Lymphangitic Melanomatosis: Case Report of Intralymphatic Spread of Melanoma in a 66-year-old Man.

ABSTRACT: Melanoma with lymphatic invasion has been associated with increased risk of metastasis, but the mechanisms and clinical implications are poorly understood. Although current reports have documented angiotropic spread of melanoma and suggest lymphatic spread of melanoma to increase the likelihood of metastasis, to our knowledge, lymphangitic metastatic melanoma resembling cutaneous carcinomatosis or presenting with facial hyperpigmentation has not been described. In this case report, we describe extensive cutaneous intralymphatic spread of melanoma, or lymphangitic melanomatosis, producing macular skin pigmentation in a 66-year-old man.

Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical implementation.

Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy worldwide, with most deaths caused by locally advanced and metastatic disease. Treatment of resectable metastases is typically limited to invasive surgery with adjuvant radiotherapy; however, many patients fail to respond and there is minimal data to predict response or propose effective alternatives. Precision medicine could improve this, though genomic biomarkers remain elusive in the high mutational background and genomic complexity of cSCC. A phenotypic approach to precision medicine using patient-derived ex vivo tumour models is gaining favour for its capacity to directly assess biological responses to therapeutics as a functional, predictive biomarker. However, the use of ex vivo models for guiding therapeutic selection has yet to be employed for metastatic cSCC. This review will therefore evaluate the existing experimental models of metastatic cSCC and discuss how ex vivo methods could overcome the shortcomings of these existing models. Disease-specific considerations for a prospective methodological pipeline will also be discussed in the context of precision medicine.

Prevalence and implications of bilateral and solely contralateral lymph node metastases in oral squamous cell carcinoma.

OBJECTIVES: Effective management of neck in oral squamous cell carcinoma (OSCC) is pivotal for oncological outcomes. Although consensus exists for ipsilateral neck dissection (ND), the necessity for contralateral ND remains controversial. This study aimed to assess the prevalence and implications of bilateral/solely contralateral (B/SC) lymph node metastases (LNMs) to determine the need for contralateral elective ND. Additionally, it examined the prevalence and implications of occult B/SC metastases. MATERIALS AND METHODS: In a retrospective cohort study, 420 OSCC patients underwent primary surgical treatment following German guidelines at a tertiary center. Preoperative contrast-enhanced computed tomography was conducted, and ND adhered to a standardized approach. RESULTS: Solely contralateral metastases occurred in 0.95% of patients, with bilateral metastases observed in 7.13%. Occult B/SC metastases occurred in 3.81% of the cases. Correlation analysis revealed a statistically significant association between B/SC metastases and higher tumor stages, tumor localization at the upper jaw or floor of the mouth, proximity to the midline, ipsilateral LNMs, and lymphatic invasion (all p < 0.05). Patients with B/SC metastases showed poorer disease-free survival, with statistical significance reached in the bilateral LNMs group (p = 0.010). Similarly, a significant difference was noted in overall survival between patients with bilateral and solely ipsilateral metastases (p = 0.044). CONCLUSIONS: B/SC LNMs are rare in patients with OSCC, especially in those who present with clinico-radiologically negative ipsilateral necks. Higher rates of B/SC metastases occur in case of advanced tumors and those localized at the upper jaw or floor of the mouth. Ipsilateral LNMs significantly elevate the risk of contralateral LNMs, tripling the associated risk. CLINICAL RELEVANCE: These findings provide valuable insights for surgeons considering contralateral ND or extended adjuvant treatment for OSCC patients. However, the absence of high-level evidence from randomized controlled trials impedes the establishment of a definitive standard of care.

Genomic Staging of Multifocal Lung Squamous Cell Carcinomas Is Independent of the Comprehensive Morphologic Assessment.

