High Risk For Nodal Metastasis Research Articles

High-risk histopathologic features in local advanced conjunctival melanoma.

To identify high-risk histopathologic and molecular features of local recurrence, nodal metastasis, distant metastasis (DM) and disease-specific death (DSD) in conjunctival melanoma (CoM). Ninety patients with pathologically diagnosed CoM between 2008 and 2023 were enrolled. Immunohistochemistry staining of BRAFV600E, NRASQ61R, CD117, PD-1 and PD-L1 was performed in 65 and 45 patients, respectively. Cox regression and Kaplan-Meier survival analysis were conducted to identify risk factors for local recurrence, nodal metastasis, DM and DSD. Pathologically, ulceration (hazard ratio [HR]: 3.170; 95% CI: 1.312-7.659; p = 0.01) and regression (HR: 3.196; 95% CI: 1.094-9.335; p = 0.034) were risk factors for DM. Tumour thickness ≥ 4 mm (HR: 4.889; 95% CI: 1.846-12.946; p = 0.001) and regression (HR: 4.011; 95% CI: 1.464-10.991; p = 0.007) were risk factors for DSD. For patients with tumour thickness < 4 mm, the presence of ulceration indicated a higher risk of nodal metastasis (log-rank p = 0.0011), DM (log-rank p = 0.00051) and DSD (log-rank p = 0.02). Patients with regression (+)/tumour-infiltrating lymphocytes (TILs) (+) had a higher risk for DM (log-rank p = 0.011) and DSD (log-rank p = 0.0032). Molecularly, the positive rate of BRAFV600E, NRASQ61R, CD117, PD-1 and PD-L1 was 40.00% (26/65), 43.08% (28/65), 70.77% (46/65), 46.67% (21/45) and 28.89% (13/45), respectively. Positive BRAFV600E was identified as an independent risk factor for DM (HR: 2.533; 95% CI: 1.046-6.136, p = 0.039). The expression level of BRAFV600E was positively correlated with vascular invasion (p = 0.01), as well as the expression levels of PD-1 (p = 0.038) and PD-L1 (p = 0.049). Tumour thickness ≥ 4 mm, ulceration, the coexistence of regression and TILs, and positive BRAFV600E were risk factors for poor prognosis of CoM patients. Besides, expression level of BRAFV600E was positively correlated with the expression levels of PD-1 and PD-L1.

Prophylactic Lymphadenectomy in Patients with Penile Cancer: Is Sooner Better?

Background: Management of penile cancer patients has its grey zones. In particular, no strong evidence or recommendations exist regarding the timing of prophylactic lymphadenectomy. Here, we aim to review the impact that the timing of inguinal and pelvic prophylactic lymph node dissection has on patient outcome. Methods: All relevant databases were searched following the preferred reporting items for systematic reviews and meta-analysis guidelines. A narrative review of indications for lymph node dissection and pathological considerations precede a systematic review of the impact of prophylactic lymph node dissection timing on prognosis. The primary endpoint is disease-free and overall survival in patients undergoing early or late lymph node dissection after penile cancer diagnosis. Results: Four clinical trials, all focusing on the role of inguinal lymph node dissection, are included. Despite the lack of randomized and controlled trials, this review suggests that lymph node dissection should be performed as soon as possible after diagnosis, with 3 months as a realistic cut-off. Conclusions: Survival of penile cancer patients is strictly related to the timing of prophylactic pelvic lymph node dissection. All patients at high risk of nodal metastasis should be offered lymph node dissection within three months of diagnosis, until new predicting tools are validated.

Novel MSH6 mutation predicted metastasis in eyelid and periocular squamous cell carcinoma.

