Pretreatment Risk Stratification Research Articles

Prediction of Response to FDA-Approved Targeted Therapy and Immunotherapy in Acute Lymphoblastic Leukemia (ALL).

Acute lymphoblastic leukemia (ALL) represents the predominant cancer in pediatric populations, though its occurrence in adults is relatively rare. Pre-treatment risk stratification is crucial for predicting prognosis. Important factors for assessment include patient age, white blood cell (WBC) count at diagnosis, extramedullary involvement, immunophenotype, and cytogenetic aberrations. Minimal residual disease (MRD), primarily assessed by flow cytometry following remission, plays a substantial role in guiding management plans. Over the past decade, significant advancements in ALL outcomes have been witnessed. Conventional chemotherapy has remarkably reduced mortality rates; however, its intensive nature raises safety concerns and has led to the emergence of treatment-resistant cases with recurrence of relapses. Consequently, The U.S. Food and Drug Administration (FDA) has approved several novel treatments for relapsed/refractory ALL due to their demonstrated efficacy, as indicated by improved complete remission and survival rates. These treatments include tyrosine kinase inhibitors (TKIs), the anti-CD19 monoclonal antibody blinatumomab, anti-CD22 inotuzumab ozogamicin, anti-CD20 rituximab, and chimeric antigen receptor (CAR) T-cell therapy. Identifying the variables that influence treatment decisions is a pressing necessity for tailoring therapy based on heterogeneous patient characteristics. Key predictive factors identified in various observational studies and clinical trials include prelymphodepletion disease burden, complex genetic abnormalities, and MRD. Furthermore, the development of serious adverse events following treatment could be anticipated through predictive models, allowing for appropriate prophylactic measures to be considered. The ultimate aim is to incorporate the concept of precision medicine in the field of ALL through valid prediction platform to facilitate the selection of the most suitable treatment approach.

Biomarkers for Pre-Treatment Risk Stratification of Prostate Cancer Patients: A Systematic Review.

Prostate cancer (PCa) is one of the most frequently occurring malignancies. Although most cases are not life-threatening, approximately 20% endure an unfavorable outcome. PSA-based screening reduced mortality but at the cost of an increased overdiagnosis/overtreatment of low-risk (lrPCa) and favorable intermediate-risk (firPCa) PCa. PCa risk-groups are usually identified based on serum Prostate-Specific Antigen (PSA), the Gleason score, and clinical T stage, which have consistent although variable specificity or subjectivity. Thus, more effective and specific tools for risk assessment are needed, ideally making use of minimally invasive methods such as liquid biopsies. In this systematic review we assessed the clinical potential and analytical performance of liquid biopsy-based biomarkers for pre-treatment risk stratification of PCa patients. Studies that assessed PCa pre-treatment risk were retrieved from PubMed, Scopus, and MedLine. PCa risk biomarkers were analyzed, and the studies' quality was assessed using the QUADAS-2 tool. The final analysis comprised 24 full-text articles, in which case-control studies predominated, mostly reporting urine-based biomarkers (54.2%) and biomarker quantification by qPCR (41.7%). Categorization into risk groups was heterogeneous, predominantly making use of the Gleason score. This systematic review unveils the substantial clinical promise of using circulating biomarkers in assessing the risk for prostate cancer patients. However, the standardization of groups, categories, and biomarker validation are mandatory before this technique can be implemented. Circulating biomarkers might represent a viable alternative to currently available tools, obviating the need for tissue biopsies, and allowing for faster and more cost-effective testing, with superior analytical performance, specificity, and reproducibility.