INTRODUCTION: Morphologic and molecular data for staging of multifocal lung squamous cell carcinomas (LSCCs) are limited. In this study, whole exome sequencing (WES) was used as the gold standard to determine whether multifocal LSCC represented separate primary lung cancers (SPLCs) or intrapulmonary metastases (IPMs). Genomic profiles were compared with the comprehensive morphologic assessment. METHODS: WES was performed on 20 tumor pairs of multifocal LSCC and matched normal lymph nodes using the Illumina NovaSeq6000 S4-Xp (Illumina, San Diego, CA). WES clonal and subclonal analysis data were compared with histologic assessment by 16 thoracic pathologists. In addition, the immune gene profiling of the study cases was characterized by the HTG EdgeSeq Precision Immuno-Oncology Panel. RESULTS: By WES data, 11 cases were classified as SPLC and seven cases as IPM. Two cases were technically suboptimal. Analysis revealed marked genomic and immunogenic heterogeneity, but immune gene expression profiles highly correlated with mutation profiles. Tumors classified as IPM have a large number of shared mutations (ranging from 33.5% to 80.7%). The agreement between individual morphologic assessments for each case and WES was 58.3%. One case was unanimously interpreted morphologically as IPM and was in agreement with WES. In a further 17 cases, the number of pathologists whose morphologic interpretation was in agreement with WES ranged from two (one case) to 15 pathologists (one case) per case. Pathologists showed a fair interobserver agreement in the morphologic staging of multiple LSCCs, with an overall kappa of 0.232. CONCLUSIONS: Staging of multifocal LSCC based on morphologic assessment is unreliable. Comprehensive genomic analyses should be adopted for the staging of multifocal LSCC.

CT predictors of sub-centimeter occult lymph node metastases in oral cavity squamous cell carcinoma: A case-control study.

BACKGROUND: For patients with oral cavity squamous cell carcinoma (OCSCC) without evidence of nodal metastasis (cN0) on pre-operative evaluation, there are no clear guidelines who should undergo elective neck dissection (END) versus clinical surveillance. OBJECTIVE: To identify CT imaging characteristics of sub-centimeter lymph nodes that would help predict the likelihood of nodal metastases on pathology. METHODS: Retrospective review of cN0 OCSCC patients at a tertiary academic medical center was performed. Inclusion criteria included elective neck dissection, pre-operative CT imaging and presence of metastatic disease within lymph nodes. Control group consisted of patients without nodal metastases on pathology. CT features that were evaluated included asymmetric size, disrupted fatty hilum, asymmetric number, presence of cortical nodule, cortical nodule size, and round/oval shape. We evaluated the associations between CT LN features and the presence of metastases using multi-level mixed-effects logistic regression models. Model evaluation was performed using 5-fold cross-validation. The positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: 26 patients in each study and control groups were included. Three-level mixed-effects logistic regression models indicated round/oval shape (OR = 1.39, p = .01), asymmetric number (OR = 7.20, p = .005), and disrupted fatty hilum (OR = 3.31, p = .04) to be independently predictive in a 3-variable model with sensitivity = 38.0%, specificity = 92.0%, and PPV = 93.8%. CONCLUSIONS: In cN0 OCSCC patients undergoing END, round/oval shape, asymmetric number, and disrupted fatty hilum of lymph nodes on pre-operative CT imaging are novel and highly predictive of occult nodal disease.

Tumour-agnostic plasma assay for circulating tumour DNA predicts outcome in recurrent and/or metastatic squamous cell carcinoma of the head and neck treated with a PD-1 inhibitor.

BACKGROUND: Only 15-20% of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) patients derive long-term benefit from nivolumab or pembrolizumab. We developed a circulating tumour DNA (ctDNA) tumour-agnostic assay aimed at the early prediction of single agent programmed cell death 1 (PD1) inhibitor efficacy in R/M SCCHN. PATIENTS AND METHODS: Our tumour-agnostic assay included 37 genes frequently mutated in R/M SCCHN and two HPV16 genes. Primary endpoint was the concordance between ctDNA kinetics (ΔctDNA) and the best overall response according to Response Evaluation Criteria in Solid Tumors version 1.1. ΔctDNA was defined as the difference in mean variant allele frequency (VAF) between the on-treatment sample harvested 6-10 weeks (FU1) after PD1 inhibitor initiation and the pre-treatment plasma sample (ΔctDNA = mean FU1 VAF - mean pre-treatment VAF). RESULTS: ctDNA was detected in 35/44 (80%) of the pre-treatment plasma samples. The concordance between ΔctDNA and imaging response was observed in 74%. Median progression-free survival was 8.6 months in the favourable ΔctDNA group and 2.5 months in the unfavourable ΔctDNA group (p = 0.057). Median overall survival (OS) was 18.1 and 8.2 months in the favourable and unfavourable ΔctDNA groups, respectively (p = 0.13). In patients with PD-L1 expressing SCCHN (Combined Positive Score ≥1), OS was significantly better in patients with favourable ΔctDNA compared with patients with unfavourable ΔctDNA: median OS was 41.5 and 8.4 months (p = 0.033), respectively. CONCLUSIONS: Tumour-agnostic ctDNA analysis for human papillomavirus (HPV)-negative and HPV-positive R/M SCCHN is feasible. ctDNA kinetics show promising results in predicting the efficacy of PD1 inhibitors in R/M SCCHN.

A rare case of cavernous sinus thrombosis following oral squamous cell carcinoma - The etiology and management dilemma.

Intracranial cavernous sinus metastases of oral squamous cell carcinoma (OSCC) are rare, with a reported incidence of 0.4 %. Due to their extremely infrequent presentation the etiology and management modalities of such complications are not clearly represented in the literature. Here we present a case of a 58-year-old male diagnosed with OSCC of Right Lower Alveolus with underlying bone invasion, cT4aN1M0, Stage IV. He underwent Right Hemi-mandibulectomy with Modified Neck Dissection, Pectoralis Major Myocutaneous Flap, and 60 Gy/30# adjuvant radiotherapy. Six months later, the patient was diagnosed with recurrence involving the right infratemporal fossa with associated right cavernous sinus thrombosis. Immunohistochemistry block review showed PDL1 - Positive. The patient was subjected to Cisplatin and Pembrolizumab immunotherapy. After receiving 35 cycles of Pembrolizumab over a period of 2 years the patient is doing well with no recurrence.

Proton pump inhibitors and antibiotics adversely effect the efficacy of nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: Several reports have shown that the use of proton pump inhibitors (PPIs) and antibiotics (Abx) can reduce the efficacy of immune checkpoint inhibitors in various cancers. To date, however, the association of immune checkpoint inhibitors with PPI and/or Abx in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M SCCHN) has not been reported. METHODS: We retrospectively reviewed patients with platinum-refractory R/M SCCHN treated with nivolumab from May 2017 and March 2020 in our institute. Primary sites included the oral cavity, oropharynx, hypopharynx and larynx. The relationship between prognostic parameters, such as overall survival (OS), progression-free survival (PFS), PFS2 and PFS3, and clinical factors, including PPI or Abx use, was examined, and the creation of prognostic classification was also attempted. RESULTS: Of 110 patients identified, 56 patients received PPI and 24 patients received Abx within 30 days before or after the initiation of nivolumab. With a median follow-up of 17.2 months (range: 13.8-25.0), median PFS, PFS2, PFS3 and OS were 3.2, 8.1, 14.0 and 17.2 months, respectively. In univariate analysis, the use of PPI and of Abx was significantly associated with poor prognosis in all parameters (PFS, PFS2, PFS3 and OS). Median OS (hazard ratio; 95%confidence interval, p-value) by these covariates were 13.6 versus 23.8 months (1.70; 1.01-2.87, p = 0.046) for PPI and 10.0 versus 20.1 months (1.85; 1.00-3.41, p = 0.048) for Abx, respectively. Furthermore, these factors showed mutually independent adverse associations on multivariate analysis. CONCLUSION: The use of PPI and Abx attenuated the efficacy of nivolumab in R/M SCCHN. Further prospective evaluation is warranted.

Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma in Older Patients: Are New Agents Bringing New Hope?

Head and neck cancer is a broad family of diseases, most of which are of squamous cell origin, affecting the epithelial mucosa lining the upper aerodigestive tract. They often recur or are progressive despite multimodality treatment approaches, resulting in a poor prognosis. Given the progressive aging of the global population, the probability to plan an active and eventually toxic treatment for an older patient, with either curative or palliative intent, can no longer be considered as an uncommon occurrence. A crucial point in offering a systemic treatment to older patients with head and neck squamous cell carcinoma is that they are underrepresented in randomised clinical trials, and evidence-based guidelines are lacking, while, from a clinical point of view, these patients may have varying grades of resilience to anticancer treatments due to differences in their health, social and/or economic status. Our aim is to draw attention to the older patient population suffering from recurrent and/or metastatic head and neck squamous cell carcinoma and to address some open questions, such as possible differences in epidemiology and biology compared with their younger counterparts; to highlight frailty and its components by discussing how to measure and use it to personalise treatment; to evaluate which outcomes should be best achieved in the older adult setting; finally, in the era of immunotherapy, to examine whether there are differences to be addressed when considering new treatments for older patients.

Metastasis from Cervical Cancer Presenting as a Pancreatic Head Mass - an Unexpected Diagnosis!

Cervical cancer is the most common malignancy in Indian women. After primary treatment, distant recurrence is rare and occurs at liver, lung or bone. Distant metastases to other abdominal sites are very rare. We present a case of pancreatic metastasis from cervical cancer, which has not been reported in literature. A 53-year-old woman presented with 3-month history of dull upper abdominal pain with anorexia and weight loss. Past medical history revealed a stage 3c squamous cell carcinoma (SCC) cervix treated by chemo-radiotherapy 2 years back. Contrast CT abdomen showed a pancreatic head mass encasing portal vein. CA-19.9 was 30.8 U/ml. 18-Fluorodeoxyglucose(FDG) PET/CT whole body scan showed avid pancreatic head mass and right lung nodule with no uptake in utero-cervix, adnexae or pelvic nodes. Endoscopic ultrasound-guided needle aspiration from the mass showed metastatic SCC, confirming pancreatic metastasis from SCC cervix with no active disease at the cervix. Being aware of recurrence at such atypical locations during post-treatment follow-up, helps in accurate diagnosis and appropriate treatment.

Rare periorbital, pseudocystic metastasis of squamous cell carcinoma of the bladder: Case report and review of the literature.

We present the case of a man in his fifties with a history of bladder carcinoma who presented with a large periorbital cystic lesion that was found to be a metastasis. Bladder carcinomas are a very rare cause of peri-/orbital metastasis. The primary tumor in this case predominately showed squamous cell differentiation and small areas of adenoid differentiation. To our knowledge only one previous case of orbital metastasis from squamous cell carcinoma of the bladder has been reported. Cyst formation in bladder cancer metastasis has not been reported and is very rare for orbital metastases in general. The pathogenesis of metastatic cyst development is not fully understood and may vary from case to case. A biopsy of an atypical cyst is indicated.

Leptomeningeal carcinomatosis in a patient with recurrent unresectable squamous cell carcinoma of the retromolar trigone-a brief report.

BACKGROUND: The reported incidence of leptomeningeal carcinomatosis is 3-8% in patients with solid tumours. More commonly, it has been described in the setting of advanced cancers of the lung, breast and malignant melanoma. CASE PRESENTATION: A 50-year-old diabetic patient with recurrent unresectable squamous cell carcinoma (SCC) of the right retromolar trigone (rT4bN0M0) presented with severe low backache and weakness in bilateral lower limbs 20 days after the completion of concurrent chemoradiotherapy. Contrast-enhanced MRI of the spine showed multiple nodular enhancing leptomeningeal lesions at the lumbar level and an intramedullary T2/FLAIR-hyperintense longitudinal lesion involving the central cord from C2 to C7 vertebral levels, suggestive of leptomeningeal metastases. Cerebrospinal fluid (CSF) analysis revealed pleocytosis, elevated protein and markedly decreased glucose. The CSF cytology revealed scattered large atypical cells, suspicious for metastasis. Non-contrast MRI of the brain showed a T2/FLAIR-hyperintense lesion involving the right caudate nucleus suggestive of either an acute infarct with haemorrhagic transformation or a haemorrhagic brain metastasis. During assessment, he had high-grade fever and was started on empirical intravenous antibiotics (ceftriaxone, vancomycin and subsequently meropenem) in line with the management for acute bacterial meningitis. Gram staining of CSF did not demonstrate the presence of any bacteria and the specimen was sterile on culture. He did not respond to empirical antibiotics, had a progressive downhill course and eventually died due to aspiration pneumonia. CONCLUSION: This brief report highlights the importance of awareness of leptomeningeal carcinomatosis as a possible cause of backache with sensorimotor deficit and autonomic dysfunction in a previously treated case of head and neck SCC.

Nivolumab for Platinum-refractory and -sensitive Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: Nivolumab has antitumor efficacy in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) who relapse within 6 months after platinum-based therapy; however, the efficacy of nivolumab for platinum-sensitive R/M HNSCC has not been shown. Therefore, this study compared the efficacy and safety of nivolumab for platinum-refractory and platinum-sensitive R/M HNSCC. PATIENTS AND METHODS: This was a retrospective study of patients who received nivolumab for R/M HNSCC who had been previously treated with platinum-based anticancer drugs. Patients were divided into a platinum-sensitive and a platinum-refractory group, and progression-free survival (PFS), overall survival (OS), the overall response rate (ORR) [complete response (CR) + partial response (PR)], the disease control rate (DCR) (CR + PR + stable disease), and the incidence of immune-related adverse events (irAEs) were compared between the two groups. RESULTS: We included 88 patients with squamous cell carcinoma: 60 with platinum-refractory disease and 28 with platinum-sensitive disease. The median PFS in the platinum-refractory and platinum-sensitive groups were 2.7 months and 5.3 months, respectively (p=0.03), and the median OS were 8.8 months and 17.1 months, respectively (p=0.06). There were no significant differences in the ORR, DCR, or incidence of irAEs between the two groups (p>0.99, p=0.11, and p>0.99, respectively). CONCLUSION: Nivolumab is a safe and effective treatment for platinum-sensitive R/M HNSCC.

Metástasis cutánea metacrónica de carcinoma escamoso de canal anal / Methachronical cutaneous metastasis of squamous carcinoma of the anal canal / Metástase cutânea metacronica de carcinoma escamoso do canal anal

El tratamiento correcto de carcinoma escamoso avanzado requiere de un manejo multidisciplinar entre cirujanos, anatomopatólogos, radioterapeutas y radiólogos. Los protocolos están claros cuando nos hallamos ante una enfermedad localizada, sin embargo, cuando la enfermedad es metastática no existe evidencia científica de los pasos a seguir. Presentamos una paciente con un carcinoma escamoso del ano con una única metástasis cutánea metacrónica que fue tratada con cirugía y radioterapia posterior con buena respuesta.

The right therapy of anal cancer needs a multidisciplinary management of surgeons, pathologists, radiotherapists and radiologist. The treatment of squamous cell carcinoma of the anal canal is well-known when the patient presents a locally disease, nevertheless, there is a lack of information with the advanced anal cancer. We report a case of a 74-year-old woman with a solitary methachronical cutaneous metastasis of anal cancer which responded perfectly to surgery and radiotherapy.

A correta terapêutica do câncer anal necessita de uma gestão multidisciplinar de cirurgiões, patologistas, radio terapeutas e radiologistas.O tratamento do carcinoma espinocelular do canal anal é bem conhecido quando o paciente apresenta uma doença local, porém, há uma falta de informação sobre o câncer anal avançado. Relatamos o caso de uma mulher de 74 anos com metástase cutânea metacrônica solitária de câncer anal que respondeu perfeitamente à cirurgia e à radioterapia.

Acrometastasis of Laryngeal Carcinoma to the Finger.

Distant metastasis of laryngeal carcinoma occurs at the rate of 4%-12%, with the most common sites being the lungs, liver and bone. Acrometastasis occurs rarely in cases of laryngeal carcinoma; to date, only three cases of acrometastasis have been reported. Herein, we describe a 66-year male, who was followed up for metastatic laryngeal carcinoma and developed paronychia. Hot compress was applied, antibiotic treatment was administered, and fine-needle biopsy of the lesion was performed. The lesion did not regress despite the administration of a broad-spectrum antibiotic. The results of cytological examinations were consistent with squamous cell carcinoma metastasis. Rarely occurring acrometastases indicate poor prognosis in cancer patients; expected survival is short and treatment is usually palliative. In such cases, finger amputation or local radiotherapy are recommended. Clinicians should be aware when treating metastatic laryngeal cancer that such atypical lesions as paronychia can be associated with the primary tumour. Key Words: Acrometastasis, Laryngeal carcinoma, Finger, Metastasis.

Intestinal metastasis from carcinoma cervix: An (un) common occurrence in a common cancer. A series of five cases from a single institution.

Carcinoma cervix usually spreads directly to contiguous structures, such as the vagina, urinary bladder, ureter, and rectum. Intestinal metastasis from cervical cancer is very uncommon and accounts for less than 4% of cases and to date, 24 cases have been reported in Medical literature. These may be asymptomatic or present with features of intestinal obstruction, bowel wall perforation, and mimic acute abdomen. Intestinal metastasis is a late occurrence and carries a poor prognosis, hence a high index of suspicion with prompt diagnosis and management is essential. We report a series of five patients with squamous cell carcinoma (SCC) of the cervix with intestinal metastasis diagnosed in our hospital.

Tumor budding to investigate local invasion, metastasis and prognosis in temporal bone squamous cell carcinoma.

BACKGROUND: Few studies have tried to go beyond the conventional clinic-pathological prognostic factors investigating the molecular markers involved in the biology of temporal bone squamous cell carcinoma (TBSSC). Tumor budding represents a very aggressive subpopulation of cancer cells and demonstrates the heterogeneity of cancer cells residing in different locations within tumors. The main aim of this exploratory study was to investigate the role of tumor budding in primary TBSCC prognosis. We also analyzed the association between TBSCC tumor budding and: (i) loco-regional aggressiveness evaluated according to the revised Pittsburgh staging system, (ii) tumor infiltrating lymphocytes, lymphovascular invasion (LVSI), perineural invasion, pattern of invasion, and type of stroma. METHODS: Thirty-two TBSCCs treated surgically were considered. The three-tier grading system recommended by the International Tumor Budding Consensus Conference was used first on TBSCC. RESULTS: Advanced (T3-4) TBSCC was related with high risk intra-tumoral budding (ITB) at two-tier risk grading (p = 0.0361). N + status was associated with intermediate/high budding (Bd2-3) at three-tier risk grading for peri-tumoral budding (PTB) (p = 0.0382). Disease-free survival (DFS) was related with T-stage (p = 0.0406), N-status (p < 0.0001), PTB two-tier risk grading (p = 0.0463), LVSI (p < 0.0001). Overall survival (OS) was associated with N-status (p = 0.0167), PTB absolute count (p = 0.0341), PTB three-tier risk grading (p = 0.0359), PTB two-tier risk grading (p = 0.0132), and LVSI (p = 0.0004). At the multivariate analysis, DFS was related with N-status (p = 0.0147) and LVSI (p < 0.0001), while OS resulted associated only with LVSI (p = 0.0144). CONCLUSIONS: Our preliminary findings suggest that tumor budding in TBSCC, regardless of its localization (the main tumor body [ITB] or invasive front [PTB]) may be a reliable predictor of neck lymph node metastasis and poor prognosis. Tumor budding and LVI could be predictive markers for precise treatment in TBSCC. Further investigations on larger prospective series should be designed to confirm this evidence both in post-operative specimens and in preoperative biopsies.

Rates of Upstaging, Between Diagnosis and Surgery, and Clinical Management of Metastatic Cutaneous Squamous Cell Carcinoma: A Case-Control Study.

BACKGROUND: Cutaneous squamous cell carcinomas (cSCC) have upstage rates of approximately 10.3% to 11.1%. Data are currently limited on the rate of upstaging for metastatic cSCC. OBJECTIVE: The aim of this study was to determine the rates of upstaging, between diagnosis and surgery, and differences in management for metastatic and non-metastatic high-risk cSCC. MATERIALS AND METHODS: This was a retrospective, case-control, single institution, multi-center study. Univariate analysis was used. RESULTS: Sixty-eight subjects (34 metastatic & 34 non-metastatic) with 69 tumors were included. The overall rate of upstaging was 46.4%. The most common reasons for upstage were undocumented tumor size and under-diagnosis of poor differentiation. There were no differences in rates of upstaging. Preoperative imaging was performed in 43.6% of wide local excisions (WLE) versus 3.3% of Mohs micrographic surgery (MMS; p < .001). The median days from surgery to sentinel lymph node biopsy (SLNB), or nodal dissection was shorter for WLE versus MMS (0 vs 221 days, p < .001). CONCLUSION: Improved clinical documentation, including documenting tumor size, and the identification of pathologic risk factors, including poor differentiation and depth of invasion, are needed for proper staging. Preoperative imaging and discussion of SLNB may be beneficial for high-risk T2b and T3 tumors.

Cost-effectiveness analysis of pembrolizumab for treatment of US patients with persistent, recurrent, or metastatic cervical cancer.

OBJECTIVE: The effectiveness of pembrolizumab for persistent, recurrent, or metastatic cervical cancer has been demonstrated. We aimed to evaluate its cost-effectiveness from the United States (US) healthcare payers perspective. METHODS: A partitioned survival model over a 30-year lifetime horizon was developed to compare the cost and effectiveness of pembrolizumab versus placebo based on clinical data from the KEYNOTE-826 phase 3 randomized trial. Costs and health state utilities were obtained from literature and publicly available databases. The incremental cost-effectiveness ratio (ICER) was measured. One-way and probabilistic sensitivity analyses were conducted. RESULTS: For the Intention-to-Treat patients, pembrolizumab was associated with an additional 0.74 quality-adjusted life-year (QALY) at an additional cost of $182,271 when compared with placebo. The ICER was $247,663/QALY. For patients with a programmed death-ligand 1 combined positive score ≥ 1 and 10, the ICER was $253,322/QALY and $214,212/QALY, respectively. One-way sensitivity analyses showed that pembrolizumab had the greatest impact on the ICER. Probabilistic sensitivity analyses showed that the probability of pembrolizumab being cost-effective was zero at the current willingness-to-pay threshold of $150,000/QALY. The price of pembrolizumab had to reduce at least to $28.336 (55.8% of the current price) for it to be cost-effective in a 50% of chance. CONCLUSION: The addition of pembrolizumab to chemotherapy is costly and might not be cost-effective for persistent, recurrent, or metastatic cervical cancer at the current price in the US.