Background
The low specificity of serum PSA resulting in the inability to effectively differentiate prostate cancer from benign prostate conditions is a persistent clinical challenge. The low ...sensitivity of serum PSA results in false negatives and can miss high‐grade prostate cancers. We describe a non‐invasive test for detection of prostate cancer based on functional enrichment of prostate adenocarcinoma associated circulating tumor cells (PrAD‐CTCs) from blood samples followed by their identification by immunostaining for pan‐cytokeratins (PanCK), prostate specific membrane antigen (PSMA), alpha methyl‐acyl coenzyme‐A racemase (AMACR), epithelial cell adhesion molecule (EpCAM), and common leucocyte antigen (CD45).
Methods
Analytical validation studies were performed to establish the performance characteristics of the test using VCaP prostate cancer cells spiked into healthy donor blood (HDB). The clinical performance characteristics of the test were evaluated in a case–control study with 160 known prostate cancer cases and 800 healthy males, followed by a prospective clinical study of 210 suspected cases of prostate cancer.
Results
Analytical validation established analyte stability as well as acceptable performance characteristics. The test showed 100% specificity and 100% sensitivity to differentiate prostate cancer cases from healthy individuals in the case control study and 91.2% sensitivity and 100% specificity to differentiate prostate cancers from benign prostate conditions in the prospective clinical study.
Conclusions
The test accurately detects PrAD‐CTCs with high sensitivity and specificity irrespective of stage, serum PSA or Gleason score, which translates into low risks of false negatives or overdiagnosis. The high accuracy of the test could offer advantages over PSA based prostate cancer detection.
Enrichment and characterization of circulating tumor cells (CTC) can aid more effective prostate cancer detection. CTC based prostate cancer detection can reduce false negatives as well as false positives.
Patient characteristics appear to influence the first-line treatment of metastatic castration-resistant prostate cancer. Patients older and with lower Gleason scores tended to receive abiraterone, ...those younger and with more advanced disease tended to receive docetaxel, and those with fewer metastases and more favourable performance tended to receive enzalutamide. The benefit to patients from these observations remains unknown.
Prostate cancer has a multifaceted treatment pattern. Evidence is lacking for optimal treatment sequences for metastatic castration-resistant prostate cancer (mCRPC).
To increase the understanding of real-world treatment pathways and outcomes in patients with mCRPC.
A prospective, noninterventional, real-world analysis of 3003 patients with mCRPC in the Prostate Cancer Registry (PCR; NCT02236637) from June 14, 2013 to July 9, 2018 was conducted.
Patients received first- and second-line hormonal treatment and chemotherapy as follows: abiraterone acetate plus prednisone (abiraterone)-docetaxel (ABI-DOCE), abiraterone-enzalutamide (ABI-ENZA), abiraterone–radium-223 (ABI-RAD), docetaxel-abiraterone (DOCE-ABI), docetaxel-cabazitaxel (DOCE-CABA), docetaxel-enzalutamide (DOCE-ENZA), and enzalutamide-docetaxel (ENZA-DOCE).
Baseline patient characteristics, quality of life, mCRPC treatments, and efficacy outcomes (progression and survival) were presented descriptively.
Data from 727 patients were eligible for the analysis (ABI-DOCE n = 178, ABI-ENZA n = 99, ABI-RAD n = 27, DOCE-ABI n = 191, DOCE-CABA n = 74, DOCE-ENZA n = 116, and ENZA-DOCE n = 42). Demographics and disease characteristics among patients between different sequences varied greatly. Most patients who started on abiraterone or enzalutamide stopped therapy because of disease progression. No randomisation to allow treatment/sequence comparisons limited this observational study.
The real-world PCR data complement clinical trial data, reflecting more highly selected patient populations than seen in routine clinical practice. Baseline characteristics play a role in mCRPC first-line treatment selection, but other factors, such as treatment availability, have an impact. Efficacy observations are limited and should be interpreted with caution.
Baseline characteristics appear to have a role in the first-line treatment selection of metastatic castration-resistant prostate cancer in the real-world setting. First-line abiraterone acetate plus prednisone seems to be the preferred treatment option for older patients and those with lower Gleason scores, first-line docetaxel for younger patients and those with more advanced disease, and first-line enzalutamide for patients with fewer metastases and more favourable performance status. The benefit to patients from these observations remains unknown.
Abstract Immunotherapy confers a small but significant overall survival advantage in metastatic renal cell carcinoma (RCC) but only for the minority of patients, i.e. the 20% with good prognostic ...features. Recent developments in the molecular biology of renal cell carcinoma have identified multiple pathways associated with the development of this cancer. Several strategies have been investigated targeting these pathways, with significant clinical benefits shown in early studies. New agents including the small molecule targeted inhibitors sunitinib, sorafenib and temsirolimus, and the monoclonal antibody bevacizumab have shown anti-tumour activity in randomised clinical trials and have become the standard of care for most patients. Sunitinib and temsirolimus have shown significant improvements in progression-free survival (sunitinib) and overall survival (temsirolimus) in separate phase III studies in the first-line setting when compared with interferon-α. Sorafenib has demonstrated prolonged progression-free survival in a phase III study in comparison with placebo in the second-line setting. More recently two phase III studies have compared bevacizumab and interferon-α with interferon-α alone. Both studies showed a statistically significant improvement in progression-free survival for the combination arm. Additional studies are needed to optimise the use of these agents by identifying those patients who most benefit and elucidating the best way of delivering them, either in combination or as sequential single agents.
Accurate whole-body staging following biochemical relapse in prostate cancer is vital in determining the optimum disease management. Current imaging guidelines recommend various imaging platforms ...such as computed tomography (CT), Technetium 99 m (
Tc) bone scan and
F-choline and recently
Ga-PSMA positron emission tomography (PET) for the evaluation of the extent of disease. Such approach requires multiple hospital attendances and can be time and resource intensive. Recently, whole-body magnetic resonance imaging (WB-MRI) has been used in a single visit scanning session for several malignancies, including prostate cancer, with promising results, providing similar accuracy compared to the combined conventional imaging techniques. The LOCATE trial aims to investigate the application of WB-MRI for re-staging of patients with biochemical relapse (BCR) following external beam radiotherapy and brachytherapy in patients with prostate cancer.
The LOCATE trial is a prospective cohort, multi-centre, non-randomised, diagnostic accuracy study comparing WB-MRI and conventional imaging. Eligible patients will undergo WB-MRI in addition to conventional imaging investigations at the time of BCR and will be asked to attend a second WB-MRI exam, 12-months following the initial scan. WB-MRI results will be compared to an enhanced reference standard comprising all the initial, follow-up imaging and non-imaging investigations. The diagnostic performance (sensitivity and specificity analysis) of WB-MRI for re-staging of BCR will be investigated against the enhanced reference standard on a per-patient basis. An economic analysis of WB-MRI compared to conventional imaging pathways will be performed to inform the cost-effectiveness of the WB-MRI imaging pathway. Additionally, an exploratory sub-study will be performed on blood samples and exosome-derived human epidermal growth factor receptor (HER) dimer measurements will be taken to investigate its significance in this cohort.
The LOCATE trial will compare WB-MRI versus the conventional imaging pathway including its cost-effectiveness, therefore informing the most accurate and efficient imaging pathway.
LOCATE trial was registered on ClinicalTrial.gov on 18th of October 2016 with registration reference number NCT02935816.
It has been highlighted that in the original article 1 there was a typesetting mistake in the Results - NNT in Strive section. This Correction article states the incorrect and correct sentence.
This analysis estimated the number needed to treat with enzalutamide versus bicalutamide to achieve one additional patient with chemotherapy-naïve metastatic castration-resistant prostate cancer who ...would obtain clinical benefit regarding progression-free survival, radiographic progression-free survival, or no prostate-specific antigen progression at 1 and 2 years following treatment initiation.
Clinical event rates were obtained from the STRIVE (NCT01664923) and TERRAIN (NCT01288911) trials, and the number needed to treat was the inverse of the absolute rate difference between the event rates of enzalutamide and bicalutamide. The 95% Confidence Interval of the number needed to treat was derived from the 95% Confidence Interval of the event rate difference.
Using STRIVE data (patients with metastatic disease: n = 128 enzalutamide; n = 129 bicalutamide) comparing enzalutamide with bicalutamide at 1 and 2 years, the numbers needed to treat to achieve one additional patient with chemotherapy-naïve metastatic castration-resistant prostate cancer with progression-free survival were 2.0 and 2.8, respectively; with radiographic progression-free survival, 2.6 and 3.0, respectively; and without prostate-specific antigen progression, 1.8 and 2.4, respectively. Using TERRAIN data (n = 184 enzalutamide; n = 191 bicalutamide) comparing enzalutamide with bicalutamide at 1 and 2 years, the numbers needed to treat to achieve one additional patient with progression-free survival were 4.3 and 3.7, respectively; with radiographic progression-free survival, 10.0 and 2.8, respectively; and without prostate-specific antigen progression, 2.1 and 3.2, respectively.
The combined data from TERRAIN and STRIVE demonstrated that treating chemotherapy-naïve metastatic castration-resistant prostate cancer with enzalutamide leads to more patients without clinical progression at 1 and 2 years than with bicalutamide.
STRIVE (NCT01664923; registration date: August 10, 2012) and TERRAIN (NCT01288911; registration date: February 1, 2011).
Insights into the biology of clear-cell renal cell carcinoma (CCRCC) have identified multiple pathways associated with the pathogenesis and progression of this cancer. This progress has led to the ...development of multiple agents targeting these pathways, including the tyrosine kinase inhibitors sorafenib, sunitinib, and pazopanib, the monoclonal antibody bevacizumab, and the mTOR inhibitors temsirolimus and everolimus. With the exception of temsirolimus, phase 3 trials tested these agents in patients with clear-cell histology; therefore, their efficacy in non-CCRCC is unclear. To date, there is no established effective therapy for patients with advanced non-CCRCC. This article focuses on treatment options for metastatic non-CCRCC.
Prostate cancer Waldron, Nick; Chowdhury, Simon
Medicine (Abingdon. 1995, UK ed.),
February 2020, Letnik:
48, Številka:
2
Journal Article
Recenzirano
Prostate cancer is a major health problem. In the UK, it is the most common male cancer and the second most common cause of male cancer death. Its strongest predeterminant is increasing age. ...Virtually all cancers are adenocarcinomas, the grade being indicated by the Gleason score. There are often no presenting symptoms. Investigations such as serum prostate specific antigen, digital rectal examination, biopsy and, increasingly, magnetic resonance imaging (MRI) are required for diagnosis. Local staging consists of MRI, with computed tomography (CT), bone scanning and, increasingly, positron emission tomography-CT for detecting metastases. Management depends on disease stage, the patient's fitness and their wishes regarding treatment. Active surveillance is increasingly used for low-volume and low-grade cancers. For localized prostate cancer, radical prostatectomy and radical radiotherapy offer high cure rates; for example survival at 10 years can be as high as 90% for a well-differentiated, localized prostate cancer. Hormonal therapy, which lowers or blocks testosterone, is used in locally advanced and metastatic disease; it slows but does not cure metastatic disease. Cytotoxic chemotherapy is increasingly used for castrate-refractory prostate cancer and has been shown to significantly improve overall survival in hormone-naive patients with metastatic prostate cancer.
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