Risk-adjusted Screening for Prostate Cancer-Defining the Low-risk Group by Data from the PROBASE Trial.

BACKGROUND: Risk-adjusted screening for prostate cancer (PCa) aims to reduce harms by less frequent retesting, especially in men at a low risk of PCa. Definitions of low risk are based mainly on studies in men starting screening at age 55-60 yr. OBJECTIVE: To identify men at age 45 yr with a low risk of PCa. DESIGN, SETTING, AND PARTICIPANTS: A population-based, risk-adjusted PCa screening trial was conducted in Germany using baseline prostate-specific antigen (PSA) starting in young men (PROBASE). INTERVENTION: PSA measurements starting at the age of 45 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The incidence of PCa within 5 yr was assessed in men with screen-negative baseline PSA <1.5 ng/ml compared with those with PSA 1.5-≤3.0 ng/ml. RESULTS AND LIMITATIONS: Of 23301 men who received a first PSA test at age 45 yr, 0.79% had a screen-positive PSA value of ≥3 ng/ml. Among the 89% of men who had a screen-negative baseline PSA value of <1.5 ng/ml, only 0.45% received a positive PSA test ≥3 ng/ml upon retesting after 5 yr. By contrast, for those with a screen-negative baseline PSA value of 1.5-3 ng/ml, 13% surpassed 3 ng/ml upon biennial testing within the next 4 yr. The incidence of PCa in subsequent screening rounds increased with increasing baseline PSA levels, from 0.13 per 1000 person-years for men with initial PSA level of <1.5 ng/ml to 8.0 per 1000 person-years for those with PSA levels of 1.5-3.0 ng/ml. A limitation is a follow-up time of only 5 yr, so far. CONCLUSIONS: Men with baseline PSA <1.5 ng/ml at age 45 yr are at a very low risk of PCa over the next 5 yr. PATIENT SUMMARY: The PROBASE study showed that men with baseline prostate-specific antigen (PSA) <1.5 ng/ml at age 45 yr have a very low prostate cancer detection rate over 5 yr and do not need PSA retesting during this time.

[Prostate cancer screening-current overview]. / Das Prostatakarzinom-Screening ­ aktueller Überblick.

BACKGROUND: The harm-to-benefit ratio of prostate cancer (PCa) screening remains controversial mainly due to the unfavorable test characteristics of prostate-specific antigen (PSA) as a screening test. METHODS: In this nonsystematic review, we present a current overview of the body of evidence on prostate cancer screening with a focus on the role of magnetic resonance imaging (MRI) of the prostate. RESULTS: Evidence generated in large randomized controlled trials showed that PSA-based screening significantly decreases cancer-specific mortality. The main obstacle in developing and implementing PCa screening strategies is the resulting overdiagnosis and as a consequence overtreatment of indolent cancers. Opportunistic screening is characterized by an adverse benefit-to-harm ratio and should, therefore, not be recommended. The German Statutory Early Detection Program for prostate cancer, which consists of a digital rectal examination (DRE) as a stand-alone screening test, is not evidence-based, neither specific nor sensitive enough and results in unnecessary diagnostics. The European Commission recently urged member states to develop population-based and organized risk-adapted PSA-based screening programs, which are currently tested in the ongoing German PROBASE trial. Finetuning of the diagnostic pathway following PSA-testing seems key to improve its positive and negative predictive value and thereby making PCa screening more accurate. Incorporation of prostatic MRI into screening strategies leads to more accurate diagnosis of clinically significant prostate cancer, while diagnosis of indolent cancers is reduced. In the future, molecular liquid-based biomarkers have the potential to complement or even replace PSA in PCa screening and further personalize screening strategies. Active surveillance as an alternative to immediate radical therapy of demographically increasing PCa diagnoses can potentially further improve the benefit-to-harm ratio of organized screening. CONCLUSION: Early detection of PCa should be organized on a population level into personalized and evidence-based screening strategies. Multiparametric MRI of the prostate may play a key role in this setting.

Value-Based Health Care for Prostate Cancer Centers by Implementing Specific Key Performance Indicators Using a Balanced Score Card.

