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13th March 2024
Prostate tumours evolve in two distinct disease types, a new artificial intelligence (AI) study by the Pan Prostate Cancer Group has revealed, which may lead to better diagnosis and tailored treatments in future.
This international consortium of researchers, led by the universities of Oxford and Manchester, analyses genetic data from thousands of prostate cancer samples across nine countries and is aiming to develop a genetic test that, when combined with conventional staging and grading, can provide a more precise prognosis for each patient, allowing tailored treatment decisions.
For this particular study, they used AI neural networks to process data on changes in the DNA of prostate cancer samples from 159 patients in the UK.
Samples were taken after radical prostatectomy in patients with intermediate or lower risk prostate adenocarcinoma who were otherwise treatment naive.
Published in the journal Cell Genomics, the results generated an evolutionary tree that took multiple routes to two ‘evotypes’, or subgroups, of prostate cancer.
These two prostate cancer subtypes were confirmed by using two other mathematical approaches applied to different aspects of the data, as well as being validated in other independent datasets from Canada and Australia.
It is hoped that these findings could save thousands of lives in future by revolutionising how prostate cancer is diagnosed and providing tailored treatments to individual patients according to a genetic test, which will also be delivered using AI, the researchers said.
Professor Colin Cooper, professor of cancer genetics at the University of East Anglia’s Norwich Medical School, who was involved in the research, said: ‘This study is really important because until now, we thought that prostate cancer was just one type of disease. But it is only now, with advancements in artificial intelligence, that we have been able to show that there are actually two different subtypes at play.
‘We hope that the findings will not only save lives through better diagnosis [of prostate cancer] and tailored treatments in the future, but they may help researchers working in other cancer fields better understand other types of cancer too.’
Prof David Wedge, lead researcher and professor of cancer genomics and data science at the Manchester Cancer Research Centre, added: ‘This realisation is what enables us to distinguish the disease types. This hasn’t been done before because it’s more complicated than HER2+ in breast cancer, for instance.
‘This understanding is pivotal as it allows us to classify tumours based on their evolutionary trajectory rather than solely on individual gene mutations or expression patterns.’
As well as this project in prostate cancer, AI is being used in a number of new clinical studies into disease areas such as cardiovascular disease.
And neural networks in particular have previously been used, for example, in an AI study of Parkinson’s disease, which revealed four subtypes of the disease.
6th October 2023
Stereotactic radiotherapy courses for men with intermediate risk, localised prostate cancer is as effective as standard care, according to the findings of a new trial presented at the recent American Society for Radiation oncology (ASTRO) annual meeting.
The phase 3 PACE B (Prostate Advances in Comparative Evidence) study found that using stereotactic body radiation therapy (SBRT) was non-inferior to standard treatment with moderately fractionated radiation in men with non-metastatic prostate cancer. SBRT had a five-year disease control rate of 96% compared to 95% for conventional radiation.
Researchers from the Royal Marsden Hospital in London, enrolled 874 men with a median age of 69.8 years from 38 centres in Canada and the UK.
Participants were randomly assigned to receive either SBRT (n = 443), which involved the delivery of five fractions over one to two weeks (36.25 Gy total dose), or a standard course of radiation (n = 441) with 39 fractions over 7.5 weeks (78 Gy) or 20 fractions over four weeks (62 Gy). The men were then followed for a median of 73.1 months.
The trial explored whether patients remained free of biochemical clinical failure (BCF), which was defined as an increase in PSA levels, distant metastases or other evidence that the cancer was returning, or death from prostate cancer.
After five years after treatment with either modality, men treated with SBRT had a BCF-event-free rate of 95.7%, compared to 94.6% for those treated with standard care radiation. This demonstrated that SBRT was non-inferior to CRT (p-value for non-inferiority = 0.007).
Side effects were low in both groups, and not significantly different between treatment arms. At five years post-treatment, 5.5% of patients who received SBRT experienced grade 2 or higher side effects affecting the genital or urinary organs, compared to 3.2% in the conventional group (p = 0.14). Only one person in each arm of the study experienced grade 2 or higher gastrointestinal side effects (p = 0.99).
In discussing these findings, Professor Nicholas van As, consultant clinical oncologist, medical director of The Royal Marsden NHS Foundation Trust and the study lead, said: ‘Standard radiation treatment is already highly effective and is very well tolerated in people with localised prostate cancer.