Abstract 1167: Prospective analysis of pretreatment circulating CD4 memory T cell features associated with severe immunotherapy toxicity

Abstract Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized melanoma treatment, significantly improving outcomes. Nevertheless, too many melanoma patients undergoing ICI treatment experience severe and often debilitating immune-related adverse events (irAEs). In a retrospective melanoma cohort treated with ICIs, we previously found that elevated baseline levels of circulating CD4 effector memory T (TEM) cells were associated with the development of severe irAEs, irrespective of the affected organ system (Lozano et al., Nature Medicine, 2022). Here, we present data from an extended prospective validation cohort from 47 patients across two academic medical centers. Methods: Of 47 patients, 26 received combination anti-PD1/anti-CTLA4 ICIs, 3 combination anti-PD1/anti-LAG3 ICIs, 17 anti-PD1 ICI, and 1 anti-CTLA4 ICI. Peripheral blood mononuclear cells (PBMCs) were prepared from pretreatment (Cycle 1 Day 1) blood samples obtained from all patients. We performed mass cytometry (CyTOF) on PBMCs using a 38-marker panel to deeply profile immune subsets. We further leveraged bulk RNA-seq from 24 patients to (i) deconvolve CD4 memory T cell abundance using CIBERSORTx and (ii) determine T cell receptor (TCR) diversity using Shannon entropy following MiXCR clonotype assembly. irAEs were graded on a 5-point scale using the Common Terminology Criteria for Adverse Events v5. Results: After treatment initiation, 14 patients experienced severe irAEs (grade 3+) at a median of 12.1 weeks (range 4-54), including 4 with life-threatening (grade 4) irAEs. CyTOF revealed elevated circulating CD4 TEM cells in patients that developed severe irAEs (P<0.0001; AUC=0.87), including those treated with combination ICIs (P=0.0001; AUC=0.89). We further observed a continuous relationship between increasing CD4 TEM levels and irAE grade (P=3e-6, Jonckheere-Terpstra test). We then combined CD4 memory T cell abundance and TCR diversity derived from bulk RNA-seq on 24 of these patients using logistic regression (trained on data from Lozano et al.) to yield a composite model score. The pretreatment composite model score was strongly associated with severe irAE development (P=0.0009, AUC=0.88), and in a median split, identified patients with shorter time to severe irAE development (3 months vs. not reached; P=0.006; HR=10.5). Notably, composite model features and the overall score had no significant association with immunotherapy benefit. Conclusion: In this prospective study, both circulating CD4 TEM levels determined by CyTOF and a composite model score measured by RNA-seq were strongly associated with severe irAE development, independent of response status. These findings hold promise for future pretreatment risk stratification of ICI therapy. Citation Format: Abul Usmani, Noah Earland, Wubing Zhang, Peter K. Harris, Antonietta Bacchiocchi, Chloe M. Sachs, Aishwarya Nene, David Y. Chen, Mario Sznol, Ruth Halaban, Aaron M. Newman, Aadel A. Chaudhuri. Prospective analysis of pretreatment circulating CD4 memory T cell features associated with severe immunotherapy toxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1167.

Impact of the extent of lymph node dissection on survival outcomes in clinically lymph node-positive bladder cancer.

To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node-positive (cN+) bladder cancer (BCa). In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin-based peri-operative chemotherapy for cTany N1-3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence-free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity-score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4-16) months, and median (IQR) follow-up of alive patients was 30 (13-51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70-1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60-1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach.

CT-based nomogram for early identification of T790M resistance in metastatic non-small cell lung cancer before first-line epidermal growth factor receptor-tyrosine kinase inhibitors therapy

BackgroundTo evaluate the value of computed tomography (CT) radiomics in predicting the risk of developing epidermal growth factor receptor (EGFR) T790M resistance mutation for metastatic non-small lung cancer (NSCLC) patients before first-line EGFR-tyrosine kinase inhibitors (EGFR-TKIs) therapy.MethodsA total of 162 metastatic NSCLC patients were recruited and split into training and testing cohort. Radiomics features were extracted from tumor lesions on nonenhanced CT (NECT) and contrast-enhanced CT (CECT). Radiomics score (rad-score) of two CT scans was calculated respectively. A nomogram combining two CT scans was developed to evaluate T790M resistance within up to 14 months. Patients were followed up to calculate the time of T790M occurrence. Models were evaluated by area under the curve at receiver operating characteristic analysis (ROC-AUC), calibration curve, and decision curve analysis (DCA). The association of the nomogram with the time of T790M occurrence was evaluated by Kaplan–Meier survival analysis.ResultsThe nomogram constructed with the rad-score of NECT and CECT for predicting T790M resistance within 14 months achieved the highest ROC-AUCs of 0.828 and 0.853 in training and testing cohorts, respectively. The DCA showed that the nomogram was clinically useful. The Kaplan–Meier analysis showed that the occurrence time of T790M difference between the high- and low-risk groups distinguished by the rad-score was significant (p < 0.001).ConclusionsThe CT-based radiomics signature may provide prognostic information and improve pretreatment risk stratification in EGFR NSCLC patients before EGFR-TKIs therapy. The multimodal radiomics nomogram further improved the capability.Relevance statementRadiomics based on NECT and CECT images can effectively identify and stratify the risk of T790M resistance before the first-line TKIs treatment in metastatic non-small cell lung cancer patients.Key points• Early identification of the risk of T790M resistance before TKIs treatment is clinically relevant.• Multimodel radiomics nomogram holds potential to be a diagnostic tool.• It provided an imaging surrogate for identifying the pretreatment risk of T790M.Graphical

Addition of Cribriform and Intraductal Carcinoma Presence to Prostate Biopsy Reporting Strengthens Pretreatment Risk Stratification Using CAPRA and NCCN Tools

BackgroundPretreatment stratification tools can help in clinical decision making in prostate cancer. To date, none incorporates well-established routinely reported adverse prognostic pathologic features such as intraductal carcinoma of prostate (IDC) or cribriform pattern 4 (CC). ObjectiveTo assess the impact of addition of CC and/or IDC on the Cancer of Prostate Risk Assessment (CAPRA) and National Cancer Comprehensive Network (NCCN) tools for predicting biochemical recurrence free survival (BCR-FS) and event-free survival (EFS) across multiple patient cohorts. Design, setting, and participantsMatched prostate biopsies and radical prostatectomies from institutions in Toronto, Wisconsin and Rotterdam. The presence/absence of CC/IDC was recorded on all biopsies. Outcome measurements and statistical analysisRelationship to outcome was assessed using Cox proportional hazard models, ANOVA and Harrell's concordance index. Results and limitationsWe included 1326 patients (Toronto- 612, Wisconsin- 542, Rotterdam- 172) with median follow up of 4.2 years (IQR 2.9-6.4 years); 306 (23.1%) had CC/IDC on biopsy with 207 (20.9%) BCR and 154 (11.6%) events (metastases/death). Addition of CC/IDC improved stratification in CAPRA scores 3 to 5 for BCR-FS (c-index increase 0.633-0.658, P < .001) and scores 6-10 for EFS (c-index increase 0.653-0.697, P < .001). For NCCN, all risk groups apart from score 1 to 2 showed improvement in BCR-FS (c-index increase 0.599-0.636, P < 0.001) and EFS prediction (c-index increase 0.648-0.697, P < .001). Sub-analysis of grade group (GG) 2 biopsies showed similar findings. The retrospective nature and inclusion of cases only reported by genitourinary pathologists are study limitations. ConclusionsThe clinical benefit of the addition of CC/IDC to both CAPRA and NCCN pretreatment tools was validated in 3 cohorts, including the subset of biopsy GG2 prostate cancer patients. Patient summaryIncluding additional pathologic features to existing pretreatment, clinical decision making tools improves the ability to predict prostate cancer recurrence, cancer spread and death of disease.

Prognostic model on overall survival in elderly nasopharyngeal carcinoma patients: a recursive partitioning analysis identifying pre-treatment risk stratification

BackgroundWe aimed to evaluate the optimal management for elderly patients with nasopharyngeal carcinoma (NPC) with intensity-modulated radiotherapy (IMRT).MethodsA total of 283 elderly patients with NPC diagnosed from 2015 to 2019 were enrolled in the study. Overall survival (OS) was the primary endpoint. Univariate and multivariate Cox regression analyses were preformed to identify potential prognostic factors. The recursive partitioning analysis (RPA) was used for risk stratification. Kaplan-Meier survival curves were applied to evaluate the survival endpoints, and log-rank test was utilized to assess differences between groups. The prognostic index (PI) was constructed to further predict patients’ prognosis displayed by nomogram model. The area under the receiver operating characteristic (ROC) curves (AUC) and the calibration curves were applied to assess the effectiveness of the model.ResultsBased on RPA-based risk stratification, we demonstrated that elderly NPC patients who were treated with IC followed by RT had similar OS as those with induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) in the middle- (stage I-III and pre-treatment EBV > 1840 copies/ml) and high-risk groups (stage IVA). IMRT alone may be the optimal treatment option for the low-risk group (stage I-III with pre-treatment EBV ≤ 1840 copies/ml). We established an integrated PI which was indicted with stronger prognostic power than each of the factors alone for elderly NPC patients (The AUC of PI was 0.75, 0.80, and 0.82 for 1-, 3-, 5-year prediction of OS, respectively).ConclusionWe present a robust model for clinical stratification which could guide individual therapy for elderly NPC patients.

Application of amide proton transfer imaging to pretreatment risk stratification of childhood neuroblastoma: comparison with neuron-specific enolase.

The diagnosis and treatment of childhood neuroblastoma (NB) varies with different risk groups, thus requiring accurate preoperative risk assessment. This study aimed to verify the feasibility of amide proton transfer (APT) imaging in risk stratification of abdominal NB in children, and compare it with the serum neuron-specific enolase (NSE). This prospective study enrolled 86 consecutive pediatric volunteers with suspected NB, and all subjects underwent abdominal APT imaging on a 3T magnetic resonance imaging scanner. A 4-pool Lorentzian fitting model was used to mitigate motion artifacts and separate the APT signal from the contaminating ones. The APT values were measured from tumor regions delineated by two experienced radiologists. The one-way analysis of variance, independent-sample t-test, Mann-Whitney U-test, and receiver operating characteristic analysis were performed to evaluate and compare the risk stratification performance of the APT value and serum NSE index-a routine biomarker of NB in clinics. Thirty-four cases (mean age, 38.6±32.4 months; 5 very-low-risk, 5 low-risk, 8 intermediate-risk and 16 high-risk ones) were included in the final analysis. The APT values were significantly higher in high-risk NB (5.80%±1.27%) than in the non-high-risk group (3.88%±1.01%) composed of the other three risk groups (P<0.001). However, there was no significant difference (P=0.18) in NSE levels between the high-risk (93.05±97.14 ng/mL) and non-high-risk groups (41.45±30.99 ng/mL). The associated area under the curve (AUC) of the APT parameter (AUC =0.89) in differentiating high-risk NB from non-high-risk NB was significantly higher (P=0.03) than that of NSE (AUC =0.64). As an emerging non-invasive magnetic resonance imaging technique, APT imaging has a promising prospect for distinguishing high-risk NB from non-high-risk NB in routine clinical applications.

MP55-03 CORRELATION BETWEEN PSMA PET/CT DATA AND PATHOLOGICAL TUMOUR STAGING AND GRADING OF PROSTATE CANCER

MP55-03 CORRELATION BETWEEN PSMA PET/CT DATA AND PATHOLOGICAL TUMOUR STAGING AND GRADING OF PROSTATE CANCER

PD39-06 INTEGRATING INDEX LESION VOLUME TO BETTER CLASSIFY MEN WITH INDOLENT PROSTATE CANCER AMONG PATIENTS WITH INTERMEDIATE RISK DISEASE. RESULTS FROM A LARGE, MULTI-INSTITUTIONAL SERIES

PD39-06 INTEGRATING INDEX LESION VOLUME TO BETTER CLASSIFY MEN WITH INDOLENT PROSTATE CANCER AMONG PATIENTS WITH INTERMEDIATE RISK DISEASE. RESULTS FROM A LARGE, MULTI-INSTITUTIONAL SERIES

Management of limited stage Hodgkin lymphoma

Hodgkin lymphoma (HL) is a lymphoid neoplasm characterized by malignant lymphocytes, known as Reed-Sternberg cells, on a background of non-neoplastic inflammatory cells. Lugano staging determines the stage of Hodgkin lymphoma, which, in turn, determines the treatment and prognosis. Limited-stage disease is defined as Stage I and Stage II, which is diagnosed in more than 50% of patients. Pre-treatment risk stratification, PET-adapted therapy, and combined modality treatment have significantly improved cure rates, making limited-stage HL one of the most curable malignancies. In this article, we discuss the current approach to managing limited-stage HL.

Quantitative contrast-enhanced endoscopic ultrasound in pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors: can we predict survival using perfusion parameters? A pilot study.

Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) parameters may be used to predict prognosis of pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (pNET). The aim of this study was to investigate the association between several perfusion parameters on CEH-EUS performed before treatment and survival outcome in patients with PDAC or pNET. Thirty patients with PDAC or pNET who underwent CEH-EUS and EUS-guided fine needle aspiration (EUS-FNA) were included. Quantitative analysis of tumor vascularity was performed using time-intensity curve (TIC) analysis-derived parameters, obtained from processing CEH-EUS recordings with a commercially available software (VueBox). Cox proportional hazards models were used to determine associations with survival outcome. Median overall survival (OS) for PDAC patients was 9.61 months (95% CI: 0.1-38.7) while the median OS for pNET patients was 15.81 months (95% CI: 5.8-24.75. In a multivariate model for OS, a lower peak enhancement (HR=1.76, p=0.02) and a lower wash-in area under the curve (HR=1.06, p=0.001) were associated with worse survival outcome for patients with PDAC. CEH-EUS parameters may be used as a surrogate to predict PDAC aggressiveness and survival before treatment. After validation by large-scale studies, CEH-EUS perfusion parameters have the potential to be used in pretreatment risk stratification of patients with PDAC and in evidence-based clinical decision support.

Exploring the role of neutrophil-to-lymphocyte ratio and blood chemistry in head and neck adenoid cystic carcinomas treated with carbon ion radiotherapy

Background and purposeIn recent years, there is an emerging interest in the prognostic role of chemistry blood biomarkers in oncological patients but their role in adenoid cystic carcinomas (ACCs) is still unknown. This study aims to assess the prognostic significance of baseline neutrophil-to-lymphocyte ratio (NLR) and blood chemistry in a series of head and neck ACC patients treated with carbon ion radiotherapy (CIRT). Material and MethodsWe retrospectively retrieved the data of 49 consecutive head and neck ACC patients treated with CIRT. Univariable and multivariable Cox proportional hazard regression (Cox-ph) analyses were performed to look for a potential association of NLR, and other blood biomarker values, with disease-free survival (DFS), Local Control (LC), Metastasis Free Survival (MFS) and overall survival (OS). ResultsNo significant association between NLR > 2,5 and DFS, LC, MFS and OS was found with univariable analysis although a trend was reported for DFS (Hazard ratio [HR]: 2,10, 95 % CI: 0,85 – 5,08, p-value = 0,11). Patients with hemoglobin (hb) ≤ 14 g/dL showed significantly better DFS, MFS and OS. Multivariable regression Cox-ph analysis for DFS, adjusted for margin status, clinical target volume and Absolute Number of Monocytes, reported the following statistically significant HRs, for both NLR > 2,5 and hb > 14 g/dL respectively: 4,850 (95 % CI = 1,408 – 16,701, p = 0,012) and 3,032 (95 % CI = 1,095 – 8,393, p = 0,033). Moreover, hb > 14 with HR = 3,69 (95 % CI: 1,23 – 11,07, p-value = 0,02), was a negative independent prognostic predictor for MFS. ConclusionsPre-treatment NLR and hb values seem to be independent prognostic predictor for clinical outcomes in head and neck ACC patients. If their role will be validated in a larger prospective cohort, they might be worthwhile for a pre-treatment risk stratification in patients treated with CIRT.

Primary tumor volume and prognosis for patients with p16-positive and p16-negative oropharyngeal squamous cell carcinoma treated with radiation therapy

BackgroundThe prescribed radiation dose to patients with oropharyngeal squamous cell carcinoma (OPSCC) is standardized, even if the prognosis for individual patients may differ. Easy-at-hand pre-treatment risk stratification methods are valuable to individualize therapy. In the current study we assessed the prognostic impact of primary tumor volume for p16-positive and p16-negative tumors and in relationship to other prognostic factors for outcome in patients with OPSCC treated with primary radiation therapy (RT).MethodsFive hundred twenty-three OPSCC patients with p16-status treated with primary RT (68.0 Gy to 73.1 Gy in 7 weeks, or 68.0 Gy in 4.5 weeks), with or without concurrent chemotherapy, within three prospective trials were included in the study. Local failure (LF), progression free survival (PFS) and overall survival (OS) in relationship to the size of the primary gross tumor volume (GTV-T) and other prognostic factors were investigated. Efficiency of intensified RT (RT with total dose 73.1 Gy or given within 4.5 weeks) was analyzed in relationship to tumor volume.ResultsThe volume of GTV-T and p16-status were found to be the strongest prognostic markers for LF, PFS and OS. For p16-positive tumors, an increase in tumor volume had a significantly higher negative prognostic impact compared with p16-negative tumors. Within a T-classification, patients with a smaller tumor, compared with a larger tumor, had a better prognosis. The importance of tumor volume remained after adjusting for nodal status, age, performance status, smoking status, sex, and hemoglobin-level. The adjusted hazard ratio for OS per cm3 increase in tumor volume was 2.3% (95% CI 0–4.9) for p16-positive and 1.3% (95% 0.3–2.2) for p16-negative. Exploratory analyses suggested that intensified RT could mitigate the negative impact of a large tumor volume.ConclusionsOutcome for patients with OPSCC treated with RT is largely determined by tumor volume, even when adjusting for other established prognostic factors. Tumor volume is significantly more influential for patients with p16-positive tumors. Patients with large tumor volumes might benefit by intensified RT to improve survival.

MP55-15 CAN MRI LOCALIZE THE PROXIMITY OF PROSTATE CANCER TO THE URETHRA IN MEN WHO ARE CANDIDATES FOR FOCAL GLAND ABLATION?

You have accessJournal of UrologyCME1 May 2022MP55-15 CAN MRI LOCALIZE THE PROXIMITY OF PROSTATE CANCER TO THE URETHRA IN MEN WHO ARE CANDIDATES FOR FOCAL GLAND ABLATION? Neal Patel, Alexa Hughes, Wayne Brisbane, Ali Rastegarpour, Sohrab Afshari, Lorna Kwan, Anissa V. Nguyen, Anthony Sisk, Steven Raman, and Robert Reiter Neal PatelNeal Patel More articles by this author , Alexa HughesAlexa Hughes More articles by this author , Wayne BrisbaneWayne Brisbane More articles by this author , Ali RastegarpourAli Rastegarpour More articles by this author , Sohrab AfshariSohrab Afshari More articles by this author , Lorna KwanLorna Kwan More articles by this author , Anissa V. NguyenAnissa V. Nguyen More articles by this author , Anthony SiskAnthony Sisk More articles by this author , Steven RamanSteven Raman More articles by this author , and Robert ReiterRobert Reiter More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002634.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Despite improvements in the localization of prostate cancer with magnetic resonance imaging, appropriate patient selection for focal ablation of prostate cancer remains a challenge. Given that certain focal therapies minimize side effects by preserving prostate tissue near the urethra, in this study, we aim to determine whether prostate MRI could accurately identify the distance of prostate cancer to the urethra in a cohort of men who were potential candidates for focal gland ablation. METHODS: A retrospective, single-institution analysis of men who underwent an MRI, targeted biopsy, had a subsequent radical prostatectomy and were candidates for focal gland ablation based on pre-treatment risk stratification (intermediate Gleason grade, PSA <20, single MRI visible lesion) was performed. The ability of MRI to identify lesions that were within 5 mm of the prostatic urethra on whole-mount pathology was determined. Multivariable regression was utilized to determine clinical characteristics associated with having prostate cancer within 5 mm of the urethra. RESULTS: A total of 90 patients were identified to be candidates for focal-gland ablation. In 66 men (73.3%), the tumor was within 5 mm of the urethra on whole-mount pathology. MRI correctly identified the cancer location either within or outside a 5 mm radius of the urethra in 68 men (75.5%). The sensitivity of MRI for identifying cancer near the urethra was 78.8% (73.5-84.1%), and specificity was 66.7% (58.1-75.3%). The PPV was 86.7% (79.4-91.6%), and NPV was 53.3% (39.8-66.4%). The overall agreement was moderate (kappa=0.47). In adjusted analysis, no clinical factors (PI-RADS, PSA density, or tumor diameter) were significantly associated with having prostate cancer within close proximity of the urethra. CONCLUSIONS: A significant number of men who are potential candidates for focal ablation may have cancer close to the urethra that could serve as a significant source of infield recurrence after treatment. MRI can be used to identify these tumors and the distance from the tumor to the urethra should be calculated to improve patient selection for focal gland ablation. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e943 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neal Patel More articles by this author Alexa Hughes More articles by this author Wayne Brisbane More articles by this author Ali Rastegarpour More articles by this author Sohrab Afshari More articles by this author Lorna Kwan More articles by this author Anissa V. Nguyen More articles by this author Anthony Sisk More articles by this author Steven Raman More articles by this author Robert Reiter More articles by this author Expand All Advertisement PDF DownloadLoading ...

The role of MRI in prostate cancer: current and future directions.

There has been an increasing role of magnetic resonance imaging (MRI) in the management of prostate cancer. MRI already plays an essential role in the detection and staging, with the introduction of functional MRI sequences. Recent advancements in radiomics and artificial intelligence are being tested to potentially improve detection, assessment of aggressiveness, and provide usefulness as a prognostic marker. MRI can improve pretreatment risk stratification and therefore selection of and follow-up of patients for active surveillance. MRI can also assist in guiding targeted biopsy, treatment planning and follow-up after treatment to assess local recurrence. MRI has gained importance in the evaluation of metastatic disease with emerging technology including whole-body MRI and integrated positron emission tomography/MRI, allowing for not only better detection but also quantification. The main goal of this article is to review the most recent advances on MRI in prostate cancer and provide insights into its potential clinical roles from the radiologist's perspective. In each of the sections, specific roles of MRI tailored to each clinical setting are discussed along with its strengths and weakness including already established material related to MRI and the introduction of recent advancements on MRI.

Early PSA density kinetics predicts biochemical and local failure following extreme hypofractionated radiotherapy in intermediate-risk prostate cancer

PurposeThe present study explores PSA density (PSA-D) as predictor of biochemical and local failure in organ-confined prostate cancer at 3–6 months after hypofractionated stereotactic ablative radiotherapy (SABR). Methods and materialsA cohort of 219, hormone-naïve, NCCN intermediate-risk prostate cancer patients were derived from a phase 2 study of 5 × 9 Gy prostate cancer SABR. PSA-D was calculated at 3 and 6 months by dividing serum PSA by the MR-derived prostate CTV, while the slope of the 3–6 months curve was used to express the kinetics of PSA-D decay. ResultsThe median follow-up was 60.3 (range 46–76) months, and the actuarial 7-year bRFS was 98.0% for intermediate-risk favorable (FIR) patients versus 84.5% for the unfavorable (UIR) subgroup (P = 0.02). Fourteen patients developed a Phoenix-defined biochemical PSA relapse (bRFS) at a median of 34.2 months, 11 confirmed with 68Ga-PSMA PET/CT scan that revealed tracer uptake at the site of dominant intraprostatic pretreatment lesion in 8 patients. The 3-month PSA-D concertation (cut-off 0.08 ng/ml2) and 3–6 months decay slope (cut-off −0.45) values were predictive of long-term bRFS. A dual adverse PSA-D permutation was detected in 25/148 UIR patients, exhibiting 47.5% 7-year bRFS compared with 94.1% for the remaining 123 UIR patients with favorable PSA-D kinetics (P = 0.0006). Intraprostatic local relapse in patients with a 3-month PSA-D > 0.080 ng/ml2 was 11.0% vs. 1.7% for patients with PSA-D ≤ 0.080 ng/ml2 (P = 0.01) and 2.3% vs. 4.3%, respectively, for nodal progression (P = 0.68). ConclusionsEarly post-treatment PSA-D kinetics transcends pre-treatment risk stratification of tumor relapse and adds a nuance in the biological characterization of intermediate-risk prostate cancer phenotypes. The dual adverse PSA-D algorithm may serve as a tool to validate current search of classifiers of radioresistance in prostate cancer with therapeutic implications.

Re: Pretreatment Risk Stratification for Endoscopic Kidney-sparing Surgery in Upper Tract Urothelial Carcinoma: An International Collaborative Study

Re: Pretreatment Risk Stratification for Endoscopic Kidney-sparing Surgery in Upper Tract Urothelial Carcinoma: An International Collaborative Study

Development of a Nomogram Model for Treatment of Elderly Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

(1) Purpose: This study aims to explore risk-adapted treatment for elderly patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) according to their pretreatment risk stratification and the degree of comorbidity. (2) Methods: A total of 583 elderly LA-NPC patients diagnosed from January 2011 to January 2018 are retrospectively studied. A nomogram for disease-free survival (DFS) is constructed based on multivariate Cox regression analysis. The performance of the model is evaluated by using the area under the curve (AUC) of the receiver operating characteristic curve and Harrell concordance index (C-index). Then, the entire cohort is divided into different risk groups according to the nomogram cutoff value determined by X-tile analysis. The degree of comorbidities is assessed by the Charlson Comorbidity Index (CCI). Finally, survival rates are estimated and compared by the Kaplan–Meier method and the log-rank test. (3) Results: A nomogram for DFS is constructed with T/N classification, Epstein-Barr virus DNA and albumin. The nomogram shows well prognostic performance and significantly outperformed the tumor-node-metastasis staging system for estimating DFS (AUC, 0.710 vs. 0.607; C-index, 0.668 vs. 0.585; both p < 0.001). The high-risk group generated by nomogram has significantly poorer survival compared with the low-risk group (3-year DFS, 76.7% vs. 44.6%, p < 0.001). For high-risk patients with fewer comorbidities (CCI = 2), chemotherapy combined with radiotherapy is associated with significantly better survival (p < 0.05) than radiotherapy alone. (4) Conclusion: A prognostic nomogram for DFS is constructed with generating two risk groups. Combining risk stratification and the degree of comorbidities can guide risk-adapted treatment for elderly LA-NPC patients.

External beam radiotherapy and radical prostatectomy are associated with better survival in Asian prostate cancer patients.

To test the effect of race/ethnicity on cancer-specific mortality after radical prostatectomy or external beam radiotherapy in localized prostate cancer patients. In the Surveillance, Epidemiology and End Results database 2004-2016, we identified intermediate-risk and high-risk white (n = 151 632), Asian (n = 11 189), Hispanic/Latino (n = 20 077) and African American (n = 32 550) localized prostate cancer patients, treated with external beam radiotherapy or radical prostatectomy. Race/ethnicity-stratified cancer-specific mortality analyses relied on competing risks regression, after propensity score matching for patient and cancer characteristics. Compared with white patients, Asian intermediate- and high-risk external beam radiotherapy patients showed lower cancer-specific mortality (hazard ratio 0.58 and 0.70, respectively, both P ≤ 0.02). Additionally, Asian high-risk radical prostatectomy patients also showed lower cancer-specific mortality than white patients (hazard ratio 0.72, P = 0.04), but not Asian intermediate-risk radical prostatectomy patients (P = 0.08). Conversely, compared with white patients, African American intermediate-risk radical prostatectomy patients showed higher cancer-specific mortality (hazard ratio 1.36, P = 0.01), but not African American high-risk radical prostatectomy or intermediate- and high-risk external beam radiotherapy patients (all P ≥ 0.2). Finally, compared with white people, no cancer-specific mortality differences were recorded for Hispanic/Latino patients after external beam radiotherapy or radical prostatectomy, in both risk levels (P ≥ 0.2). Relative to white patients, an important cancer-specific mortality advantage applies to intermediate-risk and high-risk Asian prostate cancer patients treated with external beam radiotherapy, and to high-risk Asian patients treated with radical prostatectomy. These observations should be considered in pretreatment risk stratification and decision-making.