A deep learning algorithm to detect cutaneous squamous cell carcinoma on frozen sections in Mohs micrographic surgery: A retrospective assessment.

Intraoperative margin analysis is crucial for the successful removal of cutaneous squamous cell carcinomas (cSCC). Artificial intelligence technologies (AI) have previously demonstrated potential for facilitating rapid and complete tumour removal using intraoperative margin assessment for basal cell carcinoma. However, the varied morphologies of cSCC present challenges for AI margin assessment. The aim of this study was to develop and evaluate the accuracy of an AI algorithm for real-time histologic margin analysis of cSCC. To do this, a retrospective cohort study was conducted using frozen cSCC section slides. These slides were scanned and annotated, delineating benign tissue structures, inflammation and tumour to develop an AI algorithm for real-time margin analysis. A convolutional neural network workflow was used to extract histomorphological features predictive of cSCC. This algorithm demonstrated proof of concept for identifying cSCC with high accuracy, highlighting the potential for integration of AI into the surgical workflow. Incorporation of AI algorithms may improve efficiency and completeness of real-time margin assessment for cSCC removal, particularly in cases of moderately and poorly differentiated tumours/neoplasms. Further algorithmic improvement incorporating surrounding tissue context is necessary to remain sensitive to the unique epidermal landscape of well-differentiated tumours, and to map tumours to their original anatomical position/orientation.

Clinical Significance Unveiled: Understanding the Meaning of FACE-Q Skin Cancer Scores for Improved Patient Care.

OBJECTIVE: The FACE-Q Skin Cancer Module is a Patient-Reported Outcome Measure (PROM) utilized to assess outcomes following facial skin cancer resection. However, the lack of Minimal Important Difference (MID) estimates hinders the interpretability of the PROM scores. This study established MID estimates for the four outcome scales from the FACE-Q Skin Cancer Module using distribution-based methods. METHODS: A prospective cohort study at four hospitals in the United States, enrolled participants who underwent Mohs Micrographic Surgery (MMS) for facial skin cancer between April 2020 and April 2022. Participants completed the Satisfaction with Facial Appearance, Appearance-related Psychosocial Distress, Cancer Worry, and Appraisal of Scars scales at four time points: pre-operatively, 2-week, 6-month, and 1-year post-surgery. RESULTS: A total of 990 patients participated in the study, with completion rates of 98.4% for the pre-operative assessment, 70.8% at 2 weeks, 59.3% at 6 months, and 60.4% at 1 year. MID estimates, calculated using 0.2 standard deviation and 0.2 standardized response mean, were determined for the four scales. The mean MID estimates, based on a Rasch transformed score ranging from 0 to 100, were 5 for the Appraisal of Scars scale and 4 for the remaining three scales. CONCLUSION: This multicenter study provides valuable MID estimates for the FACE-Q Skin Cancer Module, specifically for the MMS patient population, enabling clinicians and researchers to better interpret scores, determine appropriate sample sizes, and apply the findings in clinical care.

Excision margins for melanoma in situ on the head and neck-A single-center 10-year retrospective review of treatment with Mohs micrographic surgery.

BACKGROUND: Although current guidelines recommend a 5 mm surgical margin for the excision of melanoma in situ (MIS), increasing evidence has shown this may be suboptimal to achieve tumor clearance. OBJECTIVE: To evaluate margins required for optimal cure rates with excision of MIS on the head and neck and investigate tumor and/or patient factors in those requiring >5 mm margins to achieve tumor clearance. METHODS: A retrospective chart review was performed on 846 (807 primary and 39 recurrent) MIS cases on the head and neck treated in the authors' dermatologic surgery department over a 126-month (10.5 year) period. RESULTS: Sixty-two percent were cleared with 5 mm margins. A total of 15 mm margins were required to achieve a 97% clearance rate. Difference in clearance rate between margin thresholds was significant (P < .001). Tumor location on the cheek and larger preoperative size correlated with requiring >5 mm margins to achieve tumor clearance (P = .006 and P = .001, respectively). LIMITATIONS: This is a single-center retrospective study which relies on accurate documentation of clinical data. CONCLUSION: This study demonstrates that MIS on the head and neck often requires margins >5 mm margins to achieve tumor clearance. When Mohs micrographic surgery is not possible, excision margins of ≥10 mm are likely necessary for head and neck tumors.

Epidemiology, clinical characteristics, treatment, and outcomes of proliferating pilar tumors: A systematic review.

BACKGROUND: Proliferating pilar tumors (PPTs) are rare cutaneous neoplasms arising from hair follicles that have both malignant and metastatic potential. OBJECTIVE: To present a systematic review of the epidemiology, clinical characteristics, and treatment and outcome data on PPTs. METHODS: Using the OVID platform, MEDLINE and Embase were searched from inception until May 26, 2022. All studies that provided original data on PPTs in English were included. References of these studies were also cross-checked to identify any additional relevant articles. Oxford's Levels of Evidence-Based Medicine was used for quality assessment. RESULTS: A total of 114 articles, providing data on 361 cases of PPTs, were included in our synthesis. Every study included was either a case series or case report. The mean age at diagnosis was 61.7. Most patients in the synthesis were female (71%), and the majority of cases occurred on the scalp (73.1%). The presence or absence of cytological atypia was only reported in one-third of the cases; 36.8% of cases were classified as malignant and 7.5% metastasized. Although no lesions treated with Mohs micrographic surgery required adjuvant radiation and only one reported recurrence occurred after Mohs surgery, there is insufficient data to make conclusions on a superior treatment modality. LIMITATIONS: All studies in this review were either case reports or case series. CONCLUSIONS AND RELEVANCE: Our study supports the notion that PPTs occur most commonly on the scalp of elderly female patients. Moreover, our findings confirm that PPT is capable of demonstrating aggressive biology and metastasis. Given the lack of uniformity in histologic description, pathologists should be encouraged to comment on the presence and degree of cytological atypia when reporting cases of rare neoplasms such as the PPT. Greater consensus on diagnosis and classification as well as more robust data is needed regarding optimal management.

