Simulation of the effects of molecular urine markers in follow-up of patients with high-risk non-muscle invasive bladder cancer.

A plethora of urine markers for the management of patients with bladder cancer has been developed and studied in the past. However, the clinical impact of urine testing on patient management remains obscure. The goal of this manuscript is to identify scenarios for the potential use of molecular urine markers in the follow-up of patients with high-risk non-muscle-invasive BC (NMIBC) and estimate potential risks and benefits. Information on the course of disease of patients with high-risk NMIBC and performance data of a point-of-care test (UBC rapid™), an MCM-5 directed ELISA (ADXBLADDER™), and 2 additional novel assays targeting alterations of mRNA expression and DNA methylation (Xpert bladder cancer monitor™, Epicheck™) were retrieved from high-quality trials and/or meta-analyses. In addition, the sensitivity of white light cystoscopy (WLC) and the impact of a urine marker result on the performance of WLC were estimated based on fluorescence cystoscopy data and information from the CeFub trial. This information was applied to different scenarios in patient follow-up and sensitivity, estimated number of cystoscopies, and the numbers needed to diagnose were calculated. The sensitivity of guideline-based regular follow-up (SOC) at 1 year was calculated at 96%. For different marker-supported strategies sensitivities ranging from 77% to 97.9% were estimated. Calculations suggest that several strategies are effective for the SOC. While for the SOC 24.6 WLCs were required to diagnose 1 tumor recurrence (NND), this NND dropped below 5 in some marker-supported strategies. Based on the results of this simulation, a marker-supported follow-up of patients with HR NMIBC is safe and offers the option to significantly reduce the number of WLCs. Further research focusing on prospective randomized trials is needed to finally find a way to implement urine markers into clinical decision-making.

Real-world treatment of metastatic hormone-sensitive prostate cancer in the USA, Europe and Asia.

Aim: To characterize real-world patients with metastatic hormone-sensitive prostate cancer (mHSPC) and treating physicians and evaluate treatment trends and baseline concordance versus guidelines internationally. Materials & methods: Retrospective, cross-sectional data from the Ipsos Global Oncology Monitor database 2018-2020 were used for descriptive analysis of mHSPC patients, treating physicians and treatment utilization. Results: Among the 6198 mHSPC patients from five countries, the most common treatment was either androgen deprivation therapy (ADT) monotherapy or first-generation androgen receptor inhibitor + ADT. Second-generation androgen receptor inhibitor use was only initiating but increasing over the study period. Conclusion: Despite contemporaneous guidelines recommending treatment intensification of ADT in combination with novel antihormonals or docetaxel, 76.1% of reported mHSPC patients received non-guideline-concordant care.

Prostate cancer is the second most common cancer among men worldwide and a leading cause of cancer-related death globally. Metastatic hormone-sensitive prostate cancer (mHSPC) refers to the stage of prostate cancer where it has spread to other parts of the body ('metastatic') but still responds to hormonal therapy ('hormone-sensitive'), such as androgen deprivation therapy (ADT). Treatment guidelines around the world for men with mHSPC have changed over time, but there remains a lack of understanding of how well guidelines are followed in real-world practice. Consequently, this study analyzes real-world data from five countries between 2018 and 2020 to understand treatment patterns, baseline concordance versus guidelines and potential drivers of treatment trends. The study found prevalent use of ADT monotherapy and older antihormonal agents, and only marginal but increasing use of novel antihormonals in real-world practice. These practices deviate from guidelines from the study period, which generally recommended ADT combination with either newer antihormonal agents or docetaxel for patients with mHSPC. Overall, the proportion of the 6198 patients treated with non­guideline-concordant therapies was 76.1%. Since guideline-recommended care is associated with better outcomes, this baselining finding highlights the need for appropriate treatment selection and intensification for mHSPC patients.

Sunitinib for metastatic renal cell carcinoma: Real world data from the STAR-TOR registry and detailed literature review.

