Firearm Injuries to the Wrist and Hand in Children and Adults: An Epidemiologic Study.

BACKGROUND: Gunshot wounds (GSWs) to the wrist and hand are a major health and economic burden in the United States. There are few studies examining the circumstances and epidemiological factors surrounding these injuries. This study assesses the epidemiological factors, as well as the shooting circumstances, injury details, and surgical management of wrist and hand GSWs in children and adults. METHODS: Medical records and radiographs were reviewed for all patients with ballistic injury to the wrist or hand treated at an urban academic level 1 trauma center from 2016 to 2019. Fisher exact and Pearson χ2 tests were used to assess differences between groups. RESULTS: Two hundred forty-nine victims (29 children, 220 adults) with complete documentation were identified. Among 180 victims with known shooting circumstances, 132 (70%) were shot by another person and 110 (65%) were injured by intentional gunfire. Eighty-seven victims (35%) suffered a concurrent GSW to another body region. Metacarpal fracture was the most commonly diagnosed bony injury (37%), followed by proximal phalanx fracture (25%). One hundred twenty-nine victims (52%) underwent surgery following their injuries. Nerve discontinuity was diagnosed in 27 victims (11%), while 20 victims (8%) had vascular disruption. There was no significant difference between children and adult victims' type of fracture, concurrent injuries, rates of surgery, or in the most common fracture fixation method. CONCLUSIONS: Most wrist and hand GSW victims were injured due to intentional, non-self-inflicted gunfire. Most patients present with hand fractures, and fortunately, nerve and vascular disruptions are uncommon.

Acute-Phase Reactants in Operatively Treated Upper Extremity Infections: A Retrospective Review.

Background: There are limited data on the use of acute-phase markers in the diagnosis of upper extremity infections. The goal of this study was to determine the percentage of patients with elevated white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) in the setting of an upper extremity infection requiring operative debridement. Methods: In a retrospective review over 12 years, 61 patients who met the inclusion criteria were identified. Results: C-reactive protein was the most sensitive test in the detection of culture-positive infection compared with ESR and WBC (P < .001, P < .0001, respectively). Ninety percent of patients (55 of 61) presented with an abnormal CRP value. The WBC count and ESR were abnormal in 54% and 67% of our cohort, respectively. Conclusions: C-reactive protein is the most sensitive laboratory test when evaluating upper extremity infections that necessitate debridement. The WBC count and ESR should be interpreted with caution and can be normal even in the presence of an infection.

Radial Longitudinal Deficiency: Severity Differences Between U.S. and Japanese Cohorts.

PURPOSE: Radial longitudinal deficiency (RLD) presents on a spectrum of severity and associated diagnoses. The literature is limited in describing patient presentation without comparative data between countries. In a study comparing 2 cohorts of patients, 1 in the United States and 1 in Japan, we hypothesized that there would be a similar presentation of forearm deficiency severity, thumb hypoplasia severity, and associated syndromes between the 2 cohorts. METHODS: Patients with RLD were identified via a comprehensive chart review at 2 pediatric hospital cohorts, 1 in the United States and 1 in Japan, capturing patients presenting over 15 years. We assessed RLD and thumb hypoplasia severity via a modified Bayne and Klug and modified Blauth classifications. The relationship between these 2 diagnoses and the presence of common medical conditions were evaluated and correlated. RESULTS: A total of 194 Japanese patients with 290 involved extremities were compared with 107 U.S. patients with 174 involved extremities. The U.S. cohort had a significantly more severe RLD, and a higher rate of bilaterality (63% vs 50%, respectively). A total of 131 Japanese patients (68%) and 41 U.S. patients (38%) had associated medical syndromes/associations, most frequently vertebral abnormalities, anal atresia, cardiac abnormalities, tracheoesophageal fistula and/or esophageal atresia, renal agenesis and dysplasia, and limb defects (VACTERL; 46 Japanese, 14 U.S.), Holt-Oram (44 Japanese, 5 U.S.), and thrombocytopenia absent radius syndrome (0 Japanese, 12 U.S.). Correlation analysis showed that increased RLD severity was associated with increased thumb hypoplasia severity in both groups, with 95% of modified Bayne and Klug III, IV, or V patients having severely affected thumbs (type IIIb, IV, or V). CONCLUSIONS: The U.S. patients had a more severe RLD and a higher rate of bilaterality. Japanese patients had a higher incidence of associated syndromes and radial polydactyly. Both cohorts showed that increased forearm severity was associated with more severe thumb hypoplasia. TYPE OF STUDY/LEVEL OF EVIDENCE: Differential diagnosis/symptom prevalence study III.

Medial Clavicle Osseous Dimensions with Implication on Plate Fixation.

Significantly displaced medial clavicle fractures are associated with high rates of painful nonunion. Operative fixation can be challenging due to limited medial bone stock and adjacent vital vascular structures. Twenty-one consecutive chest computer topography (CT) scans were analyzed to measure anterior-posterior and superior-inferior dimensions of the medial clavicle. Correlation between height and clavicular dimensions were assessed by Pearson correlation coefficient. Two cases using dual T-locking plates are described. From anterior to posterior, the medial clavicle typically measures 1.44 (SD 0.26 cm) and 2.51 cm (SD 0.38 cm) at its narrowest and widest points, respectively. The mean superior-inferior width was 1.56 cm (SD 0.21 cm) and 2.76 cm (SD 0.39 cm) at its narrowest and widest points, respectively. Inter-observer reliability was 0.986 with combined intra-observer reliability between two time points of 0.984. Surgeons may use CT to reliably evaluate the amount of bone available for screw purchase and pre-operatively determine expected screw lengths. Locking plates using both unicortical locking screws and bicortical screws can be used for fracture fixation. Both patients healed fractures with dual T-locking plates without a short-term hardware complication. Dual T-locking plates may be a consideration for medial clavicle fracture fixation when medial bone purchase is a concern.

Making Improvements in the ED: Does ED Busyness Affect Time to Antibiotics in Febrile Pediatric Oncology Patients Presenting to the Emergency Department?

OBJECTIVES: Febrile neutropenic pediatric patients are at heightened risk for serious bacterial infections, and rapid antibiotic administration (in <60 minutes) improves survival. Our objectives were to reduce the time-to-antibiotic (TTA) administration and to evaluate the effect of overall emergency department (ED) busyness on TTA. METHODS: This study was a quality improvement initiative with retrospective chart review to reduce TTA in febrile children with underlying diagnosis of cancer or hematologic immunodeficiency who visited the pediatric ED. A multidisciplinary clinical practice guideline (CPG) was implemented to improve TTA. The CPG's main focus was delivery of antibiotics before availability of laboratory data. We collected data on TTA during baseline and intervention periods. Concurrent patient arrivals to the ED per hour served as a proxy of busyness. Time to antibiotic was compared with the number of concurrent arrivals per hour. Analyses included scatter plot and regression analysis. RESULTS: There were 253 visits from October 1, 2010 to March 30, 2012. Median TTA administration dropped from 207 to 89 minutes (P < 0.001). Eight months after completing all intervention periods, the median had dropped again to 44 minutes with 70% of patients receiving antibiotics within 60 minutes of ED arrival. There was no correlation between concurrent patient arrivals and TTA administration during the historical or intervention periods. CONCLUSIONS: Implementation of a CPG and process improvements significantly reduced median TTA administration. Total patient arrivals per hour as a proxy of ED crowding did not affect TTA administration. Our data suggest that positive improvements in clinical care can be successful despite fluctuations in ED patient volume.

Intra-articular Monteggia Fracture: A Case Study of Using the Center of Rotational Angulation to Improve a Functional Outcome.

INTRODUCTION: Elbow fractures are the most common pediatric fracture to require operative fixation and can be associated with significant morbidities such as vascular injury, neurologic injury, and loss of function. Specifically, the chronic Monteggia fracture-dislocation causes devastating losses in range of motion. Presenting as a proximal to midshaft ulna fracture and radiocapitellar joint disruption, the acute injury can be successfully managed with closed reduction, serial casting, and close follow-up. The chronic complications of this injury, however, usually occur from an unrecognized radial head dislocation. Here, we present the first known case of a chronic Monteggia fracture-dislocation in the setting of an intra-articular ulnar fracture. Using the center of rotational angulation (CORA) from injury mechanism and radiographs, an intra-articular osteotomy was performed to correct ulnar length and improve this child's range of motion. CASE REPORT: A 3-year-old Hispanic male was first seen in the emergency department for elbow pain following a fall from a sofa. He was incorrectly diagnosed with an isolated intra-articular ulna fracture. 5 weeks after the initially missed Monteggia fracture-dislocation, he presented to clinic with 90° flexion, 40° extension, and a 20° pronation/supination arc. An opening-wedge osteotomy was performed at the intra-articular CORA to restore ulnar length and allow for reduction of the radial head. The magnitude of the ulnar opening-wedge osteotomy was trialed until the radiocapitellar joint maintained reduction throughout pronosupination. CONCLUSION: 7 months after the surgery, the patient displayed functional improvements with 115° flexion, 15° extension, and a 75° pronation/supination arc. On physical examination, he had no neuropathic symptoms, with intact median, radial, and ulnar nerves. Using the CORA from the perceived injury mechanism and radiographs, an intra-articular osteotomy was performed to correct ulnar length, reduce the radial head, and thereby improve this child's range of motion.

Leptin Elevation as a Risk Factor for Slipped Capital Femoral Epiphysis Independent of Obesity Status.

BACKGROUND: Slipped capital femoral epiphysis (SCFE) is strongly associated with childhood obesity, yet the prevalence of obesity is orders of magnitude greater than the prevalence of SCFE. Therefore, it is hypothesized that obesity is not, by itself, a sufficient condition for SCFE, but rather one component of a multifactorial process requiring preexisting physeal pathology. Leptin elevation is seen to varying degrees in patients with obesity, and as leptin has been shown to cause physeal pathology similar to the changes seen in SCFE, we propose that leptin may be a factor distinguishing between patients with SCFE and equally obese children without hip abnormalities. METHODS: Serum leptin levels were obtained from 40 patients with SCFE and 30 control patients with approximate body mass index (BMI) matching. BMI percentiles were calculated according to Centers for Disease Control and Prevention population data by patient age and sex. Patients were compared by demographic characteristics, leptin levels, odds of leptin elevation, and odds of SCFE. RESULTS: The odds of developing SCFE was increased by an odds ratio of 4.9 (95% confidence interval [CI], 1.31 to 18.48; p < 0.02) in patients with elevated leptin levels, regardless of obesity status, sex, and race. When grouping patients by their obesity status, non-obese patients with SCFE showed elevated median leptin levels at 5.8 ng/mL compared with non-obese controls at 1.7 ng/mL (p = 0.006). Similarly, obese patients with SCFE showed elevated median leptin levels at 17.9 ng/mL compared with equally obese controls at 10.5 ng/mL (p = 0.039). Serum leptin levels increased in association with obesity (p < 0.001), with an increase in leptin of 0.17 ng/mL (95% CI, 0.07 to 0.27 ng/mL) per BMI percentile point. CONCLUSIONS: To our knowledge, this study is the first to clinically demonstrate an association between elevated serum leptin levels and SCFE, regardless of BMI. This adds to existing literature suggesting that SCFE is a multifactorial process and that leptin levels may have profound physiological effects on the development of various disease states. Despite a strong association with adiposity, leptin levels vary between patients of equal BMI and may be a vital resource in prognostication of future obesity-related comorbidities. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Impact of hourly emergency department patient volume on blood culture contamination and diagnostic yield.

Emergency departments (EDs) are an important diagnostic site for outpatients with potentially serious infections. EDs frequently experience high patient volumes, and crowding has been shown to negatively impact the delivery of early care for serious infections, such as pneumonia. Here, we hypothesized that other important factors in the early care of infectious diseases, the rate of blood culture contamination and the accurate detection of pathogens, would be sensitive to ED operational stress, as proper collection requires fastidious attention to technique and timing. We related all blood samples collected over 1 year and their rates of recovery of likely contaminants and pathogens to the number of patients being cared for in the ED at the time of sample collection. Likely pathogens and contaminants were classified through combined microbiological and manual chart review criteria. Zero-inflated Poisson regression was used to relate crowding to culture results. Blood samples were obtained from 7,586 patients over 82,521 adult and pediatric patient visits. The unadjusted rates of recovering a likely pathogen or a likely contaminant were 8.0% and 3.7%, respectively. Periods of increased crowding (3rd and 4th quartiles of hourly occupancy) were significantly associated (P < 0.01) with increased rates of contamination (relative risk, 1.23 compared to the least busy quartile). Collecting samples for culture during busy times was also associated with a reduced likelihood of recovering a likely pathogen (relative risk, 0.93 compared to the least busy quartile). ED crowding was associated with degraded performance of blood cultures, both increasing the rate of contamination and decreasing the diagnostic yield.

Age and comorbid illness are associated with late rectal toxicity following dose-escalated radiation therapy for prostate cancer.

PURPOSE: To assess the impacts of patient age and comorbid illness on rectal toxicity following external beam radiation therapy (EBRT) for prostate cancer and to assess the Qualitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) normal tissue complication probability (NTCP) model in this context. METHODS AND MATERIALS: Rectal toxicity was analyzed in 718 men previously treated for prostate cancer with EBRT (≥75 Gy). Comorbid illness was scored using the Charlson Comorbidity Index (CCMI), and the NTCP was evaluated with the QUANTEC model. The influence of clinical and treatment-related parameters on rectal toxicity was assessed by Kaplan-Meier and Cox proportional hazards models. RESULTS: The cumulative incidence of rectal toxicity grade ≥2 was 9.5% and 11.6% at 3 and 5 years and 3.3% and 3.9% at 3 and 5 years for grade ≥3 toxicity, respectively. Each year of age predicted an increasing relative risk of grade ≥2 (P<.03; hazard ratio [HR], 1.04 [95% confidence interval {CI}, 1.01-1.06]) and ≥3 rectal toxicity (P<.0001; HR, 1.14 [95% CI,1.07-1.22]). Increasing CCMI predicted rectal toxicity where a history of either myocardial infarction (MI) (P<.0001; HR, 5.1 [95% CI, 1.9-13.7]) or congestive heart failure (CHF) (P<.0006; HR, 5.4 [95% CI, 0.6-47.5]) predicted grade ≥3 rectal toxicity, with lesser correlation with grade ≥2 toxicity (P<.02 for MI, and P<.09 for CHF). An age comorbidity model to predict rectal toxicity was developed and confirmed in a validation cohort. The use of anticoagulants increased toxicity independent of age and comorbidity. NTCP was prognostic for grade ≥3 (P=.015) but not grade ≥2 (P=.49) toxicity. On multivariate analysis, age, MI, CHF, and an NTCP >20% all correlated with late rectal toxicity. CONCLUSIONS: Patient age and a history of MI or CHF significantly impact rectal toxicity following EBRT for the treatment of prostate cancer, even after controlling for NTCP.

Accuracy of determining small renal mass management with risk stratified biopsies: confirmation by final pathology.

PURPOSE: We assess the accuracy of a biopsy directed treatment algorithm in correctly assigning active surveillance vs treatment in patients with small renal masses by comparing biopsy results with final surgical pathology. MATERIALS AND METHODS: From 1999 to 2011, 151 patients with small renal masses 4 cm or smaller underwent biopsy and subsequent surgical excision. Biopsy revealed cell type and grade in 133 patients, allowing the hypothetical assignment of surveillance vs treatment using an algorithm incorporating small renal mass size and histological risk group. We compared the biopsy directed management recommendation with the ideal management as defined by final surgical pathology. RESULTS: Biopsy called for surveillance of 36 small renal masses and treatment of 97 small renal masses. Final pathology showed 11 patients initially assigned to surveillance should have been assigned to treatment (8.3% of all patients, 31% of those recommended for surveillance), whereas no patients moved from treatment to surveillance. Agreement between biopsy and final pathology was 92%. Using management based on final pathology as the reference standard, biopsy had a negative predictive value of 0.69 and positive predictive value 1.0 for determining management. Of the 11 misclassified cases, 7 had a biopsy indicating grade 1 clear cell renal cancer which was upgraded to grade 2 (5) or grade 3 (2). After modifying the histological risk group assignment to account for undergrading of clear cell renal cancer, agreement improved to 97%, with a negative predictive value of 0.86 and a positive predictive value of 1.0. CONCLUSIONS: Our results suggest that compared to final pathology, biopsy of small renal masses accurately informs an algorithm incorporating size and histological risk group that directs the management of small renal masses.

The role of the maximum involvement of biopsy core in predicting outcome for patients treated with dose-escalated radiation therapy for prostate cancer.

PURPOSE: To evaluate the influence of the maximum involvement of biopsy core (MIBC) on outcome for prostate cancer patients treated with dose-escalated external beam radiotherapy (EBRT). METHODS AND MATERIALS: The outcomes of 590 men with localized prostate cancer treated with EBRT (≥75 Gy) at a single institution were retrospectively analyzed. The influence of MIBC on freedom from biochemical failure (FFBF), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival (OS) was compared to other surrogates for biopsy tumor volume, including the percentage of positive biopsy cores (PPC) and the total percentage of cancer volume (PCV). RESULTS: MIBC correlated with PSA, T-stage, Gleason score, NCCN risk group, PPC, PCV, and treatment related factors. On univariate analysis, MIBC was prognostic for all endpoints except OS; with greatest impact in those with Gleason scores of 8-10. However, on multivariate analysis, MIBC was only prognostic for FFBF (hazard ratio [HR] 1.9, p = 0.008), but not for FFM (p = 0.19), CSS (p = 0.16), and OS (p = 0.99). CONCLUSIONS: In patients undergoing dose-escalated EBRT, MIBC had the greatest influence in those with Gleason scores of 8-10 but provided no additional prognostic data as compared to PPC and PCV, which remain the preferable prognostic variables in this patient population.

Perineural invasion predicts increased recurrence, metastasis, and death from prostate cancer following treatment with dose-escalated radiation therapy.

PURPOSE: To assess the prognostic value of perineural invasion (PNI) for patients treated with dose-escalated external-beam radiation therapy for prostate cancer. METHODS AND MATERIALS: Outcomes were analyzed for 651 men treated for prostate cancer with EBRT to a minimum dose ≥75 Gy. We assessed the impact of PNI as well as pretreatment and treatment-related factors on freedom from biochemical failure (FFBF), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival. RESULTS: PNI was present in 34% of specimens at biopsy and was significantly associated with higher Gleason score (GS), T stage, and prostate-specific antigen level. On univariate and multivariate analysis, the presence of PNI was associated with worse FFBF (hazard ratio = 1.7, p <0.006), FFM (hazard ratio = 1.8, p <0.03), and CSS (HR = 1.4, p <0.05) compared with absence of PNI; there was no difference in overall survival. Seven-year rates of FFBF, FFM, and CCS were 64% vs. 80%, 84% vs. 92%, and 91% vs. 95% for those patients with and without PNI, respectively. On recursive partitioning analysis, PNI predicted for worse FFM and CSS in patients with GS 8-10, with FFM of 67% vs. 89% (p <0.02), and CSS of 69% vs. 91%, (p <0.04) at 7 years for those with and without PNI, respectively. CONCLUSIONS: The presence of PNI in the prostate biopsy predicts worse clinical outcome for patients treated with dose-escalated external-beam radiation therapy. Particularly in patients with GS 8-10 disease, the presence of PNI suggests an increased risk of metastasis and prostate cancer death.

The Cancer of the Prostate Risk Assessment (CAPRA) in patients treated with external beam radiation therapy: evaluation and optimization in patients at higher risk of relapse.

BACKGROUND: The Cancer of the Prostate Risk Assessment (CAPRA) was developed to predict freedom from biochemical failure (FFBF) following radical prostatectomy (RP). Its utility following external beam radiation therapy (EBRT) has not been externally evaluated. METHODS: A retrospective study of 612 patients treated with dose-escalated EBRT at the University of Michigan Medical Center. RESULTS: Compared to the derivation cohort, EBRT treated patients had higher-risk disease (28% with CAPRA of 6-10 vs. 5%, respectively). A total of 114 patients (19%) had BF with 5-year BF ranging from 7% with CAPRA 0-3 to 35% with CAPRA 7-10. For RT patients the risk of BF at 5-year was similar to 4 surgical cohorts for CAPRA scores 0-2 but lower for all CAPRA scores ≥ 3. The difference favoring RT increased with increasing CAPRA score reaching a 27-50% absolute improved at 5-years for CAPRA scores of 6-10. On multivariate analysis each CAPRA point increased the risk of BF (p<0.0001) while Gleason pattern 5 in the biopsy also increased BF (p=0.01) and long-term androgen deprivation therapy (ADT) significantly reduced the risk of BF (p=0.015). CONCLUSIONS: Compared to surgical series the risk of BF was lower with dose-escalated EBRT with the greatest difference at the highest CAPRA scores.

Continued benefit to androgen deprivation therapy for prostate cancer patients treated with dose-escalated radiation therapy across multiple definitions of high-risk disease.

PURPOSE: To analyze prognostic factors in patients with high-risk prostate cancer treated with dose-escalated external-beam radiation therapy (EBRT) and androgen deprivation (ADT). METHODS AND MATERIALS: Between 1998 and 2008 at the University of Michigan Medical Center, 718 men were consecutively treated with EBRT to at least 75 Gy. Seven definitions of high-risk prostate cancer, applying to 11-33% of patients, were evaluated. Biochemical failure (BF), salvage ADT use, metastatic progression, and prostate cancer-specific mortality (PCSM) were estimated by the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: Each high-risk definition was associated with increased BF (hazard ratio [HR] 2.8-3.9, p < 0.0001), salvage ADT use (HR 3.9-6.3, p < 0.0001), metastasis (HR 3.7-6.6, p < 0.0001), and PCSM (HR 3.7-16.2, p < 0.0001). Furthermore, an increasing number of high-risk features predicted worse outcome. Adjuvant ADT yielded significant reductions in both metastases (HR 0.19-0.38, p < 0.001) and PCSM (HR 0.38-0.50, p < 0.05) for all high-risk definitions (with the exception of clinical Stage T3-4 disease) but improved BF only for those with elevated Gleason scores (p < 0.03, HR 0.25-0.48). When treated with ADT and dose-escalated EBRT, patients with Gleason scores 8 to 10, without other high-risk features, had 8-year freedom from BF of 74%, freedom from distant metastases of 93%, and cause-specific survival of 92%, with salvage ADT used in 16% of patients. CONCLUSION: Adjuvant ADT results in a significant improvement in clinical progression and PCSM across multiple definitions of high-risk disease even with dose-escalated EBRT. There is a subset of patients, characterized by multiple high-risk features or the presence of Gleason Pattern 5, who remain at significant risk for metastasis and PCSM despite current treatment.

Gleason pattern 5 is the greatest risk factor for clinical failure and death from prostate cancer after dose-escalated radiation therapy and hormonal ablation.

PURPOSE: The division of Gleason score (GS) into three categories (2-6, 7, 8-10) may not fully use its prognostic power, as revealed by recent reports demonstrating the presence of Gleason Pattern 5 (GP5) as a strong predictor for biochemical recurrence. Therefore, we analyzed the clinical outcomes in patients treated with dose-escalated radiation therapy (RT) based on the presence or absence of GP5. METHODS AND MATERIALS: Outcomes were analyzed for 718 men treated for localized prostate cancer with external-beam RT to a minimum planning target volume dose of at least 75 Gy. We assessed the impact of GP5 and that of pretreatment- and treatment-related factors on freedom from biochemical failure, freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival (OS). RESULTS: At biopsy, 89% of patients had no GP5, and 11% (76/718) had GP5. There were no differences in age, comorbid illness, T stage, prostate-specific antigen, or the use or duration of androgen deprivation therapy between GS8 without GP5 and GS8-10 with GP5. The presence of GP5 predicted lower FFM (p < 0.002; hazard ratio [HR] 3.4 [1.7-7.1]); CSS (p < 0.0001; HR 12.9 [5.4-31]); and OS (p < 0.0001; HR 3.6 [2.0-6.5]) in comparison with GS8 (without GP5). The 8-year FFM, CSS, and OS were 89%, 98%, and 57%, respectively, for those with Gleason 8 prostate cancer without GP5 in comparison with 61%, 55%, and 31%, respectively, for those with GP5. In addition, both FFM and CSS were strongly influenced by androgen deprivation therapy given concurrently with RT. On multivariate analysis, GP5 was the strongest prognostic factor for all clinical endpoints, including OS. CONCLUSION: The presence of GP5 predicts for worse clinical behavior, which therefore needs to be accounted for by risk stratification schemes. Further intensification of local and/or systemic therapy may be appropriate for such patients.

The percent of positive biopsy cores improves prediction of prostate cancer-specific death in patients treated with dose-escalated radiotherapy.

PURPOSE: To examine the prognostic utility of the percentage of positive cores (PPC) at the time of prostate biopsy for patients treated with dose-escalated external beam radiation therapy. METHODS AND MATERIALS: We performed a retrospective analysis of patients treated at the University of Michigan Medical Center to at least 75 Gy. Patients were stratified according to PPC by quartile, and freedom from biochemical failure (nadir + 2 ng/mL), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival (OS) were assessed by log-rank test. Receiver operator characteristic (ROC) curve analysis was used to determine the optimal cut point for PPC stratification. Finally, Cox proportional hazards multivariate regression was used to assess the impact of PPC on clinical outcome when adjusting for National Comprehensive Cancer Network (NCCN) risk group and androgen deprivation therapy. RESULTS: PPC information was available for 651 patients. Increasing-risk features including T stage, prostate-specific antigen, Gleason score, and NCCN risk group were all directly correlated with increasing PPC. On log-rank evaluation, all clinical endpoints, except for OS, were associated with PPC by quartile, with worse clinical outcomes as PPC increased, with the greatest impact seen in the highest quartile (>66.7% of cores positive). ROC curve analysis confirmed that a cut point using two-thirds positive cores was most closely associated with CSS (p = 0.002; area under ROC curve, 0.71). On univariate analysis, stratifying patients according to PPC less than or equal to 66.7% vs. PPC greater than 66.7% was prognostic for freedom from biochemical failure (p = 0.0001), FFM (p = 0.0002), and CSS (p = 0.0003) and marginally prognostic for OS (p = 0.055). On multivariate analysis, after adjustment for NCCN risk group and androgen deprivation therapy use, PPC greater than 66.7% increased the risk for biochemical failure (p = 0.0001; hazard ratio [HR], 2.1 [95% confidence interval (CI), 1.4-3.0]) and FFM (p = 0.05; HR, 1.7 [95% CI, 1.1-2.9]) and marginally increased the risk for CSS (p = 0.057; HR, 2.1 [95% CI, 1.0-4.6]). CONCLUSION: PPC at the time of biopsy adds prognostic value for clinically meaningful endpoints for patients treated with dose-escalated radiation therapy. This was particularly true for NCCN-defined intermediate- and high-risk patients.