Intermediate Risk Classification Research Articles

Trends in Active Surveillance for Men With Intermediate-Risk Prostate Cancer

Initial management of intermediate-risk prostate cancer is evolving, with no clear recommendation for treatment. Data on utilization of active surveillance for patients with newly diagnosed intermediate-risk prostate cancer may help clarify emerging trends. To further characterize US national trends of initial management of intermediate-risk prostate cancer. This cohort study included patients with intermediate-risk prostate cancer diagnosed from January 1, 2010, to December 31, 2020. Eligible patients were diagnosed in US hospitals included in the National Cancer Database; National Comprehensive Cancer Network risk stratification guidelines were used to characterize as favorable vs unfavorable intermediate risk. Analysis was performed in September 2023. Active surveillance vs intervention with surgery and/or radiation or no treatment. Temporal trends in demographic, clinical, and socioeconomic factors among men with intermediate-risk prostate cancer and their association with the use of active surveillance; further subgroup analysis was conducted for those with favorable vs unfavorable intermediate risk classification. In total, 289 584 men diagnosed with intermediate-risk prostate cancer were identified from 2010 to 2020 (46 147 Black [15.9%], 230 071 White [79.5%]). Among patients, 153 726 (53.1%) underwent prostatectomy, 107 152 (37.0%) underwent radiotherapy, and 15 847 (5.5%) underwent active surveillance as initial treatment strategy. Overall, active surveillance quadrupled from 418 of 21 457 patients (2.0%) in 2010 to 2428 of 28 192 patients (8.6%) in 2020 for the entire cohort (P < .001). Active surveillance increased from 317 of 12 858 patients (2.4%) in 2010 to 2020 of 12 902 patients (13.5%) in 2020 in men with favorable intermediate-risk prostate cancer (P < .001). In the unfavorable intermediate-risk cohort, active surveillance increased from 101 of 8181 patients (1.2%) in 2010 to 408 of 12 861 patients (3.1%) in 2020 (P < .001). On multivariable analysis, use of active surveillance was associated with increased age (age 70-80 years vs <50 years: odds ratio [OR], 3.09; 95% CI, 2.66-3.59), lower Gleason score (3 + 3 vs 3 + 4: OR, 3.45; 95% CI, 3.25-3.66), early T stage (T2c vs T1a through T2a: OR, 0.35; 95% CI, 0.32-0.38), treatment at an academic center (community vs academic center: OR, 0.72; 95% CI, 0.67-0.78), higher level of education (communities with 21% or higher population without high school vs less than 7%: OR, 0.73; 95% CI, 0.67-0.79), insurance type (Medicare or other governmental service vs private: OR, 1.11; 95% CI, 1.07-1.16), proximity to treatment facility (greater than 120 miles vs less than 60 miles: OR, 0.75; 95% CI, 0.68-0.84), facility location (South Atlantic vs New England: OR, 0.54; 95% CI, 0.46-0.53), and lower income (less than $38 000 vs $63 000 or greater: OR, 1.22; 95% CI, 1.14-1.31). These findings highlight increasing implementation of active surveillance in the initial management of intermediate risk prostate cancer. Prospective data with improved risk stratification incorporating genomics and digital pathology artificial intelligence as well as novel surveillance strategies may continue to better delineate optimal treatment recommendations in this patient population.

Androgen Deprivation Therapy Use among Intermediate Risk Prostate Cancer Patients Undergoing Radiation Therapy across a Statewide Radiation Oncology Quality Consortium

