Carlo Contreras

The NCCN Guidelines for Uveal Melanoma include recommendations for staging, treatment, and follow-up of patients diagnosed with uveal melanoma of the choroid or ciliary body. In addition, because distinguishing between uveal melanoma and benign uveal nevi is in some cases difficult, these guidelines also contain recommendations for workup of patients with suspicious pigmented uveal lesions, to clarify the tests needed to distinguish between those who should have further workup and treatment for uveal melanoma versus those with uncertain diagnosis and low risk who should to be followed and later reevaluated. These NCCN Guidelines Insights describe recommendations for treatment of newly diagnosed nonmetastatic uveal melanoma in patients who have already undergone a complete workup.

Background Acral lentiginous melanoma is associated with worse survival than other subtypes of melanoma. Understanding prognostic factors for survival and recurrence can help better inform follow-up care. Objectives To analyze the clinicopathologic features, melanoma-specific survival, and recurrence-free survival by substage in a large, multi-institutional cohort of primary acral lentiginous melanoma patients. Methods Retrospective review of the United States Melanoma Consortium database, a multi-center prospectively collected database of acral lentiginous melanoma patients treated between January 2000 and December 2017. Results Of the 433 primary acral lentiginous melanoma patients identified (median [range] age: 66 [8–97] years; 53% female, 83% white), 66% presented with stage 0–2 disease and the median time of follow-up for the 392 patients included in the survival analysis was 32.5 months (range: 0–259). The 5-year melanoma-specific survivals by stage were 0 = 100%, I = 93.8%, ...

Introduction: After melanoma diagnosis, various factors can delay therapy, including the COVID-19 pandemic. In this study, we examine the significance of surgical delay on sentinel lymph node (SLN) status in melanoma patients. Methods: Using the National Cancer Database, we examined surgical delay, defined as time from biopsy to surgical excision, for patients diagnosed with cutaneous melanoma who underwent tumor resection and SLN biopsy. Patients with clinically positive nodes were excluded. Logistic regression models were constructed to adjust for pertinent clinical factors. Results: From 2012-2017, 21,153 patients were included and 21.2% (n = 4,486) experienced a surgical delay of more than 45 days. Patients experiencing prolonged surgical delay were older (older than 75 years), lived farther from their reporting hospital, had Medicaid or were uninsured, or had multiple comorbidities (all, p < 0.05). Metastatic SLNs were more likely in younger patients (younger than 55 years), ulcerated tumors, and tumors ≥ 1 mm (p > 0.001). In adjusted analyses, the odds of SLN metastasis increased by 1% per day of surgical delay (odds ratio [OR] 1.01;95% CI, 1.00 to 1.01;p = 0.003) and by 19% for surgical delay more than 45 days (OR 1.19;95% CI, 1.02 to 1.39;p = 0.026). Surgical delay more than 45 days was associated with increased risk of SLN metastasis in the following scenarios: nonulcerated tumors (OR 1.23;95% CI, 1.04 to 1.46;p = 0.017), age 65 through 74 years (OR 1.46;95% CI, 1.06 to 2.02;p = 0.019), or thickness 1.00 to 1.99 mm (OR 1.27;95% CI, 1.00 to 1.60;p = 0.048). Conclusions: Tumor ulceration, thickness, and patient age confer increased risk of SLN metastasis when surgical delay occurs. In light of COVID-19-related delays in diagnosis and treatment, particular patients appear to benefit from timely SLN biopsy.

The clinical management of melanoma patients has been rapidly evolving with the introduction of new targeted immuno-oncology (IO) therapeutics. The current diagnostic paradigms for melanoma patients begins with the histopathologic confirmation of melanoma, initial staging of disease burden with imaging and surgical approaches, treatment monitoring during systemic cytotoxic chemotherapy or IO therapeutics, restaging after completion of adjuvant systemic, surgical, and/or external radiation therapy, and the detection of recurrent malignancy/metastatic disease following therapy. New and evolving imaging approaches with positron-emission tomography (PET) imaging technologies, imaging methodologies, image reconstruction, and image analytics will likely continue to improve tumor detection, tumor characterization, and diagnostic confidence, enabling novel precision nuclear medicine practices for managing melanoma patients. This review will examine current concepts and challenges with existing PET imaging diagnostics for melanoma patients and introduce exciting new opportunities for PET in the current era of IO therapeutics.

