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BACKGROUND: Axillary lymph node dissection is the current standard for management of the axilla in inflammatory breast cancer (IBC). The present study aims to determine whether the initially positive node identified by clip placement accurately represents the overall nodal status of axilla after neoadjuvant chemotherapy (NAC) in IBC. PATIENTS AND METHODS: A retrospective study was conducted on patients with IBC who underwent operation (2014-2023). For patients with IBC who had clip placement in a positive axillary node at diagnosis, operative notes, specimen radiographs, and pathology reports were reviewed to confirm final pathologic status of clipped nodes. RESULTS: In total, 92 patients with IBC (90 cN+) were identified (median age 54 years, 78% invasive ductal, 10% invasive lobular, and 12% mixed); 81 (90%) were biopsy-proven cN+, with a clip placed in the positive node for 62/81 (77%). All patients were treated with NAC and axillary surgery with median 19 (range 4-49) nodes removed. Among 28 (out of 56) patients with retrieved clipped nodes that were pathologically negative (ypN0), only 1 had an additional positive node with micrometastasis for a false negative rate of 4% (95% CI 1-19%). Conversely, 3/3 patients with isolated tumor cells (ITCs) only in the clipped node had additional axillary disease (ITCs in 1, macrometastasis in 2), and 20/23 (87%) of patients with pathologically positive clipped node (micrometastasis or greater) had additional positive nodes [19/20 (95%) with macrometastasis]. CONCLUSIONS: The clipped biopsy-positive axillary node in IBC accurately represented the post-NAC overall axillary nodal status. ITCs post-NAC should be considered positive as an indicator of additional nodes with metastasis.
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In inflammatory breast cancer (IBC), obstructed lymphatics present a barrier to sentinel node biopsy. In theory this challenge could be overcome by clipping the clinically positive node at presentation and surgically retrieving it after neoadjuvant chemotherapy (NAC). If the clipped node accurately reflects the axillary status, then deescalation of axillary nodal dissection could be a possibility in IBC with complete pathological nodal response post-NAC.
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BACKGROUND: Immediate lymphatic reconstruction (ILR) has been proposed to decrease lymphedema rates. The primary aim of our study was to determine whether ILR decreased the incidence of lymphedema in patients undergoing axillary lymph node dissection (ALND). METHODS: We conducted a two-site pragmatic study of ALND with or without ILR, employing surgeon-level cohort assignment, based on breast surgeons' preferred standard practice. Lymphedema was assessed by limb volume measurements, patient self-reporting, provider documentation, and International Classification of Diseases, Tenth Revision (ICD-10) codes. RESULTS: Overall, 230 patients with breast cancer were enrolled; on an intention-to-treat basis, 99 underwent ALND and 131 underwent ALND with ILR. Of the 131 patients preoperatively planned for ILR, 115 (87.8%) underwent ILR; 72 (62.6%) were performed by one breast surgical oncologist and 43 (37.4%) by fellowship-trained microvascular plastic surgeons. ILR was associated with an increased risk of lymphedema when defined as ≥10% limb volume change on univariable analysis, but not on multivariable analysis, after propensity score adjustment. We did not find a statistically significant difference in limb volume measurements between the two cohorts when including subclinical lymphedema (≥5% inter-limb volume change), nor did we see a difference in grade between the two cohorts on an intent-to-treat or treatment received basis. For all patients, considering ascertainment strategies of patient self-reporting, provider documentation, and ICD-10 codes, as a single binary outcome measure, there was no significant difference in lymphedema rates between those undergoing ILR or not. CONCLUSION: We found no significant difference in lymphedema rates between patients undergoing ALND with or without ILR.
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Among inflammatory breast cancer (IBC) patients, over one-third have HER2-overexpressing (HER2+) tumors. Pathologic complete response (pCR) rates to neoadjuvant targeted and chemotherapy for patients with HER2+ non-metastatic IBC now apporach 60% and favorable long-term survival rates are being reported for those with a pCR. Immune mechanisms contributing to this phenomenon include antibody-mediated immune activation and induction of memory T-cell reponses which may explain the sustained antitumor response seen after discontinuation of targeted therapies.
