Cumulative incidence and disease-specific survival of metastatic cutaneous squamous cell carcinoma: A nationwide cancer registry study

Tokez, Selin; Wakkee, Marlies; Kan, Wilner Christopher; Venables, Zoe C; Mooyaart, Antien L.; Louwman, Marieke; Nijsten, Tamar; Hollestein, Loes

doi:10.1016/j.jaad.2021.09.067

Cited by 36 publications

(30 citation statements)

References 27 publications

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“…While this sex disparity is a limitation of our study in that potential sex differences may have been missed, it is in keeping with the disease burden seen in our practice in NSW, Australia, particularly for advanced and metastatic cSCC (Ashford et al, manuscript under review). This is in keeping with findings that age, male sex and immunosuppression are among the risk factors for metastasis [38]. Two patients were immunocompromised; one patient was on long-term azathioprine for rheumatoid arthritis and the other was on a combination of cyclophosphamide and tacrolimus following solid organ transplantation.…”

Section: Patient Characteristics and Clinicopathologic Datasupporting

confidence: 87%

Whole genome analysis reveals the genomic complexity in metastatic cutaneous squamous cell carcinoma

Thind

Ashford

Strbenac

et al. 2022

Preprint

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Metastatic cutaneous squamous cell carcinoma (cSCC) is associated with a high risk of recurrence and poor prognosis. There is limited published data exploring whole genome sequencing (WGS). The aim of this project was to provide the first comprehensive genomic understanding of the state of metastatic cSCC. In this study, we used WGS on matched tumor and blood DNA to detect somatic genetic alterations from 25 patients with regional metastases of head and neck cSCC. Our computational analyses interrogate clinical impacts of these genetic alterations on metastatic cSCC across the cohort for both the coding and non-coding genome. In the non-coding genome, 3UTR regions of EVC (48%), PPP1R1A (48%) and LUM (16%) were significantly functionally altered (Q-value < 0.05). Further, significant functional alterations are observed in the tumor suppressing lncRNA LINC01003 ( 68% of specimens, Q-value: 0.0158). In addition, significant recurrent copy number loss in tumor suppressor genes KANSL1 and PTPRD and gain in CALR, CCND1 and FGF3 was observed for coding regions. SNVs driver analyses predicted TP53, CDKN2A, as potential drivers of the metastasis cSCC (using 3 different tools). Indel signature analysis highlight dominance of ID signature 13 followed by ID8 & ID9. Interestingly, ID 9 has previously been shown to have no association with skin melanoma, unlike ID 13 and 8, suggesting some point of difference between these two skin-based diseases. The overall landscape of variation in metastatic cSCC is dominated by cell cycle and DNA repair disruption.

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Section: Patient Characteristics and Clinicopathologic Datasupporting

confidence: 87%

Whole genome analysis reveals the genomic complexity in metastatic cutaneous squamous cell carcinoma

Thind

Ashford

Strbenac

et al. 2022

Preprint

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“…Cutaneous squamous cell carcinoma (cSCC) is the second commonest cancer worldwide 1–3 . While the majority has an excellent post‐surgical prognosis, a small subset (2–5%) of tumours metastasizes 4–8 . A low‐risk cSCC may require no clinical follow‐up or further investigations whereas a high‐risk cSCC may be considered for intense surveillance, imaging, sentinel lymph node biopsy or even adjuvant therapy.…”

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confidence: 99%

Validation of four cutaneous squamous cell carcinoma staging systems using nationwide data*

Venables

Tokez²,

Hollestein

et al. 2022

Br J Dermatol

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Summary Background Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer worldwide with relatively low metastatic potential (2–5%). Developments in therapeutic options have highlighted the need to better identify high‐risk patients who could benefit from closer surveillance, adjuvant therapies and baseline/follow‐up imaging, while at the same time safely omitting low‐risk patients from further follow‐up. Controversy remains regarding the predictive performance of current cSCC staging systems and which methodology to adopt. Objectives To validate the performance of four cSCC staging systems [American Joint Committee on Cancer 8th edition (AJCC8), Brigham and Women’s Hospital (BWH), Tübingen and Salamanca T3 refinement] in predicting metastasis using a nationwide cohort. Methods A nested case–control study using data from the National Disease Registration Service, England, 2013–2015 was conducted. Metastatic cSCC cases were identified using an algorithm to identify all potential cases for manual review. These were 1 : 1 matched on follow‐up time to nonmetastatic controls randomly selected from 2013. Staging systems were analysed for distinctiveness, homogeneity, monotonicity, specificity, positive predictive value (PPV), negative predictive value (NPV) and c‐index. Results We included 887 metastatic cSCC cases and 887 nonmetastatic cSCC controls. The BWH system showed the highest specificity [92.8%, 95% confidence interval (CI) 90.8–94.3%, PPV (13.2%, 95% CI 10.6–16.2) and c‐index (0.84, 95% CI 0.82–0.86). The AJCC8 showed superior NPV (99.2%, 95% CI 99.2–99.3), homogeneity and monotonicity compared with the BWH and Tübingen diameter and thickness classifications (P < 0.001). Salamanca refinement did not show any improvement in AJCC8 T3 cSCC staging. Conclusions We validated four cSCC staging systems using the largest nationwide dataset of metastatic cSCC so far. Although the BWH system showed the highest overall discriminative ability, PPV was low for all staging systems, which shows the need for further improvement and refining of current cSCC staging systems.