This review highlights important age-related changes at the physiologic level and their clinical consequences. Latest societal guidelines and consensus expert opinions on pre- and perioperative management of elderly surgical patients are discussed. Age-related postoperative complications, including precipitating factors and appropriate management, are summarized. The latest advancements in the management of important surgical problems in geriatric populations are outlined. This review contains 4 figures, 8 tables, and 103 references. Key words: aging, elderly patient, immunosenescence

e15714 Background: Although combination of fluorouracil, irinotecan, Leucovorin and oxaliplatin [FOLFIRINOX] significantly increases survival in metastatic pancreatic cancer (MPC) compared to gemcitabine based on ACCORD trial, the efficacy and toxicities may be different in non-metastatic setting. We reviewed our institution’s experience with FOLFIRINOX in locally advanced pancreatic cancer (LAPC). Methods: We performed a retrospective review of clinical outcomes in patients diagnosed with LAPC and receiving between June 2010 and July 2015, with at least one year of follow up from diagnosis, at University of Alabama at Birmingham. Results: Total of 41 patients with ECOG performance scale of 0 or 1, who underwent neoadjuvant chemotherapy with FOLFIRINOX were assessed for clinical and pathological characteristics. Median age was 61 years (range 38-81) with 23 (56.1%) males, 28 (68.3%) Caucasians and 16 (39.0%) underwent surgery (whipple operation) post-neoadjuvant. Median OS (time of ...

PRDM1 is a tumor suppressor that plays an important role in B and T cell lymphomas. Our previous studies demonstrated that PRDM1β is a p53-response gene in human colorectal cancer cells. However, the function of PRDM1β in colorectal cancer cells and colon tumor organoids is not clear. Here we show that PRDM1β is a p53-response gene in human colon organoids and that low PRDM1 expression predicts poor survival in colon cancer patients. We engineered PRDM1 knockouts and overexpression clones in RKO cells and characterized the PRDM1-dependent transcript landscapes, revealing that both the α and β transcript isoforms repress MYC-response genes and stem cell-related genes. Finally, we show that forced expression of PRDM1 in human colon cancer organoids prevents the formation and growth of colon tumor organoids in vitro. These results suggest that p53 may exert tumor-suppressive effects in part through a PRDM1-dependent silencing of stem cell genes, depleting the size of the normal intesti...

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cutaneous melanoma have been significantly revised over the past few years in response to emerging data on immune checkpoint inhibitor therapies and BRAF-targeted therapy. This article summarizes the data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease.

Gallbladder cancer (GBC) is an often lethal disease, but surgical resection is potentially curative. Symptoms may be misdiagnosed as biliary colic; over half of new diagnoses are made after laparoscopic cholecystectomy for presumed benign disease. Gallbladder polyps >1 cm should prompt additional imaging and cholecystectomy. For GBC diagnosed after cholecystectomy, tumors T1b and greater necessitate radical cholecystectomy. Radical cholecystectomy includes staging laparoscopy, hepatic resection, and locoregional lymph node clearance to achieve R0 resection. Patients with locally advanced disease (T3 or T4), hepatic-sided T2 tumors, node positivity, or R1 resection may benefit from adjuvant chemotherapy. Chemotherapy increases survival in unresectable disease.

This selection from the NCCN Guidelines for Merkel Cell Carcinoma (MCC) focuses on areas impacted by recently emerging data, including sections describing MCC risk factors, diagnosis, workup, follow-up, and management of advanced disease with radiation and systemic therapy. Included in these sections are discussion of the new recommendations for use of Merkel cell polyomavirus as a biomarker and new recommendations for use of checkpoint immunotherapies to treat metastatic or unresectable disease. The next update of the complete version of the NCCN Guidelines for MCC will include more detailed information about elements of pathology and addresses additional aspects of management of MCC, including surgical management of the primary tumor and draining nodal basin, radiation therapy as primary treatment, and management of recurrence.

