Project description:The objective of our study is to examine the correlation between PSA density (PSAd) at the time of diagnosis with PSA velocity (PSAV), PSA doubling time and tumour progression, on repeat biopsy, in men with prostate cancer on active surveillance. Data from 102 patients with clinically localized prostate cancer on active surveillance in the period between 1992 and 2007, who had the necessary parameters available, were collected. PSAd was calculated and correlated with PSAV, PSA doubling time (PSADT), Gleason score at diagnosis and local progression on repeated biopsies. PSAV was 0.64 and 1.31 ng ml(-1) per year (P = 0.02), PSADT of 192 and 113 months (P = 0.4) for PSAd below and above 0.15, respectively. The rate of detecting high Gleason score (≥ 7) at diagnosis was 6 and 23% for PSAd below and above 0.15, respectively. A total of 101 patients underwent at least a second biopsy and the incidence of upgrading was 10 and 31% for PSAd below and above 0.15, respectively (P = 0.001). Although low PSAd is an accepted measure for suggesting insignificant prostate cancer, our study expands its role to indicate that PSAd < 0.15 may be an additional clinical parameter that may suggest indolent disease, as measured by future PSAV and repeat biopsy over time.
Project description:BackgroundTo investigate the role of Prostate Specific Antigen density (PSAD) in selecting prostate cancer patients for active surveillance (AS) and to determine a cutoff PSAD in identifying adverse pathological outcomes.MethodsData from 287 patients who underwent radical prostatectomy for prostate cancer were retrospectively reviewed. Six different AS protocols, the University of Toronto; Royal Marsden; John Hopkins; University of California San Francisco (UCSF); Memorial Sloan Kettering Cancer Center (MSKCC) and Prostate Cancer Research International: Active Surveillance (PRIAS), were applied to the cohort. Pre-operative demographics and pathological outcomes were analysed. Statistical analyses on the predictive factors of adverse pathological outcomes and significance of PSAD were performed. A cutoff PSAD with best balance between sensitivity and specificity in identifying adverse pathological outcome was determined.ResultsPSAD predicted adverse pathological outcomes better than Prostate Specific Antigen (PSA) level alone. The PSAD was significantly lower (0.12-0.13 ng/dl/ml) in protocols including PSAD (the John Hopkins and PRIAS) compared with the other four protocols not including PSAD as a selection criteria (0.21-0.25 ng/dl/dl, P = 0.00). PSAD predicted adverse pathological outcomes in all protocols not incorporating PSAD as an inclusion criteria (P = 0.00-0.02). By the receiver operator characteristics curve analysis, it was found that a PSAD level of 0.19 ng/ml/ml had the best balance between sensitivity and specificity in predicting pathological adverse disease (Area under curve = 0.63, P = 0.004).ConclusionPSAD is necessary in selecting prostate cancer patients for active surveillance. It predicts adverse pathological outcomes in patients eligible for active surveillance better than PSA level alone. A PSAD cutoff at 0.19 ng/ml/ml has the best balance between sensitivity and specificity in predicting pathological adverse disease. We recommend using AS protocol incorporating PSAD as a selection criteria (in particular the PRIAS protocol with a cutoff PSAD at 0.2 ng/ml/ml) when recruiting prostate cancer patients for AS.
Project description:This study was conducted to describe the changes in repeat multiparametric MRI (mpMRI) occurring in prostate cancer (PCa) patients during active surveillance (AS), and to study possible associations between mpMRI-related parameters in predicting prostate biopsy (Bx) Gleason score (GS) upgrading >3+3 and protocol-based treatment change (TC).The study cohort consisted of 76 AS patients with GS 3+3 PCa and at least two consecutive mpMRIs of the prostate performed between 2006-2015. Patients were followed according to the Prostate Cancer Research International Active Surveillance (PRIAS) protocol and an additional mpMRI. The primary end points were GS upgrading (GU) (>3+3) in protocol-based Bxs and protocol-based TC.Out of 76 patients, 53 (69%) had progression (PIRADS upgrade, size increase or new lesion[s]), while 18 (24%) had radiologically stable disease, and 5 (7%) had regression (PIRADS or size decrease, disappearance of lesion[s]) in repeat mpMRIs during AS. PIRADS scores of 4-5 in the initial mpMRI were associated with GU (p = 0.008) and protocol-based TC (p = 0.009). Tumour progression on repeat mpMRIs was associated with TC (p = 0.045) but not with GU (p = 1.00). PIRADS scores of 4-5 predict GU (sensitivity 0.80 [95% confidence interval (CI); 0.51-0.95, specificity 0.62 [95% CI; 0.52-0.77]) with PPV and NPV values of 0.34 (95% CI; 0.21-0.55) and 0.93 (95% CI; 0.80-0.98), respectively.mpMRI is a useful tool not only to select but also to monitor PCa patients on AS.
Project description:Since the first publication describing the identification of prostate-specific antigen (PSA) in the 1960s, much progress has been made. The PSA test changed from being initially a monitoring tool to being also used as a diagnostic tool. Over time, the test has been heavily debated due to its lack of sensitivity and specificity. However, up to now the PSA test is still the only biomarker for the detection and monitoring of prostate cancer. PSA-based screening for prostate cancer is associated with a high proportion of unnecessary testing and overdiagnosis with subsequent overtreatment. In the early years of screening for prostate cancer, high rates of uptake were very important. However, over time the opinion on PSA-based screening has shifted towards the notion of informed choice. Nowadays, it is thought to be unethical to screen men without them being aware of the pros and cons of PSA testing, as well as the fact that an informed choice is related to better patient outcomes. Now, as the results of three major screening studies have been presented and the downsides of screening are becoming better understood, informed choice is becoming more relevant.
Project description:Nearly half of patients with prostate cancer (PCa) harbour low- or intermediate-risk disease considered suitable for active surveillance (AS). However, up to 44% of patients discontinue AS within the first five years, highlighting the unmet clinical need for robust baseline risk-stratification tools that enable timely and accurate prediction of tumour progression. In this proof-of-concept study, we sought to investigate the added value of MRI-derived radiomic features to standard-of-care clinical parameters for improving baseline prediction of PCa progression in AS patients. Tumour T2-weighted imaging (T2WI) and apparent diffusion coefficient radiomic features were extracted, with rigorous calibration and pre-processing methods applied to select the most robust features for predictive modelling. Following leave-one-out cross-validation, the addition of T2WI-derived radiomic features to clinical variables alone improved the area under the ROC curve for predicting progression from 0.61 (95% confidence interval [CI] 0.481-0.743) to 0.75 (95% CI 0.64-0.86). These exploratory findings demonstrate the potential benefit of MRI-derived radiomics to add incremental benefit to clinical data only models in the baseline prediction of PCa progression on AS, paving the way for future multicentre studies validating the proposed model and evaluating its impact on clinical outcomes.
Project description:BackgroundAlthough prostate-specific antigen (PSA) testing is used for prostate cancer detection and posttreatment surveillance, thresholds in these settings differ. The screening cutoff of 4.0 ng/mL may be inappropriately used during postsurgery surveillance, where 0.2 ng/mL is typically used, creating missed opportunities for effective salvage radiation treatment. We performed a study to determine whether guideline concordance with annual postoperative PSA surveillance increases when PSA values exceed 4 ng/mL, which represents a screening threshold that is not relevant after surgery.MethodsWe used US Veterans Health Administration data to perform a retrospective longitudinal cohort study of men diagnosed with nonmetastatic prostate cancer from 2005 to 2008 who underwent radical prostatectomy. We used logistic regression to examine the association between postoperative PSA levels and receipt of an annual PSA test.ResultsAmong 10 400 men and 38 901 person-years of follow-up, annual guideline concordance decreased from 95% in year 1 to 79% in year 7. After adjustment, guideline concordance was lower for the youngest and oldest men, Black, and unmarried men. Guideline concordance significantly increased as PSA exceeded 4 ng/mL (adjusted odds ratio 2.20 PSA > 4-6 ng/mL vs PSA > 1-4 ng/mL, 95% confidence interval 1.20-4.03; P = .01).ConclusionsGuideline concordance with prostate cancer surveillance increased when PSA values exceeded 4 ng/mL, suggesting a screening threshold not relevant after prostate cancer surgery, where 0.2 ng/mL is considered treatment failure, is impacting cancer surveillance quality. Clarification of PSA thresholds for early detection vs cancer surveillance, as well as emphasizing adherence for younger and Black men, appears warranted.
Project description:Background The current study aimed to compare the efficacy of transition zone PSA density (TZPSAD) with traditional PSA and PSA density (PSAD), for the diagnosis of prostate cancer (PCa) in Taiwanese males. Methods Men with PSA between 4.0 and 20.0 ng/ml who underwent a transrectal ultrasound (TRUS) guided prostate biopsy between the studied period were retrospectively identified. The demographic data, PSAD and TZPSAD were calculated in all patients. Receiver operating characteristic (ROC) curves were used to analyze the accuracy of a positive PCa diagnosis. Results The area under the ROC (AUC) was 0.615, 0.748 and 0.746 for PSA, PSAD and TZPSAD, respectively. The best cut-off of value for TZPSAD in predicting PCa in men with a PSA of 4.0–10.0 ng/ml was 0.367 ng/ml/ml with a sensitivity of 50% and a specificity of 77.5%. In men with a PSA of 10.1–20.0 ng/ml, the best cut-off value was 0.454 ng/ml, with a sensitivity of 74.8% and specificity of 70.9%. Conclusion The use of TZPSAD can improve the efficiency and specificity of PSA for the diagnosis of PCa in Taiwanese men with PSA 4.0–20.0 ng/ml. TZPSAD efficiency was similar to PSAD but TZPSAD had better cancer specificity.
Project description:We defined prostate-specific antigen (PSA) thresholds from a well calibrated risk prediction model for identifying and excluding advanced prostate cancer (PCa). We retrieved 902 biopsied patients with a pre-biopsy PSA determination (Roche assay). A logistic regression model predictive for PCa including the main effects [i.e., PSA, age, histological evidence of glandular inflammation (GI)] was built after testing the accuracy by calibration plots and Hosmer-Lemeshow test for goodness of fit. PSA thresholds were derived by assuming a diagnostic sensitivity of 95% (rule-out) and 80% (rule-in) for overall and advanced/poorly differentiated PCa. In patients without GI, serum PSA concentrations ≤ 4.1 (<65 years old) and ≤3.7 μg/L (≥65 years old) excluded an advanced PCa (defined as Gleason score ≥ 7 at biopsy), with a negative predictive value of 95.1% [95% confidence interval (CI): 83.0-98.7] and 88.8% (CI: 80.2-93.9), respectively, while PSA > 5.7 (<65) and >6.1 μg/L (≥65) should address biopsy referral. In presence of GI, PSA did not provide a valid estimate for risk of advanced cancer because of its higher variability and the low pre-test probability of PCa. The proposed PSA thresholds may support biopsy decision except for patients with asymptomatic prostatitis who cannot be pre-biopsy identified.
Project description:ObjectivesTo assess the predictive value and correlation to pathological progression of the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scoring system in the follow-up of prostate cancer (PCa) patients on active surveillance (AS).MethodsA total of 295 men enrolled on an AS programme between 2011 and 2018 were included. Baseline multiparametric magnetic resonance imaging (mpMRI) was performed at AS entry to guide biopsy. The follow-up mpMRI studies were prospectively reported by two sub-specialist uroradiologists with 10 years and 13 years of experience. PRECISE scores were dichotomized at the cut-off value of 4, and the sensitivity, specificity, positive predictive value and negative predictive value were calculated. Diagnostic performance was further quantified by using area under the receiver operating curve (AUC) which was based on the results of targeted MRI-US fusion biopsy. Univariate analysis using Cox regression was performed to assess which baseline clinical and mpMRI parameters were related to disease progression on AS.ResultsProgression rate of the cohort was 13.9% (41/295) over a median follow-up of 52 months. With a cut-off value of category ≥ 4, the PRECISE scoring system showed sensitivity, specificity, PPV and NPV for predicting progression on AS of 0.76, 0.89, 0.52 and 0.96, respectively. The AUC was 0.82 (95% CI = 0.74-0.90). Prostate-specific antigen density (PSA-D), Likert lesion score and index lesion size were the only significant baseline predictors of progression (each p < 0.05).ConclusionThe PRECISE scoring system showed good overall performance, and the high NPV may help limit the number of follow-up biopsies required in patients on AS.Key points• PRECISE scores 1-3 have high NPV which could reduce the need for re-biopsy during active surveillance. • PRECISE scores 4-5 have moderate PPV and should trigger either close monitoring or re-biopsy. • Three baseline predictors (PSA density, lesion size and Likert score) have a significant impact on the progression-free survival (PFS) time.
Project description:ObjectiveTo review the recent milestones in MRI and PET based imaging and evaluate their evolving role in the setting of elevated PSA as well as localized prostate cancer.BackgroundThe importance of multiparametric MRI (mpMRI) and PET based imaging for the diagnosis and staging of prostate cancer cannot be understated. Accurate staging has become another significant milestone with the use of PET scans, particularly with prostate specific radiotracers like 68-Gallium Prostate Specific Membrane Antigen (68Ga-PSMA). Integrated PET/MRI systems are commercially available and can be modulated to evaluate the unique needs of localized as well as recurrent prostate cancer.MethodsA literature search was performed using PubMed and Google Scholar using the MeSH compliant and other keywords that included prostate cancer, PSA, mpMRI, PET CT, PET/MRI.ConclusionsmpMRI has now established itself as the gold-standard of local prostate imaging and has been incorporated into international guidelines as part of the diagnostic work-up of prostate cancer. PSMA PET/CT has shown superiority over conventional imaging even in staging of localized prostate cancer based on recent randomized control data. Imaging parameters from PET/MRI have been shown to be associated with malignancy, Gleason score and tumour volume. As mpMRI and PSMA PET/CT become more ubiquitous and established; we can anticipate more high-quality data, cost optimization and increasing availability of PET/MRI to be ready for primetime in localized prostate cancer.