Dataset Information

A Feasibility Study of the Therapeutic Response and Durability of Short-term Androgen-targeted Therapy in Early Prostate Cancer Managed with Surveillance: The Therapeutics in Active Prostate Surveillance (TAPS01) Study.

ABSTRACT:

Background

Active surveillance (AS) is a preferred management option for men with prostate cancer with favourable prognosis. However, nearly half of men on AS switch to treatment within 5 years, so therapeutic strategies to prevent or delay disease progression could be considered. The androgen receptor is the pre-eminent oncogenic driver in prostate cancer.

Objective

To explore image-based tumour responses and the patient impact of short-duration androgen-targeted therapy (ATT) to abrogate disease progression during AS.

Design setting and participants

Men on AS with Cambridge Prognostic Group 1 & 2 (low and favourable intermediate risk) prostate cancer and lesions visible on magnetic resonance imaging (MRI) were recruited to an open-label, single-centre, phase 2 feasibility study of short-term ATT (the TAPS01 study).

Intervention

Apalutamide 240 mg was administered for 90 days.

Outcome measurements and statistical analysis

MRI-measured tumour volume (TV), gland volume (GV), and the TV/GV ratio were calculated at baseline, at day 90 (end of treatment), and at 6- and 18-month follow-up. Quality of life metrics were measured at day 0, day 90, and 6 weeks after ATT.

Results and limitations

Eleven patients (40% of eligible men approached) agreed to participate, of whom nine completed treatment. At day 90, the median percentage reduction was -38.2% (range -51.8% to -23.5%) for GV, -54.2% (range -74.1% to -13.8%) for TV, and -27.2% (range -61.5% to -7.5%) for TV/GV (all p < 0.0001). At 6 mo, while GV had returned to baseline (p = 0.95) both TV (-31.9%; p = 0.0007) and TV/GV (-28.7%; p = 0.0009) remained significantly reduced. This reduction was sustained at 18 months (TV -18%, TV/GV -23.8%; p = 0.01). European Organization for Research and Treatment of Cancer QoL core 30-item questionnaire scores for global, physical, role, and social functioning decreased during treatment, but all were recovering by 6 weeks. EQ-VAS scores were unchanged compared to baseline.

Conclusions

TAPS01 has demonstrated feasibility and patient tolerability for short-term ATT in men on AS. Our data suggest a selective and durable antitumour effect in the short term and support a larger-scale randomised trial.

Patient summary

We investigated the feasibility of short-term treatment with an androgen inhibitor to prevent or delay disease progression for men on active surveillance for prostate cancer. Results for a small group of patients show that 90-day treatment led to a sustained decrease in tumour volume over 18 months. The findings warrant a larger clinical trial for this approach, which could allow patients to delay or even avoid longer-term active treatments.

SUBMITTER: Barrett T

PROVIDER: S-EPMC9051967 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Feasibility Study of the Therapeutic Response and Durability of Short-term Androgen-targeted Therapy in Early Prostate Cancer Managed with Surveillance: The Therapeutics in Active Prostate Surveillance (TAPS01) Study.

Barrett Tristan T Pacey Simon S Leonard Kelly K Wulff Jerome J Funingana Ionut-Gabriel IG Gnanapragasam Vincent V

European urology open science 20220210

<h4>Background</h4>Active surveillance (AS) is a preferred management option for men with prostate cancer with favourable prognosis. However, nearly half of men on AS switch to treatment within 5 years, so therapeutic strategies to prevent or delay disease progression could be considered. The androgen receptor is the pre-eminent oncogenic driver in prostate cancer.<h4>Objective</h4>To explore image-based tumour responses and the patient impact of short-duration androgen-targeted therapy (ATT) to ...[more]