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BACKGROUND AND OBJECTIVES: Current NCCN guidelines discourage repeat sentinel lymph node (SLN) surgery in patients with local recurrence (LR) of breast cancer following prior mastectomy. This study addresses the feasibility and therapeutic impact of this approach. METHODS: We identified 73 patients managed with repeat SLN surgery for post-mastectomy isolated LR. Lymphatic mapping was performed using radioisotope with or without lymphoscintigraphy and/or blue dye. Successful SLN surgery was defined as retrieval of ≥1 SLN. RESULTS: SLN surgery was successful in 65/73 (89%), identifying a median of 2 (range 1-4) SLNs, with 10/65 (15%) SLN-positive. Among these, 5/10 (50%) proceeded to ALND. In unsuccessful cases, 1/8 (13%) proceeded to ALND. Seven of 10 SLN-positive patients and 50/55 SLN-negative patients received adjuvant radiotherapy. Chemotherapy was administered in 31 (42%) and endocrine therapy in 50 of 57 HR+ patients (88%). After 28 months median follow-up, eight patients relapsed with the first site local in two, distant in five, and synchronous local/distant in one. No nodal recurrences were observed. CONCLUSIONS: SLN surgery for patients with LR post-mastectomy is feasible and informative. This approach appears oncologically sound, decreases axillary dissection rates and may be used to tailor adjuvant radiation target volumes and systemic therapies.
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Neoplasias de la Mama , Ganglio Linfático Centinela , Humanos , Femenino , Mastectomía , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Biopsia del Ganglio Linfático Centinela , Ganglio Linfático Centinela/cirugía , Ganglio Linfático Centinela/patología , Metástasis Linfática , Escisión del Ganglio Linfático , Axila/patología , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/patologíaRESUMEN
INTRODUCTION: Melanoma guidelines stem largely from data on non-Hispanic White (NHW) patients. We aimed to identify features of melanoma within non-Hispanic Black (NHB) patients to inform strategies for earlier detection and treatment. METHODS: From 2004 to 2019 Surveillance, Epidemiology, and End Results (SEER) data, we identified nonmetastatic melanoma patients with known TN category and race. Kaplan-Meier cancer-specific survival (CSS) estimates and multivariable Cox proportional hazard modeling analyses were performed. RESULTS: Of 492 597 patients, 1499 (0.3%) were NHB, who were younger (21% vs. 17% age <50) and more commonly female (54% vs. 41%) than NHW, both p < 0.0005. For NHBs, lower extremity was the most common site (52% vs. 15% for NHWs, p < 0.0001), T category was higher (55% Tis-T1 vs. 82%; 27% T3-T4 vs. 8%, p < 0.0001) and stage at presentation was higher (19% Stage III, vs. 6%, p < 0.0001). Within the NHB cohort, males were older, and more often node-positive than females. Five-year Stage III CSS was 42% for NHB males versus 71% for females, adjusting for age and clinical nodal status (hazard ratio 2.48). CONCLUSIONS: NHB melanoma patients presented with distinct tumor characteristics. NHB males with Stage III disease had inferior CSS. Focus on this high-risk patient cohort to promote earlier detection and treatment may improve outcomes.
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Negro o Afroamericano , Melanoma , Programa de VERF , Neoplasias Cutáneas , Humanos , Melanoma/patología , Melanoma/mortalidad , Melanoma/terapia , Melanoma/etnología , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/etnología , Tasa de Supervivencia , Negro o Afroamericano/estadística & datos numéricos , Anciano , Adulto , Pronóstico , Estudios de SeguimientoRESUMEN
OBJECTIVE: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma. SUMMARY BACKGROUND DATA: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization. METHODS: We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics. RESULTS: Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients. CONCLUSIONS: There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.
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Melanoma , Ganglio Linfático Centinela , Neoplasias Cutáneas , Adulto , Humanos , Ganglio Linfático Centinela/cirugía , Ganglio Linfático Centinela/patología , Neoplasias Cutáneas/cirugía , Biopsia del Ganglio Linfático Centinela , Estudios de Cohortes , Melanoma/cirugía , Melanoma/tratamiento farmacológico , Escisión del Ganglio Linfático , Estudios RetrospectivosRESUMEN
PURPOSE: Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined. METHODS: Women with stage I-III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan-Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy. RESULTS: The median age at diagnosis for women with TN-ILC was 67 years compared to 58 years in TN-IDC (p < 0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p = 0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p < 0.001). CONCLUSION: Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC.
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Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Femenino , Humanos , Anciano , Neoplasias de la Mama/patología , Carcinoma Lobular/patología , Pronóstico , Carcinoma Ductal de Mama/patología , MastectomíaRESUMEN
Anorectal melanoma is an aggressive mucosal melanoma subtype with a poor prognosis. Although recent advancements have been seen for cutaneous melanoma, the optimal treatment paradigm for management of anorectal melanoma is evolving. In this review, we highlight differences in the pathogenesis of mucosal versus cutaneous melanoma, new concepts of staging for mucosal melanoma, updates to surgical management of anorectal melanoma, and current data for adjuvant radiation and systemic therapy in this unique patient population.
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Neoplasias del Ano , Melanoma , Neoplasias del Recto , Neoplasias Cutáneas , Humanos , Melanoma/patología , Neoplasias Cutáneas/terapia , Neoplasias del Recto/patología , Neoplasias del Ano/patología , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND AND OBJECTIVES: Previous studies have identified racial-ethnic differences in the diagnostic patterns and recurrence outcomes of women with phyllodes tumors (PT). However, these studies are generally limited in size and generalizability. We therefore sought to explore racial-ethnic differences in age, tumor size, subtype, and recurrence in a large US cohort of women with PT. METHODS: We performed an 11-institution retrospective review of women with PT from 2007 to 2017. Differences in age at diagnosis, tumor size and subtype, and recurrence-free survival according to race-ethnicity. RESULTS: Women of non-White race or Hispanic ethnicity were younger at the time of diagnosis with phyllodes tumor. Non-Hispanic Other women had a larger proportion of malignant PT. There were no differences in recurrence-free survival in our cohort. CONCLUSIONS: Differences in age, tumor size, and subtype were small. Therefore, the workup of young women with breast masses and the treatment of women with PT should not differ according to race-ethnicity. These conclusions are supported by our finding that there were no differences in recurrence-free survival.
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Neoplasias de la Mama , Tumor Filoide , Femenino , Humanos , Estados Unidos/epidemiología , Tumor Filoide/cirugía , Tumor Filoide/patología , Etnicidad , Hispánicos o Latinos , Mama/patología , Neoplasias de la Mama/patologíaRESUMEN
PURPOSE: To identify the practice patterns related to use of surveillance mammography in male breast cancer (MaBC) survivors. METHODS: Using administrative claims data from OptumLabs Data Warehouse, we identified men who underwent surgery for breast cancer during 2007-2017. We calculated the proportion of men who had at least one mammogram (a) within 13 months for all patients and (b) within 24 months amongst those who maintained their insurance coverage for at least that length of time after surgery. Multivariate logistic regression modeling was used to identify factors associated with mammography within each timeframe. RESULTS: Out of 729 total MaBC survivors, 209 (29%) underwent mammography within 13 months after surgery. Among those who had lumpectomy, 41% underwent mammography, whereas among those who had mastectomy, 27% had mammography. Amongst 526 men who maintained consistent insurance coverage for 24 months after surgery, 215 (41%) underwent mammography at least once during that 24-month period. In this cohort, the proportion who had at least one mammogram during the 24-month period was 49% after lumpectomy and 40% after mastectomy. In a multivariate logistic regression model, more recent diagnosis (2015+) and older age at diagnosis were associated with lower odds of undergoing mammography, while receipt of radiation was associated with higher odds of undergoing mammography. CONCLUSIONS: Although recent ASCO guidelines recommend surveillance mammography after lumpectomy, a minority of MaBC survivors undergo surveillance mammography, even after lumpectomy. This is likely due to the paucity of data regarding the true benefits and harms of surveillance/screening mammography for MaBC.