‘But, for a healthcare system and for patients, to have this treatment delivered just as effectively in five days as opposed to four weeks has huge implications.‘
Stereotactic radiotherapy delivers treatment with high precision from a number of different angles around the body and helps to reduce adverse effects in the surrounding tissue. A study from earlier in 2023 found MRI-guided stereotactic radiotherapy reduced physician-reported toxic GU and gastrointestinal adverse effects than CT-guided stereotactic radiotherapy in men with prostate cancer.
27th April 2023
Prostate cancer (PC) is the second most common cancer in men with over 1.4 million new cases in 2020. Findings from 2003, suggest that 5-alpha reductase inhibitors (5-ARIs) such as finasteride, prevent or delay the appearance of prostate cancer. Other work with another agent, dutasteride, also noted a lower risk of incident prostate cancer. However, in 2011, the FDA warned that 5-ARIs may increase the risk of a more serious form of prostate cancer. Despite this the available data is conflicting. For example, in one study, use of 5-ARIs led to a delay in cancer diagnosis and worsened cancer-specific outcomes in men with PC. In contrast, another could not detect an association between 5-ARI use and prostate cancer death.
In the present study, researchers undertook a meta-analysis on the association of 5-ARI use and death from prostate cancer. The primary outcome was the incidence of PC mortality among 5-alpha reductase inhibitor users and non-users.
5-alpha reductase inhibitor use and prostate cancer
There were 11 studies meeting the inclusion criteria, only one of which was an RCT and the remainder cohort studies. A total of 3,243,575 men were identified, 138,477 of whom were using a 5-ARI drug.
There was no significant association between 5-ARI use and prostate cancer death (hazard ratio, HR = 1.04, 95% CI 0.80 – 1.35, p = 0.79). In addition, there was also no association when restricting the analysis to exclude patients with a PC diagnosis at baseline (HR = 1.0, 95% CI 0.60 – 1.67, p = 0.99). When adjusting for prostate specific antigen level, there was a lower risk of prostate cancer mortality but this was non-significant (HR = 0.76, 95% CI 0.57 – 1.03, p = 0.08).
1st March 2023
A study of men with prostate cancer has revealed how just over half had three or more poorly controlled cardiovascular risk factors.
In men with prostate cancer, an international research group has found that just over half had three or more cardiovascular risk factors which are poorly controlled, highlighting a gap in care that requires attention.
It is recognised that men with prostate cancer (PC) have an elevated cardiovascular risk, with one study of nearly 2,500 male cancer patients, finding that two-thirds were deemed to be at high risk.
Other research has revealed that cardiovascular causes of death can be greater than those of the cancer itself. For instance, a study of 752,092 men with PC identified that while 17% died because of their cancer, 83% died of other causes, of which, 23% were cardiac-related.
Despite evidence that men with PC have a higher risk of cardiovascular-related death, which particular risk factors are present and how well these are controlled is unclear.
In the current study, researchers used data from the RADICAL-PC trial, a longitudinal prospective cohort study of men with PC.
Information of demographics and clinical factors were collected from participant’s medical records although individuals also completed several lifestyle questionnaires and were assessed for frailty.
Poor risk factor control for cardiovascular disease was defined in terms of low-density lipoprotein levels, physical activity, blood pressure control and a waist: hip ratio > 0.90.
A total of 2,811 men with a mean age of 68.3 years were included in the study and of whom, 91% had non-metastatic PC, with just over a third (38%) in receipt of androgen deprivation therapy.
In addition, 23% of participants had pre-existing cardiovascular disease and virtually all (98%) had at least one poorly controlled cardiovascular risk factor. In fact, 51% of men had > 3 risk factors that were poorly controlled.
The researchers found that men with > 3 poorly controlled risk factors were generally older, had advanced cancer and were receiving androgen deprivation therapy.
In multivariable analysis, there were four factors linked to having > 3 poorly controlled risk factors.
Not taking a statin (odds ratio, OR = 2.55, 95% CI 2.00 – 3.26), physical frailty (OR = 2.37), the need for blood pressure medication (OR = 2.36) and finally increasing age (OR per 10-year increase = 1.34).
The authors concluded that poor cardiovascular risk factor control in men with prostate cancer is common and requires improved interventions to target the problem.
Citation
Klimis H et al. The burden of uncontrolled cardiovascular risk factors in men with prostate cancer. A RADICAL-PC analysis. J Am Coll Cardiol CardioOnc 2023.