Our previous research revealed the relative local aggressiveness of eyelid and periocular squamous cell carcinoma (EPSCC), but its distinct genetic characteristics involved remain unknown. We conducted this study based on next-generation sequencing to identify the genetic distinctiveness of EPSCC and damaging mutations for possible aetiology and poor prognosis. We performed sequencing using a 556-gene panel (SmartOnco) in 48 EPSCCs. Cox hazards model was applied to explore mutated genes that increase the risk of metastasis and death. Pathogenesis of the mutations was predicted by sequence alignment algorithms. The most commonly mutated genes were KMT2C (N = 17, 35%), LRP1B (N = 14, 29%), KMT2D (N = 12, 25%), PTCH1 (N = 10, 21%) and TP53 (N = 10, 21%). DNA mismatch repair (MMR) genes (42%) like MSH6 (19%) and MLH3 (12%) were among the most frequently mutated genes. Cell cycle regulators including TP53 (21%) and CDKN2A (10%) were less frequently mutated than in other squamous cell carcinomas (SCCs). Ultraviolet exposure, MMR deficiency and ageing were the main aetiology. Of note, KMT2C has a deleterious mutation hotspot. Patients burdened with MSH6 mutation has a higher risk of overall metastasis (P = 0.045, HR = 5.165) and nodal metastasis (P = 0.022, HR = 14.038). Moreover, a hotspot mutation MSH6E52A brought an even higher risk of nodal metastasis (P = 0.011, HR = 18.745). EPSCCs displayed a unique mutation profile from cutaneous SCCs and mucosal SCCs. We have identified novel damaging mutations in epigenetic regulators like KMT2C boosted early onset of EPSCCs in addition to UVR, ageing or MMR deficiency. And malfunction of MMR genes worsened prognosis.

Endometrial stripe thickness: a preoperative marker to identify patients with endometrial intraepithelial neoplasia who may benefit from sentinel lymph node mapping and biopsy

ObjectivesThe goal of our study was to identify preoperative factors in patients with endometrial intraepithelial neoplasia that are associated with concurrent endometrial cancer to select patients who may benefit from...

MERLIN_001: A prospective registry study of a primary melanoma gene-signature to predict sentinel node (SN) status and determine its prognostic value for more accurate staging of patients with SN-negative melanoma.

TPS9606 Background: For patients with cutaneous melanoma, sentinel lymph node biopsy (SLNB) provides important staging and prognostic information that guides surveillance and adjuvant systemic therapy decisions. At most centers, SLNB is indicated for patients with cutaneous melanoma with at least a 5% risk of having nodal metastases, typically melanomas ≥ 0.8 mm in thickness or thinner lesions with high-risk features such as elevated mitotic rate and/or ulceration. SLNB, generally involving a separate incision, does carry a small but measurable risk of complications including seroma, infection and rarely lymphedema, and most patients have negative sentinel lymph nodes. Currently, there is an unmet clinical need to identify patients who may safely forgo SLNB due to a low (&lt;5%) risk of nodal metastasis, who otherwise meet established criteria for SLNB. Previously, a model consisting of gene expression profile (GEP) of the primary tumor combined with clinicopathological features (CP) has been developed to identify melanoma patients with a low risk of having a positive SLNB. The model has also been validated in multiple retrospective studies. The aim of the MERLIN_001 registry study is to prospectively validate the CP-GEP model in an independent multicenter cohort of primary cutaneous melanoma patients who undergo SLNB for standard indications. Methods: In the next two years, a total of 10 centers across the US will enroll 2,340 patients with clinically node-negative cutaneous melanoma undergoing SLNB using current guideline indications and will follow these patients for 5 years (ClinicalTrials.gov identifier: NCT04759781). Enrollment of patients started in September 2021 and 242 patients have been enrolled as of February 1, 2022. FFPE material from the initial melanoma biopsy will be used to assess the GEP of the primary melanoma. The CP-GEP probability scores will be expressed as a binary classification (Low Risk or High Risk for nodal metastasis) and will be compared to SLN pathology. Performance metrics for CP-GEP will be evaluated and will include: Negative Predictive Value, Positive Predictive Value, Sensitivity and Specificity, and the corresponding 95% confidence intervals. Risk for nodal metastasis will be calculated for Low Risk and High Risk CP-GEP patients. Finally, the performance of CP-GEP to stratify patients according to risk of recurrence (local, regional, distant, death) will also be studied, since data will be collected for up to 5 yrs. Clinical trial information: NCT04759781.

PD22-01 ONCOLOGICAL OUTCOMES OF SENTINEL LYMPH NODE PROCEDURE-GUIDED RADIOTHERAPY VERSUS IMAGING-GUIDED RADIOTHERAPY FOR CLINICALLY LOCALIZED PROSTATE CANCER – A MULTICENTER, RETROSPECTIVE, PROPENSITY SCORE WEIGHTED COMPARISON

You have accessJournal of UrologyCME1 May 2022PD22-01 ONCOLOGICAL OUTCOMES OF SENTINEL LYMPH NODE PROCEDURE-GUIDED RADIOTHERAPY VERSUS IMAGING-GUIDED RADIOTHERAPY FOR CLINICALLY LOCALIZED PROSTATE CANCER – A MULTICENTER, RETROSPECTIVE, PROPENSITY SCORE WEIGHTED COMPARISON Hilda de Barros, Nikolaos Grivas, Jan Duin, Daan Mulder, Vincent van der Noort, Arjen Noordzij, Esther Wit, Eva Schaake, Pim van Leeuwen, and Henk van der Poel Hilda de BarrosHilda de Barros More articles by this author , Nikolaos GrivasNikolaos Grivas More articles by this author , Jan DuinJan Duin More articles by this author , Daan MulderDaan Mulder More articles by this author , Vincent van der NoortVincent van der Noort More articles by this author , Arjen NoordzijArjen Noordzij More articles by this author , Esther WitEsther Wit More articles by this author , Eva SchaakeEva Schaake More articles by this author , Pim van LeeuwenPim van Leeuwen More articles by this author , and Henk van der PoelHenk van der Poel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002564.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Insufficient sensitivity of current imaging techniques for nodal staging has led to the exploration of the sentinel lymph node biopsy (SLNB) to select primary prostate cancer (PCa) patients that might benefit from whole-pelvic nodal radiotherapy (WPRT). In this study, we aimed to evaluate oncological outcomes of SLNB-based RT compared to imaging-based RT in cN0M0 PCa patients with an increased estimated risk of nodal metastases. METHODS: This multicenter, retrospective cohort study included 522 cN0 primary PCa patients with a Briganti nomogram-estimated nodal risk >5% treated with external beam RT (EBRT) between 2007-2018. Nodal staging was performed either by radiological staging (261 (50%) patients) or by radiological staging and an additional robot-assisted laparoscopic SLNB (261 (50%) patients). All patients received RT to the prostate and 6 months to 3 years of androgen deprivation therapy (ADT), whereas patients with a histologically positive sentinel node (pN1) also received RT to the pelvic LNs with 3 years of ADT. Endpoints included biochemical recurrence-free survival (BCR-FS) and radiological recurrence-free survival (RR-FS). Propensity score weighted (PSW) multivariable Cox regression analysis was performed to determine independent predictors of BCR and RR. RESULTS: Patients staged with SLNB had a higher rate of extracapsular extension (63% vs 35%, P <0.001) and were at higher risk of nodal metastases (43% vs 29%, P=0.002) compared to imaging-only staged patients. Median follow-up after primary treatment was 64 months (IQR 41-95). In total, 111 patients developed a BCR (SLNB=51, non-SLNB=60) and 98 patients developed a radiological recurrence (SLNB=50, non-SLNB=48; Fig 1). In PSW multivariable Cox regression analyses, SLNB-based RT was an independent predictor of both BCR (HR 0.38, 95% CI 0.25-0.59, P <0.001) and RR (HR 0.44, 95% CI 0.28-0.69, P <0.001). CONCLUSIONS: SLNB-guided RT is associated with a decreased risk of BCR and RR when compared to prostate-only RT in cN0 PCa patients. These results suggest an important role for SLNB in selecting cN0 PCa patients that might profit from WPRT and ADT intensification, and justify a prospective comparison. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e402 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hilda de Barros More articles by this author Nikolaos Grivas More articles by this author Jan Duin More articles by this author Daan Mulder More articles by this author Vincent van der Noort More articles by this author Arjen Noordzij More articles by this author Esther Wit More articles by this author Eva Schaake More articles by this author Pim van Leeuwen More articles by this author Henk van der Poel More articles by this author Expand All Advertisement PDF DownloadLoading ...

A Comprehensive Approach to Clinical Staging of Bladder Cancer.

Background: A significant number of patients with advanced urothelial cell carcinoma are under- or over-staged. Implementation of clinical variables could be useful for improving the accuracy of clinical staging. Aim: To explore the differences between clinical and pathological diagnosis in patients with UCC, and to identify clinical variables that might play a role in under- or overstating. Materials: A total of 553 patients after radical cystectomy were included in the analysis. Clinical stage of the disease was diagnosed according to CT or MRI in relation to clinical data. Results: Higher clinical stage correlated with a higher pathological stage (p < 0.00005), but in 306 patients did not correspond (142 patients were under-staged and 164 over-staged). Over half (54.2%) of the patients staged as cT1–cT2 were misdiagnosed: 137 patients were under-staged and 133 over-staged. Hydronephrosis was associated with a higher pathological stage (p < 0.000005), mostly pT3–4 (45.13% had pT4 disease) and higher risk of nodal metastasis (p = 0.0028). The highest percentage of PSM was found in patients with pT4 (33.12%). Conclusions: Clinical staging of bladder cancer is poorly executed, with one third of patients under-staged and one third over-staged. To improve accuracy, we recommend a multimodal approach, combining histopathological evaluation with results of imaging studies.

Validation of a clinicopathological and gene expression profile model to identify patients with cutaneous melanoma where sentinel lymph node biopsy is unnecessary

BackgroundIn patients with cutaneous melanoma, sentinel lymph node biopsy (SLNB) serves as an important technique to asses disease stage and to guide adjuvant systemic therapy. A model using clinicopathologic and gene expression variables (CP-GEP; Merlin Assay) has recently been introduced to identify patients that may safely forgo SLNB. Herein we present data from an independent validation cohort of the CP-GEP model in Swedish patients. MethodsArchival histological material (primary melanoma tissue) from a prospectively collected cohort of 421 consecutive patients with pT1-T4 melanoma undergoing SLNB between 2006 and 2014 was analyzed using the CP-GEP model. CP-GEP combines Breslow thickness and patient age with the expression levels of eight genes from the primary melanoma. Stratification is based on their risk for nodal metastasis: CP-GEP Low Risk or CP-GEP High Risk. ResultsThe SLNB positivity rate was 13%. Of 421 primary melanomas, the CP-GEP model identified 86 patients as having a low risk for nodal metastasis. In patients with pT1-2 melanomas, the SLNB reduction rate was 35.4% (95% CI: 29.4–41.8) with a negative predictive value (NPV) of 96.5% (95% CI: 90.0–99.3). Among patients with pT1-3 melanomas, CP-GEP suggested a SLNB reduction rate of 24.0% (95% CI: 19.7–28.8) and a NPV of 96.5% (95% CI: 90.1–99.3). Only one of 118 pT3 tumors was classified as CP-GEP Low Risk, and all pT4 tumors were classified as being high risk for nodal metastasis. ConclusionThis study demonstrates that CP-GEP can identify patients with a low risk for nodal metastasis. Patients with pT1-2 melanomas have the highest clinical benefit from using the test, where 35% of the patients could forgo a SLNB procedure.

Pedunculated early colorectal cancer with nodal metastasis: a case report

BackgroundPedunculated polyps are more likely to be amenable to complete resection than non-pedunculated early colorectal cancers and rarely require additional surgery. We encountered a patient with a pedunculated early colorectal cancer that consisted of poorly differentiated adenocarcinoma with lymphatic invasion. We performed an additional bowel resection and found nodal metastasis.Case presentationA 43-year-old woman underwent colonoscopy after a positive fecal occult blood test. The colonoscopist found a 20-mm pedunculated polyp in the descending colon and performed endoscopic resection. Histopathologic examination revealed non-solid type poorly differentiated adenocarcinoma. The lesion invaded the submucosa (3500 μm from the muscularis mucosa) and demonstrated lymphatic invasion. In spite of the early stage of this cancer, the patient was considered at high risk for nodal metastasis. She was referred to our institution, where she underwent bowel resection. Although there was no residual cancer after her endoscopic resection, a metastatic lesion was found in one regional lymph node. The patient is undergoing postoperative adjuvant chemotherapy, and there has been no evidence of recurrence 3 months after the second surgery.ConclusionsAdditional bowel resection is indicated for patients with pedunculated polyps and multiple risk factors for nodal metastasis, such as poorly differentiated adenocarcinoma and lymphatic invasion. We encountered just such a patient who did have a nodal metastasis; herein, we report her case history with a review of the literature.

Update on Sentinel Lymph Node Biopsy in Surgical Staging of Endometrial Carcinoma.

Sentinel lymph node (SLN) biopsy has emerged as an alternative staging approach in women with assumed early-stage endometrial carcinoma. Through image-guided surgery and pathologic ultrastaging, the SLN approach is introducing “precision medicine” to the surgical management of gynecologic cancers, providing a comprehensive evaluation of high-yield lymph nodes. This approach improves the surgeons’ ability to detect small-volume metastatic disease while reducing intraoperative and postoperative morbidity associated with lymphadenectomy. Although the majority of clinicians in Europe and the USA have recognized the value of SLN biopsy in endometrial carcinoma and introduced this as part of clinical practice, there is ongoing debate regarding its role in very low-risk patients as well as in patients at high risk of nodal metastasis. The significance of low-volume metastasis is not fully understood, and there is no consensus in regard to how the presence of isolated tumor cells should guide adjuvant therapy. Standardized protocols for histopathologic evaluation of SLNs are lacking. In this review article we aim to provide a framework for the introduction of SLN biopsy in endometrial cancer, give an updated overview of the existing literature, as well as discuss potential controversies and unanswered questions regarding this approach and future directions.

Lymph node dissection during radical nephrectomy: A Canadian multi-institutional analysis

ObjectivesTo determine the association between lymph node dissection (LND) at the time of radical nephrectomy and survival in a large, multi-institutional cohort using a propensity score matching design. Subjects and MethodsThe Canadian Kidney Cancer information system was used to identify patients undergoing radical nephrectomy for nonmetastatic renal cell carcinoma. Associations between LND with overall survival , recurrence free survival and cancer specific survival were determined using various propensity score techniques in the overall cohort and in patients with varying probabilities of pN1. Cox models were used to determine association of lymph node removed with outcomes. ResultsOf the 2,699 eligible patients, 812 (30%) underwent LND. Of the LND patients, 88 (10.8%) had nodal metastases. There was no association between LND and improved overall survival, recurrence free survival or cancer specific survival using various propensity score techniques (stratification by propensity score quintile, matched pairs, inverse treatment probability weighting and adjusted for propensity score quintile). There was no association between LND and a therapeutic benefit in patients with increased threshold probabilities of nodal metastases. Increased number of lymph nodes removed was not associated with improved survival outcomes. ConclusionsLND at the time of radical nephrectomy for renal cell carcinoma is not associated with improved outcomes. There was no benefit in patients at high risk for nodal metastases, and the number of nodes removed did not correlate with survival. Further studies are needed to determine which high risk patients may benefit from LND.

The modern management of Barrett's oesophagus and related neoplasia: role of pathology.

Modern management of Barrett's oesophagus and related neoplasia essentially focuses upon surveillance to detect early low-risk neoplastic lesions and offering organ-preserving advanced endoscopic therapies, while traditional surgical treatments of oesophagectomy and lymph node clearance with or without chemoradiation are preserved only for high-risk and advanced carcinomas. With this evolution towards figless invasive therapy, the choice of therapy hinges upon the pathological assessment for risk stratifying patients into those with low risk for nodal metastasis who can continue with less invasive endoscopic therapies and others with high risk for nodal metastasis for which surgery or other forms of treatment are indicated. Detection and confirmation of neoplasia in the first instance depends upon endoscopic and pathological assessment. Endoscopic examination and biopsy sampling should be performed according to the recommended protocols, and endoscopic biopsy interpretation should be performed applying standard criteria using appropriate ancillary studies by histopathologists experienced in the pathology of Barrett's disease. Endoscopic resections (ERs) are both diagnostic and curative and should be performed by clinicians who are skilled with advanced endoscopic techniques. Proper preparation and handling of ERs are essential to assess histological parameters that dictate the curative nature of the procedure. Those parameters are adequacy of resection and risk of lymph node metastasis. The risk of lymph node metastasis is determined by depth invasion and presence of poor differentiation and lymphovascular invasion. Those adenocarcinomas with invasion up to muscularis mucosae (pT1a) and those with superficial submucosal invasion (pT1b) up to 500µ with no poor differentiation and lymphovascular invasion and negative margins may be considered cured by endoscopic resections.

327 IS LOCAL ENDOSCOPIC RESECTION A VIABLE THERAPEUTIC OPTION FOR EARLY CLINICAL STAGE T1A AND T1B OESOPHAGEAL ADENOCARCINOMA? A PROPENSITY-MATCHED ANALYSIS

Abstract The role of endoscopic resection (ER) in the management of subsets of clinical T1N0 oesophageal adenocarcinoma is controversial. The aim of this study was to evaluate the outcome of ER versus oesophagectomy in node negative cT1a and cT1b oesophageal adenocarcinoma. Methods Data from the National Cancer Database (2010-2015), was used to identify patients with clinical T1aN0 (n = 2,545) and T1bN0 (n = 1,281) oesophageal adenocarcinoma that received either ER (cT1a, n = 1,581; cT1b, n = 335) or oesophagectomy (cT1a, n = 964; cT1b, n = 946). Propensity score matching (PSM) and Cox multivariable analyses were used to account for treatment selection bias. Results ER for cT1a and cT1b disease was performed more commonly over time. The rates of node-positive disease in patients with cT1a and cT1b oesophageal adenocarcinoma were 4% and 15%, respectively. In the matched cohort for cT1a cancers, ER had similar survival to oesophagectomy (HR: 0.85, 95% CI: 0.70-1.04, p = 0.1). The corresponding 5-year survival for ER and oesophagectomy were 70% and 74% (p = 0.1), respectively. For cT1b cancers, there was no statistically significant difference in overall survival between the treatment groups (HR: 0.87, 95% CI: 0.66-1.14, p = 0.3). The corresponding 5-year survival for ER and oesophagectomy were 53% vs. 61% (p = 0.3), respectively. Conclusion This study demonstrates ER has comparable long-term outcomes for clinical T1aN0 and T1bN0 oesophageal adenocarcinoma. However, 15% of patients with cT1b oesophageal cancer were found to have positive nodal disease. Future research should seek to identify the subset of T1b cancers at high risk of nodal metastasis and thus would benefit from oesophagectomy with lymphadenectomy.

Eyelid sebaceous gland carcinoma: An assessment of the T classification of the American Joint Committee of Cancer TNM staging system 8th versus 7th edition.

To assess the prognostic values of the T classification of the 8th edition of the American Joint Committee of Cancer staging system and compare it to the 7th edition. Multicenter retrospective study of patients with eyelid sebaceous gland carcinoma. The primary outcome measure was the differences between outcomes when tumors were staged with either 7th or 8th edition. The measures evaluated included presenting features, management, histopathology, metastasis, recurrence, and mortality. Of the 60 patients (median age 73 years), 31 (51.7%) were females. A change in T staging occurred in 39 patients (65%) when the 8th edition was applied. Advanced categories (T3/T4) were significantly associated with nodal metastasis (p = 0.037) using the 8th edition criteria but not with the 7th edition (p = 0.066). The 8th edition T categorization significantly correlated with eye survival (p = 0.022) while the 7th edition did not (p = 0.058). Applying the 8th edition, category T4 at presentation was associated with a higher risk of nodal metastasis (p = 0.037) but not associated with local recurrence, distant metastasis, or tumor-related death (p = 0.281, p = 0.737, p = 0.319, respectively). T3/T4 category tumors were significantly associated with poor tumor differentiation (p = 0.001), and papillary histologic pattern (p = 0.024) but not with pagetoid spread (p = 0.056). The application of the 8th edition AJCC staging system for eyelid SGC may accurately predict nodal metastasis. Local recurrence and distant metastasis were not significantly associated with T classification, using either edition. Poor tumor differentiation and papillary pattern were associated with T3/T4 categories suggesting that pathological features may assist in determining prognosis.

Is Local Endoscopic Resection a Viable Therapeutic Option for Early Clinical Stage T1a and T1b Esophageal Adenocarcinoma?: A Propensity-matched Analysis.

The aim of this study was to evaluate the outcome of endoscopic resection (ER) versus esophagectomy in node-negative cT1a and cT1b esophageal adenocarcinoma. The role of ER in the management of subsets of clinical T1N0 esophageal adenocarcinoma is controversial. Data from the National Cancer Database (2010-2015) were used to identify patients with clinical T1aN0 (n = 2545) and T1bN0 (n = 1281) esophageal adenocarcinoma that received either ER (cT1a, n = 1581; cT1b, n = 335) or esophagectomy (cT1a, n = 964; cT1b, n = 946). Propensity score matching and Cox analyses were used to account for treatment selection bias. ER for cT1a and cT1b disease was performed more commonly over time. The rates of node-positive disease in patients with cT1a and cT1b esophageal adenocarcinoma were 4% and 15%, respectively. In the matched cohort for cT1a cancers, ER had similar survival to esophagectomy [hazard ratio (HR): 0.85, 95% confidence interval (CI): 0.70-1.04, P = 0.1]. The corresponding 5-year survival for ER and esophagectomy were 70% and 74% (P = 0.1), respectively. For cT1b cancers, there was no statistically significant difference in overall survival between the treatment groups (HR: 0.87, 95% CI: 0.66-1.14, P = 0.3). The corresponding 5-year survival for ER and esophagectomy were 53% versus 61% (P = 0.3), respectively. This study demonstrates ER has comparable long-term outcomes for clinical T1aN0 and T1bN0 esophageal adenocarcinoma. However, 15% of patients with cT1b esophageal cancer were found to have positive nodal disease. Future research should seek to identify the subset of T1b cancers at high risk of nodal metastasis and thus would benefit from esophagectomy with lymphadenectomy.

Update on Sentinel Lymph Node Mapping in Endometrial Cancer Patients with a High Risk for Nodal Metastasis

Surgery is the mainstay of treatment for the majority of patients diagnosed with endometrial carcinoma. Systematic lymphadenectomy has traditionally been considered a standard part of surgical therapy. More recently, however, the value of this has been a subject of much debate. The sentinel lymph node (SLN) mapping algorithm has emerged as an acceptable alternative to conventional pelvic and para-aortic lymph node dissection in endometrial cancer. Clinical trials have demonstrated the accuracy of SLN mapping in detecting nodal spread in patients with endometrial cancer. However, data regarding the oncological outcomes of this approach, particularly in the setting of endometrial cancer with a high risk of nodal spread, is still lacking. In this review, we provide an overview of SLN mapping in endometrial cancer. We will specifically discuss its use in patients with a high risk for nodal metastasis. Controversies and future directions for research will also be discussed.

1402 Metastatic Merkel Cell Carcinoma With Isolated Pancreatic Metastases

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin malignancy. It has a high risk of nodal metastases (25%) but distant metastases are uncommon (8%). Liver and lung are the most common metastatic sites reported. Pancreatic metastases are uncommon and are associated with other sites of metastases. We report a rare case of Merkel cell carcinoma with isolated pancreatic metastases. CASE DESCRIPTION/METHODS: A 53-year-old Caucasian man presented with a 9-month history of an enlarging crusting lesion on the anterior chest wall. Physical examination showed a 15 × 20 cm crusty erythematous skin lesion in the upper mid chest. He also had palpable right axillary and left pre-clavicular lymphadenopathy. He underwent wide local excision with bilateral axillary and left neck lymph node dissection. Surgical pathology revealed node positive stage III MCC with a focus of squamous cell carcinoma. All margins were negative. He was started on adjuvant Radiation Therapy (RT) after discussion in the multidisciplinary tumor board but presented after 1-fraction with new upper abdominal discomfort. A CT scan showed areas of hypoattenuation in the pancreas with enlarged peri-pancreatic lymph nodes (Figure 1). EUS showed similar findings (Figure 2). EUS guided FNA was consistent with MCC. He underwent six cycles of chemotherapy with cisplatin/etoposide with complete resolution of the pancreatic masses and lymphadenopathy (Figure 3). However, 1 month later he passed away due to sudden cardiac arrest. DISCUSSION: Merkel cell carcinoma (MCC) is a neuroendocrine neoplasm of the skin, arising from Merkel cells at dermo-epidermal junction. It is a rare cancer with incidence of 0.7 per 100,000 persons. It predominately effects elderly, light-skinned and immunocompromised people. Merkel cell polyomavirus may play a role in the pathogenesis. Common sites of distal involvement include liver, lungs and bone. Pancreatic metastasis is rare with only a few cases reported, most of which were associated with other sites of metastases. EUS is a less-invasive means of confirming diagnosis and ruling out pancreatic adenocarcinoma. There is no standard modality of management for MCC with pancreatic metastasis. Chemotherapy, radiation therapy, surgical removal and immunotherapy with PD-L1 inhibitors are options for management. Overall prognosis is poor, with median survival around 7.5 months. Our patient responded very well to therapy but passed away from cardiac arrest 9 months after initial diagnosis.

Histologic spectrum of polymorphous adenocarcinoma of the salivary gland harbor genetic alterations affecting PRKD genes.