For men with intermediate (INT) risk prostate cancer, the addition of androgen deprivation therapy (ADT) reduces risk of PSA failure, distant metastasis, and cancer-related mortality. Moreover, the relative reduction in cancer-related adverse outcomes with ADT use appears consistent across all INT risk subgroups. The absolute benefit of ADT, however, varies by baseline risk. In contemporary practice, it is unknown which clinical factors are most strongly associated with intended ADT use. Therefore, we sought to identify such factors within the diverse practices of the Michigan Radiation Oncology Quality Consortium (MROQC). Patients with localized prostate cancer undergoing definitive radiation therapy were enrolled from 6/9/20 to 11/4/22 (n = 599). Standardized patient, physician, and physicist forms were used to collect baseline and follow-up information. Intended ADT use, defined by the treating physician, was prospectively collected and is the primary outcome of this analysis. Univariable (UVA) and multivariable analyses (MVA) associations with patient (age, race, comorbidities), tumor (T stage, Gleason, percent cores positive, and PSA), and practice-related (academic vs private) factors were performed. In addition, advanced modality testing (PET, MRI, and genomic classifiers) was available as of March 2021, and subgroup analysis were performed where appropriate. A total 351 patients across 26 centers were enrolled with INT risk disease. ADT use was intended for 46% of men (n = 162/351) which differed by men with NCCN favorable INT (21%, n = 22/105) vs unfavorable INT risk disease (57%, n = 140/246), p<0.001. Sixty two percent (n = 100/162) had an intended ADT duration of 4-6 months and 21% (n = 34/162) had ≥12 months. Older age was associated with ADT use (70 vs 67, p < 0.01); there were no significant differences by race or comorbidities number. MVA showed Gleason 4+3 (OR 4.61 [2.91 - 7.42]) and > = 50% positive cores (2.56 [1.52 - 4.37]) were significantly associated with ADT use. No significant differences were noted based on practice setting. Pelvic MRI was obtained for 71% of men (n = 197/279), genomic classifiers in 47% (n = 130/279), and PET in 2% (n = 6/282). In the subset with MRI (n = 197), adverse features (ECE, SVI, or equivocal LNs) were associated with intended ADT use (OR 3.0 [1.4 - 7.1]) after adjustment for NCCN favorable/unfavorable INT risk classification. Within a state-wide consortium, intended ADT use for intermediate prostate cancer is most strongly associated with Gleason score, ≥50% positive cores, NCCN unfavorable intermediate risk classification, and adverse features on MRI. Nearly half of men had genomic classifier testing underscoring the importance ongoing trials such as NRG/GU 010.

PD12-10 URINE COMPREHENSIVE GENOMIC PROFILING OF UROTHELIAL CARCINOMA PATIENTS UNDERGOING INTRAVESICAL THERAPY ENABLES DETECTION OF ACTIONABLE DNA MUTATIONS ASSOCIATED WITH DRUG RESPONSE AND RISK STRATIFICATION

You have accessJournal of UrologyCME1 May 2022PD12-10 URINE COMPREHENSIVE GENOMIC PROFILING OF UROTHELIAL CARCINOMA PATIENTS UNDERGOING INTRAVESICAL THERAPY ENABLES DETECTION OF ACTIONABLE DNA MUTATIONS ASSOCIATED WITH DRUG RESPONSE AND RISK STRATIFICATION Goran Rac, Shalin Desai, Hiten D. Patel, Chirag Doshi, Ryan Dornbier, Vincent Caruso, Peter Lentz, Brian C. Mazzarella, Kevin G. Phillips, Trevor Levin, Alan J. Wolfe, and Gopal N. Gupta Goran RacGoran Rac More articles by this author , Shalin DesaiShalin Desai More articles by this author , Hiten D. PatelHiten D. Patel More articles by this author , Chirag DoshiChirag Doshi More articles by this author , Ryan DornbierRyan Dornbier More articles by this author , Vincent CarusoVincent Caruso More articles by this author , Peter LentzPeter Lentz More articles by this author , Brian C. MazzarellaBrian C. Mazzarella More articles by this author , Kevin G. PhillipsKevin G. Phillips More articles by this author , Trevor LevinTrevor Levin More articles by this author , Alan J. WolfeAlan J. Wolfe More articles by this author , and Gopal N. GuptaGopal N. Gupta More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002538.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prediction of intravesical therapy (IVT) response and risk stratification in patients with urothelial carcinoma (UC) remains a challenge. Previous attempts using biomarkers have not gained broad adoption. Urinary comprehensive genomic profiling (uCGP) has significant potential to aid in both quantitative assessment of therapeutic response and risk stratification. METHODS: uCGP was performed on 26 prospectively enrolled patients undergoing IVT induction (BCG=88%, Gemcitabine=12%). Samples were collected after visually complete TURBT immediately prior to IVT instillation. Urine DNA was sequenced and profiled across 60 genes using the CLIA-validated UroAmplitude test (Convergent Genomics). Recurrence predictions were performed using a previously validated algorithm. Subjects were grouped into high, intermediate, and low risk of recurrence. RESULTS: Stage distribution was Tis (15%), Ta (23%), T1 (62%). Mean follow-up after IVT was 22 months. Among samples analyzed, 25% contained no detectable mutations while 75% contained ≥1 high confidence mutation. The high and intermediate risk classification identified 100% of pathologically confirmed recurrence. Among low recurrence risk classifications, no clinical recurrence was identified within follow-up (100% NPV). TP53 mutations were strongly correlated with post-treatment recurrence OR=28, 95%CI (1.99, 394.42), p=0.038. Two subjects had detected aneuploidy post-treatment and had T1 recurrence, supporting earlier observations of aneuploidy correlating with invasive cancer. CONCLUSIONS: uCGP is a quantitative diagnostic with potential to identify therapeutic response. Low risk patients have low mutation burden prior to treatment, intermediate risk have notable disease burden pre-treatment with notable reduction after IVT, and high risk do not respond to treatment. These data suggest that uCGP performed before and after IVT has significant potential to stratify recurrence risk in non-muscle invasive UC patients. Additional studies are underway to further support the generalizability of these findings. Source of Funding: Support for this research is provided by the NCI through a SBIR Grant, 5R44CA200174, provided to Convergent Genomics © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e199 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Goran Rac More articles by this author Shalin Desai More articles by this author Hiten D. Patel More articles by this author Chirag Doshi More articles by this author Ryan Dornbier More articles by this author Vincent Caruso More articles by this author Peter Lentz More articles by this author Brian C. Mazzarella More articles by this author Kevin G. Phillips More articles by this author Trevor Levin More articles by this author Alan J. Wolfe More articles by this author Gopal N. Gupta More articles by this author Expand All Advertisement PDF DownloadLoading ...

Trends in risk classification at diagnosis and choice of primary therapy for prostate cancer: An analysis of 10839 patients from the Nara Urological Research and Treatment Group registry between 2004 and 2015.

To evaluate trends in risk classification at diagnosis and choice of primary therapy in patients diagnosed with prostate cancer. This retrospective study included 10839 patients who were newly diagnosed with prostate cancer between 2004 and 2015 at 23 Japanese institutions. Risk classification and primary therapies between 2004 and 2015 were evaluated. The trends in risk classification and primary therapy were evaluated using chi-squared tests for trend during four periods (2004-2006; 2007-2009; 2010-2012; and 2013-2015). Binary logistic analysis was used to evaluate the extent to which factors such as age, risk classification, and institution influenced primary therapy choice in the 2013-2015 cohort. The number of patients with very-low or low-risk classification (P<0.001) and metastasis (P=0.04) decreased and the number with intermediate-risk classification (P<0.001) increased during the four periods. A tendency to choose radical prostatectomy as primary therapy for prostate cancer was not observed during the four periods (P=0.90). The number of patients who chose radiation therapy (P<0.001) and active surveillance/watchful waiting (P<0.001) as primary therapies increased during the four periods and the number of patients who chose androgen deprivation therapy (P<0.001) decreased. Age, institution, and risk classification significantly influenced primary therapy choice. We have shown the trends in risk classification of prostate cancer and primary therapy choices between 2004 and 2015 in Japan. Age, institution, and risk classification significantly influenced the decision on primary therapy for prostate cancer.