INTRODUCTION: We evaluated the effectiveness and safety profile of the tyrosine kinase inhibitor Sunitinib in patients with advanced or metastatic renal cell carcinoma (a/mRCC) in a real-world setting. METHODS: We analyzed data of adult a/mRCC patients treated with Sunitinib. Data was derived from the German non-interventional post-approval multicenter STAR-TOR registry (NCT00700258). Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated using descriptive statistics and survival analyses for the entire cohort and patient subgroups. RESULTS: A total of 116 study sites recruited 702 patients treated with Sunitinib (73.1% male; median age 68.0 years; median Karnofsky Index 90%) between November 2010 and May 2020. The most frequent histological subtype was clear cell RCC (ccRCC) (81.6%). Sunitinib was administered as first-line treatment in 83.5%, as second line in 11.7%, and as third line or beyond in 4.8% of the patients. Drug related AEs and serious AEs were reported in 66.3% and 13.9% of the patients, respectively (most common AE: gastrointestinal disorders; 39.7% of all patients). CONCLUSIONS: This study adds further real-world evidence of the persisting relevance of Sunitinib for patients with a/mRCC who cannot receive or tolerate immune checkpoint inhibitors. The study population includes a high proportion of patients with unfavorable MSKCC poor-risk score, but shows still good PFS and OS results, while the drug demonstrates a favorable safety profile.

[Geriatric assessment - What should be done and considered before starting therapy of mHSPC and mCRPC?] / Geriatrisches Assessment ­ Was sollte vor Therapiebeginn des mHSPC und des mCRPC gemacht und bedacht werden?

The systemic treatment of prostate cancer nowadays is predominantly carried out with combination therapies. A range of aspects should be respected in older and comorbid patients, in order to avoid toxicities and to achieve a successful therapy alongside good quality of life. The definition of geriatric patients is not primarily based on chronological age but rather on the overall health condition and life expectancy. Comorbid patients > 70 years should undergo a three-step geriatric screening before treatment initiation. If the G8 screening and/or mini-COG shows abnormalities (taking into account nutrition, comorbidity/medication, mobility, and cognition), a simplified geriatric assessment is recommended. Patients can then be stratified into three groups (fit, vulnerable, frail). Only a few cases warrant a complete geriatric assessment. Treatable deficits in the above mentioned domains should be improved if possible. When choosing a systemic therapy, fit patients can be treated the same as non-geriatric patients. Vulnerable and frail patients are under a higher risk for toxicities, so special care should be taken. While the diverse substances of hormonal therapy are usually well tolerated (even though some substance-specific toxicities can occur), haematotoxic substances such as taxanes or olaparib can only be recommended in select cases. As falls - especially under hormonal therapy - are a common problem, osteoprotective therapy should especially be considered. Upon progression of the tumour disease, there should not be a reflex to simply switch to the next line of treatment, but an individual concept should be established together with the patient and his relatives, taking into account aspects of palliative care and patient needs and focussing on quality of life and also setting therapy limitations.

[Individualized precision medicine]. / Individualisierte Präzisionsmedizin.

Spectacular advances have been made in personalized medicine , which has rapidly revolutionized our traditional understanding of disease diagnosis and treatment. Molecular testing of tissue and liquid samples using next generation sequencing has developed into a key technology in this scenario. It can be used for both the determination of biomarkers for diagnostic, prognostic and predictive purposes, as well as the possible improvement of treatment outcome through the use of targeted therapies and the avoidance of therapies in the event of special resistance situations. In addition to drugs that have already been approved, which among other things intervene in cellular DNA repair, many new drugs have been developed and are in clinical testing. Furthermore, new possibilities in molecular imaging have dramatically expanded our understanding of tumor spread and created new approaches for targeted therapies.

[Another encroachment on our liberal profession-The German Federal Ministry of Health continues to stubbornly ignore the self-government]. / Ein weiterer Eingriff in unsere Freiberuflichkeit ­ das Bundesgesundheitsministerium ignoriert weiter hartnäckig die Selbstverwaltung.

