Critical updates in neuroendocrine tumors: Version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine tumors.

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP-NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP-NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP-NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP-NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.

Single-Photon Emission Computed Tomography/Computed Tomography Utilization for Extremity Melanomas at a High-Volume Center.

INTRODUCTION: Planar lymphoscintigraphy (PL) is commonly used in mapping before sentinel lymph node biopsy (SLNB) for invasive cutaneous melanoma. Recently, single-photon emission computed tomography (SPECT)/ computed tomography (CT) has been utilized, in addition to PL, for detailed anatomic information and detection of sentinel lymph nodes (SLNs) outside of the primary nodal basin in truncal and head and neck melanoma. Following a protocol change due to COVID-19, our institution began routinely obtaining both PL and SPECT-CT imaging for all melanoma SLN mapping. We hypothesized that SPECT-CT is associated with higher instances of SLNBs from "nontraditional" nodal basins (NTNB) for extremity melanomas. METHODS: Patients with extremity melanoma (2017-2022) who underwent SLNB were grouped into SPECT-CT with PL versus PL alone. Outcomes were total SLNs removed, + or-SLN status, total NTNB sampled, and postoperative complication rate. Poisson regression and logistic regression models were used to assess association of SPECT-CT with patient outcomes. RESULTS: Of 380 patients with extremity melanoma, 42.11% had SPECT-CT. There were no differences between the groups with regards to age at diagnosis or sex. From 2020 to 2022, all patients underwent SPECT-CT. SPECT-CT was associated with increased odds of SLNB from an NTNB, (odds ratio = 2.39 [95% confidence interval: 1.25-4.67]). There was no difference in odds of number of SLNs sampled, SLN positivity rate, or postoperative complication rate with SPECT-CT. CONCLUSIONS: Routine SPECT-CT was associated with higher incidence of SLNB in NTNB but did not increase number of SLNs removed or SLN positivity rate. The added value of routine SPECT-CT in cutaneous melanoma of the extremities remains to be defined.

Data-driven optimization of version 9 American Joint Committee on Cancer staging system for anal cancer.

INTRODUCTION: The American Joint Committee on Cancer (AJCC) staging system undergoes periodic revisions to maintain contemporary survival outcomes related to stage. Recently, the AJCC has developed a novel, systematic approach incorporating survival data to refine stage groupings. The objective of this study was to demonstrate data-driven optimization of the version 9 AJCC staging system for anal cancer assessed through a defined validation approach. METHODS: The National Cancer Database was queried for patients diagnosed with anal cancer in 2012 through 2017. Kaplan-Meier methods analyzed 5-year survival by individual clinical T category, N category, M category, and overall stage. Cox proportional hazards models validated overall survival of the revised TNM stage groupings. RESULTS: Overall, 24,328 cases of anal cancer were included. Evaluation of the 8th edition AJCC stage groups demonstrated a lack of hierarchical prognostic order. Survival at 5 years for stage I was 84.4%, 77.4% for stage IIA, and 63.7% for stage IIB; however, stage IIIA disease demonstrated a 73.0% survival, followed by 58.4% for stage IIIB, 59.9% for stage IIIC, and 22.5% for stage IV (p <.001). Thus, stage IIB was redefined as T1-2N1M0, whereas Stage IIIA was redefined as T3N0-1M0. Reevaluation of 5-year survival based on data-informed stage groupings now demonstrates hierarchical prognostic order and validated via Cox proportional hazards models. CONCLUSION: The 8th edition AJCC survival data demonstrated a lack of hierarchical prognostic order and informed revised stage groupings in the version 9 AJCC staging system for anal cancer. Thus, a validated data-driven optimization approach can be implemented for staging revisions across all disease sites moving forward.

Survival outcomes used to validate version 9 of the American Joint Committee on Cancer staging system for appendiceal cancer.