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“…However, there was a small number of studies reporting disease-specific death, and the risk factors were variably defined across studies [ 15 ]. A nationwide cancer registry study in 11,137 patients with cSCC reported that, among the 71 cSCC-specific deaths, 39 patients did not have metastases, highlighting a group of non-metastatic cSCC leading to disease-specific death [ 28 ]. Similarly, Eigentler et al reported that disease-specific death occurred in 70% of patients due to either local infiltration by the tumor or nodal infiltration.…”

Section: Definition Of High-risk Csccmentioning

confidence: 99%

“…Factors to consider regarding the frequency and intensity of the follow-up schedule include the risk and possible time of metastasis development. Most metastatic cSCCs are diagnosed within 2 years of the primary cSCC [ 28 , 59 ]. A nationwide cancer registry study showed that, from all mcSCCs, 74% resulted from the first cSCC and 26% arose from subsequent cSCCs [ 28 ].…”

Section: Follow-up Of Patients With High-risk Csccmentioning

confidence: 99%

“…Most metastatic cSCCs are diagnosed within 2 years of the primary cSCC [ 28 , 59 ]. A nationwide cancer registry study showed that, from all mcSCCs, 74% resulted from the first cSCC and 26% arose from subsequent cSCCs [ 28 ]. High-risk cSCC has increased risk of nodal metastases, which was quantified based on the high-risk features in the meta-analysis of Thompson et al, reporting a 11-fold risk for invasion beyond subcutaneous fat, 10-fold risk for thickness > 2 mm, 7-fold risk for thickness >6 mm, 6-fold risk for diameter > 20 mm, 5-fold risk for poor differentiation, 3-fold risk for PNI, and a 3-fold risk for location on temple [ 14 ].…”

Section: Follow-up Of Patients With High-risk Csccmentioning

confidence: 99%

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Recent Advances in the Diagnosis and Management of High-Risk Cutaneous Squamous Cell Carcinoma

Dessinioti

Stratigos

2022

Cancers

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High-risk cSCC is defined as invasive cSCC staged as N0 (without detectable regional lymph nodes) and M0 (without distant metastasis), that has features associated with a higher risk of poorer prognosis. The focus of this review is on the recent advances in the diagnosis and management of high-risk cSCC. The interest in high-risk cSCC relies on its higher risk of progression to advanced cSCC, as it represents the main pool of cSCCs that give rise to advanced tumors. Assessment of the risk is thus particularly relevant for common cSCC to identify the few with a high-risk risk of local recurrence, metastasis, or disease-specific death among all other low-risk tumors. The timely diagnosis and effective treatment of high-risk cSCCs may halt their further progression and aim to prevent and lower the incidence of advanced cSCCs. Clearance of the tumor with negative surgical margins is the main goal of surgery, which is the primary treatment of cSCC. It seems that it is difficult to discern the group of high-risk cSCCs that may benefit from adjuvant RT, as a universal beneficial effect for a cSCC with any high-risk factor which was resected with clear surgical margins has not been established. In the case of a high-risk cSCC with positive margins after surgery, and re-excision not feasible, post-operative radiotherapy is performed when possible. Recommendations on further management are discussed. Regarding the follow-up of patients diagnosed with high-risk cSCC, factors to consider regarding the frequency and intensity of the follow-up schedule include the risk and possible time of occurrence of metastasis from cSCC.

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Cumulative incidence and disease-specific survival of metastatic cutaneous squamous cell carcinoma: A nationwide cancer registry study

Cited by 36 publications

References 27 publications

Whole genome analysis reveals the genomic complexity in metastatic cutaneous squamous cell carcinoma

Whole genome analysis reveals the genomic complexity in metastatic cutaneous squamous cell carcinoma

Validation of four cutaneous squamous cell carcinoma staging systems using nationwide data*

Recent Advances in the Diagnosis and Management of High-Risk Cutaneous Squamous Cell Carcinoma

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