, the indication to irradiate the pelvic lymphatic pathways in clinical node-negative patients is solely based on clinical nomograms. To define biological risk patterns of lymphatic spread, we studied DNA-methylation and genomic copy number in primary tumors and corresponding lymph nodes metastases. Methods/Patients: DNA-methylation and genomic copy number profiles of primary tumors (PT) and paired synchronous lymph node metastases (LN) from Gleason Score (GS)-6/7a (n = 20 LN-positive, n = 20 LN-negative) and GS-9/10 patients (LN-positive n = 20) after prostatectomy and lymphonodectomy were analyzed. Results: GS-6/7a pN0 PTs and GS-6/7a pN1 PTs differed in histone H3K27me3/H3K9me3 mediated methylation. PTs compared to LNs, in both, GS-6/7a pN1 and GS-9/10 pN1 patients showed large differences in DNA-methylation mediated by histones H3K4me1/2, in addition to copy number changes of chromosomal regions 11q13.1, 14q11.2 and 15q26.1. Between GS-6/7a pN1 and GS-9/10 pN1 patients, methylation levels differed more when comparing LNs than PTs. 16q21-22.1 was specifically lost in GS-9/10 pN0 PTs. Immune system-related pathways characterized the differences between PTs and LNs in both GS-6/7a pN1 and GS-9/10 pN1 patients. Comparing PTs and LKs between GS-6/7a pN1 and GS-9/10 pN1 patients revealed altered transmembrane and G-protein-coupled receptor signaling. Conclusions: Our data suggest that progression of prostate cancer, including lymphatic spread, is associated with histone-mediated DNA-methylation and we hypothesize a methylation signature predicting lymphatic spread in GS-6/7a patients from primary tumors. Lymphatic spread in GS-6/7a patients, flanked by DNA-methylation and CNA alterations, appears to be more complex than in GS-9/10 patients, in whom the primary tumors already appear to bear lymph node metastasis-enabling alterations.