Mapping PSA density to outcome of MRI-based active surveillance for prostate cancer through joint longitudinal-survival models.
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ABSTRACT:
SUBMITTER: Stavrinides V
PROVIDER: S-EPMC8616763 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
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Mapping PSA density to outcome of MRI-based active surveillance for prostate cancer through joint longitudinal-survival models.
Stavrinides Vasilis V Papageorgiou Georgios G Danks Dominic D Giganti Francesco F Pashayan Nora N Trock Bruce B Freeman Alex A Hu Yipeng Y Whitaker Hayley H Allen Clare C Kirkham Alex A Punwani Shonit S Sonn Geoffrey G Barratt Dean D Emberton Mark M Moore Caroline M CM
Prostate cancer and prostatic diseases 20210506 4
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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.
| S-EPMC3036981 | biostudies-literature
Project description:The global uptake of prostate cancer (PCa) active surveillance (AS) is steadily increasing. While prostate-specific antigen density (PSAD) is an important baseline predictor of PCa progression on AS, there is a scarcity of recommendations on its use in follow-up. In particular, the best way of measuring PSAD is unclear. One approach would be to use the baseline gland volume (BGV) as a denominator in all calculations throughout AS (nonadaptive PSAD, PSADNA), while another would be to remeasure gland volume at each new magnetic resonance imaging scan (adaptive PSAD, PSADA). In addition, little is known about the predictive value of serial PSAD in comparison to PSA. We applied a long short-term memory recurrent neural network to an AS cohort of 332 patients and found that serial PSADNA significantly outperformed both PSADA and PSA for follow-up prediction of PCa progression because of its high sensitivity. Importantly, while PSADNA was superior in patients with smaller glands (BGV ≤55 ml), serial PSA was better in men with larger prostates of >55 ml.Patient summaryRepeat measurements of prostate-specific antigen (PSA) and PSA density (PSAD) are the mainstay of active surveillance in prostate cancer. Our study suggests that in patients with a prostate gland of 55 ml or smaller, PSAD measurements are a better predictor of tumour progression, whereas men with a larger gland may benefit more from PSA monitoring.
| S-EPMC10172696 | biostudies-literature
Project description:BackgroundActive surveillance (AS) is generally recognized as the preferred option for men with low-risk prostate cancer. Current guidelines use prostate-specific antigen (PSA) of 10-20 ng/mL or low-volume biopsy Gleason grade group (GG) 2 as features that, in part, define the favorable intermediate-risk disease and suggest that AS may be considered for some men in this risk category.MethodsWe identified 26,548 men initially managed with AS aged <80 years, with clinically localized prostate cancer (cT1-2cN0M0), PSA ≤ 20 ng/mL, biopsy GG ≤ 2 with percent positive cores ≤33% and who converted to treatment with radical prostatectomy from the surveillance, epidemiology, and end results prostate with the watchful waiting database. Multivariable logistic regression was performed to determine predictors of adverse pathology at RP according to PSA level (<10 vs 10-20 ng/mL) and GG (1 vs 2).ResultsOf 1731 men with GG 1 disease and PSA 10-20 ng/mL, 382 (22.1%) harbored adverse pathology compared to 2340 (28%) of 8,367 men with GG 2 and a PSA < 10 ng/mL who had adverse pathology at RP. On multivariable analysis, the odds of harboring adverse pathology with a PSA 10-20 ng/mL (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.71-2.05, p < 0.001) was less than that of GG 2 (OR 2.56, 95%CI 2.40-2.73, p < 0.001) after adjustment.ConclusionsOur results support extending AS criteria more permissively to carefully selected men with PSA 10-20 ng/mL and GG 1 disease.
| S-EPMC9705238 | biostudies-literature
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.
| S-EPMC6664316 | biostudies-literature
Project description:PurposeThis study was designed to identify a useful clinical parameter or model for prostate biopsy in surgery-indicated benign prostate hyperplasia (BPH) patients with elevated PSA levels and negative multiparametric prostate magnetic resonance imaging (MRI) results.Patients and methodsWe retrospectively analyzed clinical and pathological data from patients who were diagnosed with BPH and admitted to the inpatient department for surgery between January 2010 and September 2020. Clinical data, including age, prostate specific antigen (PSA) level, F/T PSA ratio, prostate volume, and PSA density (PSAD), were used for comprehensive analysis. Univariate and multivariate logistic regression analyses were performed to develop a predictive model. Receiver operating characteristic (ROC) analysis and decision curve analysis (DCA) were performed to assess the diagnostic value of the predictive model, PSA concentration, F/T PSA ratio and PSAD.ResultsA total of 318 patients were included in the study, 8.2% (26/318) of whom were histologically diagnosed with prostate cancer (PCa). Univariate and multivariate logistic regression analyses revealed that PSAD was the only independent predictor of PCa biopsy. ROC curve analysis of PCa detection revealed a larger area under the curve (AUC) for the predictive model (AUC 0.855) and for PSAD (AUC 0.848) than for PSA (AUC 0.722) or the F/T PSA ratio (AUC 0.635). DCA demonstrated that the optimal strategy would be to restrict biopsies to men with a PSAD of 0.30 ng/ml/cm3.ConclusionsOur study suggested that for BPH patients with surgical indications who present with PSA abnormalities and negative imaging findings, the use of a new PSAD threshold of 0.30 ng/ml/cm3 could facilitate convenient and sound biopsy decisions. This approach could reduce the complications and length of hospital stay associated with biopsies and reduce hospital costs.
| S-EPMC11874838 | biostudies-literature
Project description:IntroductionThis 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).Materials and methodsThe 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.ResultsOut 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.ConclusionmpMRI is a useful tool not only to select but also to monitor PCa patients on AS.
| S-EPMC5744936 | biostudies-literature
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.
| S-EPMC3739214 | biostudies-other
Project description:ObjectivesTo compare the effect of different PSA density (PSAD) thresholds on the accuracy for clinically significant prostate cancer (csPCa) of the Prostate Imaging Reporting And Data System v.2.1 (PI-RADSv2.1).MethodsWe retrospectively included 123 biopsy-naïve men who underwent multiparametric magnetic resonance imaging (mpMRI) and transperineal mpMRI-targeted and systematic prostate biopsy between April 2019 and October 2020. mpMRI, obtained on a 3.0T magnet with a PI-RADSv2.1-compliant protocol, was read by two radiologists (>1500/>500 mpMRI examinations). csPCa was defined as International Society of Urogenital Pathology grading group ≥2. Receiver operating characteristic analysis was used to calculate per-index lesion sensitivity, specificity, and area under the curve (AUC) of PI-RADSv.2.1 categories after adjusting for PSAD ≥0.10,≥0.15, and ≥0.20 ng/mL ml-1. Per-adjusted category cancer detection rate (CDR) was calculated, and decision analysis performed to compare PSAD-adjusted PI-RADSv.2.1 categories as a biopsy trigger.ResultscsPCa prevalence was 43.9%. PSAD-adjustment increased the CDR of PI-RADSv2.1 category 4. Sensitivity/specificity/AUC were 92.6%/53.6%/0.82 for unadjusted PI-RADS, and 85.2%/72.4%/0.84, 62.9%/85.5%/0.83, and 92.4%/53.6%/0.82 when adjusting PI-RADS categories for a 0.10, 0.15, and 0.20 ng/ml ml-1 PSAD threshold, respectively. Triggering biopsy for PI-RADS four lesions and PSAD ≥0.10 ng/mL ml-1 was the strategy with greatest net benefit at 30 and 40% risk probability (0.307 and 0.271, respectively).ConclusionsPI-RADSv2.1 category four with PSAD ≥0.10 ng/mL ml-1 was the biopsy-triggering cut-off with the highest net benefit in the range of expected prevalence for csPCa.Advances in knowledge0.10 ng/mL ml-1 is the PSAD threshold with higher clinical utility in stratifying the risk for prostate cancer of PI-RADSv.2.1 categories.
| S-EPMC8978227 | biostudies-literature
Project description:PurposeTo investigate the accuracy of surface-based ultrasound-derived PSA-density (US-PSAD) versus gold-standard MRI-PSAD as a risk-stratification tool.MethodsSingle-centre prospective study of patients undergoing MRI for suspected prostate cancer (PCa). Four combinations of US-volumes were calculated using transperineal (TP) and transabdominal (TA) views, with triplanar measurements to calculate volume and US-PSAD. Intra-class correlation coefficient (ICC) was used to compare US and MRI volumes. Categorical comparison of MRI-PSAD and US-PSAD was performed at PSAD cut-offs <0.15, 0.15-0.20, and >0.20 ng/mL2 to assess agreement with MRI-PSAD risk-stratification decisions.Results64 men were investigated, mean age 69 years and PSA 7.0 ng/mL. 36/64 had biopsy-confirmed prostate cancer (18 Gleason 3+3, 18 Gleason ≥3+4). Mean MRI-derived gland volume was 60 mL, compared to 56 mL for TA-US, and 65 mL TP-US. ICC demonstrated good agreement for all US volumes with MRI, with highest agreement for transabdominal US, followed by combined TA/TP volumes. Risk-stratification decisions to biopsy showed concordant agreement between triplanar MRI-PSAD and ultrasound-PSAD in 86-91% and 92-95% at PSAD thresholds of >0.15 ng/mL2 and >0.12 ng/mL2, respectively. Decision to biopsy at threshold >0.12 ng/mL2, demonstrated sensitivity ranges of 81-100%, specificity 85-100%, PPV 86-100% and NPV 83-100%. Transabdominal US provided optimal sensitivity of 100% for this clinical decision, with specificity 85%, and transperineal US provided optimal specificity of 100%, with sensitivity 87%.ConclusionTransperineal-US and combined TA-TP US-derived PSA density values compare well with standard MRI-derived values and could be used to provide accurate PSAD at presentation and inform the need for further investigations.
| S-EPMC9462719 | biostudies-literature
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.
| S-EPMC8217549 | biostudies-literature