P0931 - Improving intermediate risk classification of prostate cancer with radiomics features

P0931 - Improving intermediate risk classification of prostate cancer with radiomics features

Improvement of the intermediate risk prostate cancer sub-classification by integrating MRI and fusion biopsy features

IntroductionTreatment decision-making for intermediate-risk prostate cancer (CaP) is mainly based on grade and tumor involvement on systematic biopsy. We aimed to assess the added value of multi-parametric magnetic resonance imaging (mpMRI) and targeted biopsy (TB) features for predicting final pathology and for improving the well-established favourable/unfavourable systematic biopsy-based sub-classification. Materials and MethodsFrom a prospective database of 377 intermediate risk CaP cases, we evaluated the performance of the standard intermediate risk classification (IRC), and the predictive factors for unfavourable disease on final pathology aiming to build a new model. Overall unfavourable disease (OUD) was defined by any pT3-4 and/or pN1 and/or grade group (GG) ≥ 3. ResultsThe standard IRC was found to be predictive for unfavourable disease in this population. However, in multivariable analysis regression, ECE on mpMRI and GG ≥3 on TB remained the 2 independent predictive factors for OUD disease (HR = 2.7, P = 0.032, and HR = 2.41, P = 0.01, respectively). By using the new IRC in which unfavorable risk was defined by ECE on mpMRI and/or GG ≥3 on TB, the proportion of unfavorable cases decreased from 62.3% to 34.1% while better predicting unfavorable disease in RP speciments. The new model displayed a better accuracy than the standard IRC for predicting OUD (AUC: 0.66 vs. 0.55). ConclusionsThe integration of imaging and TB features drastically improves the intermediate risk sub-classification performance and better discriminates the unfavourable risk group that could benefit from more aggressive therapy such as neo-adjuvant and/or adjuvant treatment, and the favourable group that could avoid over-treatment. External validation in other datasets is needed.

Abstract P3-08-06: Prognostic value of OncoMasTR: A novel multigene signature based on master transcriptional regulators

Abstract Background Multigene prognostic signatures (MGPS) enable identification of candidate patients for treatment de-escalation in early stage breast cancer (BC). Here we present OncoMasTR, a MGPS for classifying the risk of distant metastasis (DM) in ER-positive, HER2-negative BC patients with up to 3 involved lymph nodes (LNs). OncoMasTR was discovered via a novel transcriptional network analysis methodology that identified genes that regulate previously identified prognostic biomarkers. These upstream genes, termed master transcriptional regulators (MTRs), were shown to provide improved prognostic performance compared with downstream genes. OncoMasTR has been mechanistically verified by RT-qPCR, immunohistochemistry and chromatin immunoprecipitation. OncoMasTR has been further trained to include clinicopathological information (CPI) to maximise its prognostic performance. Methods Two independent sample sets: 225 patients from Malmö University Hospital and 100 patients from Skåne University Hospital were used for training, cross-validation and refinement of OncoMasTR. RNA extracted from 225 archived tissues was analysed by RT-qPCR to measure the expression levels of the MTRs. Statistical models of all possible combinations of MTRs were trained and cross-validated (1,000 times x 2-fold) using the first set of 225 samples. Statistical models with the best cross-validated performance were further evaluated on RT-qPCR data from the second independent set of 100 samples. Robustness of the data was verified by assessing the reproducibility of OncoMasTR across 6 days, using 6 unique kit lots, conducted by 4 operators on 3 RT-qPCR instruments. Results In the first training set of 225 patients, OncoMasTR classified up to 72% of LN0 patients and 58% of LN0-3 patients as low risk, with ≤ 5.0% DM within each group. When incorporating CPI, its prognostic performance further improved to a c (concordance) index &amp;gt; 0.8. Results showed that the OncoMasTR molecular score and CPI add statistically significant prognostic value to each other. In the independent verification set, all patients with DM were correctly classified as high risk (p&amp;lt;0.01). In relation to reproducibility, the OncoMasTR test displayed robust performance; the molecular score coefficient of variation was 2.6% across days, kit lots, operators and instruments. Individual MTR assays demonstrated linearity over &amp;gt;2000-fold RNA input range and PCR efficiencies ranged from 92% to 101%. Conclusions OncoMasTR development and verification results show analytical robustness and clinically accurate risk stratification. Furthermore, OncoMasTR's binary classification of risk avoids an ambiguous intermediate risk classification and has potential to provide clinicians with useful, actionable information to support treatment decisions. The OncoMasTR test is now ready for large-scale clinical validation. Citation Format: Barron S, Jirström K, Jernström H, Ingvar C, Moran B, Wang C-JA, Loughman T, Fender B, Dynoodt P, Lopez-Ruiz C, Russell N, Gallagher WM. Prognostic value of OncoMasTR: A novel multigene signature based on master transcriptional regulators [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-08-06.

Genexpressionsbasierte Risikoscores

The decoding of the human genome and its targeted analysis using different techniques has raised great hopes encompassing improvement in the estimation of prognosis and prediction of treatment as well as the identification of new therapeutic targets. The gene expression analysis and identification of appropriate predictive and/or prognostic gene expression signatures is a paradigm for this process. Great expectations have been placed on these new molecular markers, however, there are numerous methodological and clinical questions which need to be determined in prospective, randomized studies but which are currently in the recruiting stage. It is very much the question as to whether the new gene expression-based risk scores will bring any information gain in comparison to classical histopathology markers. However, these studies also begin to show that not only the identification of a high risk subgroup, but also reducing the risk by a specific treatment is possible. As yet it is not clear whether the practical application of this test system will actually be applicable in clinical practice.Only molecular tests which allow a dichotomous result are helpful in clinical decision-making in contrast to an intermediate risk classification which does not provide further information and only leads to uncertainty for patients and therapists. Global molecular test methods will gain in importance in the future with regards to identification of new predictive markers, because for many new substances it is not known for which patient subgroups they can be used with highest treatment success.

Comparative performance of subclinical atherosclerosis tests in predicting coronary heart disease in asymptomatic individuals

The prognostic performance of subclinical atherosclerosis in predicting coronary heart disease (CHD) needs to be clarified because of the existence of many non-invasive tests available for its detection in the clinical setting: ultrasound measurement of carotid intima-media thickness (IMT) and plaque, cardiac computed tomography assessment of coronary artery calcium, Doppler stethoscope measurement of ankle-arm index pressure (AAI), and mechanographic or Doppler determination of aortic pulse wave velocity (PWV). Data analysis of the main prospective studies in asymptomatic populations allows the establishment of a dose-response relationship between subclinical atherosclerosis burden and cumulative incidence of future CHD event (absolute risk). Negative subclinical atherosclerosis testing conveys a low 10-year CHD risk inferior to 10% whatever the test considered, i.e. IMT less than the 1st tertile or 1st quintile, AAI > or = 0.90, PWV less than the first tertile, no discernible carotid plaque, or zero coronary calcium score. Positive testing for IMT (>95th percentile or 5th quintile), AAI (<0.90), or PWV (>3rd tertile) conveys a moderately high 10-year CHD risk between 10 and 20%. Positive testing for carotid plaque (focal protrusion >1.5 mm or mineralization) or coronary calcium (total score >300 or 400 units) conveys a high 10-year CHD risk superior to 20%. Therefore, positive subclinical atherosclerosis measurement seems to have its place in the context of existing prediction models, namely for intermediate risk classification. It also remains to be established whether individuals with negative subclinical atherosclerosis may be considered at low CHD risk and receive conservative management.