National Comprehensive Cancer Network Risk Research Articles

Association of Baseline Magnetic Resonance Imaging Prostate Imaging Reporting and Data System Score With Prostate Cancer Active Surveillance Early Biopsy Reclassification: Data From the Michigan Urological Surgery Improvement Collaborative (MUSIC).

The purpose of our study was to evaluate the association of baseline MRI Prostate Imaging Reporting and Data System (PI-RADS) score with biopsy reclassification in a multicenter active surveillance (AS) cohort. We identified men in the Michigan Urological Surgery Improvement Collaborative registry (46 hospital-based/academic/private practice urology groups) with National Comprehensive Cancer Network (NCCN) low-risk and favorable intermediate-risk prostate cancer who underwent MRI within 6 months before or after initial biopsy and enrolled in AS from June 2016 to January 2021. The primary objective was to determine the association of baseline MRI PI-RADS score (≥4 lesion) with reclassification to high-grade prostate cancer (≥grade group 3) on surveillance biopsy. Multivariable Cox proportional hazards regression models were constructed and adjusted for pathologic, MRI, and clinical/biopsy factors, with landmark time of 6 months from diagnostic biopsy. We included an interaction term between PI-RADS score and NCCN group in the Cox model. A total of 1491 men were included with median age 64 years (IQR: 59-69) with median follow-up 11.0 months (IQR: 6.0-23.0) after landmark. Baseline PI-RADS ≥ 4 lesion was associated with an increased hazard of biopsy reclassification (HR: 2.3 [95% CI: 1.6-3.2], P < .001), along with grade group 2 vs 1 (HR: 2.5 [95% CI: 1.7-3.7], P < .001), and increasing age (per 10 years; HR: 1.8 [95% CI: 1.4-2.4], P < .001). The interaction between NCCN risk group with MRI findings was not significant (P = .7). In this multicenter cohort study of real-world data, baseline MRI PI-RADS score was significantly associated with early biopsy reclassification in men undergoing AS with NCCN low- or favorable intermediate-risk prostate cancer.

Long-term follow-up results of multiparametric prostate MRI and the prognostic value of PI-RADS: a single-center retrospective cohort study

We aim to examine the long-term outcomes of patients who underwent multiparametric prostate magnetic resonance imaging (mp-MRI) for suspected prostate cancer (PCa), specifically based on their initial Prostate Imaging Reporting and Data System (PI-RADS) categories and various clinical factors. Our secondary aim is to evaluate the prognostic value of the PI-RADS through the National Comprehensive Cancer Network (NCCN) risk group distribution. This research was conducted as a single-center retrospective cohort study in a tertiary care hospital. A total of 1,359 cases having at least one histopathological examination after the initial mp-MRI and/or adequate clinical/radiological follow-up data were included in the clinically significant PCa (cs-PCa) diagnosis-free survival analysis. Initial mp-MRI dates were accepted as the start of follow-up for the time-to-event analysis. The event was defined as cs-PCa diagnosis (International Society of Urological Pathology ≥2). Patients who were not diagnosed with cs-PCa during follow-up were censored according to predefined literature-based criteria at the end of the maximum follow-up duration with no reasonable suspicion of PCa and no biopsy indication. The impact of various factors on survival was assessed using a log-rank test and multivariable Cox regression. Subsequently, 394 cases diagnosed with PCa during follow-up were evaluated, based on initial PI-RADS categories and NCCN risk groups. Three main risk factors for cs-PCa diagnosis during follow-up were an initial PI-RADS 5 category, initial PI-RADS 4 category, and high MRI-defined PSA density (mPSAD), with average hazard ratios of 29.52, 14.46, and 3.12, respectively. The PI-RADS 3 category, advanced age group, and biopsy-naïve status were identified as additional risk factors (hazard ratios: 2.03, 1.54-1.98, and 1.79, respectively). In the PI-RADS 1-2 cohort, 1, 3, and 5-year cs-PCa diagnosis-free survival rates were 99.1%, 96.5%, and 93.8%, respectively. For the PI-RADS 3 cohort, 1, 3, and 5-year cs-PCa diagnosis-free survival rates were 94.9%, 90.9%, and 89.1%, respectively. For the PI-RADS 4 cohort, 1, 3, and 5-year cs-PCa diagnosis-free survival rates were 56.6%, 55.1%, and 55.1%, respectively. These rates were found to all be 24.2% in the PI-RADS 5 cohort. Considering the 394 cases diagnosed with PCa during follow-up, PI-RADS ≥4 cases were more likely to harbor unfavorable PCa compared to PI-RADS ≤3 cases (P < 0.001). In the PI-RADS 3 subgroup analysis, a low mPSAD (<0.15 ng/mL2) was found to be a protective prognostic factor against unfavorable PCa (P = 0.005). The PI-RADS category has a significant impact on patient management and provides important diagnostic and prognostic information. Higher initial PI-RADS categories are associated with decreased follow-up losses, a shorter time to PCa diagnosis, increased biopsy rates, a higher likelihood of developing cs-PCa during follow-up, and a worse PCa prognosis. Combining mPSAD with PI-RADS categories could enhance diagnostic stratification in the identification of cs-PCa.

Using the Cell-Cycle Risk Score to Predict the Benefit of Androgen-Deprivation Therapy Added to Radiation Therapy in Patients With Newly Diagnosed Prostate Cancer.

Guidelines recommend adding androgen-deprivation therapy (ADT) to radiation therapy (RT) in certain patients with localized prostate cancer. Individualized genomic testing may improve the prognostic accuracy of risk assessments. Herein, we describe a mathematical model of the benefit of adding ADT to RT as a function of the personalized clinical cell-cycle risk (CCR) score to inform 10-year metastasis risk. A model of absolute risk reduction (ARR) was built using a retrospective cohort of men tested with Prolaris who received RT alone (N = 467). The relative benefit of ADT added to RT to reduce distant metastasis was estimated at 41% on the basis of a meta-analysis of randomized trials. The ARR and number needed to treat (NNT) were computationally derived in patients clinically tested with Prolaris between January 1, 2020, and October 31, 2022 (N = 56,485). Risks were predicted using a cause-specific Cox proportional hazards model with CCR score predicting time to metastasis. A CCR score of 2.112 represents the validated multimodal treatment (MMT) threshold. The ARR from ADT increased from almost zero at low CCR scores to 17.1% at CCR = 3.690 with the corresponding NNT = 6, indicating that adding ADT to RT would prevent metastasis within 10 years for one of every six treated individuals. In the clinical cohort, the average ARR was 0.86% in individuals under the MMT threshold (NNT = 116). The average ARR was 8.19% in individuals above the MMT threshold (NNT = 12). Broad ranges of ADT benefit were observed within National Comprehensive Cancer Network risk categories. The precise and personalized risk estimate of metastasis provided by the CCR score can help inform patients and physicians when considering treatment intensification.

The haemoglobin levels of patients with prostate cancer treated with radical radiotherapy

Introduction: The worldwide estimate points to prostate cancer as the second most frequent cancer in men worldwide, where radiotherapy has been an important modality of curative treatment in managing this neoplasia. The prevalence and impact of cancer-related anemia are not widely known, and it may be overlooked or considered clinically significant. It is believed that the outcomes and toxicity of radiotherapy in prostate cancer treatment may be influenced by blood hemoglobin levels. Objective: To evaluate hemoglobin levels in patients with prostate cancer before and after radiotherapy treatment. Methods: Retrospective, longitudinal study of patients diagnosed with malignant prostate neoplasms undergoing external radiotherapy. Hemoglobin levels were measured before radiotherapy and after treatment completion (20-40 days). Anemia was defined by the World Health Organization as men with values less than 13 g/dl. Prostate cancer recurrence risk classification was based on the National Comprehensive Cancer Network risk criteria. Results: Forty patients were evaluated with measurement of Hemoglobin levels before and after radiotherapy treatment. The mean age was 67 years. According to the risk group classification, 4 patients were low-risk (10%), 27 patients were intermediate-risk (67.5%), and 9 patients were high-risk (22.5%). The mean pre-radiotherapy Hemoglobin levels were 13.3 g/dL, and the mean post-radiotherapy Hemoglobin levels were 10.4 g/dL, p &lt; 0.0001. Conclusion: In this study, a reduction in serum Hemoglobin levels was observed after radiotherapy, highlighting the need for better monitoring of these patients.

Does intensity-modulated radiation therapy by helical tomotherapy for prostate cancer increase the subsequent risk of bladder cancer? A propensity score-matched analysis.

This study aimed to evaluate the risk of bladder cancer after intensity-modulated radiation therapy (IMRT) using helical tomotherapy for prostate cancer in comparison to the risk post-radical prostatectomy (RP) using propensity score-matched analysis and to assess the risk factors for bladder cancer. This retrospective study included 2067 patients with non-metastatic prostate cancer treated at our institution between June 2007 and December 2016. Of these, 1547 patients were treated with IMRT and 520 underwent RP. The propensity scores were calculated using age, National Comprehensive Cancer Network risk classification, prostate volume, Brinkman index, and follow-up time as matched covariates. A propensity score-matched patient cohort (n = 718; IMRT: 359, RP: 359) was created, and the risk of bladder cancer after treatment was compared. In total, bladder cancer was detected in 33 patients. Five patients in the IMRT group and one in the RP group died of bladder cancer. In the propensity score-matched analysis, the 5-year bladder cancer-free survival rate was significantly lower in the IMRT group than in the RP group (91.7% and 96.2%, respectively; p < 0.001). Multivariate analysis revealed that IMRT and the Brinkman index were the risk factors for bladder cancer in this cohort (odds ratio = 5.085, 95% confidence interval = 1.436-18.008, p = 0.012 and odds ratio = 1.001, 95% confidence interval = 1.000-1.001, p = 0.010, respectively). IMRT for prostate cancer using helical tomotherapy increases the subsequent risk of bladder cancer compared with RP and is an independent risk factor for bladder cancer similar to smoking.

Active Surveillance for Taiwanese Men with Localized Prostate Cancer: Intermediate-Term Outcomes and Predictive Factors.

Active surveillance (AS) is one of the management options for patients with low-risk and select intermediate-risk prostate cancer (PC). However, factors predicting disease reclassification and conversion to active treatment from a large population of pure Asian cohorts regarding AS are less evaluated. This study investigated the intermediate-term outcomes of patients with localized PC undergoing AS. This cohort study enrolled consecutive men with localized non-high-risk PC diagnosed in Taiwan between June 2012 and Jan 2023. The study endpoints were disease reclassification (either pathological or radiographic progression) and conversion to active treatment. The factors predicting endpoints were evaluated using the Cox proportional hazards model. A total of 405 patients (median age: 67.2 years) were consecutively enrolled and followed up with a median of 64.6 months. Based on the National Comprehensive Cancer Network (NCCN) risk grouping, 70 (17.3%), 164 (40.5%), 140 (34.6%), and 31 (7.7%) patients were classified as very low-risk, low-risk, favorable-intermediate risk, and unfavorable intermediate-risk PC, respectively. The 5-year reclassification rates were 24.8%, 27.0%, 18.6%, and 25.3%, respectively. The 5-year conversion rates were 20.4%, 28.8%, 43.6%, and 37.8%, respectively. A prostate-specific antigen density (PSAD) of ≥0.15 ng/mL² predicted reclassification (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.17-2.88) and conversion (HR 1.56, 95% CI 1.05-2.31). A maximal percentage of cancer in positive cores (MPCPC) of ≥15% predicted conversion (15% to <50%: HR 1.41, 95% CI 0.91-2.18; ≥50%: HR 1.97, 95% CI 1.1453-3.40) compared with that of <15%. A Gleason grade group (GGG) of 3 tumor also predicted conversion (HR 2.69, 95% CI 1.06-6.79; GGG 3 vs 1). One patient developed metastasis, but none died of PC during the study period (2,141 person-years). AS is a viable option for Taiwanese men with non-high-risk PC, in terms of reclassification and conversion. High PSAD predicted reclassification, whereas high PSAD, MPCPC, and GGG predicted conversion.

The impact of NCCN-compliant multidisciplinary conference on the uptake of active surveillance among eligible patients with localized prostate cancer

IntroductionWe sought to investigate the impact of National Comprehensive Cancer Network (NCCN)-compliant multidisciplinary conference on the uptake of active surveillance (AS) among eligible patients with prostate cancer. MethodsRetrospective review of our AS database was performed. Patients who are eligible for AS who sought a second opinion at a comprehensive cancer center (2010–2021) were presented to the multidisciplinary Localized Prostate Cancer Conference (LPCC) that includes urologists, radiation oncologists, pathologists, and patient advocates. Cochrane Armitage test was used to examine trends over time. Multivariable regression models were fit to evaluate variables associated with the receipt of AS. ResultsSeven hundred twelve patients were identified (19% NCCN very low risk, 32% low risk, and 49% intermediate favorable risk). 43% were recommended AS as the preferred option by the community compared to 68% by LPCC, and 65% elected AS. Recommending AS significantly increased between 2010 and 2021 by the community (from 26% to 57%) and by LPCC (from 52% to 82%), while the proportion of men who received AS increased from 47% to 80% during the same period (P < 0.0001 for all). More recent LPCC era 2017 to 2021 (OR 12.31, 95% CI, 5.60–27.03, P < 0.0001), African American race (OR 0.42, 95% CI, 0.18–0.96, P = 0.04), positive cores at biopsy (OR 0.96, 95% CI, 0.94–0.97, P < 0.0001), age (OR 1.14, 95% CI, 1.10–1.18, P < 0.0001), NCCN low risk (OR 0.25, 95% CI, 0.08–0.81, P = 0.02) and NCCN intermediate favorable risk (OR 0.03, 95% CI, 0.01–0.09, P < 0.0001) were associated with receipt of AS. ConclusionAS recommendation increased significantly over time by community urologists and to a higher extent by NCCN-compliant multidisciplinary conference. The Uptake of AS significantly increased within the same period. More recent LPCC era 2017 to 2021, African American race, the proportion of positive cores at biopsy, age, and NCCN risk were the main determinants of receipt of AS.

Prostate cancer risk stratification using magnetic resonance imaging-ultrasound fusion vs systematic prostate biopsy.

Image-guided approaches improve the diagnostic yield of prostate biopsy and frequently modify estimates of clinical risk. To better understand the impact of magnetic resonance imaging-ultrasound fusion targeted biopsy (MRF-TB) on risk assessment, we compared the distribution of National Comprehensive Cancer Network (NCCN) risk groupings, as calculated from MRF-TB vs systematic biopsy alone. We performed a retrospective analysis of 713 patients who underwent MRF-TB from January 2017 to July 2021. The primary study objective was to compare the distribution of National Comprehensive Cancer Network risk groupings obtained using MRF-TB (systematic + targeted) vs systematic biopsy. Systematic biopsy alone classified 10% of samples as very low risk and 18.7% of samples as low risk, while MRF-TB classified 10.5% of samples as very low risk and 16.1% of samples as low risk. Among patients with benign findings, low-risk disease, and favorable/intermediate-risk disease on systematic biopsy alone, 4.6% of biopsies were reclassified as high risk or very high risk on MRF-TB. Of 207 patients choosing active surveillance, 64 (31%), 91 (44%), 42 (20.2%), and 10 (4.8%) patients were classified as having very low-risk, low-risk, and favorable/intermediate-risk and unfavorable/intermediate-risk criteria, respectively. When using systematic biopsy alone, 204 patients (28.7%) were classified as having either very low-risk and low-risk disease per NCCN guidelines, while 190 men (26.6%) received this classification when using MRF-TB. The addition of MRF-TB to systematic biopsy may change eligibility for active surveillance in only a small proportion of patients with prostate cancer. Our findings support the need for routine use of quantitative risk assessment over risk groupings to promote more nuanced decision making for localized cancer.

Clinical-Genomic Risk Group Classification of Suspicious Lesions on Prostate Multiparametric-MRI.

The utilization of multi-parametric MRI (mpMRI) in clinical decisions regarding prostate cancer patients' management has recently increased. After biopsy, clinicians can assess risk using National Comprehensive Cancer Network (NCCN) risk stratification schema and commercially available genomic classifiers, such as Decipher. We built radiomics-based models to predict lesions/patients at low risk prior to biopsy based on an established three-tier clinical-genomic classification system. Radiomic features were extracted from regions of positive biopsies and Normally Appearing Tissues (NAT) on T2-weighted and Diffusion-weighted Imaging. Using only clinical information available prior to biopsy, five models for predicting low-risk lesions/patients were evaluated, based on: 1: Clinical variables; 2: Lesion-based radiomic features; 3: Lesion and NAT radiomics; 4: Clinical and lesion-based radiomics; and 5: Clinical, lesion and NAT radiomic features. Eighty-three mpMRI exams from 78 men were analyzed. Models 1 and 2 performed similarly (Area under the receiver operating characteristic curve were 0.835 and 0.838, respectively), but radiomics significantly improved the lesion-based performance of the model in a subset analysis of patients with a negative Digital Rectal Exam (DRE). Adding normal tissue radiomics significantly improved the performance in all cases. Similar patterns were observed on patient-level models. To the best of our knowledge, this is the first study to demonstrate that machine learning radiomics-based models can predict patients' risk using combined clinical-genomic classification.

Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study

PurposeCurrently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk.MethodsUrine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC).ResultsIn Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS.ConclusionThis urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.

Association between Artificial Intelligence-Derived Tumor Volume and Oncologic Outcomes for Localized Prostate Cancer Treated with Radiation Therapy.

Although clinical features of multi-parametric magnetic resonance imaging (mpMRI) have been associated with biochemical recurrence in localized prostate cancer, such features are subject to inter-observer variability. We evaluated whether the volume of the dominant intraprostatic lesion (DIL), as provided by a deep learning segmentation algorithm, could provide prognostic information for patients treated with definitive radiation therapy (RT). We conducted a retrospective study of 438 patients with localized prostate cancer who underwent an endorectal coil, high B-value, 3-Tesla mpMRI and were treated with definitive RT at our institution between 2010 and 2017. We utilized the publicly available nnUNet to train a segmentation model which was used to identify the DIL. We examined the association between the artificial intelligence (AI)-generated DIL volume and oncologic outcomes, including biochemical recurrence and metastasis risk, using cause-specific Cox regression and time-dependent receiver operating characteristic analysis. The AI model identified DILs with an area under the receiver operating characteristic (AUROC) of 0.827 at the patient level. For the 233 patients with available PI-RADS scores, with a median follow-up of 5.6 years, there were 28 biochemical failures. AI-defined DIL volume was significantly associated with biochemical failure (adjusted hazard ratio 1.60, 95% confidence interval 1.14-2.24, p = 0.007) after adjustment for PI-RADS score. Among all 438 patients with a median follow-up of 6.9 years, there were 49 biochemical failures and 22 metastases. The AUROC for predicting 7-year biochemical failure for AI volume (0.790) was similar to that for National Comprehensive Cancer Network (NCCN) category (p = 0.17). The AUROC for predicting 7-year metastasis for AI volume trended towards being higher compared to NCCN category (0.854 vs 0.769, p = 0.06). An AI algorithm using deep learning could identify the DIL with good performance. AI-defined DIL volume may be able to provide prognostic information independent of the NCCN risk group or other radiologic factors for patients with localized prostate cancer treated with RT.

Increasing Use of Conservative Management of Low-Risk Prostate Cancer in the Veterans Affairs System from 2012 to 2021

Conservative management (CM), including either active surveillance or watchful waiting, is the preferred management strategy for men with low-risk prostate cancer. We sought to describe contemporary trends in CM among men with localized prostate cancer across the equal-access Veterans Affairs (VA) system. Using VA tumor registry data, we identified all men with a new diagnosis of biopsy-proven, clinically node-negative, non-metastatic prostatic adenocarcinoma from 2012 to 2021, excluding men with missing National Comprehensive Cancer Network risk group. We quantified the yearly proportion of patients with low and favorable intermediate-risk (FIR) prostate cancer undergoing conservative management and examined age-specific rates. Multivariable logistic regression was used to identify independent clinical predictors of CM among men with low-risk and FIR disease. The cohort included 86,415 patients with localized prostate cancer, of whom 20,290 (23.5%) had low risk and 25,447 (29.5%) had FIR disease. The proportion of men diagnosed with low-risk disease decreased from 27.7% in 2012 to 20.1% in 2021. The proportion of men with localized prostate cancer who were 70 years or older at diagnosis increased from 19.5% in 2012 to 46.4% in 2021, with similar increases seen across risk groups. The proportion of men with low-risk disease undergoing CM increased from 63.1% in 2012 to 86.6% in 2021. CM rates in 2021 among low-risk patients were largely consistent across age groups (50-59: 85.1%; 60-69: 87.4%; 70+: 86.3%). For FIR patients, CM rates increased among the subset with Gleason 6 disease (49.5% in 2012 to 80.7% in 2021). In multivariable models, independent predictors of CM in low-risk patients included older age, more recent year, lower PSA at diagnosis, North Atlantic or Pacific region, and presence of another cancer at diagnosis; similar predictors were found in FIR patients. Self-reported race (Black, White, or Other) was not associated with CM. While there was wide geographic variation in CM rates among low-risk patients early in the study period (2012-2014: 56.1% in Southeast region vs 74.1% in Pacific), these disparities resolved in recent years (2019-2021: 83.2% in Southeast vs 83.8% in Pacific). Rates of conservative management for localized prostate cancer increased dramatically over time in the VA, with over 85% of low-risk patients managed conservatively in 2021. Recent years showed no differences in CM rates by self-reported race, geographic region, or age group. Despite this progress, we observed a concomitant increase in the proportion of men 70 years or older diagnosed with localized prostate cancer, including low risk disease. This raises a need to consider strategies to reduce the diagnosis of low-risk disease in elderly Veterans.

Impact of Multiparametric Magnetic Resonance Imaging for the Prediction of Extraprostatic Extension According to the National Comprehensive Cancer Network Risk Stratification in Prostate Cancer

Purpose: The accuracy of extraprostatic extension (EPE) on multiparametric magnetic resonance imaging (mpMRI) for the preoperative staging of prostate cancer (PCa) remains controversial. This study aimed to determine the effect of mpMRI for EPE prediction in the final pathology after radical prostatectomy (RP) according to the National Comprehensive Cancer Network (NCCN) risk stratification in patients with clinically localized PCa.Materials and Methods: This retrospective study analyzed 340 consecutive patients diagnosed with clinically localized PCa who underwent RP with preoperative mpMRI between March 2020 and December 2021. They were stratified according to the NCCN risk stratification into low (LR), favorable intermediate (FIR), unfavorable intermediate (UIR), and high risk (HR) groups to assess final pathological EPE. The accuracy of staging mpMRI was assessed in each group. Univariate and multivariate analyses evaluated the predictors of EPE in the final pathology after RP.Results: Preoperative mpMRI showed suspicious EPE in 87 patients (25.6%), whereas postoperative pathological evaluation revealed EPE in 137 patients (40.3%). The LR group showed relatively low sensitivity and positive predictive value compared with other groups. In the multivariate analysis, suspicious EPE on mpMRI was a significant predictive factor for EPE in the final pathology in the FIR, UIR, and HR groups (p=0.012, p=0.011, and p=0.001, respectively), whereas no correlation was observed in the LR group (p=0.711).Conclusions: A strong correlation was observed between suspicious EPE on mpMRI and EPE in the final pathology in the FIR, UIR, and HR groups but not in the LR group.

Biochemical recurrence after chemohormonal therapy followed by robot-assisted radical prostatectomy in very-high-risk prostate cancer patients.

Robot-assisted radical prostatectomy (RARP) has become one of the standard radical treatments for prostate cancer (PCa). A retrospective single-center cohort study was conducted on patients with PCa who underwent RARP at Gifu University Hospital between September 2017 and September 2022. In this study, patients were classified into three groups based on the National Comprehensive Cancer Network risk classification: low/intermediate-risk, high-risk, and very-high-risk groups. Patients with high- and very-high-risk PCa who were registered in the study received neoadjuvant chemohormonal therapy prior to RARP. Biochemical recurrence-free survival (BRFS) after RARP in patients with PCa was the primary endpoint of this study. The secondary endpoint was the relationship between biochemical recurrence (BCR) and clinical covariates. We enrolled 230 patients with PCa in our study, with a median follow-up of 17.0months. When the time of follow-up was over, 19 patients (8.3%) had BCR, and the 2years BRFS rate for the enrolled patients was 90.9%. Although there was no significant difference in BRFS between the low- and intermediate-risk group and the high/very-high-risk group, the 2years BRFS rate was 100% in the high-risk group and 68.3% in the very-high-risk group (P = 0.0029). Multivariate analysis showed that positive surgical margins were a significant predictor of BCR in patients with PCa treated with RARP. Multimodal therapies may be necessary to improve the BCR in patients with very-high-risk PCa.

Validation of the 2022 National Comprehensive Cancer Network Risk Stratification for Cutaneous Squamous Cell Carcinoma

The 2022 National Comprehensive Cancer Network (NCCN) reclassified cutaneous squamous cell carcinoma (CSCC) into low-, high-, and very high-risk groups to better risk stratify tumors. Mohs micrographic surgery (Mohs) or peripheral and deep en face margin assessment (PDEMA) became preferred surgical modalities for high- and very high-risk tumors. This new risk stratification and the recommendation for Mohs or PDEMA in high- and very high-risk groups have not been validated. To compare outcomes in very high-, high-, and low-risk NCCN groups of CSCCs and in CSCCs treated with Mohs or PDEMA compared with wide local excision (WLE). This retrospective cohort study of CSCCs was performed in 2 tertiary care academic medical centers. Patients 18 years or older and diagnosed between January 1, 1996, and December 31, 2019, at Brigham and Women's Hospital and Cleveland Clinic Foundation were included. Data were analyzed from October 20, 2021, to March 29, 2023. NCCN risk group, Mohs or PDEMA, and WLE. Local recurrence (LR), nodal metastasis (NM), distant metastasis (DM), and disease-specific death (DSD). A total of 10 196 tumors from 8727 patients were stratified by NCCN guidelines into low-, high-, and very high-risk groups (6003 [59.0%] men; mean [SD] age, 72.4 [11.8] years). Compared with the low-risk group, the high- and very high-risk groups demonstrated a greater risk of LR (high-risk subhazard ratio [SHR], 1.99 [95% CI, 1.21-3.27; P = .007]; very high-risk SHR, 12.66 [95% CI, 7.86-20.39; P < .001]), NM (high-risk SHR, 4.26 [95% CI, 1.28-14.23; P = .02]; very high-risk SHR, 62.98 [95% CI, 19.24-206.17; P < .001]), DM (high-risk SHR, 2.2 × 107 [95% CI, 4.7 × 103-1.1 × 1011; P < .001]; very high-risk SHR, 6.3 × 108 [95% CI, 1.4 × 105-2.9 × 1012; P < .001]), and DSD (high-risk SHR, 4.02 [95% CI, 1.18-13.71; P = .03]; very high-risk SHR, 93.87 [95% CI, 29.19-301.85; P < .001]). Adjusted 5-year cumulative incidence was significantly higher in very high- vs high- and low-risk groups for LR (9.4% [95% CI, 9.2%-14.0%] vs 1.5% [95% CI, 1.4%-2.1%] and 0.8% [95% CI, 0.5%-1.2%], respectively), NM (7.3% [95% CI, 6.8%-10.9%] vs 0.5% [95% CI, 0.4%-0.8%] and 0.1% [95% CI, 0.03%-0.3%], respectively), DM (3.9% [95% CI, 2.6%-5.6%] vs 0.1% [95% CI, 0.04%-0.2%] and 0.01% [95% CI, not applicable], respectively), and DSD (10.5% [95% CI, 10.3%-15.4%] vs 0.5% [95% CI, 0.4%-0.8%] and 0.1% [95% CI, 0.04%-0.3%], respectively). Compared with CSCCs treated with WLE, those treated with Mohs or PDEMA had lower risk of LR (SHR, 0.65 [95% CI, 0.46-0.90]; P = .009), DM (SHR, 0.38 [95% CI, 0.18-0.83]; P = .02), and DSD (SHR, 0.55 [95% CI, 0.36-0.84]; P = .006). The findings of this cohort study suggest that the NCCN high- and very high-risk groups identify CSCCs at greatest risk for developing poor outcomes. Further, Mohs or PDEMA resulted in lower LR, DM, and DSD compared with WLE.

Predicting absolute benefit in risk of metastasis of androgen deprivation therapy added to radiation therapy in patients with newly diagnosed prostate cancer using Prolaris.

5030 Background: Most patients would defer using androgen deprivation therapy (ADT) with radiation therapy (RT) when the number-needed-to-treat (NNT) exceeds 25 persons to prevent 1 from developing metastasis, corresponding to an absolute benefit of 4%.1 However, no tools for estimating personalized NNT or absolute benefit from ADT exist. We aimed to quantify personalized absolute benefit and NNT for persons receiving ADT added to single modality RT. Methods: The clinical cell-cycle risk (CCR) score combines the University of California, San Francisco’s Cancer of the Prostate Risk Assessment and the cell cycle progression molecular score to accurately assess prostate cancer aggressiveness. The effect of ADT added to RT was modeled using a 10-year risk of metastasis as a function of continuous CCR score for patients treated with RT alone. The relative benefit of ADT added to RT to reduce distant metastasis was modeled using published data from The Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) which utilized several prospectively randomized RT±ADT trials.2 The average absolute benefit was calculated for patients with CCR scores above and below a prespecified multimodality treatment threshold (MTT) using the distribution of scores in a cohort of patients commercially tested by Myriad Genetics. Results: The commercially tested cohort consisted of 56,485 patients spanning all National Comprehensive Cancer Network risk categories (33.7% very low/low risk, 29.8% favorable intermediate risk, 25.6% unfavorable intermediate risk, 11.0% high/very high risk), with 87.2% having CCR scores at or below the MTT and 12.7% with CCR scores above the threshold. The average absolute benefit of ADT treatment was 0.86% (NNT=116) for patients with CCR scores below the MTT and 8.2% (NNT=12) for patients with CCR scores above the MTT. Patients with CCR scores at precisely the MTT had a predicted absolute benefit of 3.7% (NNT=27). Conclusions: The Prolaris test can accurately predict an individual's benefit of adding ADT to RT, and the risk threshold is consistent with patient attitudes about when to use or omit ADT. 1. Spratt DE, Tward JD: IJROBP 108:899-902, 2020. 2. Kishan AU, Sun Y, Hartman H, et al. Lancet Oncol 23:304-316, 2022.

Case-Matched Outcomes of Proton Beam and Intensity-Modulated Radiation Therapy for Localized Prostate Cancer.

Although both intensity-modulated radiation therapy (IMRT) and proton beam therapy (PBT) offer effective long-term disease control for localized prostate cancer (PCa), there are limited data directly comparing the 2 modalities. The data from 334 patients treated with conventionally fractionated (79.2 GyRBE in 44 fractions) PBT or IMRT were retrospectively analyzed. Propensity score matching was used to balance factors associated with biochemical failure-free survival (BFFS). Age, race, and comorbidities (not BFFS associates) remained imbalanced after matching. Univariable and covariate-adjusted multivariable (MVA) Cox regression models were used to determine if modality affected BFFS. Of 334 patients, 176 (52.7%) were included in the matched cohort with exact matching to National Comprehensive Cancer Network (NCCN) risk group. With a median follow-up time of 9.0 years (interquartile range [IQR]: 7.8-10.2 years), long-term BFFS was similar between the IMRT and PBT matched arms with 8-year estimates of 85% (95% CI: 76%-91%) and 91% (95% CI: 82%-96%, P = .39), respectively. On MVA, modality was not significantly associated with BFFS in both the unmatched (hazard ratio [HR] = 0.75, 95% CI: 0.35-1.63, P = .47) and matched (HR = 0.87, 95% CI: 0.33-2.33, P = .78) cohorts. Prostate cancer-specific survival (PCSS) and overall survival (OS) were also similar (P > .05). However, in an unmatched analysis, the PBT arm had significantly fewer incidences of secondary cancers within the irradiated field (0.6%, 95% CI: 0.0%-3.1% versus 4.5%, 95% CI: 1.8%-9.0%, P = .028). Both PBT and IMRT offer excellent long-term disease control for PCa, with no significant differences between the 2 modalities in BFFS, PCSS, and OS in matched patients. In the unmatched cohort, fewer incidences of secondary malignancy were noted in the PBT group; however, owing to overall low incidence of secondary cancer and imbalanced patient characteristics between the 2 groups, these data are strictly hypothesis generating and require further investigation.

Multiparametric imaging guided HDR interventional radiotherapy (brachytherapy) boost in localized prostate cancer: a multidisciplinary experience.

The aim of this study was to report a monoinstitutional multidisciplinary experience about the use of multiparametric imaging to identify the areas with higher risk of relapse in localized prostate cancer, with the purpose of allowing a biologically planned target dose escalation. We performed a retrospective evaluation of patients diagnosed with prostate cancer who received treatments at our Interventional Oncology Center with interstitial interventional radiotherapy from 2014 to 2022. Inclusion criteria were histologically confirmed localized prostate cancer; and National Comprehensive Cancer Network (NCCN) risk class unfavorable intermediate or high/very high risk. The diagnostic work-up included multiparametric Magnetic resonance imaging (MRI), multiparametric Transrectal ultrasound (TRUS), Positron Emission Tomography Computed Tomography (PET-CT) with choline or PSMA (or alternatively bone scan). All patients were assessed and received one treatment with interstitial high-dose-rate interventional radiotherapy (brachytherapy) delivering external beam radiotherapy (46 Gy). All procedures were performed using transrectal ultrasound guidance under general anesthesia and the prescribed doses were 10 Gy to the whole prostate, 12 Gy to the peripheral zone and 15 Gy to the areas at risk. We report the data of 21 patients who were considered for the statistical analysis with a mean age of 62.5 years. The mean PSA nadir was 0.03 ng/ml (range 0-0.09). So far, no biochemical nor radiological recurrences have been recorded in our series. Regarding acute toxicity, the most commonly reported side effects were G1 urinary in 28.5% of patients and G2 urinary in 9.5%; all recorded acute toxicities resolved spontaneously. We present a real-life experience of biologically planned local dose escalation by interventional radiotherapy (brachytherapy) boost, followed by external beam radiotherapy in patients with intermediate unfavorable- or high/very high risk. The local control and the biochemical control rates are proved to be excellent and the toxicity profile tolerable.

A novel scoring system for the quantitative prediction of prognosis in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy. Patient prognosis cannot be accurately assessed in National Comprehensive Cancer Network (NCCN) risk stratification subgroups based on the current criteria. This study aimed to develop a novel prognostic score model for the quantitative prediction of prognosis in AML. We developed a prognostic risk scoring model of AML using differentially expressed genes to predict prognosis in patients with AML. Furthermore, we evaluated the effectiveness and clinical significance of this prognostic model in 4 AML cohorts and 905 patients with AML. A prognostic risk scoring model of AML containing eight prognosis-related genes was constructed using a multivariate Cox regression model. The model had a higher predictive value for the prognosis of AML in the training and validation sets. In addition, patients with lower scores had significantly better overall survival (OS) and even-free survival (EFS) than those with higher scores among patients with intermediate-risk AML according to the NCCN guidelines, indicating that the model could be used to further predict the prognosis of the intermediate-risk AML populations. Similarly, patients with high scores had remarkably poor OS and EFS in the normal-karyotype populations, indicating that the scoring model had an excellent predictive performance for patients with AML having normal karyotype. Our study provided an individualized prognostic risk score model that could predict the prognosis of patients with AML.

Role of magnetic resonance imaging for preoperative prediction of early biochemical failure in localized prostate cancer.

The purpose of our study was to assess preoperative clinical biological and Magnetic Resonance Imaging (MRI) predictive factors of early biochemical failure (BF), defined as persistence of significant post-operative plasmatic prostate specific antigen (PSA) level after radical prostatectomy (RP) in patients with localized prostate cancer (PCa). In a retrospective cohort study we included 142 patients from our university hospital with newly diagnosed PCa, who underwent 3T multiparametric MRI prior to RP. Only the MRI target lesions [Prostate Imaging Reporting and Data System (PIRADS) ≥3] with histological correspondence were considered significant. Clinical, biological, MRI and pathological preoperative data were studied. We performed univariate and multivariate logistic regression analysis to identify significant parameters associated with early BF. Early BF occurred in 14% of patients (20/142). Patients with BF had higher PSA level at diagnosis, Gleason score, number of positive biopsies, size of the largest positive biopsy and higher National Comprehensive Cancer Network (NCCN) risk score (P<0.001 for all). According to MRI, they also had higher T stage and a higher size of capsular contact (P<0.001 for all). In contrast, there was no difference concerning neither ADC value, perfusion profile and zonal location of the index lesion. In multivariate analysis, the best combination of predictive factors of early BF was the association of preoperative Gleason score ≥4+3 [odds ratio (OR) =6.8 (1.4-32.5); P=0.002] and T stage ≥3 on preoperative MRI [OR =17.4 (3.2-94.9); P<0.001] with an area under the curve (AUC) of 0.89 [99% confidence interval (CI): 0.77-1], a negative predictive value of 94% and a positive predictive value of 75%. Combination of simple preoperative biomarkers as Gleason score and T stage according to MRI accurately stratify the risk of early BF following RP. These results emphasize the pivotal role of preoperative MRI for the management of localized PCa.