The standard for cancer staging in the United States for all cancer sites, including primary carcinomas of the appendix, is the American Joint Committee on Cancer (AJCC) staging system. AJCC staging criteria undergo periodic revisions, led by a panel of site-specific experts, to maintain contemporary staging definitions through the evaluation of new evidence. Since its last revision, the AJCC has restructured its processes to include prospectively collected data because large data sets have become increasingly robust and available over time. Thus survival analyses using AJCC eighth edition staging criteria were used to inform stage group revisions in the version 9 AJCC staging system, including appendiceal cancer. Although the current AJCC staging definitions were maintained for appendiceal cancer, incorporating survival analysis into the version 9 staging system provided unique insight into the clinical challenges in staging rare malignancies. This article highlights the critical clinical components of the now published version 9 AJCC staging system for appendix cancer, which (1) justified the separation of three different histologies (non-mucinous, mucinous, signet-ring cell) in terms of prognostic variance, (2) demonstrated the clinical implications and challenges in staging heterogeneous and rare tumors, and (3) emphasized the influence of data limitations on survival analysis for low-grade appendiceal mucinous neoplasms.

Survival outcomes used to generate version 9 American Joint Committee on Cancer staging system for anal cancer.

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including anal cancer, is the standard for cancer staging in the United States. The AJCC staging criteria are dynamic, and periodic updates are conducted to optimize AJCC staging definitions through a panel of experts charged with evaluating new evidence to implement changes. With greater availability of large data sets, the AJCC has since restructured and updated its processes, incorporating prospectively collected data to validate stage group revisions in the version 9 AJCC staging system, including anal cancer. Survival analysis using AJCC eighth edition staging guidelines revealed a lack of hierarchical order in which stage IIIA anal cancer was associated with a better prognosis than stage IIB disease, suggesting that, for anal cancer, tumor (T) category has a greater effect on survival than lymph node (N) category. Accordingly, version 9 stage groups have been appropriately adjusted to reflect contemporary long-term outcomes. This article highlights the changes to the now published AJCC staging system for anal cancer, which: (1) redefined stage IIB as T1-T2N1M0 disease, (2) redefined stage IIIA as T3N0-N1M0 disease, and (3) eliminated stage 0 disease from its guidelines altogether.

Feasibility of personalized circulating tumor DNA detection in stage II and III melanoma.

The objective of this study was to evaluate the feasibility of developing personalized, tumor-informed assays for patients with high-risk resectable melanoma and examine circulating tumor DNA (ctDNA) levels in relation to clinical status. Pilot prospective study of clinical stage IIB/C and resectable stage III melanoma patients. Tumor tissue was used to design bespoke somatic assays for interrogating ctDNA in patients' plasma using a multiplex PCR (mPCR) next-generation sequencing (NGS)-based approach. Plasma samples for ctDNA analysis were collected pre-/post-surgery and during surveillance. Out of 28 patients (mean 65 years, 50% male), 13 (46%) had detectable ctDNA prior to definitive surgery and 96% (27/28) tested ctDNA-negative within 4 weeks post-surgery. Pre-surgical detection of ctDNA was significantly associated with the later-stage ( P  = 0.02) and clinically evident stage III disease ( P  = 0.007). Twenty patients continue in surveillance with serial ctDNA testing every 3-6 months. With a median follow-up of 443 days, six out of 20 (30%) patients developed detectable ctDNA levels during surveillance. All six of these patients recurred with a mean time to recurrence of 280 days. Detection of ctDNA in surveillance preceded the diagnosis of clinical recurrence in three patients, was detected concurrent with clinical recurrence in two patients and followed clinical recurrence in one patient. One additional patient developed brain metastases without detection of ctDNA during surveillance but had positive pre-surgical ctDNA. Our results demonstrate the feasibility of obtaining a personalized, tumor-informed mPCR NGS-based ctDNA assay for patients with melanoma, particularly in resectable stage III disease.

Melanoma metastatic to the adrenal gland: An update on the role of adrenalectomy in multidisciplinary management.