PMID: 35495285

Similar Datasets

Project description:To determine the role that magnetic resonance (MR) imaging and MR spectroscopic imaging findings obtained at the time of diagnosis play in the progression of disease in patients whose prostate cancer is being managed with active surveillance and to compare the role of these findings with the role of transrectal ultrasonography (US) findings.The institutional review board approved this HIPAA-compliant retrospective study, and informed consent was obtained from all patients whose records were to be entered into the research database. All patients who had prostate cancer managed with active surveillance and who had undergone both MR imaging and MR spectroscopic imaging of the prostate and transrectal US at time of diagnosis were identified. Two urologists blinded to the clinical outcome in these patients independently reviewed and dichotomized the MR imaging report and the MR spectroscopic imaging report as normal or suggestive of malignancy. One experienced urologist performed all US examinations that were then dichotomized similarly. Uni- and multivariate (with use of standard clinical variables) Cox models were fitted to assess time to cancer progression, defined as Gleason score upgrading, prostate-specific antigen velocity of more than 0.75 (microg x L(-1))/y, or initiation of treatment more than 6 months after diagnosis.The final cohort included 114 patients with a median follow-up of 59 months. Patients with a lesion that was suggestive of cancer at MR imaging had a greater risk of the Gleason score being upgraded at subsequent biopsy (hazard ratio, 4.0; 95% confidence interval: 1.1, 14.9) than did patients without such a lesion. Neither MR spectroscopic imaging nor transrectal US could be used to predict cancer progression.Abnormal prostate MR imaging results suggestive of cancer may confer an increased risk of Gleason score upgrade at subsequent biopsy. Although expensive, prostate MR imaging may help in counseling potential candidates about active surveillance.

Project description:ObjectivesTo evaluate the feasibility of automatic longitudinal analysis of consecutive biparametric MRI (bpMRI) scans to detect clinically significant (cs) prostate cancer (PCa).MethodsThis retrospective study included a multi-center dataset of 1513 patients who underwent bpMRI (T2 + DWI) between 2014 and 2020, of whom 73 patients underwent at least two consecutive bpMRI scans and repeat biopsies. A deep learning PCa detection model was developed to produce a heatmap of all PIRADS ≥ 2 lesions across prior and current studies. The heatmaps for each patient's prior and current examination were used to extract differential volumetric and likelihood features reflecting explainable changes between examinations. A machine learning classifier was trained to predict from these features csPCa (ISUP > 1) at the current examination according to biopsy. A classifier trained on the current study only was developed for comparison. An extended classifier was developed to incorporate clinical parameters (PSA, PSA density, and age). The cross-validated diagnostic accuracies were compared using ROC analysis. The diagnostic performance of the best model was compared to the radiologist scores.ResultsThe model including prior and current study (AUC 0.81, CI: 0.69, 0.91) resulted in a higher (p = 0.04) diagnostic accuracy than the current only model (AUC 0.73, CI: 0.61, 0.84). Adding clinical variables further improved diagnostic performance (AUC 0.86, CI: 0.77, 0.93). The diagnostic performance of the surveillance AI model was significantly better (p = 0.02) than of radiologists (AUC 0.69, CI: 0.54, 0.81).ConclusionsOur proposed AI-assisted surveillance of prostate MRI can pick up explainable, diagnostically relevant changes with promising diagnostic accuracy.Key points• Sequential prostate MRI scans can be automatically evaluated using a hybrid deep learning and machine learning approach. • The diagnostic accuracy of our csPCa detection AI model improved by including clinical parameters.