We have performed a genome-wide synthetic lethal screen for pathways that are essential for the survival of colon cancer cells with TP53 mutations. RKO colon cancer cells are wild-type for TP53, and display robust p53-dependent growth arrest and apoptosis. We have utilized an isogenic pair of RKO cells differing only in TP53 gene status (Wild Type vs homozygous null derivative) to screen a genome-wide GeCKO CRISPR library and identified pathways that are novel therapeutic targets for TP53-mutant colon cancers. After infection of these cells with the GeCKO CRISPR library and one week of culturing in vitro, we performed deep GeCKO CRIPSR amplicon sequencing to enumerate and identify all CRISPRs that were underrepresented in TP53 mutant compared to wild type cells. We identified multiple CRISPRs targeting the CHEK1 and the SHH genes which were underrepresented in TP53 knockout cells. We then tested small molecule inhibitors of CHEK1 (UCN01) and the SHH receptor SMO (Cyclopamine) against isogenic pairs of RKO, HCT116, and DLD1 cells and confirmed that each molecule is significantly more toxic to cells with mutant TP53 than to those with wild-type TP53. Future studies will focus on testing these and additional targets alone and in combination against primary colon tumor and normal avatars, and preclinical models of TP53-mutant colon cancer. Citation Format: Charles C. Weige, Erin L. Anderson, Joseph Richardson, Carlo Contreras, Phillip J. Buckhaults. Synthetic lethal screen to identify novel therapies targeting TP53-mutant colon cancer cells. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B10.

147 Background: The CROSS trial established the role of neoadjuvant radiation in the treatment of esophageal adenocarcinoma (EAC). While response to radiation is an important factor in predicting long-term outcomes, the vast majority of patients succumb to systemic disease. The purpose of this study is to assess predictors of survival in patients with EAC following radiation therapy. Methods: All patients who underwent resection after radiation therapy for EAC at a single institution were retrospectively identified from January 2004 to December 2014. Patients who died within 30 days of surgery were excluded. Cox-proportional hazard analyses were performed to identify clinico-pathological factors associated with survival after surgery. Results: In the time period, 334 patients underwent esophagectomy for EAC. Univariable/multivariable analyses are shown in the table. The presence of a pathologic complete response (pCR) did not correlate to survival. The most important factors in pred...

456 Background: Ampullary carcinoma [AC] is a rare malignancy associated with favorable prognosis among pancreatobiliary tumors. Pancreaticoduodenectomy [PDY] is considered to be curative for early stage cancers. The role of adjuvant chemotherapy [CT] or combination chemoradiation [CRT] remains uncertain for stage I/II. In this analysis we reviewed our institution’s experience with AC. Methods: From 2005 to 2015, 62 patients with stage 1 and 2 AC with at least one year follow up after PDY were reviewed. Clinical and pathologic factors and disease status were obtained from chart review. The patients’ demographical and oncological characteristics are summarized. The univariate Cox proportional hazard model was conducted for evaluating the parameters associated with overall survival. Kaplan-Meier method and log-rank was used to compare the time-to-events. Results: Adjuvant treatment was administered in 61%: CT (32%), CRT (29%) 39% surgical alone. The median overall survival [OS] for th...

Chemical genetic screening of small-molecule libraries has been a promising strategy for discovering unique and novel therapeutic compounds. However, identifying the targets of lead molecules that arise from these screens has remained a major bottleneck in understanding the mechanism of action of these compounds. Here, we have coupled the screening of a cysteine-reactive fragment-based covalent ligand library with an isotopic tandem orthogonal proteolysis-enabled activity-based protein profiling (isoTOP-ABPP) chemoproteomic platform to rapidly couple the discovery of lead small molecules that impair pancreatic cancer pathogenicity with the identification of druggable hotspots for potential cancer therapy. Through this coupled approach, we have discovered a covalent ligand DKM 2-93 that impairs pancreatic cancer cell survival and in vivo tumor growth through covalently modifying the catalytic cysteine of the ubiquitin-like modifier activating enzyme 5 (UBA5), thereby inhibiting its a...

Abstract Case: A 47-year-old female presented with hypoglycemia for 1 year. The 72-hour fast was terminated for hypoglycemic symptoms and glucose of 40 mg/dL. Laboratories revealed low insulin level and low–normal C-peptide with elevated proinsulin, suggesting proinsulin-secreting neuroendocrine tumor (NET). Insulinoma is the most common functioning pancreatic NET and presents with symptoms of hypoglycemia. CT was negative for pancreatic mass. Endoscopic ultrasonography (EUS) revealed an 8 × 7 mm midbody pancreatic mass and biopsy confirmed NET. Fiducial markers were placed with EUS guidance to aid intraoperative localization during partial pancreatectomy. Intraoperative fluoroscopy (IOF) and laparoscopic ultrasonography (LUS) localized the peritumoral fiducials. The mass was close to the splenic vessels and nearly abutting the pancreatic duct. A 60-mm laparoscopic stapler was inserted, and the fiducials were used to achieve ≥1 cm surgical margin (video). The total laparoscopic distal pancreatectomy was c...

To conduct a telephone survey establishing pancreatic cancer survivors' level of interest in, preferences for, and perceived barriers and facilitators to participating in exercise and diet intervention programming. These data will inform the development of such interventions for newly-diagnosed patients. Seventy-one survivors treated for resectable pancreatic adenocarcinoma from October 2011 to August 2014 were identified through an institutional cancer registry and contacted via telephone. A telephone survey was conducted to query survivors' level of interest in, preferences for, and perceived barriers and facilitators to participating in an exercise and dietary intervention program shortly after disease diagnosis. Acceptability of a technology-based visual communication (e.g., Skype™, FaceTime®) intervention was also assessed. Fifty participants completed the survey (response rate 71.8 %). Over two-thirds of participants reported interest in exercise and diet intervention ...

Pancreatic ductal secretions are an abundant source of proteins that may serve as biomarkers for the early detection of pancreatic adenocarcinoma. Most pancreatic ductal secretion proteomes published in the literature are dominated by serum proteins. Due to the invasive nature of procedures used to sample pancreatic secretions, it remains uncertain whether the serum proteins present in the samples are artifacts of blood introduced during sampling or true indicators of disease. In addition, serum proteins are not generally useful as specific disease markers and mask other less abundant pancreas-specific proteins of interest in the sample. The enrichment of pancreas-specific proteins in pancreatic ductal secretions increases the opportunity for uncovering specific biomarkers of pancreatic cancer. Pancreatic ductal secretions were collected from ten patients with pancreatic adenocarcinoma undergoing pancreatectomy during surgery according to IRB-approved protocols. Protease inhibitors were added and samples were stored at -80°C. Samples were extracted 3x with chloroform to remove hydrophobic contaminants followed by IgA depletion using SSL-7 agarose (Invivogen) and depletion with a Vivapure Anti-HSA human albumin depletion (Sartorius) or Seppro IgY 14 Spin Column (Sigma) serum protein depletion column. Depleted samples were precipitated with methanol/chloroform/water, dissolved into 2M urea with 50mM ammonium bicarbonate/ 10mM TCEP and digested with trypsin. The digest was processed on a C-18 column on an HPLC, dried, resuspended in 0.1% TFA and characterized by ESI-LC-MS/MS on an LTQ-Orbitrap. Data were searched using Mascot against the NCBI RefSeq database. The top 20 proteins in pancreatic secretions taken from pancreatic adenocarcinoma patients in order of abundance without depletion were albumin, transferrin, beta globin, alpha 2 globin, IgA-1 chain constant region, alpha-1 antitrypsin, complement component 3, carboxyl ester lipase, keratin 1, apolipoprotein A-1, haptoglobin, delta globin, Predicted protein similar to complement component C3, alpha-2 macroglobulin, pancreatic carboxypeptidase B1, IgA-2 chain constant region, apolipoprotein E, polymeric immunoglobulin receptor, IgG-1 constant region, and Ig lambda chains. Mascot scores for albumin were about 20 times higher than scores for the pancreas-specific proteins and about three times higher than scores for the other serum proteins. Twelve of the fourteen proteins which are depleted by the Seppro IgY 14 depletion columns are present as dominant proteins in most pancreatic secretion samples. Of the remaining top proteins, alpha-2, beta and delta globin are blood proteins which are not depleted. These are most likely the result of hemolyzed red blood cells during freezing. Carboxyl ester lipase, pancreatic carboxypeptidases A1, B1, elastase 3A and 3B, trypsin, regenerating islet-derived 1 alpha and beta, pancreatic lipase, chymotrypsin B1 and B2, pancreatitis-associated protein, pancreatic amylase alpha 2A and B, mesotrypsin, and phospholipase A2 are pancreas specific proteins which are detected with increased sensitivity once the interfering serum proteins are depleted. Data will be shown comparing the performance of the two columns in depletion efficiency as well as the effect of the addition of an additional depletion step of secretory IgA from the samples, which depleted IgA-1, IgA-2, polymeric immunoglobulin receptor, Ig-lambda and Ig-kappa chain proteins. In conclusion, IgA, albumin, and IgY 14 serum protein depletion improve the LC-MS analysis of pancreas-derived proteins in pancreatic secretions by reducing interference from abundant serum proteins. Citation Format: Jana D. Rocker, Carlo Contreras, Lee W. Thompson, Russell E. Brown, Jack A. DiPalma, Lewis K. Pannell. Depletion of antibodies and serum-derived proteins to facilitate LC-MS detection of pancreas-specific proteins in pancreatic ductal secretions. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr B4.

From a surgeon's perspective, the AJCC 6th edition is the staging system of choice due to its simplified clinicopathologic schema, discriminatory accuracy, extensive external validation, widespread geographic reproducibility, and applicability to both the resection and transplantation patient population with hepatocellular carcinoma.

The use of staging laparoscopy has been highly institutional dependent. We sought to assess the incidence of occult intra-abdominal metastases identified at the time of staging laparoscopy for patients with either potentially resectable or locally advanced pancreatic adenocarcinoma (LAPC). We also compared the rate of occult metastases in patients who underwent staging laparoscopy versus laparotomy. Patients were confirmed to have potentially resectable or LAPC at a multidisciplinary hepatopancreaticobiliary conference. Patients with potentially resectable lesions were initially explored via staging laparoscopy or laparotomy, based on surgeon preference. Over a 4-year period, 25 patients with potentially resectable tumors and 33 patients with LAPC were staged with laparoscopy, with an equivalent prevalence of occult metastases found at laparoscopy (28% potentially resectable vs. 33% LAPC, P = 0.8). Fifty-two patients with potentially resectable lesions were explored initially via laparotomy. Occult peritoneal metastases were more likely to be detected in patients with potentially resectable tumors that were explored via laparoscopy than via laparotomy (32% vs. 10%, P = 0.018). Staging laparoscopy is more likely than open exploration to detect occult metastases. Current preoperative imaging inadequately identifies unresectable pancreatic adenocarcinoma; therefore, all patients with potentially resectable disease should undergo staging laparoscopy.

The purpose of this study was to identify preoperative clinical and radiographic factors relevant to treatment selection and outcomes in patients with advanced cancer presenting with bowel obstruction. Clinical and radiographic data were retrospectively obtained from records of inpatients with suspected bowel obstruction referred for palliative surgical consultation (2000-2006). Patients were stratified according to site of obstruction: gastric outlet obstruction (GOO), small bowel obstruction (SBO), and large bowel obstruction (LBO). We utilized the Cox proportional hazards model to identify preoperative clinical and radiologic variables associated with overall survival (OS). Of 191 patients, the site of obstruction was classified as GOO in 41 (21%), SBO in 122 (64%), and LBO in 28 (15%). Almost half of the patients (47%) had received systemic therapy in the 6 weeks prior to evaluation. The most common sites of disease identified on imaging included abdominal visceral metastases (37%), carcinomatosis/sarcomatosis (46%), and an intact primary tumor or recurrence (31%). Most patients (62%) exhibited 2 or more sites of disease on imaging. Treatment strategies included nonoperative/nonprocedural management in 41% (n = 79), endoscopic/interventional radiology procedures in 25% (n = 48), and surgery in 34% (n = 64). Median OS for the cohort was 3.5 months (95% confidence interval [CI]: 2.7-4.6). Median OS for GOO, SBO, and LBO was 2.7 (95% CI: 1.7-4.1), 3.5 (95% CI: 2.5-4.9), and 7.0 (95% CI: 2.1-11) months, respectively (p = 0.17). Adverse prognostic factors for OS included endoscopic/interventional radiology procedures and ≥3 radiologically evident sites of disease. OS, although low, was not significantly different among GOO, SBO, and LBO. Single sites of disease identified on imaging were not associated with OS, although multiple sites of disease were associated with diminished OS.