13th February 2023
A team of UK researchers have developed a novel prostate cancer (PaC) screening test based on measurement of five chromosome conformations that were originally detected in association with advanced PaC and which, together with the prostate specific antigen (PSA) test, has a high degree of accuracy for detecting the cancer.
Prostate cancer is the second most common cancer in men and in 2020, there were just over 1.4 million new cases worldwide. Further investigations for suspected PaC are based on the results of a PSA test and the threshold has conventionally been set at 3 to 4 to differentiate between ‘normal’ and ‘abnormal’ although cancer can be present at lower PSA levels. However, while other tests have been developed, these all generally have a low positive predictive value. While imaging modalities have shown promise as screening tests, the recent PROSTAGRAM study which compared PSA test, MRI and ultrasound, found that all provided a similar level of accuracy for detecting PaC.
In the current study, researchers developed an assay based on specific chromosome conformation changes in certain genes in the blood of men with PaC. Using samples from the PROSTAGRAM study, which included men diagnosed with PaC and control patients, the team set out to establish whether their novel assay (EpiSwitch) in combination with a PSA test could improve the accuracy of PaC diagnosis.
Novel prostate cancer test performance
Samples from 109 men (88 control and 21 with PaC) were analysed. Based on a PSA cut-off level of 3 ng/mL, the test had an accuracy of 79%. The EpiSwitch test alone had an accuracy of only 64% but when the EpiSwitch test was combined with the PSA test, the accuracy was 94%.
The researchers reported that using the EpiSwitch test and the PSA level taken as a continuous variable, there was a high positive predictive (92%) and negative predictive value (94%) for the diagnosis of PaC. Although the study was based on a relatively small number of patient samples, the authors called for further studies to examine the value of the test in larger patient samples.
Citation
Pchejetski D et al. Circulating Chromosome Conformation Signatures Significantly Enhance PSA Positive Predicting Value and Overall Accuracy for Prostate Cancer Detection. Cancers 2023
20th January 2023
MRI guided stereotactic radiotherapy is superior than that provided via CT guidance with respect to adverse effects for men with prostate cancer.
A randomised trial by Californian researchers has shown that magnetic resonance imaging (MRI)-guided stereotactic body radiation, significantly reduced grade 2 or higher acute physician-scored genitourinary and gastrointestinal toxic effects as well as patient self-reported prostate cancer symptom scores, compared to computed tomography (CT)-guided radiotherapy.
Stereotactic radiotherapy delivers treatment with high precision from a number of different angles around the body and is designed to reduce adverse effects on the tissue surrounding a tumour. Furthermore, results from several trials, indicate that this approach does not increase gastrointestinal or genitourinary acute toxicity.
While stereotactic radiotherapy has traditionally been delivered using linear accelerators and guided by computed tomography (CT) imaging, MRI-guided adaptive radiotherapy is seen as an emerging and alternative approach.
Moreover, it may also be possible using MRI to reduce the radiotherapy planning target volume (PTV) which encompasses the clinical target volume to account for possible uncertainties in beam alignment, patient positioning, organ motion, and organ deformation.
In the present study, the US researchers undertook a phase 3 study, with a view to demonstrating a reduced PTV with MRI compared to CT guidance, following stereotactic body radiotherapy for men with localised prostate cancer. Eligible men were randomised 1:1 to either MRI- or CT-guided stereotactic radiotherapy although neither the treating physician or patient were blinded to the treatment allocation.
The primary outcome was set as the incidence of acute (defined by occurring less than 90 days after stereotactic therapy) grade 2 or higher genitourinary (GU) toxic effects, whereas secondary outcomes included gastrointestinal toxic effects.
Other measures assessed included changes in the international prostate symptom score (IPSS) and for which increases of 15 points or more are considered to be clinically relevant.
A total of 156 men with a mean age of 71 years were randomised to the MRI arm (77) or the CT arm.
The proportion of GU toxic effects of grade 2 or higher was significantly lower among those receiving MRI-guided stereotactic therapy (24.4% vs 43.4%, p = 0.01). There were no reported gastrointestinal toxic effects at grade 2 or higher compared to 10.5% in the CT-guided group (p = 0.003).
The researchers also observed a significantly lower proportion of men with an IPSS score increase of 15 points or more after 4 weeks (6.8% vs 19.4%, p = 0.01).