BACKGROUND AND OBJECTIVES: Modern systemic therapy (immune checkpoint blockade [ICB], targeted therapy) has improved survival for patients with metastatic melanoma. The role of adrenal metastasectomy is not well characterized in this setting. METHODS: Consecutive patients treated with adrenalectomy 1/1/2007-1/1/2019 were retrospectively compared to patients treated with systemic therapy alone in the same time period. Overall survival and survival after adrenal metastasis were compared, prognostic factors associated with survival after adrenal metastasis development were evaluated. RESULTS: A total of 74 patients underwent adrenalectomy and were compared to 69 treated with systemic therapy alone. The most common indications for adrenalectomy were to render the patient disease-free in the setting of isolated adrenal metastasis (n = 32, 43.2%) or treatment of isolated progression in the setting of other stable/responding metastases (n = 32, 43.2%). Patients treated surgically had longer survival (116.9 vs. 11.0 months after adrenal metastasis diagnosis, p < 0.001). On multivariate analysis, receipt of ICB (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: [0.40-0.95]) and selection for adrenalectomy (HR: 0.27, 95% CI: [0.17-0.42]) were the strongest factors associated with improved survival after adrenal metastasis diagnosis. CONCLUSIONS: Selective application of adrenal metastasectomy is associated with prolonged survival benefit and remains an important consideration in the multidisciplinary management of patients with metastatic melanoma.

Setting the Standard for Cutaneous Melanoma Wide Local Excision: An Overview of the American College of Surgeons Commission on Cancer Standard 5.5.

The purpose of this article is to review the objectives of the American College of Surgeons Commission on Cancer Operative Standards with a specific focus on Standard 5.5, which pertains to curative intent wide local excision of primary cutaneous melanoma lesions. We review the details and rationale of the standard itself, including its requirement to include specific elements and responses in synoptic format in operative reports.

Landmark Series on Disparities in Surgical Oncology: Melanoma.

BACKGROUND: Although the lifetime risk of melanoma is disproportionately higher in whites, blacks have a poorer overall survival with an absolute survival difference of 25%. Significant progress has been made in melanoma treatment in the past decade; however, these successes may not be available or accessible to all segments of the population. METHODS: In this review, we highlight important studies in melanoma as well as informative retrospective studies from databases and nonmelanoma cancers where appropriate. RESULTS: There are no level I evidence-based studies on disparities in melanoma, and most likely there will never be, but the studies presented herein and clinical experience demonstrate that disparities in clinical outcomes from melanoma exists. CONCLUSIONS: By becoming aware of the disparities, we can help mitigate them by engagement, education, and corrective and empowering actions through awareness campaigns, appropriate clinical trial design, encouraging participation in clinical trials, increasing the diversity of providers, and advocacy.

Trends in the management of anorectal melanoma: A multi-institutional retrospective study and review of the world literature.

BACKGROUND: Anorectal melanoma (ARM) is a rare disease with a poor prognosis. Evidence on optimal treatment is limited and surgical management varies widely. We hypothesized that the frequency of abdominoperineal resection used as primary treatment of ARM has decreased over the past several decades. AIM: To update our understanding of outcomes for patients with ARM and analyze management trends around the world. METHODS: This is a multi-institutional, retrospective study of patients treated for ARM at 7 hospitals. Hospitals included both large, academic, tertiary care centers and smaller, general community hospitals. Using prospectively maintained institutional tumor registries, we identified 24 patients diagnosed with ARM between January 2000 and May 2019. We analyzed factors prognostic for recurrence and survival. We then used Cox regression to measure overall survival (OS) and melanoma-specific survival. We also performed a literature review to assess trends in surgical management and outcomes. RESULTS: Of the 24 patients diagnosed with ARM, 12 (50.0%) had local, 8 (33.3%) regional, and 4 (16.7%) distant disease at diagnosis. Median time to recurrence was 10.4 mo [interquartile range (IQR) 7.5-17.2] with only 2 patients (9.3%) not developing recurrence following surgical resection. Median OS was 18.8 mo (IQR 13.5-33.9). One patient is still alive without recurrence at 21.4 mo from diagnosis; no other patient survived 5 years. Primary surgical management with abdominoperineal resection (APR) vs wide excision (WE) did not lead to differences in OS [hazard ratio = 1.4 (95%CI: 0.3-6.8)]. Review of the literature revealed geographic differences in surgical management of ARM, with increased use of WE in the United States and Europe over time and more frequent use of APR in Asia and India. There was no significant improvement in survival over time. CONCLUSION: There is wide variation in the management of ARM and survival outcomes remain poor regardless of approach. Surgical management should aim to minimize morbidity.