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Neoplasias de la Mama Masculina , Neoplasias de la Mama , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama Masculina/diagnóstico por imagen , Neoplasias de la Mama Masculina/epidemiología , Detección Precoz del Cáncer , Humanos , Masculino , Mamografía , Mastectomía , SobrevivientesRESUMEN
INTRODUCTION: The effect of neoadjuvant systemic therapies (NST) on technical aspects of operation for resectable stage III melanoma is unknown. Prospective capture of the estimated and actual degree of difficulty of therapeutic lymphadenectomy at presentation and after NST may inform the relative merits of NST versus surgery followed by adjuvant therapy. METHODS: We designed surgeon survey tools to capture key impressions at baseline prior to NST and postoperatively. We conducted a sub-study within a multi-institutional clinical trial for high-risk operable stage III melanoma (NeoACTIVATE, NCT03554083) which enrolls clinically node-positive patients to 12 weeks of combinatorial NST determined by BRAF status. Survey data were analyzed. RESULTS: Surveys were completed for 24 of 25 patients (96%). Affected nodal basins were cervical (3, 13%) axillary (9, 38%), inguinal ± pelvic (14, 58%); 2 (8%) involved ≥ 2 basins. Baseline estimates included largest affected node size (median/range 4/1.4-11 cm), number of involved nodes (median/range 3/1-10) and tumor fixation (present in 12, 50%). At operation, actual degree of difficulty increased from the baseline estimate in 4 (17%) and decreased in 6 (25%). Surgery was less difficult, average, or more difficult versus usual operation in 4, 9, and 11 cases (17%, 38%, 46%), respectively. CONCLUSIONS: Although many operations were judged to be more difficult than the usual therapeutic lymphadenectomy, operation following NST was more often perceived as easier than more difficult versus baseline impression. Engaging surgical oncologists to perform similar structured assessments across clinical trials will permit cross-study analysis of the effect of NSTs on the technical conduct of lymphadenectomy.
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Melanoma , Neoplasias Cutáneas , Cirujanos , Humanos , Escisión del Ganglio Linfático , Melanoma/tratamiento farmacológico , Melanoma/cirugía , Terapia Neoadyuvante , Estadificación de Neoplasias , Estudios Prospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugíaRESUMEN
The Operative Standards for Cancer Surgery manuals define critical elements of optimal cancer surgery based on data and expert opinion. These key aspects of commonly performed cancer operations define technical standards that can be used as a quality assurance tool for practicing surgical oncologists and as an educational tool for trainees. This article provides background on these operative standards and their subsequent integration into synoptic operative report templates. With the goal of codifying the most important aspects of surgical oncology care to elevate and harmonize cancer care, the American College of Surgeons Cancer Programs has developed comprehensive synoptic operative reports. Synoptic operative reports are structured so that key data elements are recorded in a standardized format with prespecified terminology. In contrast to the narrative or structured operative reports frequently used by surgeons, these synoptic operative reports improve semantic clarity, provide uniform fields for abstraction, and facilitate passive data collection and real-time analytics while delivering key information for downstream multidisciplinary patient care. In this way, the synoptic operative report is a key component of a comprehensive effort to elevate the quality of cancer care nationally.
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Neoplasias , Cirujanos , Recolección de Datos , Humanos , Neoplasias/cirugía , Atención al PacienteRESUMEN
BACKGROUND: The distinct histologic appearance of invasive lobular carcinoma (ILC) may pose diagnostic challenges for sentinel lymph node (SLN) analysis. We evaluated the impact of cytokeratin immunohistochemistry (IHC) on SLN assessment in ILC and its contribution to pathologic nodal upstaging. METHODS: We identified ILC patients treated with SLN surgery at our institution between September 2008 and August 2021. IHC for SLN assessment was employed at the discretion of the pathologist. Differences between groups evaluated with and without IHC were compared using Chi-square tests. RESULTS: Overall, 608 cases of ILC were identified in patients who underwent SLN surgery. IHC was used in 301 cases (49.5%) and was not associated with cT category, pT category, or tumor grade. Use of IHC increased detection of SLN+ disease when isolated tumor cells (ITCs) were included in the analysis (35.9% with IHC vs. 21.2% without IHC; p < 0.001). There was no effect on nodal upstaging to micrometastatic disease (pN1mi) or greater (21.9% with IHC vs. 21.2% without IHC; p = 0.82). IHC did not increase the number of positive SLNs detected (median 1 with and without IHC) nor did it increase axillary lymph node dissection (ALND) rates (11.6% with IHC vs. 15.3% without IHC; p = 0.18). CONCLUSION: IHC improved detection of pN0(i+) disease among ILC patients undergoing SLN surgery. IHC did not increase upstaging to pN1mi or higher categories of nodal disease, detection of a greater number of positive SLNs, or ALND rates. Our data suggest routine use of IHC for SLN assessment in ILC patients does not add clinical utility.
