BACKGROUND AND OBJECTIVE: In prostate cancer treated with androgen deprivation therapy (ADT), the initial sign of treatment resistance is often prostate-specific antigen (PSA) progression, followed by radiographic progression. However, the association between these two forms of progression remains unclear, especially in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with androgen receptor pathway inhibitors. We sought to evaluate the association between radiographic progression, PSA progression, and outcomes of apalutamide therapy in mCSPC. METHODS: We analyzed individual participant-level data for patients randomized within the TITAN trial who experienced radiographic progression during follow-up (N = 326). This study investigated radiographic progression without simultaneous or preceding PSA progression, as defined by the Prostate Cancer Working Group 2 (discordant progression), and explored the association of such progression with radiographic progression-free survival. KEY FINDINGS AND LIMITATIONS: Among the patients who developed radiographic progression, 115 (35.3%) had been treated with apalutamide plus ADT (the apalutamide group) and 211 (64.7%) with placebo plus ADT (the placebo group). Discordant progression occurred in 52.2% of patients (60 of 115) in the apalutamide group and 27.5% (58 of 211) in the placebo group (p < 0.001). A multivariable logistic regression analysis showed that discordant progression was associated with apalutamide treatment. We found evidence of an association between discordant progression and shorter radiographic progression-free survival. CONCLUSIONS AND CLINICAL IMPLICATIONS: This study found that nearly half of the patients with mCSPC treated with apalutamide who experienced radiographic progression developed it without corresponding PSA progression, suggesting that heavy reliance on PSA monitoring may be inadequate for assessing disease activity in this context. PATIENT SUMMARY: In patients who have metastatic castration-sensitive prostate cancer (mCSPC) and are being treated with apalutamide, radiographic images may show cancer progression even if prostate-specific antigen tests indicate no change. This highlights the importance of regular imaging when using apalutamide to manage mCSPC.

• MeSH
• Androgen Antagonists therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• Prostatic Neoplasms, Castration-Resistant drug therapy   pathology   blood   diagnostic imaging   MeSH
• Disease Progression * MeSH
• Prostate-Specific Antigen * blood   MeSH
• Aged MeSH
• Thiohydantoins * therapeutic use   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH

Androgen receptor-targeting agents, particularly enzalutamide, show promise in enhancing prostate cancer diagnostic and therapeutic strategies by modulating prostate-specific membrane antigen (PSMA). Methods: A retrospective clinical cohort study investigated 9 men with metastatic castration-resistant prostate cancer on enzalutamide. PSMA PET/CT scans were obtained before and after enzalutamide initiation to assess PSMA expression changes. Lesions and organs at risk were evaluated visually and semiquantitatively. The flare phenomenon was characterized by a significant increase (≥20%) in the SUVmax of existing lesions or the appearance of new PSMA-positive lesions. Results: Exposure to enzalutamide led to a significant PSMA expression increase in 56% of assessed lesions (n = 42), with new lesions detected in 1 patient (11%). PSMA expression in organs at risk remained largely unaffected, indicating a tumor-specific response. Conclusion: Enzalutamide induces PSMA upregulation in metastatic castration-resistant prostate cancer, potentially enhancing diagnostic and therapeutic strategies. Further exploration of the flare phenomenon's clinical implications is warranted.