The authors concluded that MRI-guided stereotactic radiotherapy reduced physician-reported toxic GU and gastrointestinal adverse effects than CT-guided stereotactic radiotherapy and called for future studies to examine the sustainability of these benefits.
Citation
Kishan AU et al. Magnetic Resonance Imaging-Guided vs Computed Tomography-Guided Stereotactic Body Radiotherapy for Prostate Cancer: The MIRAGE Randomized Clinical Trial. JAMA Oncol 2023
7th November 2022
The use of an inherited polygenic risk score and an individual’s family history of prostate or breast cancer provides a much better method for risk stratification for disease mortality according to the findings of a study by US researchers.
Prostate cancer is the second most frequent cancer diagnosis made in men and the fifth leading cause of death worldwide. Moreover, global data suggests that in 2020 there were 1,414,259 new cases and 375,304 deaths from the cancer. The importance of family history as a risk factor has been known for several decades and a 1990 case-control study found that men with a father or brother affected by the cancer were twice as likely to develop prostate cancer compared to men without affected relatives.
Given the higher risk for men with a family history of the cancer, in recent years, genome-wide association studies have been used to identify a polygenic risk score (PRS) and which influences prostate cancer susceptibility. In fact, the PRS can be used to identify a substantial proportion of men at high-risk for prostate cancer.
Interestingly, some evidence indicates that men with a family history of breast or prostate cancer had elevated prostate cancer risks, including the risk of lethal disease. With both a PRS and the presence of a family history able to evaluate an individual’s risk of developing prostate cancer, for the present study, the US researchers wondered about the prognostic value of combining these two risk scores.
The researchers used data from the Health Professionals Follow-up Study (HPFS) in which information on a family history of prostate and breast cancer had been collected. In addition, men in the HPFS study were invited to provide a blood or buccal sample for genotyping.
The US team then collated data for men who had genotyped samples and who were prostate cancer free. They defined genetic risk in terms of a family history (Yes/No) of either prostate or breast cancer and divided the polygenic risk score into quartiles. The primary outcomes were prostate cancer and prostate cancer-specific death and the researchers used regression models to assess the association between PRS, family history and the risk of developing prostate cancer and of dying from the cancer.
Polygenic risk score and prostate cancer
Data were available for 10,120 men with a median age of 65.3 years at entry into the study of whom 49.9% reported a family history of prostate cancer and 7.7% had a history of both prostate and breast cancer.
A total of 1,915 cases of prostate cancer and 166 fatal prostate cancers were detected during a median follow-up of 18.3 and 23.2 years respectively.
When researchers considered a family history of prostate cancer, this was associated with a 58% higher risk of developing the cancer (Hazard ratio, HR = 1.58, 95% CI 1.38 – 1.81) and a 60% higher risk of prostate cancer-related death (HR = 1.60, 95% CI 1.06 – 2.42). In addition, using the top quartile polygenic risk score, the hazard ratio for prostate cancer was 5.29 (95% CI 4.47 – 6.27) and 3.68 (95% CI 2.29 – 5.90) for mortality.
But when both the PRS and a family history of prostate or breast cancer were included in a model, the hazard ratio increased to 6.95 (95% CI 5.57 – 8.66) and the associated hazard ratio for prostate cancer mortality was 4.84 (95% CI 2.59 – 9.03) compared to men in the lowest quartile and without a family history of either prostate or breast cancer. Overall, men within the upper two PRS quartiles (i.e., 50 to 100%) and who had a family history or prostate, or breast cancer accounted for 97.5% of prostate cancer deaths by age 75.
The authors concluded that using both the polygenic risk score and the presence of a family history, can enable the identification of men who at the highest risk of dying from prostate cancer before the age of 75.
Citation
Plym A et al. Family history of prostate and breast cancer integrated with a polygenic risk score identifies men at highest risk of dying from prostate cancer before age 75 years. Clin Cancer Res 2022
24th October 2022
A gallium positron emission tomography/computed tomography (Ga PET-CT) scan-based radiomics model was better able to distinguish between benign prostate disease and prostate cancer than radiologists according to a retrospective study by Chinese researchers.