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Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Ganglio Linfático Centinela , Axila/patología , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/patología , Femenino , Humanos , Inmunohistoquímica , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática/patología , Ganglio Linfático Centinela/patología , Ganglio Linfático Centinela/cirugía , Biopsia del Ganglio Linfático CentinelaRESUMEN
BACKGROUND: Fine needle aspiration (FNA) of sonographically suspicious axillary lymph nodes is helpful to clinically stage patients and guide consideration of neoadjuvant therapy in breast cancer. However, data are limited for suspicious nodes that are FNA negative. Our goal is to compare the frequency of node positivity between patients with negative axillary ultrasound (AUSneg) versus suspicious AUS with negative FNA (FNAneg). METHODS: With IRB approval, we identified all clinically node-negative (cN0) patients with invasive breast cancer treated with upfront surgery at our tertiary care center between 2016 and 2021. AUS is routinely performed with FNA of suspicious lymph node(s). We compared clinicopathologic characteristics and nodal positivity rates between AUSneg and FNAneg groups. RESULTS: A total of 1580 cN0 patients with invasive breast cancer were analyzed, including 1240 AUSneg and 340 FNAneg patients. The FNAneg group was younger (median age 59.7 years versus 63.5 years, p < 0.001) and had higher clinical T (cT) category (29.1% versus 21.7% with cT2-cT4 disease, p = 0.005). Final axillary pathologic node positivity did not differ significantly between the AUSneg and FNAneg groups (16.5% versus 19.1%, p = 0.25). Among FNAneg patients, 58/340 (17.1%) had a clip placed, with retrieval confirmed in 28/58 (48.3%). Of the 28 retrieved clipped nodes, 27 were sentinel nodes. Final pathologic nodal status (pN+%) did not differ between patients in whom retrieval of the clipped node was confirmed versus not confirmed (28.6% versus 16.7%, p = 0.28). CONCLUSIONS: Both patients with sonographically suspicious node(s) and negative FNA and patients with negative AUS have a similarly low chance of positive nodes. Additionally, routine targeted excision of FNA-negative clipped nodes is not warranted.
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Neoplasias de la Mama , Biopsia del Ganglio Linfático Centinela , Axila/patología , Biopsia con Aguja Fina , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática/patología , Persona de Mediana EdadRESUMEN
INTRODUCTION: The primary aim of this study was to evaluate patient-reported outcome measures in patients undergoing mastectomy with and without breast reconstruction (immediate or delayed) with and without nipple preservation. METHODS: All female patients undergoing mastectomy between 2011 and 2015 at Mayo Clinic Rochester were identified and were mailed the BREAST-Q survey. Breast satisfaction, psychosocial well-being, and sexual well-being were evaluated and compared by surgery type using Wilcoxon rank-sum tests for univariate analysis and linear regression for multivariable analysis adjusting for potential confounders. RESULTS: Of 1547 patients, 771 completed the BREAST-Q survey (response rate 50%). Of these 771 respondents, 237 (31%) did not have reconstruction, 198 (26%) had nipple-sparing mastectomy with reconstruction (NSM), and 336 (44%) had skin-sparing mastectomy with reconstruction (SSM) ± nipple-areolar complex (NAC) reconstruction (via surgery ± tattoo). Patients with breast reconstruction had consistently higher BREAST-Q scores versus those without. Comparing NSM with all SSMs, there was no difference in satisfaction with breasts (mean 71.8 vs. 70.2, p = 0.21) or psychosocial well-being (mean 81.9 vs. 81.3, p = 0.47); however, sexual well-being was significantly higher in the NSM group on univariate (mean 64.5 vs. 58.0, p = 0.002) and multivariable (ß = -4.69, p = 0.03) analysis. Sexual well-being scores were similar for NSM and the SSM subgroups with any type of NAC reconstruction. CONCLUSIONS: This study demonstrates that NSM positively impacts patient sexual well-being after breast reconstruction compared with SSM, particularly SSM without nipple reconstruction or tattoo. SSM with any type of NAC reconstruction achieved similar satisfaction and sexual well-being to those undergoing NSM.
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Exciting advances in melanoma systemic therapies have presented the opportunity for surgical oncologists and their multidisciplinary colleagues to test the neoadjuvant systemic treatment approach in high-risk, resectable metastatic melanomas. Here we describe the state of the science of neoadjuvant systemic therapy (NAST) for melanoma, focusing on the surgical aspects and the key role of the surgical oncologist in this treatment paradigm. This paper summarizes the past decade of developments in melanoma treatment and the current evidence for NAST in stage III melanoma specifically. Issues of surgical relevance are discussed, including the risk of progression on NAST prior to surgery. Technical aspects, such as the definition of resectability for melanoma and the extent and scope of routine surgery are presented. Other important issues, such as the utility of radiographic response evaluation and method of pathologic response evaluation, are addressed. Surgical complications and perioperative management of NAST related adverse events are considered. The International Neoadjuvant Melanoma Consortium has the goal of harmonizing NAST trials in melanoma to facilitate rapid advances with new approaches, and facilitating the comparison of results across trials evaluating different treatment regimens. Our ultimate goals are to provide definitive proof of the safety and efficacy of NAST in melanoma, sufficient for NAST to become an acceptable standard of care, and to leverage this platform to allow more personalized, biomarker-driven, tailored approaches to subsequent treatment and surveillance.