Polymorphous adenocarcinoma (PAC) and cribriform adenocarcinoma of (minor) salivary gland (CASG) are salivary gland tumors with overlapping spectrum of morphology. Whether these represent distinct entities or a histologic spectrum of the same tumor remains contentious. PACs harbor recurrent PRKD1 E710D hotspot mutations in >70% of cases, whereas 80% of CASGs display rearrangements involving PRKD1, PRKD2 or PRKD3 (PRKD1/2/3). We studied the molecular and morphologic features of 37 PACs/CASGs, seeking to identify the associations among genotype, histologic phenotype and classification. DNA was subjected to Sanger sequencing analysis of the PRKD1 hotspot locus. Fluorescence in situ hybridization (FISH) analysis for PRKD1/2/3 was performed using dual-color break-apart probes. Tumors were classified into four categories as described previously: PAC, CASG, tumor with indeterminate features (TIF) and tumor with a predominant papillary pattern (TPPP). PRKD1 E710D hotspot mutations were identified in 56%, 20%, 43% and 0% of PACs, CASGs, TIFs, and TPPPs, respectively. FISH demonstrated PRKD1/2/3 rearrangements in 13%, 78%, 36% and 75% of PACs, CASGs, TIFs and TPPPs, respectively. Histologically, fusion-positive tumors were associated with a high percentage of papillary growth, low percentage of single filing arrangement, a propensity of base of tongue location, and frequent (50%) lymph node metastasis, compared with the mutation-related tumors which had negligible nodal metastasis risk. Our results demonstrated that 1) PACs/CASGs are underpinned by genetic alterations affecting PRKD genes; 2) despite the associations between PAC and PRKD1 hotspot mutations and CASG and PRKD1/2/3 fusion, such distinction is not absolute; and 3) there is of a novel genotypic-phenotypic association whereby fusion-positive tumors are usually located in the base of tongue, show papillary architecture and have a high risk of nodal metastasis. Genetic analysis of PRKD genes appears to be useful characterizing this spectrum of tumors, not only histologically but clinically identifying those tumors with high risk of nodal metastasis.

Elective Node Irradiation With Integrated Boost to the Prostate Using Helical IMRT-Clinical Outcome of the Prospective PLATIN-1 Trial.

Introduction: This prospective, non-randomized phase II trial aimed to investigate the role of additional irradiation of the pelvic nodes for patients with prostate cancer and a high risk for nodal metastases using helical intensity-modulated radiotherapy with daily image guidance (IMRT/IGRT).Methods and materials: Between 2009 and 2012, 40 men with treatment-naïve prostate cancer and a risk of lymph node involvement of more than 20% were enrolled in the PLATIN-1 trial. All patients received definitive, helical IMRT of the pelvic nodes (total dose of 51.0 Gy) with a simultaneous integrated boost (SIB) to the prostate (total dose of 76.5 Gy) in 34 fractions. Antihormonal therapy (AHT) was administered for a minimum of 2 months before radiotherapy continuing for at least 24 months.Results: After a median follow-up of 71 months (range: 5–95 months), pelvic irradiation was associated with a 5-year overall survival (OS) and biochemical progression-free survival (bPFS) of 94.3% and 83.6%, respectively. For our cohort, no grade 4 gastrointestinal (GI) and genitourinary (GU) toxicity was observed. Quality of life (QoL) assessed by EORTC QLQ-C30 questionnaire was comparable to EORTC reference values without significant changes.Conclusion: The current trial demonstrates that elective IMRT/IGRT of the pelvic nodes with SIB to the prostate for patients with a high-risk of lymphatic spread is safe and shows an excellent clinical outcome without compromising the quality of life. The PLATIN-1 trial delivers eminent baseline data for future studies using modern irradiation techniques.

Prostate-only Versus Whole-pelvis Radiation with or Without a Brachytherapy Boost for Gleason Grade Group 5 Prostate Cancer: A Retrospective Analysis

BackgroundThe role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases. ObjectiveTo assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). Design, setting, and participantsWe identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT+BT). Outcome measurements and statistical analysisBiochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment. Results and limitationsA total of 299 EBRT patients (41%) and 320 EBRT+BT patients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT+BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT+BT groups were 58% and 78%, respectively. The median follow-up was 5.6yr. WPRT was associated with improved bRFS among patients treated with EBRT+BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2–0.9, p=0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6–1.2, p=0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7–1.7, p=0.8 for DMFS and HR 0.7, 95% CI 0.4–1.1, p=0.1 for PCSS), or in the EBRT+BT group (HR 0.6, 95% CI 0.3–1.4, p=0.2 for DMFS and HR 0.5 95% CI 0.2–1.2, p=0.1 for PCSS). ConclusionsWPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT+BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT+BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted. Patient summaryWhen men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.