Overall, the German healthcare system is shaped by numerous players and institutions. With the state medical associations as public corporations for self-governance and the Heilberufsgesetz (German Health Professions Act), professional practice, professional representation and professional jurisdiction are regulated at the state level. The Joint Federal Committee ("Gemeinsame Bundesausschuss"), the highest decision-making body of joint self-governance in the German health care system, plays a central role. Practicing a liberal profession is intended to guarantee an undisturbed physician-patient relationship. Neither in hospitals nor in outpatient care can medical care be separated from economic constraints, but the fundamental binding of medical care to pure service catalogs leads to mismanagement. The goal of the hospital reform proposals currently being developed by the German Federal Ministry of Health is to avoid unnecessary hospital closures and to ensure high-quality care throughout the country, even in rural regions. In the age of strict separation of outpatient and inpatient care, the diagnosis-related group (DRG) system has primarily led to services migrating to the inpatient sector. It may no longer be possible to offer all continuing education courses at all continuing education centers following a reform of the care structure.

Sarcopenia assessments as predictors of overall survival in patients with metastatic renal cell carcinoma.

BACKGROUND: Sarcopenia represents an important prognostic marker in tumor patients. However, measurement methods and threshold values are not uniformly defined. The aim of this study is therefore to determine the prognostic value of current definitions of sarcopenia in patients with metastatic renal cell carcinoma treated with tyrosine-kinase-inhibitors (TKIs). METHODS: In 93 patients with metastatic renal cell carcinoma, sarcopenia was assessed based on manually assisted software measurements of sarcopenia indices based on different muscle areas. Whole muscle area and psoas muscle area at L3 were estimated and adjusted to patient's height in routine CT imaging before the start of first-line TKI therapy. The correlation of different sarcopenia definitions to overall survival was investigated in a univariate analysis as well as in a multivariate analysis. RESULTS: The mean patients' age at inclusion was 65.8 years (21-86 years). Median survival was 12.3 months (IQR: 5.7-29.8 months), and mean survival was 18.8 months (SD: 17.2 months). As the definitions of sarcopenia differ considerably, 7.6% to 96.7% of the patients were classified as sarcopenic. In univariate analysis, sarcopenia was significantly associated with overall survival. Multivariate analysis, taking into account the Memorial Sloan Kettering Cancer Center risk score, revealed that some sarcopenia-indices are additional and independent prognostic markers. The risk of death was approximately doubled in sarcopenic patients. CONCLUSIONS: Sarcopenia is an important prognostic factor in patients with metastatic renal cell carcinoma treated with TKIs. Multivariate analysis demonstrates a doubling of the risk of death in sarcopenic patients. The assessment of sarcopenia can be performed by the analysis of routine staging imaging using indices of the total muscle area or the psoas muscle area.

25 years International Bladder Cancer Network (IBCN): The past, the present, and the future.

In 1997 an international group of scientists organized a meeting in Barcelona, Spain, to discuss the use of biomarkers in the management of patients with bladder cancer. This meeting was the offspring of an - initially informal - group that finally resulted in the foundation and incorporation of the International Bladder Cancer Network (IBCN) e.V. in 2005. Over the years the group has supported several research initiatives and generated several recommendations on the use of biomarkers in the diagnosis and treatment of bladder cancer. Meeting quality was generated by inviting experts presenting state-of-the-art lectures or work in progress reports, interdisciplinarity and the limited number of participants supporting an open and personal exchange resulted in a format increasingly attracting participants from all over the world. The recent limitations caused by the Covid-19 pandemic were partially met by organizing several well attended webinars. The future challenge is to maintain the IBCN meeting spirit despite an increasing interest of the scientific community and industrial partners to participate. However, the integration of and interaction between increasingly more specialized disciplines is a challenge that can be better catalyzed by an international multidisciplinary network than mostly national professional associations.

Discriminative capacity of guideline recommendations in the assessment of patients with asymptomatic microhematuria.

BACKGROUND & OBJECTIVE: Asymptomatic microhematuria (aMh) remains a diagnostic challenge in urological practice: while aMh is a risk factor of urothelial carcinoma (UC), prevalence of aMh is high. Guidelines were developed to permit risk stratification and reduce diagnostic workload. This study investigates the efficacy of several recommendations. MATERIAL & METHODS: Sixty hundred eight patients with newly diagnosed aMh without previous UC from an academic referral center (A; n = 320) and a private outpatient clinic (B; n = 288) were included. All patients underwent clinical workup including medical history, urine cytology, upper tract imaging and cystoscopy. Eleven former and current guidelines were applied to each patient individually; every patient was classified as either low risk (no further workup recommended) or high risk. Furthermore, a recently developed nomogram for hematuria assessment was included. RESULTS: The cohort comprised 142 females and 466 males (mean age 62 [range 18-92] years). Sixty-one patients (10.0%) were diagnosed with UC. Excluding the Swedish and recent NICE guideline generally advising against urologic workup, application of 9 other recommendations would have diagnosed all UCs and saved 1.6% to 16.1% of patients from workup. For the 2020 US guideline, solely applied to cohort B, 10.6% of patients were classified as low risk. The use of the nomogram would have saved 17.1% to 25% of patients from workup. CONCLUSIONS: Practical relevance of current guidelines is limited as they do not sufficiently identify patients not requiring clinical work up. Thus, guideline adherence may trigger overdiagnosis and even overtreatment. New ways of risk stratification are needed to improve aMh assessment.

Lifestyle aspects in a contemporary middle-European cohort of patients undergoing androgen deprivation therapy for advanced prostate cancer: data from the non-interventional LEAN study.

Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) is associated with significant side effects. With the transition of PCa from a foudroyant course to a chronic disease, managing these side effects has become increasingly important. There is growing evidence that nutritional changes and physical activity are beneficial in these patients. Here we examine the impact of written patient information on the physical activity and dietary habits of PCa patients receiving ADT and behaviour changes between baseline and 1 year, in the open-label, non-interventional LEAN study. In total, 959 patients with advanced hormone-sensitive PCa requiring ADT with the Leuprorelin Sandoz® implant were included from January 2014 to July 2015 and followed for ≥ 12 months. At the start of the study, urologists received a questionnaire concerning the written information provided to patients regarding their disease, patient advocacy groups, diet and physical activity. Patients received a questionnaire on their dietary habits and physical activity at the start and end of the study. Urologists from 147 study centres and 540 patients responded to the questionnaires. While 69 % of these patients received disease-specific information, only 30 % and 17 % received information regarding nutrition and physical activity, respectively. The majority of urologists estimate that their patients rarely or never follow guidance on nutrition or physical activity, yet > 90 % of patients indicate they would make use of this information, if provided. Few patients showed behavioural changes between baseline and 1 year without evident differences between patients that received information and those that did not.

The Non-Interventional PAZOREAL Study to Assess the Effectiveness and Safety of Pazopanib in a Real-Life Setting: Reflecting a Changing mRCC Treatment Landscape.

The approval of tyrosine kinase inhibitors and checkpoint inhibitors represented a remarkable progression in the therapeutic landscape for the treatment of metastatic renal cell carcinoma (mRCC). Yet, in the ever-evolving landscape of mRCC treatment, real-world data on these agents, including pazopanib, are scarce. The non-interventional PAZOREAL study investigated the effectiveness and safety of pazopanib (first-line), nivolumab (second-line), and everolimus (second- and third-line) in a real-life setting. The multicentric study included 376 mRCC patients who received first-line treatment with pazopanib and assessed time on the drug (primary endpoint), overall survival, best responses, disease control rates, as well as safety signals and health-related quality of life. The median overall time on the drug was 10.0 months, with first-line pazopanib having a median time on drug of 6.3 months. The median overall survival was 35.9 months. The disease control rate for first-line pazopanib was 56.9%. No new safety signals were detected. PAZOREAL provides valuable real-world data for first-line treatment with pazopanib.

Cell-Free DNA Sequencing Reveals Gene Variants in DNA Damage Repair Genes Associated with Prognosis of Prostate Cancer Patients.

In the present study, we further analyzed the data obtained in our previous study, where we investigated the cell-free DNA (cfDNA) of 34 progressive prostate cancer patients via targeted sequencing. Here, we studied the occurrence and prognostic impact of sequence variants according to their clinical pathological significance (CPS) or their functional impact (FI) in 23 DNA damage repair (DDR) genes with a focus on the ATM serine/threonine kinase gene (ATM). All patients had at least one DDR gene with a CPS or FI variant. Kaplan-Meier analysis indicated that the group with a higher number of CPS variants in DDR genes had a shorter time to treatment change (TTC) compared to the group with a lower number of CPS variants (p = 0.038). Analysis of each DDR gene revealed that CPS variants in the ATM gene and FI variants in the nibrin (NBN) gene showed a shorter TTC (p = 0.034 and p = 0.042). In addition, patients with CPS variants in the ATM gene had shorter overall survival (OS; p = 0.022) and disease-specific survival (DSS; p = 0.010) than patients without these variants. Interestingly, patients with CPS variants in seven DDR genes possessed a better OS (p = 0.008) and DSS (p = 0.009), and patients with FI variants in four DDR genes showed a better OS (p = 0.007) and DSS (p = 0.008). Together, these findings demonstrated that the analysis of cfDNA for gene variants in DDR genes provides prognostic information that may be helpful for future temporal and targeted treatment decisions for advanced PCa patients.

New Oral Antitumor Drugs and Medication Safety in Uro-Oncology: Implications for Clinical Practice Based on a Subgroup Analysis of the AMBORA Trial.

Oral antitumor therapeutics (OAT) bear a high risk for medication errors, e.g., due to drug-drug or drug-food interactions or incorrect drug intake. Advanced age, organ insufficiencies, and polymedication are putting uro-oncological patients at an even larger risk. This analysis sets out to (1) investigate the frequency and relevance of medication errors in patients with prostate cancer or renal cell carcinoma treated with OAT and (2) compile recommendations for clinical practice. This post-hoc subgroup analysis used data collected in the randomized AMBORA trial (2017-2020; DRKS00013271). Clinical pharmacologists/pharmacists conducted advanced medication reviews over 12 weeks after initiation of a new oral regimen and assessed the complete medication process for drug-related problems. Medication errors related to either the OAT, prescribed or prescription-free concomitant medication, or food were classified regarding cause and severity. We identified 67 medication errors in 38 patients within the complete medication within 12 weeks. Thereof, 55% were detected at therapy initiation, 27% were caused by the patients, and 25% were drug-drug or drug-food interactions. Problem-prone issues are summarized in a 'medication safety table' to provide recommendations for clinical practice in uro-oncology. Tailored strategies including intensified care by clinical pharmacologists/pharmacists should be implemented in clinical practice to improve medication safety.

Analysis of the Impact of Clinical Factors on Low-Intensity Extracorporeal Shockwave Therapy for Erectile Dysfunction.

INTRODUCTION: Predictive factors for the treatment success of low-intensity extracorporeal shockwave therapy (Li-ESWT) for erectile dysfunction (ED) are still under debate. METHODS: Li-ESWT was performed in 50 patients suffering from ED by applying 3,000 shock waves once a week over a period of 6 weeks. Treatment success was defined as an increase in the International Index of Erectile Function 5 (IIEF-5) score by ≥5 points or an Erectile Hardness Score (EHS) of ≥3 points. IIEF-5 and EHS were measured at baseline and at 3 and 6 months of follow-up. RESULTS: Treatment success according to either the IIEF-5 score or EHS at any time of follow-up was achieved in 28 patients (56%). Twenty-five patients (50%) experienced an improvement during the first 3 months, which lasted for 6 months in 8 cases (16%). Three patients reported improved erectile function only after 6 months. When stratifying the cohort with regard to potential influencing factors, a significantly improved IIEF-5 score could be achieved in men with cardiovascular risk factors (p = 0.026) and in men with antihypertensive medication (p = 0.009). Men without cardiovascular risk factors showed no therapeutic benefit from Li-ESWT. DISCUSSION/CONCLUSION: Li-ESWT is a valid but often short-lived treatment option for ED, especially in men with cardiovascular risk factors or controlled hypertension. Future studies should assess the feasibility and safety of repeated applications of Li-ESWT.