The optimal duration, safety, and benefit of preoperative chemotherapy in patients with colorectal liver metastases (CLM) are unclear. We evaluated the association between the duration of preoperative chemotherapy with 5-fluorouracil (5-FU), leucovorin, oxaliplatin (FOLFOX) ± bevacizumab, pathologic response, and hepatotoxicity after hepatic resection for CLM. A total of 219 patients underwent hepatic resection following FOLFOX with or without bevacizumab and were divided into 2 groups according to the chemotherapy duration: 1-8 cycles (short duration [SD]; N = 157) and ≥9 cycles (long duration [LD]; N = 62). The frequency of complete or major pathologic response, sinusoidal injury, and major postoperative morbidity were compared. Treatment consisting of ≥9 cycles was not associated with an increase in complete or major pathologic response (SD vs. LD, 57% vs. 55%; P = .74). The incidence of sinusoidal injury was higher in the LD group (26% vs. 42%; P = .017). The incidence of liver insufficiency was higher in the LD group (4% vs. 11%; P = .035). Sinusoidal injury did not predict postoperative liver insufficiency; multivariate analysis revealed ≥9 cycles was the only independent predictor of postoperative liver insufficiency (P = .031; odds ratio = 3.90). Chemotherapy including bevacizumab was associated with a significantly higher frequency of complete or major response in both SD and LD groups. Extended preoperative chemotherapy increases the risk of hepatotoxicity in CLM without improving the pathologic response. The type of chemotherapy (FOLFOX with bevacizumab) has more impact on pathologic response than the duration of chemotherapy.

We have performed a genome-wide screen for pathways that are synthetic lethal with TP53 mutations in colon cancer. RKO colon cancer cells are wild type for TP53, and display robust p53-dependent growth arrest and apoptosis. We utilized an isogenic pair of RKO cells differing only in TP53 gene status (wild type vs homozygous null derivative) to screen a genome-wide GeCKO CRISPR library. After infection of these cells with the library and culturing for one week in vitro, we performed deep amplicon sequencing to identify CRISPR guide RNAs that were underrepresented in TP53 knockout cells. Multiple CRISPR guide RNAs targeting the CHEK1 and SHH genes were underrepresented in TP53 knockout cells. To validate these targets, we used CRISPR genome engineering to create an independent panel of six RKO clones with biallelic disruption of TP53, and tested small molecule inhibitors of CHEK1 (UCN01) and the SHH receptor SMO (Cyclopamine). TP53 null cells were tenfold more sensitive to UCN01, and 100-fold more sensitive to Cyclopamine, compared to TP53 wild type cells. Finally, the relevance of these findings to human colon cancers was confirmed by the establishment and treatment of colon cancer organoid avatars with either wild type or mutant TP53. Normal colon organoids, and tumor organoids with wild type TP53 were unaffected by either drug, whereas TP53 mutant organoids were significantly growth inhibited. Future studies will focus on testing these and additional targets, alone and in combination, against primary colon tumor and normal avatars and other preclinical models of TP53-mutant colon cancer. Citation Format: Charles C. Weige, Changlong Liu, Erin L. Anderson, Carolyn E. Banister, Joseph Richardson, Carlo Contreras, Phillip J. Buckhaults. TP53 synthetic lethal targets in colon cancer. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B14.

Deep transection of invasive melanoma precludes accurate measurement of Breslow depth, which may affect tumor staging. To determine the frequency of upstaging of transected invasive melanomas after excision, characterize the impact on National Comprehensive Cancer Network (NCNN)-recommended treatment, and determine predictors of subsequent upstaging. A retrospective review of invasive melanomas between January 2017 and December 2019 at a single institution. Deeply transected biopsy reports were compared with subsequent excisions to calculate the frequency of upstaging. Three hundred sixty (49.6%) of 726 invasive melanomas identified were transected. Forty-nine (13.6%) transected tumors had upstaging that would have altered NCCN-recommended management. "Broadly" transected tumors had upstaging that would have resulted in a change in the management in 5/23 cases (21.7%) versus 2/41 cases (4.9%) for "focally" transected tumors (p = .038). Breslow depth increased by 0.59 mm on average for "broad" transection versus 0.06 mm for "focal" transection (p =< .01). Of the 89 transected pT1a melanomas, specimens with gross residual tumor or pigment after biopsy were upstaged in 8/17 (47.1%) of cases versus 5/72 (6.9%) of specimens without (p =< .01). Upstaging of deeply transected invasive melanomas that would alter NCCN-recommended management occurred in 13.6% of cases. Broad transection and gross residual tumor or pigment after biopsy predicted higher likelihood of upstaging.