Oncologic outcomes of patients with Merkel Cell Carcinoma (MCC): A multi-institutional cohort study.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine tumor that primarily affects elderly patients. Despite aggressive treatment, overall survival (OS) remains low. METHODS: This study is a multi-institutional, retrospective review of 102 patients with MCC. We evaluated OS, disease-specific survival (DSS), and risk factors for recurrence. RESULTS: Median age of patients was 71.46% of patients recurred. Patients with stage I disease had median 5-year OS of 59.3%, compared to 68.1% DSS. For stage III, median 5-year OS was 46.0% vs 58.2% DSS. Disease stage and advanced age were risk factors for recurrence and decreased OS. Immunocompromised status and disease stage were the strongest predictors of DSS. CONCLUSIONS: DSS is significantly better than OS for patients with MCC. Many elderly patients with newly diagnosed MCC have low remaining life expectancy, regardless of their MCC diagnosis. Patient age and overall health status should be considered to personalize care plans for patients with MCC.

Recurrence patterns in patients with Stage II melanoma: The evolving role of routine imaging for surveillance.

BACKGROUND AND OBJECTIVES: The relatively recent availability of effective systemic therapies for metastatic melanoma necessitates reconsideration of current surveillance patterns. Evidence supporting surveillance guidelines for resected Stage II melanoma is lacking. Prior reports note routine imaging detects only 21% of recurrent disease. This study aims to define recurrence patterns for Stage II melanoma to inform future surveillance guidelines. METHODS: This is a retrospective study of patients with Stage II melanoma. We analyzed risk factors for recurrence and methods of recurrence detection. We also assessed survival. Yearly hazards of recurrence were visualized. RESULTS: With a median follow-up of 4.9 years, 158 per 580 patients (27.2%) recurred. Overall, most recurrences were patient-detected (60.7%) or imaging-detected (27.3%). Routine imaging was important in detecting recurrence in patients with distant recurrences (adjusted rate 43.1% vs. 9.4% for local/in-transit; p = .04) and with Stage IIC melanoma (42.5% vs. 18.5% for IIA; p = .01). Male patients also self-detected recurrent disease less than females (52.1% vs. 76.8%; p < .01). CONCLUSIONS: Routine imaging surveillance played a larger role in detecting recurrent disease for select groups in this cohort than noted in prior studies. In an era of effective systemic therapy, routine imaging should be considered for detection of asymptomatic relapse for select, high-risk patient groups.

Postoperative pancreatic fistula after distal pancreatectomy for non-pancreas retroperitoneal tumor resection.

INTRODUCTION: Short-term outcomes after distal pancreatectomy (DP) for retroperitoneal (RP) tumors are unknown. We sought to identify rates of postoperative pancreatic fistula (POPF) and morbidity after en bloc DP with RP tumor resection. METHODS: A retrospective review of 43 patients who underwent DP with RP tumor resection (1/2011-12/2017) was performed. RESULTS: Seventeen patients had RP sarcoma, 12 renal cell carcinoma, 11 gastrointestinal stromal tumor, and 3 adrenocortical carcinoma. Grade III-IV complications occurred in 7 patients. Grade B POPF occurred in 14 patients, grade C POPF in none, and biochemical leak in 6. Of 22 patients who developed radiographically evident peri-pancreatic fluid collections, 7 required percutaneous drainage. The 90-day readmission rate was 33%. CONCLUSIONS: DP with RP tumor resection is associated with high rates of clinically relevant POPF compared to historical results for DP for primary pancreatic tumors. Multi-center studies to identify targetable predictors and risk mitigation strategies for POPF in this rare high-risk population are needed.