Prostate cancer is the 2nd most commonly occurring cancer in men and the 4th most common cancer overall with more than 1.4 million new cases reported in 2020 cancer and 375,304 recorded deaths. Prostate specific membrane antigen (PSMA) is a transmembrane protein that is expressed by virtually all prostate cancers and molecules targeting PSMA can be labelled with radionuclides to become both diagnostic and/or therapeutic agents. Gallium-68 prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has increasingly been utilised globally to assess the local and metastatic burden of prostate cancer. Moreover, a meta-analysis of 37 studies concluded that Ga-68-PSMA PET improves detection of metastases with biochemical recurrence, particularly at low pre-PET PSA levels. A Ga PET-CT scan is normally interpreted by nuclear medicine specialists although there is some evidence to suggest that lesions can be missed. The use of radiomics focuses on improvements in image analysis, using an automated high-throughput extraction of large amounts (200+) of quantitative features of medical images. To date however, the predictive value of a Ga PET-CT scan radiomics model has not been explored for patients with prostate cancer and was the subject of the present study.
The Chinese team retrospectively examined patients who underwent a Ga PET-CT scan and who had pathologically proven prostate cancer or biopsy benign prostate disease. Radiomics prostate cancer features were extracted from the scans and a model created and the ability of the model to differentiate between prostate cancer and benign disease tested. The sensitivity, specificity, positive and negative predictive values of the model were calculated and compared with those of two radiologists who visually inspected the scans.
Ga PET-CT scan radiomics model performance
A total of 125 patients were included and split into a training set (87) and a test set (38). All patients underwent biopsy or surgery and their pathological examination results were assessed.
On the test set, the radiomics model had a sensitivity of 84%, specificity of 77% and and a positive predictive value of 88% for distinguishing between cancer and benign disease.
The agreement between the two radiologists for visual inspection of the scans were very close (kappa = 0.81). However, the corresponding sensitivity for the radiologists on the test set were 74% and specificity was 55% and both were significantly different to the radiomics model (p = 0.036 and 0.002 respectively).
The authors concluded that they had successfully developed and validated a radiomics model based on data extracted from a Ga PET-CT scan and that this non-invasive model was able to predict intraprostatic lesions in men with prostate cancer.
Citation
Zang S et al. Development and validation of 68Ga-PSMA-11 PET/CT-based radiomics model to detect primary prostate cancer EJNMMI Res 2022
29th September 2022
A caffeine genotype is associated with a longer prostate cancer specific survival among men who drink higher amounts of coffee in comparison to other genotypes, according the findings of a study by an international team of researchers.
Prostate cancer the 2nd most common cancer in men worldwide and there were more than 1.4 million new cases in 2020. One possible lifestyle factor that may have a protective role against the development of prostate cancer is intake of coffee. In fact, a 2015 meta-analysis of 13 cohort studies including 539,577 participants concluded that coffee consumption may be associated with a reduced risk of prostate cancer and it that there was also has an inverse association with non-advanced prostate cancer.
Caffeine is metabolised by the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme although single nucleotide polymorphisms (SNPs) have been identified which impact on the speed with which caffeine is metabolised giving rise to differences in caffeine genotype. For example, rs762551 (also known as -164A>C or -163C>A) is a SNP encoding the CYP1A2*1F allele of the CYP1A2 gene (which metabolises caffeine).
Furthermore, rs762551 SNP can affect CYP1A2 enzyme activity and has been used to categorise individuals as either ‘fast’ (AA genotype) or ‘slow’ (AC or CC genotype) caffeine metabolisers. Moreover, there is some data to suggest that individuals with a ‘fast’ caffeine genotype with localised prostate cancer and a low to moderate coffee intake, are less likely to experience grade progression than non-consumers.
Based on this earlier work, suggesting that a caffeine genotype may affect prostate cancer survival, for the present study, researchers examined the association between coffee intake, rs762551 genotype and survival among men with prostate cancer.
Using data from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium, researchers included individuals with the caffeine genotype of interest (i.e. -163C>A rs762551). Coffee consumption before their diagnosis of prostate cancer was categorised as none/very low (0 to 3 or more cups/week); low’ (3 or more cups/week) or high (2 or more cups/day). The low consumption level was used as the reference point for statistical analysis.
Caffeine genotype and prostate cancer survival
The whole cohort comprised 5,727 men with a median age of 63 years and who consumed a median of 2.5 cups of coffee/day. Individuals were followed for a median of 5.1 years. In the overall cohort there were 906 deaths including 481 due to prostate cancer.
A high intake of coffee was associated with a 15% lower (but non-significant) reduction in prostate cancer-specific survival in the overall cohort (Hazard ratio, HR = 0.86, 95% CI 0.68 – 1.08, p = 0.19). A similar, non-significant reduction was also observed for overall survival (HR = 0.90, 95% CI 0.77 – 1.07, p = 0.24).
For men in the group with localised disease, a higher intake of coffee was associated with a significantly longer prostate cancer-specific survival (HR = 0.66, 95% CI 0.44 – 0.98, p =0.04). However, among those with more advanced disease (e.g., node positive, distant metastases), higher coffee intake was not associated with better survival (HR = 0.92, 95% CI 0.69 – 1.27, p = 0.60).
When researchers considered survival among those with different caffeine genotypes, those with the AA genotype (i.e., the fast metabolisers), there was a significantly longer prostate cancer specific survival (HR = 0.67, 95% CI 0.49 – 0.93, p = 0.017) for the highest level of coffee intake. In contrast, this relationship was non-significant for the other genotype (AA/CC) examined (HR = 1.04, 95% CI 0.74 – 1.47, p = 0.8).
The authors concluded that coffee intake was associated with longer prostate cancer specific survival among men with a CYP1A2 -163AA genotype and suggested that this finding would require further replication.
Citation
Gregg JR et al. Coffee Intake, Caffeine Metabolism Genotype, and Survival Among Men with Prostate Cancer. Eur Urol Oncol 2022
19th August 2022
Use of a genetic risk score (GRS) in men with symptoms suggestive of prostate cancer could enable the identification of those at risk and fast track them for further investigation according to the results of a study by UK researchers using a cohort from the UK Biobank database.
Prostate cancer was responsible for 1.4 million global cases in 2020 and is the 2nd most commonly occurring cancer in men. Screening for the cancer may help to save lives and a European study which followed-up on men for 13 years found that one prostate cancer death was averted per 781 men invited for screening although the authors concluded that ‘despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening.’
Symptoms potentially suggestive of prostate cancer include lower urinary tract symptoms (LUTS) including nocturia, urinary frequency or poor stream but these are often present at the time of a prostate cancer diagnosis.
The use of prostate-specific antigen (PSA) in men with LUTS is another means of screening though a 2022 systematic review concluded that the available evidence suggests PSA is highly sensitive but poorly specific for prostate cancer detection in symptomatic patients.
Prostate cancer is a highly heritable disease and there are 269 known genetic risk variants such that the use of a genetic risk score offers an approach for personalised risk prediction.
Moreover, it has been suggested that the use of a GRS provides additional information to improve upon current practices in prostate cancer screening by risk-stratifying patients before initial prostate-specific antigen testing.
However, to date, GRS is not routinely used and for the present study, researchers set out to assess whether a GRS was able to predict a new diagnosis of prostate cancer in men with LUTS over the next 2 years.
The team used information held in the UK Biobank and included men with LUTS but no recorded diagnosis of prostate cancer and a GRS was calculated for each participant based on the known genetic variants.
The association between the GRS and prostate cancer diagnosis within 2 years of symptom onset was calculated using logistic regression and GRS scores were split into quintiles for analysis.
Genetic risk score and prostate cancer
A total of 6777 men with prostate cancer symptoms were included and of whom, 247 men had a record of prostate cancer within 2 years. For the remaining 6530 men, 62 died during the 2-year follow-up period, leaving 6448 as control patients.
Among men with symptoms, the GRS was associated with the development of symptoms over the next 2-years (odds ratio, OR = 2.12, 95% CI 1.86 – 2.41). The risk of prostate cancer was also age dependent such that men in the highest GRS quintile had a 13% greater incidence than those in the lowest (2.3%).
When researchers added age to the GRS score, the predictive power of the model improved with an area under (AUC) the receiver operating characteristic curve of 0.77 (95% CI 0.74 – 0.80) which was higher than either the GRS (AUC = 0.70) or age (AUC = 0.68) alone.
The authors discussed how the results of the study could be used to enable identification of men at low risk of prostate cancer and therefore avoid further testing but also to fast track those with the highest risk.
A recognised limitation of the study was that genetic sequencing is not currently available in the UK so that the GRS approach cannot be implemented at present.
Citation
Green HD et al. Applying a genetic risk score for prostate cancer to men with lower urinary tract symptoms in primary care to predict prostate cancer diagnosis: a cohort study in the UK Biobank Br J Cancer 2022
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