RESUMO
BACKGROUND: There is a strong clinical need to fill the gap of identifying clinically significant prostate cancer (csPCa) in men with prostate-specific antigen (PSA) gray zone values. Promising, but not definitive results have been obtained using PSA derivatives such as prostate health index (PHI) and PHI density (PHID) and the percentage (-2)proPSA/free PSA (%p2PSA/fPSA). Thus, this study aimed to compare the diagnostic value of PHI, PHID, %proPSA/fPSA, and (-2)proPSA/freePSA density (-2pPSA/fPSAD) for csPCa in the patients with PSA within 2-10 ng/mL. METHODS: Serum samples and clinicopathological features were prospectively collected from 142 patients who underwent robot-assisted radical prostatectomy between September 2021 and December 2023. According to the inclusion criteria, the patients with total PSA within 2 and 10 ng/mL and negative or suspicious digital rectal examination were enrolled. We used two different classifications for csPCa: 1) patients with Gleason score (GS) ≥ 7(4 + 3) and 2) patients with GS ≥ 7(3 + 4). The receiver operating characteristic curves and the area under the curve (AUC) values were used to assess the diagnostic performance. RESULTS: Of the 142 men included, 116 (82%) patients were diagnosed with csPCa as GS ≥ 3 + 4 and 107 (75%) defined as csPCa as GS ≥ 7(4 + 3), respectively. We found that p2PSA/fPSA, p2PSA/fPSAD, PHI, and PHID were significantly higher in csPCa classified as GS ≥ 7(3 + 4) as well as GS ≥ 7(4 + 3), with p-values 0.027, 0.054, 0.0016, and 0.0027, respectively. AUCs of the analyzed variables were higher when used to predict csPCa as GS ≥ 6 compared to csPCa as GS ≥7(4 + 3), with an AUC equal, respectively, to 0.679 (95% CI: 0.571-0.786), 0.685 (95% CI: 0.571-0.799), 0.737 (95% CI: 0.639-0.836), and 0.736 (95% CI: 0.630-0.841) in the first subgroup and with an AUC equal, respectively, to 0.653 (95% CI: 0.552-0.754), 0.665 (95% CI: 0.560-0.770), 0.668 (95% CI: 0.568-0.769), and 0.670 (95% CI: 0.567-0.773) in the second, respectively. Both PHID and p2PSA/fPSAD allowed improvement in the diagnostic accuracy with respect to PHI and p2PSA/fPSA ratio, however the differences were not statistically significant (p = 0.409, 0.180 for csPCa as G ≥ Gleason grade (GG) 2 and 0.558 and 0.087 for csPCa as G ≥ GG3, respectively). We found that PHI, PHID, p2PSA/fPSA ratio, and p2PSA/fPSAD showed higher sensitivity, specificity, and positive predictive value when used to predict csPCa as GG ≥ 2, whereas negative predictive value of all four parameters was higher when used to predict GG ≥ 3. CONCLUSIONS: In men with a PSA level between 2 and 10 ng/mL, PHI and PHID, p2PSA/fPSA, and p2PSA/fPSAD showed good diagnostic performance for postoperative csPCa. However, PHID and p2PSA/fPSAD had a small advantage over PHI which needs to be further investigated for the reduction of unnecessary surgical interventions. This finding suggests that it could be a promising biomarker for making the treatment-decision strategy.
Assuntos
Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/sangue , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/diagnóstico , Antígeno Prostático Específico/sangue , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Próstata/patologia , Próstata/cirurgiaRESUMO
OBJECTIVE: Blood neurofilament light chain (NfL) is robustly associated with disease worsening in multiple sclerosis (MS), though potentially affected by concomitant factors also determining neuro-axonal loss. We investigated the association between plasma NfL (pNfL) measured with Lumipulse™ immunoassay and demographic and clinical variables in MS. METHODS: This cross-sectional study included 685 people with MS (age 49.7 ± 12.4 years; sex 65.55% females). On the same day, we collected plasma samples, along with demographics, comorbidities, and clinical variables (MS disease duration, expanded disability status scale (EDSS), Symbol Digit Modalities Test (SDMT), descriptor of disease progression, current disease modifying treatment (DMT), number of previous DMTs, evidence of disease activity in the past year (i.e. relapse or MRI new lesions), EDSS progression). pNfL was evaluated using Lumipulse™ fully automated chemiluminescent enzyme immunoassay. RESULTS: On multivariable linear regression model, higher pNfL was associated with higher EDSS (Coeff = 1.73; 95%CI 0.78, 2.68; p < 0.01), recent disease activity (Coeff = 15.70; 95%CI = 5.35, 26.06; p < 0.01), and presence of cardiovascular comorbidity (Coeff = 3.84; 95%CI 0.48, 7.20; p = 0.025). Lower pNfL was found in patients on DMT treatment (Coeff = -10.23; 95%CI -18.42, -2.04; p = 0.015), when compared with no DMT (reference). For 77.81% of our population there was correspondence between pNfL levels and two previously-validated cutoffs. CONCLUSIONS: pNfL measured using Lumipulse™ confirms known associations with MS activity, disability and treatments, and related confounding (e.g., cardiovascular comorbidity), thus granting further utilization in research and clinical practice.
Assuntos
Esclerose Múltipla , Proteínas de Neurofilamentos , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/sangue , Estudos Transversais , Esclerose Múltipla/sangue , Esclerose Múltipla/diagnóstico , Imunoensaio/métodos , Adulto , Biomarcadores/sangue , Progressão da Doença , Avaliação da DeficiênciaRESUMO
BACKGROUND: Black men residing in Western countries are more likely to develop prostate cancer (PCa), have higher mortality and are younger than the general population at initial diagnosis. In addition to genetic and environmental factors, the reasons for these racial disparities can also be attributed to social determinants of health such as low health literacy of this population and poor awareness of health services. Little is known about laboratory tests for PCa in black men. METHODS: In this preliminary study. we investigated whether ethnicity affect PSA molecular forms, PHI, estradiol and testosterone levels in healthy men. RESULTS: We found that healthy black men had lower PHI, [-2]proPSA/fPSA and testosterone/estradiol ratios. CONCLUSIONS: Our findings even if on a small study population could have a relevant clinical impact. since PCa screening is particularly relevant in black men who are at high risk of clinically significant PCa. PSA-based screening is needed and overdiagnosis must be avoided. Our findings could be particularly impactful. Future research on larger population needs to consider whether ethnicity specific laboratory tests thresholds could help to reduce the ethnic inequalities in prostate cancer diagnosis.