Project description:Many men diagnosed with localized prostate cancer can postpone definitive treatment without raising their risk of metastasis or death from disease. Active surveillance (AS) is a method of monitoring select men, with the option of switching to active treatment upon signs of progression, thereby avoiding the well-known side-effects of surgery and radiotherapy. This review analyzes the data from long-running AS cohorts to determine the safety and efficacy of AS. We conducted a narrative review of recently published data, including 14 articles from 13 AS cohorts. The cohorts used varying inclusion criteria, with reported differences in clinical T stage and Gleason Score (Grade Group), among other features. Some studies (n=5) limited their cohorts to low-risk patients, while others (n=8) also included intermediate-risk patients. The heterogeneity of the cohorts produced mixed results, with the risk of prostate cancer metastasis ranging from 0.1-1.0% at 10 years and the risk of prostate cancer mortality ranging from 0-1.9% at 10 years. However, the majority of studies reported risks of less than 0.5% at 10 years for both metastasis and death. For most cohorts, half of men remained untreated for 5-10 years, with estimates ranging from 37% receiving active treatment in the Toronto cohort to 73% in the Prostate Cancer Research International AS (PRIAS) study. Current data do not support the use of negative magnetic resonance imaging (MRI) to avoid scheduled biopsy. Taken together, the data collected from these AS cohorts suggests that AS is a safe approach for men with low-grade prostate cancer and some men with intermediate risk disease. AS should be more broadly implemented for eligible patients to avoid the decreases in quality of life from undergoing active treatment. Studies expanding the inclusion criteria and further defining a subset of men with favorable intermediate-risk prostate cancer who might safely benefit from AS are needed to assess the long-term outcomes of using AS in intermediate-risk groups.

Project description:BackgroundThe routine clinical use of serum prostatic specific antigen (PSA) testing has allowed earlier detection of low-grade prostate cancer (PCa) with more favourable characteristics, leading to increased acceptance of management by active surveillance (AS). AS aims to avoid over treatment in men with low and intermediate-risk PCa and multiple governing bodies have described several AS protocols. This study provides a descriptive profile of the Guy's and St Thomas NHS Foundation Trust (GSTT) AS cohort as a platform for future research in AS pathways in PCa.MethodsDemographic and baseline characteristics were retrospectively collected in a database for patients at the GSTT AS clinic with prospective collection of follow-up data from 2012. Seven hundred eighty-eight men being monitored at GSTT with histologically confirmed intermediate-risk PCa, at least 1 follow-up appointment and diagnostic characteristics consistent with AS criteria were included in the profile. Descriptive statistics, Kaplan-Meier survival curves and multivariable Cox proportion hazards regression models were used to characterize the cohort.DiscussionA relatively large proportion of the cohort includes men of African/Afro-Caribbean descent (22%). More frequent use of magnetic resonance imaging and trans-perineal biopsies at diagnosis was observed among patients diagnosed after 2012. Those who underwent trans-rectal ultrasound diagnostic biopsy received their first surveillance biopsy 20 months earlier than those who underwent trans-perineal diagnostic biopsy. At 3 years, 76.1% men remained treatment free. Predictors of treatment progression included Gleason score 3 + 4 (Hazard ratio (HR): 2.41, 95% Confidence interval (CI): 1.79-3.26) and more than 2 positive cores taken at biopsy (HR: 2.65, CI: 1.94-3.62). A decreased risk of progressing to treatment was seen among men diagnosed after 2012 (HR: 0.72, CI: 0.53-0.98).ConclusionAn organised biopsy surveillance approach, via two different AS pathways according to the patient's diagnostic method, can be seen within the GSTT cohort. Risk of patients progressing to treatment has decreased in the period since 2012 compared with the prior period with more than half of the cohort remaining treatment free at 5 years, highlighting that the fundamental aims of AS at GSTT are being met. Thus, this cohort is a good resource to investigate the AS treatment pathway.

Dataset Information

A Feasibility Study of the Therapeutic Response and Durability of Short-term Androgen-targeted Therapy in Early Prostate Cancer Managed with Surveillance: The Therapeutics in Active Prostate Surveillance (TAPS01) Study.

Background

Objective

Design setting and participants

Intervention

Outcome measurements and statistical analysis

Results and limitations

Conclusions

Patient summary

Publications

A Feasibility Study of the Therapeutic Response and Durability of Short-term Androgen-targeted Therapy in Early Prostate Cancer Managed with Surveillance: The Therapeutics in Active Prostate Surveillance (TAPS01) Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets