High-grade Disease Research Articles

S1795 Incidental Finding of a MALT Lymphoma of the Rectum

INTRODUCTION: Extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue (MALT) are a subtype of Non-Hodgkin lymphoma (NHL), accounting for only 5% of all NHL. MALT lymphomas can be found in different tissues of the body, the stomach being the most commonly affected gastrointestinal site. Primary colorectal MALT lymphoma is a rare entity and few cases have been reported in the literature; its presentation is often indistinguishable from that of other colonic malignancies, or it can be found incidentally during screening colonoscopies. CASE DESCRIPTION/METHODS: We report the case of an asymptomatic 51-year-old female with a family history of colorectal cancer who underwent routine screening colonoscopy. Prior colonoscopies performed since age 40 were unremarkable. Colonoscopy revealed a subepithelial nodule in the recto-sigmoid colon (Figure 1). Subsequently, a lower endoscopic ultrasound (EUS) was performed and revealed a 15 mm polypoid multi-lobulated lesion with central umbilication in the recto-sigmoid colon. Endosonographically, the lesion was hypoechoic, and it appeared to be confined to both the luminal interface/superficial mucosa and deep mucosa without evidence of extension into the submucosa or muscularis propria. The lesion was successfully removed in its entirety by endoscopic mucosal resection (EMR). The procedure was uneventful, and the patient was discharged home the same day. Pathology revealed large intestinal mucosa of the rectum with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (Figure 2). Immunohistochemistry demonstrated lymphoid cells that were positive for CD20 (Figure 3), CD23, and BCL2 but negative for CD3, CD5, CD43, CD10, and BCL6; confirming the above diagnosis. Whole-body positron emission tomography did not reveal systemic extension. Repeat colonoscopy 3 months later revealed visually prominent infiltration at post-mucosectomy scar negative for residual lymphoma on biopsy. However, due to a strong concern for submucosal spread on site, a decision was made to start radiation therapy. DISCUSSION: The treatment for patients with MALT lymphoma includes surgical resection, chemotherapy, and radiation among others. However, due to the rarity of colonic MALT lymphomas, the optimal treatment modality for them is not well defined and though its prognosis tends to be excellent, periodic surveillance colonoscopies are needed due to increased risk for other primaries and localized recurrence or transformation into higher-grade disease in some instances.Figure 1.: A subepithelial nodule is seen in recto-sigmoid colon during endoscopy.Figure 2.: Rectal mucosa with dense infiltration of lymphoid cells (H&E, 50x).Figure 3.: Diffuse expression of CD20 on immunohistochemical staining suggests lymphoid infiltrate to be composed mostly of B-cells (50x).

Linear mixed-effects models for predicting sarcoma local recurrence growth rates: Implications for optimal surveillance imaging frequency

PurposeSarcomas are rare tumours of mesenchymal origin that are often treated with surgical resection and radiation to prevent local recurrence (LR). Surveillance for LR after surgical resection is often done with contrast-enhanced MRI, however, the optimal frequency of surveillance imaging is unknown. The aims of this study are to calculate LR growth, and to evaluate the factors that affect LR growth and to use this data to predict the optimal imaging surveillance frequency. MethodRetrospective cohort study of patients with sarcoma who were treated at a tertiary care academic institution between 01/01/2007 and 01/03/2020 identified 34 patients with 60 histologically confirmed LRs. The maximum LR length was measured on each surveillance MRI. Linear mixed-effects models were used to calculate the maximum LR length growth rate. We evaluated whether age, sex, primary sarcoma tumour size, sarcoma grade, margins, chemotherapy or radiation therapy affected the growth rate of the maximum LR length. Results: One patient had 6 LRs (2.9 %), two patients (5.9 %) had 5 LRs, two patients (5.9 %) had 4 LRs, two patients (5.9 %) had 3 LRs, three patients (8.8 %) had 2 LRs, and twenty-four patients (70.6 %) had 1 LR. Most patients had high grade (Grade II/III) disease (88.2 %). 41.2 % of the patients had microscopically positive surgical margins. The median time (range) from surgery to LR was 264 days (17 – 8013) days, and 90 % occurred within 42.8 months (1284 days). Microscopically positive margins were associated with faster growth of the maximum LR length (P = 0.036). Assuming that a 1 cm sarcoma LR is actionable and that the previous surveillance MRI was negative, the data predicts that patients with microscopically positive margins should have surveillance MRIs every 6.2 months when LRs are expected to achieve a length of 1.0 cm (95 % CI (0.4–2.3 cm)). ConclusionsPatients with microscopically positive resection margins had LRs that grew faster than patients with negative margins. Surveillance imaging with contrast-enhanced MRI could be conservatively performed every 6 months when LRs are expected to be just less than 1.0 cm in length.

Clinicopathologic Study of Gleason Pattern 5 Prostatic Adenocarcinoma With "Single-cell" Growth Reveals 2 Distinct Types, One With "Plasmacytoid" Features.

Each Gleason score category of prostatic adenocarcinoma (or Grade Group) may encompass a diverse group of architectural patterns such as well-formed glands, poorly formed glands, cribriform structures, single cells, and/or solid sheets. We have noted heterogeneity within the single-cell subtype of Gleason pattern 5 prostatic adenocarcinoma that has not been fully addressed. Therefore, we retrospectively reviewed a series of radical prostatectomies with high-grade prostatic adenocarcinoma (Grade Group 4 or 5), identifying tumors with a component of single-cell infiltration. Additional cases identified prospectively were also included. TNM status, association with other histologic patterns, and clinical follow-up status were determined. Immunohistochemistry for NKX3.1, E-cadherin, p120 catenin, and prostate-specific antigen (PSA) were performed in each case. Eighteen cases with a component of well-developed Gleason pattern 5 characterized by single infiltrative cells that comprised ≥5% of the tumor were identified (15/202 retrospective radical prostatectomies with the high-grade disease [7.5%]). The single-cell pattern ranged from 5% to 50% of the tumor volume, with 5 cases containing ≥40%, and variable secondary architecture included diffuse infiltrating single cells with targetoid growth pattern around benign glands, solid expansive nests of noncohesive cells, and corded/single file growth pattern. Further morphologic analysis demonstrated 2 distinct histologic subtypes: (1) (subtype 1; n=9) monomorphic "plasmacytoid" tumor cells with eccentrically placed nuclei and variable intracytoplasmic vacuoles with bland cytology and discohesion and (2) (subtype 2; n=9) more cohesive tumor cells with greater cytologic atypia characterized by prominent nucleoli, greater variability in nuclear size/shape, occasional mitotic figures, and more irregular infiltration. By immunohistochemistry, NKX3.1 nuclear expression and PSA cytoplasmic expression was retained in all cases. Concomitant membranous E-cadherin loss and strong cytoplasmic p120 catenin expression were present in 5 of the 18 (28%) cases, all in subtype 1 (5/9, 56%). Overall, 56% (10/18) of patients had advanced-stage disease (≥pT3b), and 70% (7/10) of these patients had associated lymphovascular invasion. All patients had concomitant cribriform patterns of carcinoma. The outcome was available for 14 patients: 4 died of unknown cause; 6 had biochemical recurrence with distant bone metastasis in 5 of the 6; and 4 patients with <3 years of follow-up currently have undetectable serum PSA levels (2 patients received salvage radiotherapy with androgen deprivation and 2 remain on routine follow-up). In summary, the single-cell pattern of Gleason pattern 5 prostatic adenocarcinoma is uniformly associated with other high-risk histologic patterns (eg, cribriform growth), and high-stage disease with distant metastasis is not uncommon. Our data suggest that the "single-cell" Gleason pattern 5 prostatic adenocarcinoma contains 2 distinct subtypes. Somatic CDH1 alterations may play a role in the development of the "plasmacytoid" pattern characterized by monomorphic cytology with concomitant E-cadherin loss and aberrant p120 catenin expression.

Practice patterns related to prostate cancer grading: results of a 2019 Genitourinary Pathology Society clinician survey

PurposeTo survey urologic clinicians regarding interpretation of and practice patterns in relation to emerging aspects of prostate cancer grading, including quantification of high-grade disease, cribriform/intraductal carcinoma, and impact of magnetic resonance imaging-targeted needle biopsy. Materials and methodsThe Genitourinary Pathology Society distributed a survey to urology and urologic oncology-focused societies and hospital departments. Eight hundred and thirty four responses were collected and analyzed using descriptive statistics. ResultsEighty percent of survey participants use quantity of Gleason pattern 4 on needle biopsy for clinical decisions, less frequently with higher Grade Groups. Fifty percent interpret “tertiary” grade as a minor/<5% component. Seventy percent of respondents would prefer per core grading as well as a global/overall score per set of biopsies, but 70% would consider highest Gleason score in any single core as the grade for management. Seventy five percent utilize Grade Group terminology in patient discussions. For 45%, cribriform pattern would affect management, while for 70% the presence of intraductal carcinoma would preclude active surveillance. ConclusionThis survey of practice patterns in relationship to prostate cancer grading highlights similarities and differences between contemporary pathology reporting and its clinical application. As utilization of Gleason pattern 4 quantification, minor tertiary pattern, cribriform/intraductal carcinoma, and the incorporation of magnetic resonance imaging-based strategies evolve, these findings may serve as a basis for more nuanced communication and guide research efforts involving pathologists and clinicians.

Low-level laser therapy for the treatment of early stage cutaneous leishmaniasis: A pilot study.

Low-Level Laser Therapy (LLLT) has been investigated for the treatment of various dermatological disorders. Here, we investigate the efficacy of LLLT for the treatment of cutaneous leishmaniasis (CL). This study comprised of 53 patients (total 123 lesions) with a confirmed diagnosis of CL via positive smear of LD-bodies. The CL lesions were classified in Grade I (ie, papule of size ≤1 cm) to Grade V (ie, vesicle formation, ulceration, and superadded infection of size >4 cm). All the patients were divided into group 1 with low grade (ie, Grade I and II) CL lesions and group 2 with high-grade disease (ie, Grade III-V). Red laser light (wavelength = 635 nm) was used for the lesion irradiation, with a light dose of 75 J/cm2 and at a low power of 300 mW. The treatment was divided into four sessions, one session per week. Disease assessment at 10 months follow-up revealed complete response in 91% and partial response in 9% patients of group 1, while no response was observed in patients of group 2. LLLT offers a promising treatment modality for patients presenting with early-stage (ie, Grade I and II) CL lesions.

Survival Outcomes in Neoadjuvant Chemotherapy for High-grade Upper Tract Urothelial Carcinoma: A Nationally Representative Analysis

ObjectiveTo assess the impact of neoadjuvant chemotherapy (NAC) on survival outcomes in a contemporary cohort of patients with in upper tract urothelial carcinoma (UTUC). MethodsThe National Cancer Database was queried from 2004 to 2015 to identify subjects who underwent nephroureterectomy for UTUC. Kaplan-Meier method with log-rank test was performed to compare all-cause mortality between patients who received preoperative chemotherapy to those who did not at each pathologic (p) TNM stage group: T1-4N0, N+, and M+ disease. Associations for all-cause mortality were identified using an adjusted Cox regression analysis. ResultsA total of 10,315 chemoeligible subjects were included in the analysis. A total of 296 (2.9%) of patients received NAC prior to NU. Kaplan-Meier survival curves of the entire cohort demonstrated an overall survival advantage associated with administration of NAC (P = .017). Stratified by clinical staging, subjects with nonorgan-confined tumors had improved overall survival outcomes with NAC administration (P = .012). On multivariate analysis there was a statistically significant improvement in overall survival between in patients who received NAC. Of patients in the preoperative chemotherapy group who had clinically nonorgan-confined disease, 27.1% had organ-confined disease at time of surgery compared to 1.4% of those who underwent surgery as initial therapy. ConclusionIn a contemporary cohort of subjects who underwent nephroureterectomy for UTUC, administration of NAC in patients with high-grade nonorgan-confined disease led to higher rates of pathologic downstaging and was associated with improved overall survival.

Gender Differences in the Clinical Management of clinical T1a Renal Cell Carcinoma

To evaluate gender differences in the management of clinical T1a (cT1a) renal cell carcinoma (RCC) before and after release of the AUA guidelines for management in 2009, which prioritized nephron-sparing approaches. Patients aged ≥66 years diagnosed with cT1a RCC from 2004 to 2013 in Surveillance, Epidemiology, and End Results-Medicare were analyzed. Multivariable mixed-effects logistic regression models were used to evaluate factors associated with radical nephrectomy (RN) for cT1a RCC before (2004 to 2009) and after (2010 to 2013) guidelines release. Predictors of pathologic T3 upstaging and high grade pathology in the postguidelines period were examined using multivariable logistic regression among patients who underwent RN or partial nephrectomy. Twelve thousand four hundred and two patients with cT1a RCC were identified, 42% of whom were women. Overall, the likelihood of RN decreased postguidelines (odds ratio [OR]=0.44, P <.001), but women were at increased odds of undergoing RN both before and after guideline release (OR=1.27, P <.001 and OR=1.37, P <.001, respectively) upon multivariable mixed-effects logistic regression. Tumor size >2 cm was also associated with increased likelihood of RN before and after guidelines (OR=2.61, P <.001 and OR=2.51, P <.001, respectively). In the postguidelines period, women had significantly lower odds of pathologic upstaging (OR=0.75, P=.024) and harboring high grade pathology (OR=0.71, P <.001) compared to men. Gender differences persist in the management of cT1a RCC, with women having higher odds of undergoing RN, even after release of AUA guidelines and despite having lower odds of pathologic upstaging and high-grade disease.

Histologic Heterogeneity of Extirpated Renal Cell Carcinoma Specimens: Implications for Renal Mass Biopsy.

Pathologic characteristics of extirpated renal cell carcinoma (RCC) specimens <7 cm were reviewed to get better information on technical nuances of renal mass biopsy (RMB). Specimens were stratified according to tumor stage, nuclear grade, size, histology, presence of lymphovascular invasion (LVI), necrosis, and sarcomatoid features. When considering pT1 (0–7 cm) tumors, pT1b (4–7 cm) RCC masses were more likely to have necrosis (43% vs 16%, P < 0.001), LVI (6% vs 2%, P = 0.024), high-grade nuclear elements (29% vs 17%, P < 0.001), and sarcomatoid features (2% vs 0%, P = 0.006) compared with pT1a (0–4 cm) tumors. Additionally, pT3a tumors were more highly associated with necrosis (P = 0.005), LVI, sarcomatoid features, and high-grade disease (P for all < 0.001) when compared to pT1 masses. For masses <4 cm, pT3a cancers were more likely to demonstrate necrosis (38% vs 16%, P < 0.001), LVI (22% vs 2%, P < 0.001), high-grade nuclear elements (45% vs 17%, P < 0.001), and sarcomatoid features (12% vs 0%, P < 0.001) compared to pT1a tumors. Similarly, for masses 4–7 cm, pathologic T3a tumors were significantly more likely to have sarcomatoid features (12% vs 2%, P = 0.006) and LVI (22% vs 6%, P = 0.003) compared to pT1b tumors. In summary, pT3a tumors and those RCC masses >4 cm exhibit considerable histologic heterogeneity and may harbor elements that are not easily appreciated with limited renal sampling. Therefore, if RMB is considered for renal masses greater than 4 cm or those that abut sinus fat, a multi-quadrant biopsy approach is necessary to ensure adequate sampling and characterization of the mass.

Histologic Heterogeneity of Extirpated Renal Cell Carcinoma Specimens: Implications for Renal Mass Biopsy

Pathologic characteristics of extirpated renal cell carcinoma (RCC) specimens &lt;7 cm were reviewed to get better information on technical nuances of renal mass biopsy (RMB). Specimens were stratified according to tumor stage, nuclear grade, size, histology, presence of lymphovas-cular invasion (LVI), necrosis, and sarcomatoid features. When considering pT1 (0–7 cm) tumors pT1b (4–7 cm), RCC masses were more likely to have necrosis (43% vs 16%, P &lt; 0.001), LVI (6% vs 2%, P = 0.024), high-grade nuclear elements (29% vs 17%, P &lt; 0.001), and sarcomatoid features (2% vs 0%, P = 0.006) compared with pT1a (0–4 cm) tumors. Additionally, pT3a tumors were more highly associated with necrosis (P = 0.005), LVI, sarcomatoid features, and high-grade disease (P for all &lt; 0.001) when compared to pT1 masses. For masses &lt;4 cm, pT3a cancers were more likely to demonstrate necrosis (38% vs 16%, P &lt; 0.001), LVI (10% vs 2%, P = 0.037), high-grade nuclear elements (31% vs 17%, P = 0.05), and sarcomatoid features (3% vs 0%, P = 0.065) compared to pT1a tumors. Similarly, for masses 4–7 cm, pathologic T3a tumors were significantly more likely to have sarcomatoid features (16% vs 2%, P &lt; 0.001) and LVI (28% vs 6%, P &lt; 0.001) compared to pT1b tumors. In summary, pT3a tumors and those RCC masses &gt;4 cm exhibit considerable histologic heterogeneity and may harbor elements that are not easily appreciated with limited renal sampling. Therefore, if RMB is considered for renal masses greater than 4 cm or those that abut sinus fat, a multi-quadrant biopsy approach is necessary to ensure adequate sampling and characterization of the mass.

Exposure to tobacco smoke measured by urinary nicotine metabolites increases risk of p16/Ki-67 co-expression and high-grade cervical neoplasia in HPV positive women: A two year prospective study

BackgroundHuman papillomavirus (HPV) is considered the strongest epidemiologic risk factor for cervical cancer. However, it is not a sufficient cause given the high prevalence of transient infections. We examined the relationship between exposure to tobacco smoke, measured using urinary nicotine metabolite concentrations, and p16/Ki-67 co-expression in cervical smears and subsequent risk of developing CIN2+/CIN3+ lesions in HPV positive women. MethodsThis prospective longitudinal study enrolled women presenting to colposcopy with cytological abnormalities LSIL/ASCUS at the National Maternity Hospital, Dublin. Women gave a urine sample which was used to perform the Nicotine Metabolite Assay (Siemens). HPV positive (HC2) cervical smears were stained by immunocytochemistry for p16/Ki-67 (CINtec PLUS, Roche). Two year follow-up data, including histological diagnosis, was collected for each woman. Crude and adjusted odds ratios were calculated using logistic regression to investigate associations between tobacco smoke, p16/Ki-67 positivity and CIN2+/CIN3 +. ResultsIn total, 275 HPV positive women were included. Women with nicotine metabolite concentrations above 500 ng/mL, indicative of smoking, were classified as smokers. Smokers were at an increased risk of testing positive for p16/Ki-67 (OR 1.678; 1.027−2.740) and CIN2+ and CIN3+ (OR 1.816; 1.107−2.977 and OR 2.453; 1.200−5.013) in compared to non-smokers. In p16/Ki-67 positive women, smoking further increased their risk of CIN2+/CIN3+ (OR 2.290; 1.017−5.159 and OR 3.506 (1.534−8.017). ConclusionHPV positive women exposed to tobacco smoke are at a higher risk of testing positive for p16/Ki-67 co-expression. Risk of high-grade disease is almost doubled in women who are exposed to tobacco smoke.

Chronic Intervillositis of Unknown Etiology (CIUE): Prevalence, patterns and reproductive outcomes at a tertiary referral institution

Introductionthe objective of this study was to evaluate the incidence of Chronic Intervillositis of Unknown Etiology (CIUE) at our institution and to report on the pregnancy outcomes based on severity of lesions. Methodsretrospective cohort study including 29 889 perinatal specimens from 27 968 patients. The pathology database at our institution was queried for the keywords “intervillositis” and “CIUE” between February 2006 and April 2019. Histology was re-examined using a standardized diagnostic criterion to confirm diagnosis. Cases in which diagnosis was confirmed were categorized as low grade (5–49% intervillous space involvement) or high grade (≥50% involvement). Interventions and pregnancy outcomes were recorded. ResultsThe overall prevalence of CIUE is 0.17% (47 of 27 968 patients), with significantly higher prevalence in 1st trimester products of conception compared with 2nd and 3rd trimester specimens (0.38% vs 0.09%; p < 0.0001). A total of 97 specimens were initially diagnosed with chronic intervillositis. 56 out of 97 (57.7%) specimens met our diagnostic criteria for CIUE on review. Pregnancies with confirmed CIUE had significantly higher rates of pregnancy loss compared with pregnancies with chronic intervillositis not meeting our study criteria for CIUE (94% vs 71%; p = 0.003). Pregnancy loss between low grade (42.9%; 24 out of 56 cases of CIUE) and high grade (57.1%; 32 out of 56 cases) CIUE were not significantly different. DiscussionCIUE prevalence is low at 0.17%, but it is associated with pregnancy loss, particularly in the first trimester. High grade disease may be associated with worse pregnancy outcomes than low grade disease.

Significance of Nodal Metastasis in Parotid Gland Acinar Cell Carcinoma.

To evaluate the rate of lymph node metastasis in parotid gland acinar cell carcinoma, to identified factors associated with increased risk of metastasis, and to evaluate the effect of nodal metastasis on survival. This is a retrospective cohort study utilizing data from a large population-based cancer database. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) 18 database. The study cohort included patients with parotid gland acinar cell carcinoma diagnosed between 2000 and 2015. The overall rate of lymph node metastasis was 6.8%. T3/T4 (OR 6.17, 95% CI, 3.03 to 13.16) disease along with High Grade (OR 15.95) disease were associated with increased risk of nodal metastasis. Non-white, non-Black race was associated with decreased risk. Age and sex were not associated with nodal metastasis. Nodal metastasis was associated with worse OS (HR 6.27, 95% CI, 3.85 to 10.20) and DSS (HR 6.96, 95% CI, 3.81 to 12.73) after adjusting for covariates. Parotid gland acinar cell carcinoma carries a low risk of nodal metastasis. Both advanced T stage and high grade are associated with increased risk of nodal metastasis. Nodal metastasis is associated with decreased overall survival. 3 Laryngoscope, 131:E1125-E1129, 2021.

The role of metabolic syndrome in high grade prostate cancer: development of a clinical nomogram.

The aim of our study is to develop a clinical nomogram including metabolic syndrome status for the prediction of high-grade prostate cancer (HG PCa). A series of men at increased risk of PCa undergoing prostate biopsies were enrolled in a single center. Demographic and clinical characteristics of the patients were recorded. Metabolic syndrome was defined according to the adult treatment panel III. A nomogram was generated based on the logistic regression model and used to predict high grade prostate cancer defined as grade group ≥3 (ISUP 2014). ROC curves, calibration plots and decision curve analysis were used to evaluate the performance of the nomogram. Overall, 738 patients were enrolled. Greater than or equal to 294/738 (40%) of the patients presented PCa and of those patients, 84/294 (39%) presented high grade disease (Grade Group ≥3). On multivariate analysis, DRE (OR: 3.24, 95% CI: 1.80-5.84), PSA (OR: 1.10, 95% CI: 1.05-1.16), PV (OR: 0.98, 95% CI: 0.97-0.99) and MetS (OR: 2.02, 95% CI: 1.13-3.59) were predictors of HG PCa. The nomogram based on the model presented good discrimination (AUC: 0.76), good calibration (Hosmer-Lemeshow Test, P>0.05) and a net benefit in the range of probabilities between 10% and 70%. Metabolic syndrome is highly prevalent in patients at risk of prostate cancer and is particularly associated with high-grade prostate cancer. Our nomogram offers the possibility to include metabolic status in the assessment of patients at risk of prostate cancer to identify men who may have a high-grade form of the disease. External validation is warranted before its clinical implementation.

The Discrepancy between Needle Biopsy and Radical Prostatectomy Gleason Score in Patients with Prostate Cancer.

Gleason score (GS), as well as other prognostic and diagnostic modalities, can predict the possibility of tumor growth and metastasis during the life of patients with prostate cancer. Based on the prostate biopsy GS, clinicians choose the most appropriate therapy for managing patients. The objective of this cross-sectional study was to determine the discrepancy between needle biopsy and radical prostatectomy GS and to identify its predictive factors among the Iranian population. A total of 1147 patients who underwent radical prostatectomy from 2009 to 2019 were initially enrolled in this study. After consideration of the inclusion and exclusion criteria, 439 patients were finally included. The demographic variables and clinical data including age, PSA level, prostate volume, PSA density, GS derived from ultrasonography-guided core needle biopsy specimen, and GS derived from radical prostatectomy specimen were collected from the medical records of patients with prostate adenocarcinoma and were reviewed by a urology resident. Statistical analysis was done by using the Social Sciences Software version 21. The average age of patients was 64.5 years (range 48-84 years), and the average preoperative PSA level was 14.8 ng/mL. On histopathological examination, no changes in GS were observed in 237 (53.9%) patients, whereas GS was upgraded in 144 (32.8%) patients and downgraded in 58 (13.2%) patients at radical prostatectomy. The number of patients who had extracapsular extension, seminal vesicle invasion and positive lymph nodes was significantly higher in the upgraded group compared with the non-upgraded group. Conclusion: In this study, there was a steady decrease in GS upgrading with the prostate size extending up to 49.7 g. There was also an association between downgrading and extending prostate size. Due to the greater risk of high-grade disease in men with small prostates, smaller prostate bulks are most probably upgraded after radical prostatectomy. A higher maximum percentage of involvement per core was an independent predictive factor of upgrading from biopsy grade 1 to grade ≥ 2. Our study showed that patients' age was not predictive of upgrading, which is consistent with other studies. Also, we demonstrated a non-significant relationship between PSA level and upgraded GS. Findings in this study did not demonstrate a significant relationship between PSA level and upgrading.

Abstract IA07: Potential benefits of and obstacles to use of urine-based tumor markers

Abstract There are many potential uses of urine-based tumor markers in improving detection and surveillance of bladder cancer. Prior to incorporation of urine markers into clinical care, it is important to demonstrate improved efficacy over standard clinical tools. The main areas where urine markers may improve care is in triaging patients with hematuria who need evaluation, reducing frequency of cystoscopy in patients with low-grade disease, improving detection of high-grade patients, and improving prediction of outcomes in patients with bladder cancer. There are currently limitations in white light cystoscopy, especially in detection of carcinoma in situ (CIS). Also, the most widely used urine marker, cytology, has low sensitivity for detecting low-grade cancer and can miss up to 40% of high-grade bladder cancer. Most urine markers have improved sensitivity over urine cytology but reduced specificity. The prevalence of disease impacts the positive and negative predictive values of these tests. For hematuria, the prevalence of cancer is very low in microhematuria patients; as such, the positive predictive value of urine markers is low. Clinicians need markers to provide clinically useful information by either having a high positive predictive value or high negative predictive value (NPV). In the context of microhematuria, many patients are not adequately evaluated and this can result in delays in diagnosis. A urine marker with a high NPV could reduce need for cystoscopy for low-risk patients and enrich the cohort of patients more likely to have cancer. For surveillance, the sensitivity of urine markers has not been sufficient to replace cystoscopy. It is possible that replacing some cystoscopy procedures by alternating a marker with cystoscopy for patients with low-grade disease may be possible, but trials are needed to demonstrate the safety and efficacy of this approach. In high-grade patients, there is need for improved detection of recurrent tumors, especially CIS, since white light cystoscopy has been shown to miss tumors compared to enhanced cystoscopy. A high-performing urine marker could improve detection, but appropriate studies need to be performed to demonstrate sufficient PPV to justify modifying clinical care. There is also a potential role for using markers to improve management of patients with atypical cytology or cystoscopic findings. They could also improve prediction of outcomes in patients with high-grade disease, especially in those patients treated with intravesical therapies. In order for urine markers to be incorporated into guidelines, it is important to develop appropriate trials to validate their utility. There is also a need to consider overall cost of care and patient perspectives. Citation Format: Yair Lotan. Potential benefits of and obstacles to use of urine-based tumor markers [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA07.

Future strategies to enhance kidney preservation in upper urinary tract urothelial carcinoma.

Though radical nephroureterectomy remains the gold standard treatment for high grade or invasive disease in upper tract urothelial cancer (UTUC), kidney-sparing surgery has become preferred for low risk disease, in order to minimize morbidity and preserve renal function. Many methods exist for endoscopic management, whether via an antegrade percutaneous or retrograde ureteroscopic approach, including electroresection, laser ablation, and fulguration. There has been an increase in use of adjuvant intracavitary therapy, predominantly using mitomycin and bacillus Calmette-Guerin (BCG), to reduce recurrence after primary endoscopic management for noninvasive tumors, although efficacy remains questionable. Intraluminal BCG has additionally been used for primary treatment of CIS in the upper tract, with around 50% success. Newer investigations include use of narrow band imaging or photodynamic diagnosis with ureteroscopy to improve visualization during diagnosis and treatment. Genomic characterization may improve selection for kidney-sparing surgery as well as identify actionable mutations for systemic therapy. The evolution in adjuvant management has seen strategies to increase the dwell time and the urothelial contact of intraluminal agents. Lastly, chemoablation using a hydrogel for sustained effect of mitomycin is under investigation with promising early results. Continued expansion of the armamentarium available and better identification and characterization of tumors ideal for organ-sparing treatment will further improve kidney preservation in UTUC.

Risk stratification for upper tract urinary carcinoma.

Upper tract urinary carcinoma (UTUC) is a heterogeneous group of rare tumors. The aim of this article is to critically review current therapeutic strategies and to propose a change in the risk-stratification of the disease. A non-systematic review of the literature was performed using the Medline database with the search terms: “upper tract urothelial carcinoma” together with “prognostic factor”, “risk stratification”, “risk factor”, “recurrence”, “predictive tool”, “nomograms” and “treatment”. Preoperative risk factors can be viewed as patient-related risk factors (gender, age, ethnicity, body mass index, smoking status, or genetic factors), or tumor-related risk factors (stage, grade, size, architecture, multifocality, ureteric obstruction). Several biomarkers, available either in blood, urine, or the tumor itself have also been proposed. However, many of these prognostic factors lack accuracy and validation in predicting oncological outcomes, despite their use in predictive tools. After risk stratification, kidney-sparing strategies should be considered (endoscopic management and segmental ureterectomy) and could benefit from new diagnostic tools and technical improvements in in situ adjuvant endocavitary instillations. Radical nephroureterectomy remains the first choice therapy for high-grade disease and will probably be associated with other treatments in the future (lymphadenectomy, perioperative chemotherapy, or immunotherapy). In view of the major recent improvements in UTUC treatment strategies, a new classification should be proposed, including low-, intermediate-, high- and very high-risk disease. Subgroup analysis of good quality trials and better understanding of UTUC risk factors will help validate this new approach toward more personalized medicine.

Ocular adnexal lymphoma in Denmark: a nationwide study of 387 cases from 1980 to 2017

BackgroundNationwide studies of ocular adnexal lymphoma (OAL) are very rare in the literature, and knowledge on incidence, subtype distribution and long-term survival data is limited. This is the largest national...

Impact of tumor size on the oncological outcome of high-grade nonmuscle invasive bladder cancer – examining the utility of classifying Ta bladder cancer based on size

PurposeTo examine survival rates and to calculate the risk of disease recurrence, progression, overall, and cancer-specific mortality in patients diagnosed with high-risk NMIBC using a multi-institutional dataset to evaluate differences between the guidelines of the European Association of Urology and the guidelines of the National Comprehensive Cancer Network (NCCN) with regard to tumor size in risk stratification. Methods and MaterialIn total 1,116 individuals diagnosed with high-risk NMIBC between 2001 and 2013 were included in the analysis. Patients were stratified to NCCN guideline recommendations (high-grade T1, high-grade Ta ≤ 3 cm, and high-grade Ta > 3 cm). Recurrence and progression rates were calculated. Kaplan-Meier curves were fitted to examine differences in recurrence-free (RFS) and progression-free survival (PFS). Multivariable Cox proportional hazards regression models were employed to calculate differences in the RFS, PFS, overall, and cancer-specific survival (CSS). ResultsThe majority of patients were diagnosed with high-grade T1 disease (N = 576, 51.6%), while 34.2% and 14.2% of patients were diagnosed with high-grade Ta ≤ 3 cm and Ta > 3 cm NMIBC, respectively. The 1- and 5-year RFS (1-year: 80.5% vs. 64.9%; 5-year: 58.6% vs. 48.3%, P = 0.048) and PFS (1-year: 99.1% vs. 98.6%; 5-year: 97.7% vs. 92.4%, P = 0.054) rates were higher in patients with Ta ≤ 3 cm. Patients diagnosed with high-grade Ta > 3 cm experienced unfavorable progression-free, and cancer-specific survival compared to high-grade Ta ≤ 3 cm, respectively (PFS: 2.41, 95% confidence interval [CI] 1.05–5.56, P = 0.038; CSS: hazard ratios [HR] 2.22, 95% CI 1.02–4.89, P = 0.048). ConclusionPatients diagnosed with high-grade Ta NMIBC ≤3 cm demonstrated a favorable progression-free, and cancer-specific survival compared to patients diagnosed with high-grade Ta > 3 cm and high-grade T1 NMIBC.

Hypofractionated spinal stereotactic body radiation therapy for high-grade epidural disease.

To characterize the clinical outcomes when stereotactic body radiation therapy (SBRT) alone is used to treat high-grade epidural disease without prior surgical decompression, the authors conducted a retrospective cohort study of patients treated at the Memorial Sloan Kettering Cancer Center between 2014 and 2018. The authors report locoregional failure (LRF) for a cohort of 31 cases treated with hypofractionated SBRT alone for grade 2 epidural spinal cord compression (ESCC) with radioresistant primary cancer histology. High-grade epidural disease was defined as grade 2 ESCC, which is notable for radiographic deformation of the spinal cord by metastatic disease. Kaplan-Meier survival curves and cumulative incidence functions were generated to examine the survival and incidence experiences of the sample level with respect to overall survival, LRF, and subsequent requirement of vertebral same-level surgery (SLS) due to tumor progression or fracture. Associations with dosimetric analysis were also examined. Twenty-nine patients undergoing 31 episodes of hypofractionated SBRT alone for grade 2 ESCC between 2014 and 2018 were identified. The 1-year and 2-year cumulative incidences of LRF were 10.4% (95% CI 0-21.9) and 22.0% (95% CI 5.5-38.4), respectively. The median survival was 9.81 months (95% CI 8.12-18.54). The 1-year cumulative incidence of SLS was 6.8% (95% CI 0-16.0) and the 2-year incidence of SLS was 14.5% (95% CI 0.6-28.4). All patients who progressed to requiring surgery had index lesions at the thoracic apex (T5-7). In carefully selected patients, treatment of grade 2 ESCC disease with hypofractionated SBRT alone offers a 1-year cumulative incidence of LRF similar to that in low-grade ESCC and postseparation surgery adjuvant hypofractionated SBRT. Use of SBRT alone has a favorable safety profile and a low cumulative incidence of progressive disease requiring open surgical intervention (14.5%).