• MeSH
• Antigens, Surface * metabolism   MeSH
• Benzamides * MeSH
• Phenylthiohydantoin * therapeutic use   analogs & derivatives   MeSH
• Glutamate Carboxypeptidase II * metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Prostatic Neoplasms, Castration-Resistant * drug therapy   diagnostic imaging   metabolism   MeSH
• Nitriles * therapeutic use   MeSH
• Positron Emission Tomography Computed Tomography * MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Up-Regulation * MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: To validate the clinical utility of a previously identified circulating tumor DNA methylation marker (meth-ctDNA) panel for disease detection and survival outcomes, meth-ctDNA markers were compared to PSA levels and PSMA PET/CT findings in men with different stages of prostate cancer (PCa). METHODS: 122 PCa patients who underwent [68Ga]Ga-PSMA-11 PET/CT and plasma sampling (03/2019-08/2021) were analyzed. cfDNA was extracted, and a panel of 8 individual meth-ctDNA markers was queried. PET scans were qualitatively and quantitatively assessed. PSA and meth-ctDNA markers were compared to PET findings, and their relative prognostic value was evaluated. RESULTS: PSA discriminated best between negative and tumor-indicative PET scans in all (AUC 0.77) and hormone-sensitive (hsPC) patients (0.737). In castration-resistant PCa (CRPC), the meth-ctDNA marker KLF8 performed best (AUC 0.824). CHST11 differentiated best between non- and metastatic scans (AUC 0.705) overall, KLF8 best in hsPC and CRPC (AUC 0.662, 0.85). Several meth-ctDNA markers correlated low to moderate with the tumor volume in all (5/8) and CRPC patients (6/8), while PSA levels correlated moderately to strongly with the tumor volume in all groups (all p < 0.001). CRPC overall survival was independently associated with LDAH and PSA (p = 0.0168, p < 0.001). CONCLUSION: The studied meth-ctDNA markers are promising for the minimally-invasive detection and prognostication of CRPC but do not allow for clinical characterization of hsPC. Prospective studies are warranted for their use in therapy response and outcome prediction in CRPC and potential incremental value for PCa monitoring in PSA-low settings.

• MeSH
• Circulating Tumor DNA genetics   blood   MeSH
• Edetic Acid analogs & derivatives   MeSH
• Gallium Isotopes * MeSH
• Middle Aged MeSH
• Humans MeSH
• DNA Methylation * genetics   MeSH
• Biomarkers, Tumor * genetics   blood   MeSH
• Prostatic Neoplasms, Castration-Resistant genetics   blood   diagnostic imaging   MeSH
• Prostatic Neoplasms * genetics   blood   diagnostic imaging   MeSH
• Positron Emission Tomography Computed Tomography * methods   MeSH
• Prognosis MeSH
• Prostate-Specific Antigen * blood   genetics   MeSH
• Cross-Sectional Studies MeSH
• Gallium Radioisotopes * MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

Doba precizní a personalizované onkologie je zde, navzdory tomu dochází při zavádění nových terapeutických postupů a nových léčiv k mnohým dosud nepozorovaným překážkám. V drtivé většině případů jsou to onkologicky nemocní starších věkových skupin s komorbiditami a chronickou medikací, která často komplikuje aplikaci nových léků nebo lékových kombinací. V kazuistice bychom rádi prezentovali průběh nemoci a výzev spojených s protinádorovou terapií u pacienta po jaterní transplantaci s karcinomem prostaty.

The age of precision and personalized oncology is now, but application of new therapeutic possibilities and new pharmaceuticals brings new challenges. In most cases, patients with malignant tumors are of older age with chronic diseases, which complicate usage of new pharmaceuticals or their combination. In this clinical case, we would like to present treatment challenges on a patient with hepatic transplantation, who was diagnosed with prostate carcinoma.

• MeSH
• Precision Medicine * methods   MeSH
• Skeleton diagnostic imaging   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Prostatic Neoplasms, Castration-Resistant diagnostic imaging   drug therapy   pathology   therapy   MeSH
• Prostatic Neoplasms * diagnostic imaging   drug therapy   pathology   therapy   MeSH
• Disease Progression MeSH
• Antineoplastic Agents administration & dosage   MeSH
• Radionuclide Imaging MeSH
• Tacrolimus administration & dosage   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

Functional imaging with prostate-specific membrane antigen (PSMA) ligands has emerged as the standard imaging method for prostate cancer (PCA). In parallel, the analysis of blood-derived, cell-free DNA (cfDNA) has been shown to be a promising quantitative biomarker of PCA aggressiveness and patient outcome. This study aimed to evaluate the relationship and prognostic value of cfDNA concentrations and the PSMA-positive tumor volume (PSMA-TV) in men with PCA undergoing [68Ga]Ga-PSMA-11 PET/CT imaging. Methods: We recruited 148 men with histologically proven PCA (mean age, 70.7 ± 7.7 y) who underwent [68Ga]Ga-PSMA-11 PET/CT (184.9 ± 18.9 MBq) and blood sampling between March 2019 and August 2021. Among these, 74 (50.0%) had hormone-sensitive PCA and 74 (50.0%) had castration-resistant PCA (CRPC). All patients provided written informed consent before blood sample collection and imaging. The cfDNA was extracted and quantified, and PSMA-expressing tumor lesions were delineated to extract the PSMA-TVs. The Spearman coefficient assessed correlations between PSMA-TV and cfDNA concentrations and cfDNA's relation with clinical parameters. The Kruskal-Wallis test examined the mean cfDNA concentration differences based on PSMA-TV quartiles for significantly correlated patient groups. Log-rank and multivariate Cox regression analyses evaluated the prognostic significance of high and low cfDNA and PSMA-TV levels for overall survival. Results: Weak positive correlations were found between cfDNA concentration and PSMA-TV in the overall group (r = 0.16, P = 0.049) and the CRPC group (r = 0.31, P = 0.007) but not in hormone-sensitive PCA patients (r = -0.024, P = 0.837). In the CRPC cohort, cfDNA concentrations significantly differed between PSMA-TV quartiles 4 and 1 (P = 0.002) and between quartiles 4 and 2 (P = 0.016). Survival outcomes were associated with PSMA-TV (P < 0.0001, P = 0.004) but not cfDNA (P = 0.174, P = 0.12), as per the log-rank and Cox regression analysis. Conclusion: These findings suggest that cfDNA might serve as a biomarker of advanced, aggressive CRPC but does not reliably reflect total tumor burden or prognosis. In comparison, [68Ga]Ga-PSMA-11 PET/CT provides a highly granular and prognostic assessment of tumor burden across the spectrum of PCA disease progression.

• MeSH
• Biomarkers MeSH
• Edetic Acid MeSH
• Hormones MeSH
• Gallium Isotopes MeSH
• Middle Aged MeSH
• Humans MeSH
• Prostatic Neoplasms, Castration-Resistant * diagnostic imaging   MeSH
• Prostatic Neoplasms * diagnostic imaging   pathology   MeSH
• Positron Emission Tomography Computed Tomography methods   MeSH
• Prognosis MeSH
• Prospective Studies MeSH
• Gallium Radioisotopes MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Tumor Burden MeSH
• Cell-Free Nucleic Acids * MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH

Nemetastazující kastračně rezistentní karcinom prostaty je heterogenní onemocnění, které může mít u vysoce rizikových pacientů agresivní průběh. V posledních letech byly publikovány tři pozitivní studie s novými antagonisty androgenních receptorů (ARTA přípravky), které právě zařazovaly pacienty s nemetastazujícím vysoce rizikovým kastračně rezistentním karcinomem prostaty. Všechny ve shodě prokázaly prodloužení přežití bez metastáz, vliv na celkové přežití je prokázán také minimálně ve dvou z nich. Všechny tři léky (apalutamid, darolutamid, enzalutamid) měly podobný klinický přínos. Rozhodnutí o léčbě by mělo být založeno na potenciálních nežádoucích účincích v kontextu daného onemocnění a komorbidit pacienta. Studie využívaly k eventuální detekci metastazujícího onemocnění konvenční zobrazovací metody. V současnosti, v éře pozitronové emisní tomografie s prostatickým specifickým membránovým antigenem (prostate specific membrane antigen positron emission tomography, PSMA PET) se ze skupiny kastračně rezistentního karcinomu prostaty mohou rekrutovat ti, kteří budou profitovat i z radioterapie v případě oligometastáz, oligoprogrese či oligorekurence.

Non-metastatic castration-resistant prostate cancer is a heterogeneous disease that can have an aggressive course in high-risk patients. In recent years, three positive trials with novel androgen receptor antagonists (ARTA agents) have been published, that specifically enrolled patients with high-risk castration-resistant prostate cancer. In agreement, all of them showed prolongation of metastasis free survival, with an effect on overall survival also demonstrated in at least two of them. All three drugs (apalutamide, darolutamide, enzalutamide) had similar clinical benefit. Treatment decisions should be based on potential adverse effects in the context of the patient's disease and comorbidities. Studies have used conventional imaging methods to detect metastatic disease when appropriate. Nowadays, in the prostate specific membrane antigen positron emission tomography (PSMA PET) era, the castration-resistant prostate cancer group may recruit those who will also benefit from radiotherapy in the case of oligometastases, oligoprogression or oligorecurrence.

• MeSH
• Androgen Receptor Antagonists adverse effects   therapeutic use   MeSH
• Progression-Free Survival MeSH
• Drug Interactions MeSH
• Humans MeSH
• Prostatic Neoplasms, Castration-Resistant * diagnostic imaging   drug therapy   therapy   MeSH
• Positron-Emission Tomography MeSH
• Prostate-Specific Antigen analysis   MeSH
• Radiosurgery MeSH
• Check Tag
• Humans MeSH
• Male MeSH

• MeSH
• Receptors, Androgen MeSH
• Androgen Antagonists administration & dosage   pharmacology   therapeutic use   MeSH
• Antibodies, Monoclonal, Humanized therapeutic use   MeSH
• Clinical Studies as Topic MeSH
• Humans MeSH
• Prostatic Neoplasms, Castration-Resistant * diagnostic imaging   drug therapy   pathology   MeSH
• Prostatic Neoplasms diagnosis   therapy   MeSH
• Prostate-Specific Antigen MeSH
• Check Tag
• Humans MeSH

• Keywords
• enzalutamid,
• MeSH
• Benzamides * therapeutic use   MeSH
• Docetaxel therapeutic use   MeSH
• Remission Induction MeSH
• Humans MeSH
• Prostatic Neoplasms, Castration-Resistant * diagnostic imaging   diagnosis   drug therapy   MeSH
• Prostatic Neoplasms diagnostic imaging   diagnosis   drug therapy   MeSH
• Antineoplastic Agents therapeutic use   MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Case Reports MeSH

• Keywords
• enzalutamid,
• MeSH
• Survival Analysis MeSH
• Androgen Receptor Antagonists administration & dosage   pharmacology   metabolism   MeSH
• Benzamides therapeutic use   MeSH
• Progression-Free Survival MeSH
• Double-Blind Method MeSH
• Phenylhydrazines therapeutic use   MeSH
• Humans MeSH
• Neoplasm Metastasis diagnostic imaging   drug therapy   MeSH
• Prostatic Neoplasms, Castration-Resistant * diagnostic imaging   drug therapy   MeSH
• Nitriles therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Clinical Trial, Phase III MeSH
• Review MeSH

• Keywords
• kabazitaxel (Jevtana),
• MeSH
• Androgen Receptor Antagonists administration & dosage   pharmacology   MeSH
• Docetaxel analogs & derivatives   administration & dosage   MeSH
• Middle Aged MeSH
• Multimorbidity MeSH
• Bone Neoplasms drug therapy   secondary   MeSH
• Prostatic Neoplasms, Castration-Resistant * diagnostic imaging   drug therapy   MeSH
• Prostate-Specific Antigen blood   MeSH
• Neoplasm Grading MeSH
• Taxoids administration & dosage   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Male MeSH
• Publication type
• Case Reports MeSH