BACKGROUND: Prostate cancer (PC) is the most common cancer in men in 112 countries, and accounts for 15% of cancers. Because it cannot be prevented, the rise in cases is inevitable, and improvements in diagnostic pathways and treatments are needed, as there is still a shortage of cost-effective diagnostics and widespread oncologically safe treatment options with measurable quality. As part of the implementation of a Full Cycle of Care, instruments have been developed to achieve value-based medicine, such as consistent commitment to measurability. One of these instruments is the Balanced Scorecard (BSC). Here, we propose the first BSC for prostate cancer (PC) treatment. METHODS: BSCs are used to assess performance in healthcare organizations across four dimensions: financial, patient and referrer, process, and learning and development. This study aimed to identify Key Performance Indicators (KPIs) for each perspective. A systematic literature search was conducted according to PRISMA guidelines using multiple databases and specific search terms to identify KPIs for PC care, excluding case reports and conference abstracts. In total, 44 reports were included in analyses and development of the PC-specific BSC. RESULTS: In the present study, a PC-specific BSC and KPIs were defined for the four classic perspectives, as well as for a newly developed PC-Specific Disease and Outcome perspective, including patient-related parameters from the German Cancer Society and the International Consortium for Health Outcomes Measurement. In addition, the Process perspective includes KPIs of fulfillment of continuing education of residents and the metrics of structured training of the radical prostatectomy procedure in the Learning and Development perspective. CONCLUSIONS: The developed BSC provides a comprehensive set of perspectives for an Integrated Practice Unit or center in PC care, ensuring that the indicators remain manageable and applicable. The BSC facilitates value creation in line with Porter's Full Cycle of Care by systematically collecting and providing economic, personnel, and medical results, actions, and indicators. In particular, this BSC includes KPIs of structured training of practitioners and metrics of the German Cancer Society, that recently proved to improve PC patients outcomes.

Value of magnetic resonance angiography before prostatic artery embolization for intervention planning.

Knowledge about anatomical details seems to facilitate the procedure and planning of prostatic artery embolization (PAE) in patients with symptomatic benign prostatic hyperplasia (BPS). The aim of our study was the pre-interventional visualization of the prostatic artery (PA) with MRA and the correlation of iliac elongation and bifurcation angles with technical success of PAE and technical parameters. MRA data of patients with PAE were analysed retrospectively regarding PA visibility, PA type, vessel elongation, and defined angles were correlated with intervention time, fluoroscopy time, dose area product (DAP), cumulative air kerma (CAK), contrast media (CM) dose and technical success of embolization. T-test, ANOVA, Pearson correlation, and Kruskal-Wallis test was applied for statistical analysis. Between April 2018 and March 2021, a total of 78 patients were included. MRA identified the PA origin in 126 of 147 cases (accuracy 86%). Vessel elongation affected time for catheterization of right PA (p = 0.02), fluoroscopy time (p = 0.05), and CM dose (p = 0.02) significantly. Moderate correlation was observed for iliac bifurcation angles with DAP (r = 0.30 left; r = 0.34 right; p = 0.01) and CAK (r = 0.32 left; r = 0.36 right; p = 0.01) on both sides. Comparing the first half and second half of patients, median intervention time (125 vs. 105 min.) and number of iliac CBCT could be reduced (p < 0.001). We conclude that MRA could depict exact pelvic artery configuration, identify PA origin, and might obviate iliac CBCT. Vessel elongation of pelvic arteries increased intervention time and contrast media dose while the PA origin had no significant influence on intervention time and/or technical success.

Magnetic Resonance Imaging-guided Active Surveillance Without Annual Rebiopsy in Patients with Grade Group 1 or 2 Prostate Cancer: The Prospective PROMM-AS Study.

Background: Multiparametric magnetic resonance imaging (mpMRI) may allow patients with prostate cancer (PC) on active surveillance (AS) to avoid repeat prostate biopsies during monitoring. Objective: To assess the ability of mpMRI to reduce guideline-mandated biopsy and to predict grade group upgrading in patients with International Society of Urological Pathology grade group (GG) 1 or GG 2 PC using Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scores. The hypothesis was that the AS disqualification rate (ASDQ) rate could be reduced to 15%. Design setting and participants: PROMM-AS was a prospective study assessing 2-yr outcomes for an mpMRI-guided AS protocol. A 12 mo after AS inclusion on the basis of MRI/transrectal ultrasound fusion-guided biopsy (FBx), all patients underwent mpMRI. For patients with stable mpMRI (PRECISE 1-3), repeat biopsy was deferred and follow-up mpMRI was scheduled for 12 mo later. Patients with mpMRI progression (PRECISE 4-5) underwent FBx. At the end of the study, follow-up FBx was indicated for all patients. Outcome measurements and statistical analysis: We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for upgrading to GG 2 in the GG 1 group, and to GG 3 in the GG 2 group on MRI. We performed regression analyses that included clinical variables. Results and limitations: The study included 101 patients with PC (60 GG 1 and 41 GG 2). Histopathological progression occurred in 31 patients, 18 in the GG 1 group and 13 in the GG 2 group. Thus, the aim of reducing the ASDQ rate to 15% was not achieved. The sensitivity, specificity, PPV, and NPV for PRECISE scoring of MRI were 94%, 64%, 81%, and 88% in the GG 1 group, and 92%, 50%, 92%, and 50%, respectively, in the GG 2 group. On regression analysis, initial prostate-specific antigen (p < 0.001) and higher PRECISE score (4-5; p = 0.005) were significant predictors of histological progression of GG 1 PC. Higher PRECISE score (p = 0.009), initial Prostate Imaging-Reporting and Data System score (p = 0.009), previous negative biopsy (p = 0.02), and percentage Gleason pattern 4 (p = 0.04) were significant predictors of histological progression of GG 2 PC. Limitations include extensive MRI reading experience, the small sample size, and limited follow-up. Conclusions: MRI-guided monitoring of patients on AS using PRECISE scores avoided unnecessary follow-up biopsies in 88% of patients with GG 1 PC and predicted upgrading during 2-yr follow-up in both GG 1 and GG 2 PC. Patient summary: We investigated whether MRI (magnetic resonance imaging) scores can be used to guide whether patients with lower-risk prostate cancer who are on active surveillance (AS) need to undergo repeat biopsies. Follow-up biopsy was deferred for 1 year for patients with a stable score and performed for patients whose score progressed. After 24 months on AS, all men underwent MRI and biopsy. Among patients with grade group 1 cancer and a stable MRI score, 88% avoided biopsy. For patients with MRI score progression, AS termination was correctly recommended in 81% of grade group 1 and 92% of grade group 2 cases.

Assessing the risk to develop a growing teratoma syndrome based on molecular and epigenetic subtyping as well as novel secreted biomarkers.

In germ cell tumors (GCT), a growing teratoma during chemotherapy with decreasing tumor markers was defined as 'growing teratoma syndrome' (GTS) by Logothetis et al. in 1982. So far, its pathogenesis and specific treatment options remain elusive. We aimed at updating the GTS definition based on molecular and epigenetic features as well as identifying circulating biomarkers. We selected 50 GTS patients for clinical characterization and subsequently 12 samples were molecularly analyzed. We further included 7 longitudinal samples of 2 GTS patients. Teratomas (TER) showing no features of GTS served as controls. GTS were stratified based on growth rates into a slow (<0.5 cm/month), medium (0.5-1.5) and rapid (>1.5) group. By analyzing DNA methylation, microRNA expression and the secretome, we identified putative epigenetic and secreted biomarkers for the GTS subgroups. We found that proteins enriched in the GTS groups compared to TER were involved in proliferation, DNA replication and the cell cycle, while proteins interacting with the immune system were depleted. Additionally, GTSrapid seem to interact more strongly with the surrounding microenvironment than GTSslow. Expression of pluripotency- and yolk-sac tumor-associated genes in GTS and formation of a yolk-sac tumor or somatic-type malignancy in the longitudinal GTS samples, pointed at an additional occult non-seminomatous component after chemotherapy. Thus, updating the Logothetis GTS definition is necessary, which we propose as follows: The GTS describes a continuously growing teratoma that might harbor occult non-seminomatous components considerably reduced during therapy but outgrowing over time again.

Adjunctive Surgery Is Often Without Oncological Benefit at Time of Postchemotherapy Retroperitoneal Lymph Node Dissection.

PURPOSE: Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for advanced nonseminomatous germ cell tumors (GCTs) aims to resect all remaining metastatic tissue. Resection of adjacent visceral or vascular organs is commonly performed for complete resection. Resection of organs harboring only necrosis results in relevant overtreatment. The study aimed to describe the frequency of metastatic involvement of resected organs with teratoma or viable cancer and to analyze perioperative complications and relapse-free survival. MATERIALS AND METHODS: In a 2-center study, we reviewed a cohort of 1204 patients who underwent PC-RPLND between 2008 and 2021 and identified 242 (20%) cases of adjunctive surgery during PC-RPLND. We analyzed the removed adjacent structures and the pathohistological presence of GCT elements in the resected organs: viable GCT, teratoma, or necrosis/fibrosis. Surgery-associated complications were reported according to the Clavien-Dindo classification. RESULTS: Viable GCT, teratoma, and necrosis were present in 54 (22%), 94 (39%), and 94 (39%), respectively, of all patients with adjunctive resection of adjacent organs. Vascular resections or reconstructions (n = 112; viable: 23%, teratoma: 41%, necrosis: 36%) were performed most frequently, followed by nephrectomies (n = 77; viable: 29%, teratoma: 39%, necrosis: 33%). Perioperative complications of grade ≥ IIIa occurred in 6.6% of all patients, with no difference between the viable GCT and teratoma/necrosis groups (P = .1). A total of 76 patients have been followed without a relapse for at least 36 months. Median follow-up of the whole cohort was 22 months (quartile 7 and 48). Patients with viable GCT/teratoma in the resected specimens had a significantly increased risk of recurrence by 5 years compared to patients with only necrosis (19% vs 59% vs 81%, P < .001). CONCLUSIONS: This study shows that 33% to 40% of all resections of adjacent organs do not harbor teratoma or viable GCT. This highlights the need for better patient selection for these complex patients.

Updated Overall Survival by Circulating Tumor DNA Status from the Phase 3 IMvigor010 Trial: Adjuvant Atezolizumab Versus Observation in Muscle-invasive Urothelial Carcinoma.

BACKGROUND: Interim results from IMvigor010 showed an overall survival (OS) benefit for adjuvant atezolizumab (anti-PD-L1) versus observation in patients with circulating tumor DNA (ctDNA)-positive muscle-invasive urothelial carcinoma (MIUC). OBJECTIVE: To report updated OS and safety by ctDNA status. DESIGN, SETTING, AND PARTICIPANTS: This ad hoc analysis from a global, open-label, randomized, phase 3 trial (NCT02450331) included intention-to-treat (ITT) population with evaluable cycle 1 day 1 (C1D1) ctDNA samples. INTERVENTION: Atezolizumab (1200 mg every 3 wk) or observation for ≤1 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: OS, relapse rates, and safety by ctDNA status were assessed. RESULTS AND LIMITATIONS: Among 581 of 809 ITT patients included, 214 (37%) were ctDNA positive. Atezolizumab did not improve OS versus observation in ITT patients (hazard ratio [HR] 0.91 [95% confidence interval {CI} 0.73-1.13]; median follow-up 46.8 mo [interquartile range, 36.1-53.6]). In the observation arm, ctDNA positivity versus negativity was associated with shorter OS (HR 6.3 [95% CI 4.3-9.3]). The ctDNA positivity identified patients with an OS benefit favoring atezolizumab versus observation (HR 0.59 [95% CI 0.42-0.83]). A greater reduction in ctDNA levels with atezolizumab (C3D1) was associated with longer OS (100% clearance, 60.0 mo [95% CI 35.5-not estimable]; 50-99% reduction, 34.3 mo [95% CI 15.2-not estimable]; <50% reduction, 19.9 mo [95% CI 16.4-32.2]). The ctDNA positivity at C1D1 + C3D1 was associated with relapse with greater sensitivity than C1D1 alone (68% vs 57%). Adverse events were more frequent with atezolizumab than with observation, regardless of ctDNA status. A study limitation was its exploratory design. CONCLUSIONS: Evidence suggests that ctDNA positivity in MIUC predicts a benefit with atezolizumab. An in-progress prospective study will further evaluate these findings. PATIENT SUMMARY: Among patients with urothelial cancer after surgery, survival was poorer if tumor-derived DNA was detected in their bloodstream; these patients' survival was longer with atezolizumab versus observation. Bloodstream tumor-derived DNA may identify patients who benefit from atezolizumab.

Multiparametric Magnetic Resonance Imaging in Prostate Cancer Screening at the Age of 45 Years: Results from the First Screening Round of the PROBASE Trial.

BACKGROUND: Magnetic resonance imaging (MRI) has been suggested as a tool for guiding biopsy recommendations in prostate cancer (PC) screening. OBJECTIVE: To determine the performance of multiparametric MRI (mpMRI) in young men at age 45 yr who participated in a PC screening trial (PROBASE) on the basis of baseline prostate-specific antigen (PSA). DESIGN, SETTING, AND PARTICIPANTS: Participants with confirmed PSA ≥3 ng/ml were offered mpMRI followed by MRI/transrectal ultrasound fusion biopsy (FBx) with targeted and systematic cores. mpMRI scans from the first screening round for men randomised to an immediate PSA test in PROBASE were evaluated by local readers and then by two reference radiologists (experience >10 000 prostate MRI examinations) blinded to the histopathology. The PROBASE trial is registered as ISRCTN37591328 OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The local and reference Prostate Imaging-Data and Reporting System (PI-RADS) scores were compared, and the sensitivity, negative predictive value (NPV), and accuracy were calculated for both readings for different cutoffs (PI-RADS 3 vs 4). RESULTS AND LIMITATIONS: Of 186 participants, 114 underwent mpMRI and FBx. PC was detected in 47 (41%), of whom 33 (29%) had clinically significant PC (csPC; International Society of Urological Pathology grade group ≥2). Interobserver reliability between local and reference PI-RADS scores was moderate (k = 0.41). At a cutoff of PI-RADS 4, reference reading showed better performance for csPC detection (sensitivity 79%, NPV 91%, accuracy of 85%) than local reading (sensitivity 55%, NPV 80%, accuracy 68%). Reference reading did not miss any PC cases for a cutoff of PI-RADS <3. If PI-RADS ≥4 were to be used as a biopsy cutoff, mpMRI would reduce negative biopsies by 68% and avoid detection of nonsignificant PC in 71% of cases. CONCLUSIONS: Prostate MRI in a young screening population is difficult to read. The MRI accuracy of for csPC detection is highly dependent on reader experience, and double reading might be advisable. More data are needed before MRI is included in PC screening for men at age 45 yr. PATIENT SUMMARY: Measurement of prostate specific antigen (PSA) is an effective screening test for early detection of prostate cancer (PC) and can reduce PC-specific deaths, but it can also lead to unnecessary biopsies and treatment. Magnetic resonance imaging (MRI) after a positive PSA test has been proposed as a way to reduce the number of biopsies, with biopsy only recommended for men with suspicious MRI findings. Our results indicate that MRI accuracy is moderate for men aged 45 years but can be increased by a second reading of the images by expert radiologists. For broad application of MRI in routine screening, double reading may be advisable.

Digital Rectal Examination Is Not a Useful Screening Test for Prostate Cancer.

BACKGROUND: Annual digital rectal examination (DRE) is recommended as a stand-alone screening test for prostate cancer (PCa) in Germany for 45+ yr olds. DRE diagnostic performance in men as young as 45 yr old has not been proved by a screening trial. OBJECTIVE: To determine DRE diagnostic performance in a screening trial. DESIGN, SETTING, AND PARTICIPANTS: This analysis was conducted within the multicentric, randomized PROBASE trial, which enrolled >46 000 men at age 45 to test risk-adapted prostate-specific antigen (PSA) screening for PCa. INTERVENTION: (1) DRE was analyzed as a one-time, stand-alone screening offer at age 45 in 6537 men in one arm of the trial and (2) PCa detection by DRE was evaluated at the time of PSA-screen-driven biopsies (N = 578). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: (1) True-/false-positive detection rates of DRE as compared with PSA screening and (2) DRE outcome at the time of a prostate biopsy were evaluated. RESULTS AND LIMITATIONS: (1) A prospective analysis of 57 men with suspicious DRE at age 45 revealed three PCa. Detection rate by DRE was 0.05% (three of 6537) as compared with a four-fold higher rate by PSA screening (48 of 23 301, 0.21%). The true-positive detection rate by DRE relative to screening by PSA was 0.22 (95% confidence interval [CI] = [0.07-0.72]) and the false-positive detection rate by DRE was 2.2 (95% CI = [1.50-3.17]). (2) Among PSA-screen-detected PCa cases, 86% had unsuspicious DRE (sensitivity relative to PSA was 14%), with the majority of these tumors (86%) located in the potentially accessible zones of the prostate as seen by magnetic resonance imaging. CONCLUSIONS: The performance of stand-alone DRE to screen for PCa is poor. DRE should not be recommended as a PCa screening test in young men. Furthermore, DRE does not improve the detection of PSA-screen-detected PCa. PATIENT SUMMARY: Our report demonstrated the poor diagnostic performance of digital rectal examination in the screening for prostate cancer in young men.

In situ real-time neutron imaging of gaseous H2 adsorption and D2 exchange on carbon-supported Pd catalysts.

We use in situ neutron imaging to observe the adsorption/absorption of hydrogen within a packed catalyst bed of a Pd/C catalyst at a spatial and temporal resolution of ∼430 µm and a ∼9 s respectively. Additionally, the H2/D2 exchange process across the catalyst bed is followed in real time.

Quantum State Assignment Flows.

This paper introduces assignment flows for density matrices as state spaces for representation and analysis of data associated with vertices of an underlying weighted graph. Determining an assignment flow by geometric integration of the defining dynamical system causes an interaction of the non-commuting states across the graph, and the assignment of a pure (rank-one) state to each vertex after convergence. Adopting the Riemannian-Bogoliubov-Kubo-Mori metric from information geometry leads to closed-form local expressions that can be computed efficiently and implemented in a fine-grained parallel manner. Restriction to the submanifold of commuting density matrices recovers the assignment flows for categorical probability distributions, which merely assign labels from a finite set to each data point. As shown for these flows in our prior work, the novel class of quantum state assignment flows can also be characterized as Riemannian gradient flows with respect to a non-local, non-convex potential after proper reparameterization and under mild conditions on the underlying weight function. This weight function generates the parameters of the layers of a neural network corresponding to and generated by each step of the geometric integration scheme. Numerical results indicate and illustrate the potential of the novel approach for data representation and analysis, including the representation of correlations of data across the graph by entanglement and tensorization.

Characterizing the mutational burden, DNA methylation landscape, and proteome of germ cell tumor-related somatic-type malignancies to identify the tissue-of-origin, mechanisms of therapy resistance, and druggable targets.

BACKGROUND: Germ cell tumors (GCT) might undergo transformation into a somatic-type malignancy (STM), resulting in a cell fate switch to tumors usually found in somatic tissues, such as rhabdomyosarcomas or adenocarcinomas. STM is associated with a poor prognosis, but the molecular and epigenetic mechanisms triggering STM are still enigmatic, the tissue-of-origin is under debate and biomarkers are lacking. METHODS: To address these questions, we characterized a unique cohort of STM tissues on mutational, epigenetic and protein level using modern and high-throughput methods like TSO assays, 850k DNA methylation arrays and mass spectrometry. RESULTS AND CONCLUSIONS: For the first time, we show that based on DNA methylation and proteome data carcinoma-related STM more closely resemble yolk-sac tumors, while sarcoma-related STM resemble teratoma. STM harbor mutations in FGF signaling factors (FGF6/23, FGFR1/4) highlighting the corresponding pathway as a therapeutic target. Furthermore, STM utilize signaling pathways, like AKT, FGF, MAPK, and WNT to mediate molecular functions coping with oxidative stress, toxin transport, DNA helicase activity, apoptosis and the cell cycle. Collectively, these data might explain the high therapy resistance of STM. Finally, we identified putative novel biomarkers secreted by STM, like EFEMP1, MIF, and DNA methylation at specific CpG dinucleotides.

[Prostate cancer-multiparametric MRI and alternative approaches in intervention and therapy planning]. / Multiparametrische MRT und alternative Methoden in der Interventions- und Behandlungsplanung beim Prostatakarzinom.

BACKGROUND: In recent years, multiparametric magnetic resonance imaging (mpMRI) of the prostate has gained importance and plays a crucial role in both personalized diagnostics and increasingly in the treatment planning for patients with prostate cancer. OBJECTIVE: The aim of this study is to present established and innovative applications of MRI in the diagnosis and treatment of localized prostate cancer, evaluating their strengths and weaknesses. Furthermore, it will explore alternative approaches and compare them in a comprehensive manner. MATERIALS AND METHODS: A systematic literature review on the application of mpMRI for biopsy and therapy planning was conducted. RESULTS: The integration of modern imaging techniques, especially mpMRI, into the diagnostic algorithm has revolutionized prostate cancer diagnosis. MRI and MRI-guided biopsy detect more significant prostate cancer, with the potential to reduce unnecessary biopsies and the diagnosis of clinically insignificant carcinomas. In addition, MRI provides crucial information for risk stratification and treatment planning in prostate cancer patients, both before radical prostatectomy and during active surveillance. CONCLUSION: Multiparametric MRI offers significant added value for the diagnosis and treatment of localized prostate cancer. The advancement of MRI analysis, such as the implementation of artificial intelligence algorithms, holds the potential for further enhancing imaging diagnostics.

Misuse of tumor marker levels leads to an insufficient International Germ Cell Consensus Classification (IGCCCG) risk group assignment and impaired treatment.

BACKGROUND: Metastatic germ cell tumors of the testis (GCTs) are risk-stratified according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification system. This risk classification is based on anatomical risk factors as well as tumor marker levels of AFP, HCG, and LDH assessed pre-chemotherapy after orchiectomy treatment. An incorrect classification is possible when pre-orchiectomy marker levels are used, possibly resulting in over- or undertreatment of patients. The aim was to investigate the potential frequency and clinical relevance of incorrect risk stratification using pre-orchiectomy tumor marker levels. METHODS: A multicenter registry analysis, including patients with metastasized nonseminomatous GCT (NSGCT), was conducted by investigators of the German Testicular Cancer Study Group (GTCSG). Based on the marker levels at different timepoints, IGCCCG risk groups were calculated. The agreement was tested using Cohen's kappa. RESULTS: A total of 672 of 1910 (35%) patients were diagnosed with metastatic NSGCTs, and 523 (78%) had sufficient data for 224 follow-up data points. By using pre-orchiectomy tumor marker levels, 106 patients (20%) would have been incorrectly classified. Seventy-two patients (14%) were classified into a higher risk category, and 34 patients (7%) were classified into a lower risk category. Cohen's kappa was 0.69 (p < 0.001), showing a strong agreement between the use of both marker timepoints. The treatment of misclassified patients would have resulted in an overtreatment of 72 patients or undertreatment of 34 patients. CONCLUSIONS: The use of pre-orchiectomy tumor marker levels may lead to an incorrect risk classification and might subsequently lead to under- or overtreatment of patients.

Intra-Individual Comparison of Physiologic [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 Uptake in Ganglia in Patients with Prostate Cancer: A Retrospective, Monocentric Analysis.

BACKGROUND: Several studies indicate, particularly in the case of [18F]PSMA-1007, a relatively high rate of detection of ganglia in PSMA PET imaging. Ganglia are an integral part of the sympathetic portion of the autonomous nervous system. To date, no studies have directly compared [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 ganglionic uptake intra-individually and analyzed the underlying molecular and physical mechanisms of different detection rates. With this monocentric retrospective study, we sought to evaluate the intra-individual physiological ganglion uptake of these different PSMA ligands in evidence-based imaging for prostate cancer. METHODS: Our cohort consists of 19 male patients (median age 72 ± 9 with a range of 56-85) with biochemical recurrence of prostate cancer who underwent both [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 PET/CT in our clinic on the same scanner per standard care between March 2015 and March 2022. Tracer uptake was quantified according to maximum standardized uptake value (SUVmax) for both [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 PET/CT scans. Ganglia-to-background ratios (GBRs) were determined to quantify the image contrast through dividing the SUVmax of the ganglia by the background value (SUVmax of blood pool in the descending aorta, fatty tissue, and skeletal muscle in gluteal region). We used descriptive analyses for demographics and tumor characteristics and performed two-way repeated-measures ANOVA (analysis of variance) for SUV metrics including GBR measurements. RESULTS: In total, we examined 101 ganglia with [18F]PSMA-1007 scanning, localized mostly in pairs as stellate, coeliac, and sacral, of which 76 were also detected with [68Ga]Ga-PSMA-11 PET/CT scanning. There was no statistically significant difference in PSMA uptake in terms of SUVmax between [18F]PSMA-1007 and [68Ga]Ga-PSMA-11 (p value: 0.052). In contrast, the comparison of GBRs revealed a higher detectability rate of ganglia with [18F]PSMA-1007 imaging (p < 0.001). Furthermore, a separate comparison of ganglia with respect to their anatomical location also demonstrated statistically significant differences both within and between [18F]PSMA-1007 and [68Ga]Ga-PSMA-11 PET/CT scans. CONCLUSION: Given the impression of more accentuated [18F]PSMA-1007 uptake in ganglia compared with 68Ga-labelled counterparts, our study demonstrated that the better detectability of ganglia is not due to more intense [18F]PSMA-1007 uptake by these small structures but to much more favorable physical properties of the radionuclide 18F. The most relevant limitations of our study are its retrospective design and the small patient cohort.

Adjuvant vs. progression-triggered treatment with gemcitabine in platinum-ineligible high-risk bladder cancer patients: Long-term follow-up of a randomized phase 3 trial.

BACKGROUND: Cisplatin-based chemotherapy (ChT) is the preferred perioperative treatment in muscle-invasive urothelial carcinoma of the urinary bladder (UCUB). Nevertheless, a certain number of patients are ineligible for platinum-based ChT. This trial compared immediate adjuvant vs. delayed gemcitabine ChT at progression in platinum-ineligible patients with high-risk UCUB. METHODS: High-risk platinum-ineligible UCUB patients (n = 115) were randomized 1:1 to adjuvant gemcitabine (n = 59) or gemcitabine at progression (n = 56). Overall survival was analyzed. Additionally, we analyzed progression-free survival (PFS), toxicity and quality of life (QoL). RESULTS: After a median follow-up of 3.0 years (inter quartile range [IQR]: 1.3-11.6), adjuvant ChT did not significantly prolong overall survival (OS) (HR: 0.84; 95% CI: 0.57-1.24; P = 0.375), with 5-year OS of 44.1% (95% CI: 31.2-56.2) and 30.4% (95% CI: 19.0-42.5), respectively. We noted no significant difference in PFS (HR: 0.76; 95% CI: 0.49-1.18; P = 0.218), with 5-year PFS of 36.2% (95% CI: 22.8-49.7) in the adjuvant group and 22.2% (95% CI: 11.5%-35.1%) when treated at progression. Patients with adjuvant treatment showed a significantly worse QoL. The trial was prematurely closed after recruitment of 115 of the planned 178 patients. CONCLUSIONS: There was no statistically significant difference in terms of OS and PFS for patients with platinum-ineligible high-risk UCUB receiving adjuvant gemcitabine compared to patients treated at progression. These findings underline the importance of implementing and developing new perioperative treatments for platinum-ineligible UCUB patients.