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Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Melanoma/cirugía , Terapia Neoadyuvante/métodos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND AND OBJECTIVES: Of clinically node-negative (cN0) cutaneous melanoma patients with sentinel lymph node (SLN) metastasis, between 10% and 30% harbor additional metastases in non-sentinel lymph nodes (NSLNs). Approximately 80% of SLN-positive patients have a single positive SLN. METHODS: To assess whether state-of-the-art clinicopathologic models predicting NSLN metastasis had adequate performance, we studied a single-institution cohort of 143 patients with cN0 SLN-positive primary melanoma who underwent subsequent completion lymph node dissection. We used sensitivity (SE) and positive predictive value (PPV) to characterize the ability of the models to identify patients at high risk for NSLN disease. RESULTS: Across Stage III patients, all clinicopathologic models tested had comparable performances. The best performing model identified 52% of NSLN-positive patients (SE = 52%, PPV = 37%). However, for the single SLN-positive subgroup (78% of cohort), none of the models identified high-risk patients (SE > 20%, PPV > 20%) irrespective of the chosen probability threshold used to define the binary risk labels. Thus, we designed a new model to identify high-risk patients with a single positive SLN, which achieved a sensitivity of 49% (PPV = 26%). CONCLUSION: For the largest SLN-positive subgroup, those with a single positive SLN, current model performance is inadequate. New approaches are needed to better estimate nodal disease burden of these patients.
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Metástasis Linfática/diagnóstico , Melanoma/secundario , Neoplasias Cutáneas/patología , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Curva ROC , Biopsia del Ganglio Linfático CentinelaRESUMEN
BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy that usually occurs in the head/neck or extremities. However, there are reports of MCC developing in the lymph nodes or parotid gland without evidence of a primary cutaneous lesion. METHODS: We reviewed 415 patients with biopsy-proven MCC. Patients with MCC of unknown primary (n = 37, 9%, MCCUP) made up the study cohort. The primary endpoints of the study were rate of recurrence, disease-free survival, and overall survival. RESULTS: Patients with MCCUP presented with tumors in lymph nodes (n = 34) or parotid gland (n = 3). Nodal disease was most commonly detected in the inguinal/external iliac (n = 15) or axillary (n = 14) regions. The mean age at diagnosis was 70 years and 24% were female. Patients presented with distant metastases in 24.3% of cases. Patients with stage IIIA disease treated with regional lymph node dissection (RLND) had a lower risk of disease recurrence (hazard ratio 0.26, p = 0.046). Recurrence-free survival was 59.3% at 5 years. Disease-specific survival was 63.3% at 5 years. CONCLUSION: Patients with MCCUP have a high risk of recurrence and mortality. The optimal treatment for MCCUP has yet to be elucidated, although therapeutic RLND appears beneficial for these patients.
Asunto(s)
Carcinoma de Células de Merkel , Neoplasias Primarias Desconocidas , Neoplasias Cutáneas , Carcinoma de Células de Merkel/cirugía , Femenino , Humanos , Ganglios Linfáticos/patología , Masculino , Recurrencia Local de Neoplasia/patología , Neoplasias Primarias Desconocidas/patología , Neoplasias Primarias Desconocidas/terapia , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugíaRESUMEN
BACKGROUND: For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown. METHODS: In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models. RESULTS: Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti-PD-1 immunotherapy. After a median follow-up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty-eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk-adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15-0.88), but not all-site RFS (HR, 0.68; 95% CI, 0.45-1.02). Adjuvant therapy improved all-site RFS (HR, 0.52; 95% CI, 0.47-0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment. CONCLUSIONS: Active surveillance has been adopted for most SLN-positive patients. At initial assessment, real-world outcomes align with randomized trial findings, including in adjuvant therapy recipients. LAY SUMMARY: For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real-world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up-front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma.