Risks of leukemia, intracranial tumours and lymphomas in childhood and early adulthood after pediatric radiation exposure from computed tomography.

BACKGROUND: Children are more susceptible to radiation-induced damage than adults, but little research has compared the risk of cancer after exposure to radiation during computed tomography (CT) among children at different ages. We aimed to explore the risk of intracranial tumours, leukemia or lymphoma among children, adolescents and young adults (aged < 25 yr) after radiation exposure from CT at or before the age of 18 years. METHODS: We conducted a nested, population-based case-control study using data from Taiwan's publicly funded health care system. We identified participants younger than 25 years with newly diagnosed intracranial tumours, leukemia or lymphoma, from Jan. 1, 2000, to Dec. 31, 2013. We assigned 10 non-cancer controls for each case, matching by sex, date of birth and day of entry to the cohort. We considered CT scans received at or before the age of 18 years and 3 or more years before the index date (the date of cancer diagnosis for cases) as exposure. We used conditional logistic regression models and incidence rate ratios (IRRs) to estimate the relationship between risk of these cancers and CT radiation exposure. RESULTS: We identified 7807 cases and matched to 78 057 controls. Compared with no exposure, exposure to a single pediatric CT scan did not increase risk of intracranial tumours, leukemia or lymphoma. However, participants exposed to 4 or more CT scans had an elevated incidence (IRR 2.30, 95% confidence interval 1.43-3.71) of one of the cancer outcomes of interest. Receiving 4 or more CT scans at or before 6 years of age was associated with the highest risks of cancer, followed by ages 7-12 years and 13-18 years (p for trend < 0.001). INTERPRETATION: Exposure to a single CT scan was not associated with increased risks of subsequent intracranial tumours, leukemia or lymphoma among children; however, we observed increased cancer risks among those with 4 or more CT scans, especially among younger children. Although these cancers are uncommon, the findings of this study underscore the importance of prudent use of CT in the pediatric population.

Cardiovascular risk of gonadotropin-releasing hormone antagonist versus agonist in men with prostate cancer: an observational study in Taiwan.

BACKGROUND: The impact of gonadotropin-releasing hormone (GnRH) antagonist and agonist (GnRHa) treatment on cardiovascular disease (CVD) risk in prostate cancer (PCa) remains inconclusive due to conflicting findings. We compared the effects of GnRH antagonist and GnRHa treatments on CVD risk in patients with PCa and pre-existing CVD, in a Taiwan population-based database. METHODS: We assessed the risk of major adverse CV events (MACE: ischemic heart disease [IHD], stroke, congestive heart failure [CHF] or all cause deaths) and composite CV events (IHD, stroke, CHF or CV deaths) occurring ≥90 days after androgen deprivation therapy (ADT) initiation in patients with PCa after 90 days of treatment with either GnRH antagonist (degarelix; n = 499) or GnRHa (goserelin, leuprolide, triptorelin; n = 15,127). Patients identified with pre-existing CVD had received cardiac therapy for IHD, reported a stroke or CHF within a year before ADT initiation. Adjusted hazard ratios (aHR) and 95% confidence interval (CI) were obtained for MACE and composite CV events risk after adjusting for age, baseline status of diabetes, hypertension and treatments received. RESULTS: All GnRH antagonist-treated patients showed lower risk of composite CV events than the GnRHa-treated patients. The lower composite CV events risk associated with GnRH antagonist was also observed in patients with metastasis at diagnosis (aHR 0.16; 95% CI, 0.04-0.38; p = 0.013) and those receiving ADT for more than six months (aHR 0.30; 95% CI, 0.16-0.54; p < 0.0001). In patients with pre-existing CVD, the MACE risk was 33% lower (aHR 0.67; 95% CI, 0.46-0.96; p = 0.0299) and composite CV events risk was 84% lower (aHR 0.16; 95% CI, 0.05-0.50; p = 0.0017) in GnRH antagonist-treated than the GnRHa-treated patients. CONCLUSIONS: In patients with PCa and pre-existing CVD, GnRH antagonist use was associated with lower risks for composite CV events and MACE compared with GnRHa.

Radiation Exposure and Lifetime Attributable Risk of Cancer Incidence and Mortality from Low- and Standard-Dose CT Chest: Implications for COVID-19 Pneumonia Subjects.

Since the novel coronavirus disease 2019 (COVID-19) outbreak, there has been an unprecedented increase in the acquisition of chest computed tomography (CT) scans. Nearly 616 million people have been infected by COVID-19 worldwide to date, of whom many were subjected to CT scanning. CT exposes the patients to hazardous ionizing radiation, which can damage the genetic material in the cells, leading to stochastic health effects in the form of heritable genetic mutations and increased cancer risk. These probabilistic, long-term carcinogenic effects of radiation can be seen over a lifetime and may sometimes take several decades to manifest. This review briefly describes what is known about the health effects of radiation, the lowest dose for which there exists compelling evidence about increased radiation-induced cancer risk and the evidence regarding this risk at typical CT doses. The lifetime attributable risk (LAR) of cancer from low- and standard-dose chest CT scans performed in COVID-19 subjects is also discussed along with the projected number of future cancers that could be related to chest CT scans performed during the COVID-19 pandemic. The LAR of cancer Incidence from chest CT has also been compared with those from other radiation sources, daily life risks and lifetime baseline risk.

The Effects of Statins on Prostate Cancer Patients Receiving Androgen Deprivation Therapy or Definitive Therapy: A Systematic Review and Meta-Analysis.

Mortality associated with statin use has been reported in prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) or definitive therapy in several observational studies, although the results have varied. This study aimed to analyze the association of statin use with all-cause mortality and cancer-specific mortality among PCa patients receiving ADT or definitive therapy as their primary treatment and to examine the effect of statin initiation (pre-ADT) timing on outcomes. A systematic literature search of PubMed, the Cochrane library, and Embase was conducted from database inception to 4 October 2021. In total, 12 eligible studies from 976 references were included in the final analysis. The results showed that statin use was associated with a significant reduction in the risks of all-cause mortality (hazard ratio (HR) = 0.73, 95% confidence interval (CI) = 0.64-0.84, p < 0.0001) and cancer-specific mortality (HR = 0.61, 95% CI = 0.49-0.77, p < 0.0001) in PCa patients receiving ADT. However, statin use before ADT initiation did not significantly lower the risk of all-cause mortality (HR = 0.87, 95% CI = 0.66-1.16, p = 0.35) or cancer-specific mortality (HR = 0.84, 95% CI = 0.62-1.13, p = 0.25) in advanced PCa patients receiving ADT. In contrast, statin use was not associated with a significantly reduced risk of all-cause mortality (HR = 0.69, 95% CI = 0.39-1.21, p = 0.20), but it was associated with a reduced risk of cancer-specific mortality (HR = 0.82, 95% CI = 0.68-0.98, p = 0.03) in PCa patients receiving definitive therapy. This review indicated that statin use in combination with ADT was correlated with better all-cause and cancer-specific mortality in PCa patients. However, the beneficial effect might not come from statin use before ADT initiation. In addition, statin use in combination with definitive therapy was correlated with a reduced risk of cancer-specific mortality in PCa patients. In the future, randomized controlled trials are needed to validate the efficacy of statin use in combination with primary treatment for PCa among PCa patients.

Early-onset prostate cancer is associated with increased risks of disease progression and cancer-specific mortality.

OBJECTIVE: Prostate cancer (PCa) incidence has stabilized but not in patients at a young age. We assessed patient characteristics and disease progression in early-onset PCa. METHODS: A retrospective cohort of 28,039 newly diagnosed PCa patients aged ≥35 years was constructed using the Taiwan Cancer Registry in 2008-2016. Patients were categorized by age at diagnosis (≤54, 55-59, 60-69, 70-74, and ≥75 years). The clinical stage at diagnosis, Gleason score, prostate-specific antigen level at diagnosis, Charlson's comorbidity index, and primary and secondary treatments for PCa were included in the analysis. All-cause mortality and prostate cancer-specific mortality (PCSM) were reported. Hazard ratios (HRs) and 95% confidence intervals (CIs) estimating the risks of death and of receiving secondary cancer treatment were generated by Cox hazard models. RESULTS: In patients aged ≤54, 55-59, and 60-69 years, about 60% of them in each group were classified into the high-risk, very high-risk, or metastatic group. However, young patients ≤54 years had a higher risk of PCSM than patients aged 60-69 years (HR = 1.22; 95% CI = 1.10-1.49). This trend of an increased risk in PCSM remained for high-risk, very high-risk, or metastatic patients (HR = 1.24; 95% CI = 1.01-1.51), but not in low- or intermediate-risk patients. Besides, young patients diagnosed with high-risk diseases had the highest risk of receiving secondary cancer treatment within 180 days after completing primary treatment among all age groups (HR = 1.32; 95% CI = 1.07-1.63). CONCLUSIONS: PCa arising in young patients ≤54 years of age, especially those with a high risk or metastatic form, might be more aggressive than that in other age groups.

Exposure to Tomographic Scans and Cancer Risks.

BACKGROUND: Worldwide use of computed tomography (CT) scans has increased. However, the ionizing radiation from CT scans may increase the risk of cancer. This study examined the association between medical radiation from CT scans and the risk of thyroid cancer, lymphoma, and non-Hodgkin lymphoma (NHL) in adults. METHODS: We conducted a nested case-control study in a cohort constructed from a population-based universal health insurance dataset in Taiwan in 2000-2013. In total, 22 853 thyroid cancer, 13 040 leukemia, and 20 157 NHL cases with their matched controls were included. Median follow-up times were 9.29-9.90 years for the three case-control groups. Medical radiation from CT scans was identified through physician order codes in medical insurance data from the index date to 3 years before a cancer diagnosis. Conditional logistic regression modeling was used for the overall and subsets of the population defined by sex and age groups to estimate the odds ratio (OR) and 95% confidence interval (CI) of the cancer risk associated with medical radiation. RESULTS: Exposure to medical radiation from CT scans was associated with elevated risk of thyroid cancer (OR = 2.55, 95% CI = 2.36 to 2.75) and leukemia (OR = 1.55, 95% CI = 1.42 to 1.68). The elevated risk of thyroid cancer and leukemia in association with medical CT was stronger in women than in men. No statistically significant association between the risk of cancer and CT scans was observed in overall patients with NHL (OR = 1.05, 95% CI = 0.98 to 1.12); however, increased risks were found in patients aged 45 years or younger. A clear dose-response relationship was observed in patients 45 years or younger for all three cancers. CONCLUSIONS: CT scans may be associated with an increased risk of thyroid cancer and leukemia in adults and in those diagnosed with NHL at a younger age.

Influence of Baseline Cardiovascular Comorbidities on Mortality after Androgen Deprivation Therapy for Metastatic Prostate Cancer.

Few studies have assessed the benefits of androgen deprivation therapy (ADT) in men with metastatic prostate cancer (PC; mPC) at an old age or with major cardiovascular conditions. A retrospective cohort consisted of 3835 men with newly diagnosed mPC from the Taiwan Cancer Registry of 2008-2014. Among them, 2692 patients received only ADT in the first year after the cancer diagnosis, and 1143 patients were on watchful waiting. The inverse probability of treatment-weighted Cox model was used to estimate the effects of ADT on all-cause mortality and PC-specific mortality according to age, and the status of congestive heart failure (CHF), coronary arterial diseases (CADs), and stroke at the baseline. After a median follow-up of 2.65 years, 1650 men had died. ADT was associated with a 17-22% risk reduction in all-cause and PC-specific mortality in men without stroke, CAD, or CHF in the 65-79-year group. The survival benefit diminished in men with any of these preexisting conditions. In contrast, ADT was not found to be associated with any survival benefit in the ≥80-year group, even though they did not present with any major cardiovascular disease at the baseline. Patients who had CHF, CAD, or stroke at the baseline did not show a survival benefit following ADT in any of the age groups. Men who have preexisting major cardiovascular diseases or are ≥80 years do not demonstrate a survival benefit from ADT for mPC. The risk-benefit ratio should be considered when using ADT for mPC in older men especially those with major cardiovascular comorbidities.

Mortality associated with statins in men with advanced prostate cancer treated with androgen deprivation therapy.

OBJECTIVES: Before launching large clinical trials to confirm the effects of statins in improving outcomes among men with prostate cancer (PC), the most appropriate target patient population and the type of statins need to be clearly identified. PATIENTS AND METHODS: A retrospective cohort study was conducted using the Taiwan Cancer Registry of 2008-2014. This study included 5749 men with locally advanced and metastatic PC who received only androgen deprivation therapy (ADT) in the first year after their cancer diagnosis. Statin users were defined as anyone who was prescribed statins for >28 days. An inverse probability of treatment-weighted Cox model was used to estimate the effects of statin use on all-cause mortality and PC-specific mortality (PCSM) while treating the statin status as a time-dependent variable. RESULTS: Overall, 2259 patients died, and 1495 of them died of PC during a median follow-up of 3.6 years from 1 year after their diagnosis. Statin use was associated with significant reductions in all-cause mortality (hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.70-0.86) and PCSM (HR = 0.76, 95% CI: 0.68-0.86) for metastatic disease and all-cause mortality (HR = 0.66, 95% CI: 0.54-0.81) for locally advanced disease. Patients who received atorvastatin, pravastatin, rosuvastatin or pitavastatin showed a stronger reduction in mortality than those who received other statins. Benefits of statins were consistently observed in men who received post-diagnostic statins, even in those with high comorbidities or an old age. CONCLUSIONS: Our results suggest that only atorvastatin, pravastatin and rosuvastatin were associated with improved survival in advanced PC patients receiving ADT.

Multi-omics analysis reveals the BRCA1 mutation and mismatch repair gene signatures associated with survival, protein expression, and copy number alterations in prostate cancer.

BACKGROUND: Recent genomic analysis reveals that DNA repair gene mutations can be detected in 15-30% of patients in metastatic castration resistant prostate cancer depending on the population and clinical setting when comparing to a very small fraction in those with indolent localized diseases. The discovery and characterization of function associated with DNA repair gene mutations in prostate cancer patients may increase therapeutic options and lead to improved clinical outcomes. METHODS: To understand the role of DNA repair genes associated with other genomic alteration and signaling pathway, we applied an integrative analysis of multi-omics to The Cancer Genome Atlas (TCGA) prostate cancer dataset which contains 498 patients. We concurrently analyzed gene expression profiles, reverse phase protein lysate microarray (RPPA) data, and copy number alterations to examine the potential genomic mechanisms. RESULTS: We identified the signature of "chromosome condensation", "BRCA1 mutation", and "mismatch repair" were associated with disease-free survival in prostate cancer. Through the concurrent analysis of gene expression profiles, reverse RPPA data, and copy number alterations, we found the three signatures are associated with cell cycle and DNA repair pathway and also most events of copy number gains. CONCLUSIONS: This study presents a unique extension from DNA mutations to expressional functions, proteomic activities, and copy numbers of DNA repair genes in prostate cancer. Our findings revealed crucial prognostic markers and candidates for further biological and clinical investigations.

scdNet: a computational tool for single-cell differential network analysis.

BACKGROUND: Single-cell RNA sequencing (scRNA-Seq) is an emerging technology that has revolutionized the research of the tumor heterogeneity. However, the highly sparse data matrices generated by the technology have posed an obstacle to the analysis of differential gene regulatory networks. RESULTS: Addressing the challenges, this study presents, as far as we know, the first bioinformatics tool for scRNA-Seq-based differential network analysis (scdNet). The tool features a sample size adjustment of gene-gene correlation, comparison of inter-state correlations, and construction of differential networks. A simulation analysis demonstrated the power of scdNet in the analyses of sparse scRNA-Seq data matrices, with low requirement on the sample size, high computation efficiency, and tolerance of sequencing noises. Applying the tool to analyze two datasets of single circulating tumor cells (CTCs) of prostate cancer and early mouse embryos, our data demonstrated that differential gene regulation plays crucial roles in anti-androgen resistance and early embryonic development. CONCLUSIONS: Overall, the tool is widely applicable to datasets generated by the emerging technology to bring biological insights into tumor heterogeneity and other studies. MATLAB implementation of scdNet is available at https://github.com/ChenLabGCCRI/scdNet .

Proton pump inhibitors and risk of periampullary cancers--A nested case-control study.

Considerable attention has been focused on long-term use of proton pump inhibitor (PPI) medications in relation to increased risk of cancer via stimulation of DNA-damaged cells. The aim of this study is to examine the dose-dependent effect of PPI on periampullary cancers in a national population-based cohort. A nested case-control analysis was constructed based on Taiwan's National Health Insurance Research Database and the Taiwan Cancer Registry between the years 2000 and 2010. Cases involving patients diagnosed with periampullary cancers were selected and controls were matched to cases according to age, sex and observational period. A "PPI user" was defined as any patient receiving more than 28 cumulative defined daily doses as measured by prescription drug claims. Conditional logistic regression analysis was conducted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) according to the level of PPI exposure. A total of 7,681 cases and 76,762 matched controls were included with a mean follow-up period of 6.6 years (SD: 2.0). The odds of PPI exposure in patients with periampullary cancers were higher than that of control patients with an adjusted OR of 1.35 (95% CIs: 1.16-1.57). Our results also showed that PPI exposure was slightly linked to periampullary cancers in dose-dependent manner. A similar association was observed in patients who solely took PPI but no eradication therapy for Helicobacter pylori infection. Long-term PPI use was associated with an increased risk of periampullary cancers in the current population-based study. Physicians must weigh potential risks of long-term maintenance against therapeutic benefit.

Cancer-specific survival after metastasis following primary radical prostatectomy compared with radiation therapy in prostate cancer patients: results of a population-based, propensity score-matched analysis.

BACKGROUND: Data regarding the difference in the clinical course from metastasis to prostate cancer-specific mortality (PCSM) following radical prostatectomy (RP) compared with radiation therapy (RT) are lacking. OBJECTIVE: To examine the association between primary treatment modality and prostate cancer-specific survival (PCSS) after metastasis. DESIGN, SETTING, AND PARTICIPANTS: We used the Surveillance Epidemiology and End Results-Medicare linked database from 1994 to 2007 for patients diagnosed with localized prostate cancer (PCa). We used cancer stage and Gleason score to stratify patients into low and intermediate-high risks. INTERVENTION: Radical prostatectomy or radiation therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Our outcome is time from onset of metastases to PCSM. Propensity score matching and Cox regression were used to analyze the PCSM hazard for the RP group compared with the RT group. RESULTS AND LIMITATIONS: Our study consisted of 66,492 men diagnosed with PCa, 51,337 men receiving RT, and 15,155 men undergoing RP within 1 yr of cancer diagnosis. During the study period, 2802 men were diagnosed as having metastatic disease. A total of 916 men with metastases were included in the propensity-matched cohort; of these men, 186 died from PCa. During the follow-up, for the low-risk patients, the adjusted PCSS after metastasis was 86.2% and 79.3% in the RP and RT groups, respectively; for the intermediate-high-risk patients, the PCSS after metastasis was 76.3% and 63.3% in the RP and RT groups, respectively. The hazard ratios estimating the risk of PCSM between the RP and RT groups were 0.64 (95% confidence interval [CI], 0.36-1.16) and 0.55 (95% CI, 0.39-0.77) for the low- and intermediate-high-risk groups, respectively. Because of the nature of observational studies, the results may be affected by residual confounders and treatment indication. CONCLUSIONS: Following the development of metastases, men who received primary RP have a longer PCSS than men who received primary RT. Our results may have implications for the timing and nature of local PCa treatment.

Fracture after androgen deprivation therapy among men with a high baseline risk of skeletal complications.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Receipt of androgen deprivation therapy (ADT) has been associated with an increased risk of skeletal-associated complications, such as a decrease in bone mineral density and an increase in fracture risk. Many men with pre-existing health conditions receive ADT as their primary treatment because they are considered to be inappropriate candidates for attempted curative treatments. However, several chronic health conditions, such as diabetes, rheumatoid disease and chronic liver disease, are strong predictors for osteoporosis and fractures. We undertook the present study aiming to quantify the impact of treating men with ADT who carry known risk factors for skeletal complications. Among these high-risk men, more than 58% develop at least one fracture after ADT within the 12 years of follow-up. Men who sustained a fracture within 48 months experienced an almost 40% higher risk of mortality than those who did not. Our findings suggest that treating men with a high fracture risk at baseline with long-term ADT may have serious adverse consequences. OBJECTIVE: To quantify the impact of androgen deprivation therapy (ADT) in men with a high baseline risk of skeletal complications and evaluate the risk of mortality after a fracture. PATIENTS AND METHODS: We studied 75994 men, aged ≥ 66 years, with localized prostate cancer from the Surveillance, Epidemiology and End Results-Medicare linked data. Cox proportional hazard models were employed to evaluate the risk. RESULTS: Men with a high baseline risk of skeletal complications have a higher probability of receiving ADT than those with a low risk (52.1% vs 38.2%, P < 0.001). During the 12-year follow-up, more than 58% of men with a high risk and 38% of men with a low risk developed at least one fracture after ADT. The dose effect of ADT is stronger among men who received ADT only compared to those who received ADT with other treatments. In the high-risk group, the fracture rate increased by 19.9 per 1000 person-years (from 52.9 to 73.0 person-years) for men who did not receive ADT compared to those who received 18 or more doses of gonadotropin-releasing hormone agonist among men who received ADT only, and by 14.2 per 1000 person-years (from 45.2 to 59.4 person-years) among men who received ADT and other treatments. Men experiencing a fracture had a 1.38-fold higher overall mortality risk than those who did not (95% CI, 1.34-1.43). CONCLUSIONS: Men with a high baseline risk of skeletal complications developed more fractures after ADT. The mortality risk is 40% higher after experiencing a fracture. Consideration of patient risk before prescribing ADT for long-term use may reduce both fracture risk and fracture-associated mortality.

Severe genitourinary toxicity following radiation therapy for prostate cancer--how long does it last?

PURPOSE: Radiation therapy is a common treatment for localized prostate cancer but long-term data are sparse on treatment related toxicity compared to observation. We evaluated the time course of grade 2-4 genitourinary toxicities in men treated with primary radiation or observation for T1-T2 prostate cancer. MATERIALS AND METHODS: We performed a population based cohort study using Medicare claims data linked to SEER (Surveillance, Epidemiology and End Results) data. Cumulative incidence functions for time to first genitourinary event were calculated based on the competing risks model with death before any genitourinary event as a competing event. The generalized estimating equation method was used to evaluate the risk ratios of recurrent events. RESULTS: Of the study patients 60,134 received radiation therapy and 25,904 underwent observation. The adjusted risk ratio for genitourinary toxicity was 2.49 (95% CI 2.00-3.11) for 10 years and thereafter. Patients who had required prior procedures for obstruction/stricture, including transurethral prostate resection, before radiation therapy were at significantly increased risk for genitourinary toxicity (risk ratio 2.78, 95% CI 2.56-2.94). CONCLUSIONS: This study demonstrates that the increased risk of grade 2-4 genitourinary toxicities attributable to radiation therapy persists 10 years after treatment and thereafter. Patients who required prior procedures for obstruction/stricture were at higher risk for genitourinary toxicity than those without these preexisting conditions.

Authentication of Algorithm to Detect Metastases in Men with Prostate Cancer Using ICD-9 Codes.

BACKGROUND: Metastasis is a crucial endpoint for patients with prostate cancer (PCa), but currently lacks a validated claims-based algorithm for detection. OBJECTIVE: To develop an algorithm using ICD-9 codes to facilitate accurate reporting of PCa metastases. METHODS: Medical records from 300 men hospitalized at Robert Wood Johnson University Hospital for PCa were reviewed. Using the presence of metastatic PCa on chart review as the gold standard, two algorithms to detect metastases were compared. Algorithm A used ICD-9 codes 198.5 (bone metastases), 197.0 (lung metastases), 197.7 (liver metastases), or 198.3 (brain and spinal cord metastases) to detect metastases, while algorithm B used only 198.5. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the two algorithms were determined. Kappa statistics were used to measure agreement rates between claim data and chart review. RESULTS: Algorithm A demonstrated a sensitivity, specificity, PPV, and NPV of 95%, 100%, 100%, and 98.7%, respectively. Corresponding numbers for algorithm B were 90%, 100%, 100%, and 97.5%, respectively. The agreement rate is 96.8% for algorithm A and 93.5% for algorithm B. CONCLUSIONS: Using ICD-9 codes 198.5, 197.0, 197.7, or 198.3 in detecting the presence of PCa metastases offers a high sensitivity, specificity, PPV, and NPV value.