A Prospectivly Randomized Phase-II Trial of Axitinib versus Everolimus as Second-Line Therapy in Metastatic Renal Cell Carcinoma (BERAT Study).

INTRODUCTION: Inhibition of neo-angiogenesis is a cornerstone of medical treatment in metastatic renal cell carcinoma (mRCC). While 1st line therapies were previously dominated by inhibitors of the vascular endothelial growth factor axis, 2nd line options were less clearly defined. We investigated the role of everolimus (EVE) or a tyrosine kinase inhibitor (TKI) in 2nd line treatment of mRCC patients. METHODS: Key inclusion criteria were measurable mRCC, ECOG 0-1, IMDC risk: good or intermediate and adequate organ function. Patients who progressed on or were intolerant to bevacizumab + interferon were subject for randomization between TKI and EVE treatment. Cross-over occurred at time of progression during 2nd line treatment. Improvement of 2nd line progression-free survival (PFS) rate (PFR) at 6 months from 50% to 65% was the primary endpoint. Secondary endpoints were PFS, total PFS, objective response rate (ORR), overall survival (OS), safety, and patient reported outcomes. RESULTS: In 2012-2015, a total of 22 patients were included. The study was stopped for poor accrual. Ten patients (46%) were randomized to receive 2nd line treatment with EVE (n = 5) or axitinib (n = 4)/sunitinib (n = 1). ECOG 0 was recorded in 20% (EVE) and 60% (TKI). Severe adverse events occurred in approx. 60% in each arm. ORR was 1/5 (20%) for TKI and 0/5 (0%) for EVE. PFR at 6 months was 20% in each arm. Median PFS was 3.7 months (EVE) and 2.2 months (TKI) (hazard ratio [HR] 1.0 [95% confidence interval [CI]: 0.26-3.85]). The OS was comparable between arms HR 1.12 (95% CI: 0.27-4.61). CONCLUSION: The rapid change of the treatment landscape, the limited use of bevacizumab and interferon in 1st line and the duration of 1st line treatment jeopardized BERAT trial recruitment. The small number of patients is a major limitation of our trial. Our observation indicated the poor prognosis in progressive patients and the limited efficacy of TKI or mTOR inhibitors in 2nd line treatment.

Geriatric Assessments Can Predict Functional Outcome and Mortality after Urological Tumor Surgery.

INTRODUCTION: Older patients undergoing major urological tumor surgery are at severe risk of functional deterioration, complications, and mortality. We prospectively evaluated geriatric assessment tools and developed a novel easy-to-use assessment tool for clinical use. METHODS: In 159 patients, geriatric assessment tools were used prior to cystectomy, prostatectomy, and renal tumor surgery, and their peri- and postoperative courses were recorded. Using all the tests, a short and easy-to-use assessment tool was developed, and nomograms were generated to predict functional outcomes and mortality. RESULTS: Of all the patients, 13.8% underwent radical cystectomy, 37.7% underwent radical prostatectomy, and 48.4% underwent tumor surgery of the kidney at the age of 70 years or older. The average age was 75.6 years. Incomplete functional recovery at day 30 and day 180 was observed in 37.7% and 36.1% of the patients, respectively, and incomplete functional recovery was associated with impaired mobility, previous care dependency, frailty, comorbidities, and a high ASA score. The only predictor for high-grade complications was comorbidities, whereas mortality was associated with the geriatric screening tool scores, impaired mobility, preoperative care dependency, and comorbidities. The Erlangen Index (EI), a combination of the selected assessment tools, showed a good prediction of early (p = 0.002) and medium-term (p = 0.002) functional outcomes and mortality (p = 0.001). CONCLUSION: Our prospective evaluation confirms the high risk of incomplete functional recovery, high-grade complications, and mortality in older patients undergoing major urological tumor surgery. The EI is an easy-to-use preoperative assessment tool and therefore should be used in preoperative patient counseling.

Cell-Free DNA Variant Sequencing Using Plasma and AR-V7 Testing of Circulating Tumor Cells in Prostate Cancer Patients.

Prostate cancer (PCa) is the second most common malignant cancer and is a major cause of morbidity and mortality among men worldwide. There is still an urgent need for biomarkers applicable for diagnosis, prognosis, therapy prediction, or therapy monitoring in PCa. Liquid biopsies, including cell-free DNA (cfDNA) and circulating tumor cells (CTCs), are a valuable source for studying such biomarkers and are minimally invasive. In our study, we investigated the cfDNA of 34 progressive PCa patients, via targeted sequencing, for sequence variants and for the occurrence of CTCs, with a focus on androgen receptor splice variant 7 (AR-V7)-positive CTCs. The cfDNA content was associated with overall survival (OS; p = 0.014), disease-specific survival (DSS; p = 0.004), and time to treatment change (TTC; p = 0.001). Moreover, when considering all sequence variants grouped by their functional impact and allele frequency, a significant association with TTC (p = 0.017) was observed. When investigating only pathogenic or likely pathogenic gene variants, variants of the BRCA1 gene (p = 0.029) and the AR ligand-binding domain (p = 0.050) were associated with a shorter TTC. Likewise, the presence of CTCs was associated with a shorter TTC (p = 0.031). The presence of AR-V7-positive CTCs was associated with TTC (p < 0.001) in Kaplan-Meier analysis. Interestingly, all patients with AR-V7-positive CTCs also carried TP53 point mutations. Altogether, analysis of cfDNA and CTCs can provide complementary information that may support temporal and targeted treatment decisions and may elucidate the optimal choice within the variety of therapy options for advanced PCa patients.

Thrombospondin-2 and LDH Are Putative Predictive Biomarkers for Treatment with Everolimus in Second-Line Metastatic Clear Cell Renal Cell Carcinoma (MARC-2 Study).

There is an unmet need for predictive biomarkers in metastatic renal cell carcinoma (mRCC) therapy. The phase IV MARC-2 trial searched for predictive blood biomarkers in patients with predominant clear cell mRCC who benefit from second-line treatment with everolimus. In an exploratory approach, potential biomarkers were assessed employing proteomics, ELISA, and polymorphism analyses. Lower levels of angiogenesis-related protein thrombospondin-2 (TSP-2) at baseline (≤665 parts per billion, ppb) identified therapy responders with longer median progression-free survival (PFS; ≤665 ppb at baseline: 6.9 months vs. 1.8, p = 0.005). Responders had higher lactate dehydrogenase (LDH) levels in serum two weeks after therapy initiation (>27.14 nmol/L), associated with a longer median PFS (3.8 months vs. 2.2, p = 0.013) and improved overall survival (OS; 31.0 months vs. 14.0 months, p < 0.001). Baseline TSP-2 levels had a stronger relation to PFS (HR 0.36, p = 0.008) than baseline patient parameters, including IMDC score. Increased serum LDH levels two weeks after therapy initiation were the best predictor for OS (HR 0.21, p < 0.001). mTOR polymorphisms appeared to be associated with therapy response but were not significant. Hence, we identified TSP-2 and LDH as promising predictive biomarkers for therapy response on everolimus after failure of one VEGF-targeted therapy in patients with clear cell mRCC.