Therapeutic outcomes and survival analysis of Extramammary Paget's disease: A multicentre retrospective study of 249 patients.

BACKGROUND: Evidence regarding long-term therapeutic outcomes and disease-specific survival (DSS) in Extramammary Paget's disease (EMPD) is limited. OBJECTIVES: To assess the DSS and outcomes of surgical and nonsurgical therapeutic modalities in a large cohort of EMPD patients. METHODS: Retrospective chart review of EMPD patients from 20 Spanish tertiary care hospitals. RESULTS: Data on 249 patients with a median follow-up of 60 months were analyzed. The estimated 5-, 10-, and 15-year DSS was 95.9%, 92.9%, and 88.5%, respectively. A significantly lower DSS was observed in patients showing deep dermal invasion (≥1 mm) or metastatic disease (P < .05). A ≥50% reduction in EMPD lesion size was achieved in 100% and 75.3% of patients treated with surgery and topical therapies, respectively. Tumor-free resection margins were obtained in 42.4% of the patients after wide local excision (WLE). The 5-year recurrence-free survival after Mohs micrographic surgery (MMS), WLE with tumor-free margins, WLE with positive margins, radiotherapy, and topical treatments was 63.0%, 51.4%, 20.4%, 30.1%, and 20.8%, respectively. LIMITATIONS: Retrospective design. CONCLUSIONS: EMPD is usually a chronic condition with favorable prognosis. MMS represents the therapeutic alternative with the greatest efficacy for the disease. Recurrence rates in patients with positive margins after WLE are similar to the ones observed in patients treated with topical agents.

How dermatologic surgeons decide to proceed with surgery for nonmelanoma skin cancer when site identification is initially uncertain: A nationwide, multicenter, prospective study.

BACKGROUND: Few studies show how dermatologic surgeons manage problems with site identification. OBJECTIVE: To estimate frequency and characterize management of skin cancer treated by surgery when the anatomic location of the tumor is in question. METHODS: Nationwide, prospective, multisite cohort study. RESULTS: Among 17,076 cases at 22 centers, 98 (0.60%) were lesions in question for which site identification was initially uncertain, with these more often in patients who were male, older, and biopsied more than 30 days ago. Surgeons employed on average 5.0 (95% CI: 4.61-5.39) additional techniques to confirm the site location, with common approaches including: re-checking available documentation (90 lesions, 92%); performing an expanded physical examination (89 lesions, 91%); and asking the patient to point using a mirror (61 lesions, 62%). In 15%, photographs were requested from the biopsying provider, and also in 15%, frozen section biopsies were obtained. In 10%, the referring physician was contacted. Eventually, surgeons succeeded in definitively identifying 82% (80 of 98) of initially uncertain sites, with the remaining 18% (18 of 98) postponed. Most postponed surgeries were at non-facial sites. LIMITATIONS: Sites were academic centers. CONCLUSIONS: When the anatomic location of the tumor is uncertain, dermatologic surgeons use multiple methods to identify the site, and sometimes cases are postponed.

Extramammary Paget disease. Part II. Evidence-based approach to management.

Extramammary Paget disease is a rare cutaneous malignancy that most commonly affects the genitals, perianal area, and axilla of elderly patients. Delays in care often lead to high levels of disease burden for patients. Thus, evidence-based recommendations are paramount in mitigating morbidity and mortality for this unique patient population. This 2-part continuing medical education series provides a complete picture of extramammary Paget disease. Part 2 of this continuing medical education series focuses on the complex management of extramammary Paget disease including surgical and noninvasive therapies, as well as novel approaches for advanced disease.

Factors associated with residual tumor at time of Mohs micrographic surgery for basal cell and squamous cell carcinomas.

BACKGROUND: Residual tumor is not always clinically apparent following biopsy of cutaneous carcinomas, which may prompt patients to question the need for definitive treatment. OBJECTIVE: We investigated the percentage of cases in which residual tumor was histologically present at the time of Mohs micrographic surgery (MMS) for basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) and investigated factors associated with residual tumor. METHODS: We examined 483 MMS cases performed for biopsy-proven BCC (n = 287) and SCC (n = 196) between October 2022 and April 2023. Single-stage MMS specimens were step-sectioned en face to exhaust the block. Univariate and multivariable logistic regression models were created. RESULTS: Residual tumor was identified in 83.3% of BCC and 66.8% of SCC at the time of MMS (P = .01). In patients clinically appearing tumor-free following biopsy, residual histologic tumor was identified in 68.2% of BCC and 41.5% of SCC. Residual tumor was significantly more likely in men (P = .04), high-risk sites (P = .002), smaller biopsy sizes (P = .0003), and larger preoperative sizes (P < .0001). LIMITATIONS: Single center, retrospective cohort. CONCLUSION: The majority of patients with BCC and SCC have residual histologic tumor at the time of MMS, oftentimes even when tumor is not clinically apparent. Multiple factors impact the presence/absence of residual tumor.

Mohs micrographic surgery in the surgical treatment paradigm of melanoma in situ and invasive melanoma: A clinical review of treatment efficacy and ongoing controversies.

Mohs Micrographic Surgery (MMS) for treatment of melanoma offers several advantages over wide local excision (WLE), including complete histologic margin evaluation, same-day resection and closure, and sparing of healthy tissue in critical anatomic sites. Recently, a large volume of clinical data demonstrating efficacy in MMS treatment of melanoma was published, leading to emerging patient safety considerations of incurred treatment costs, risk of tumor upstaging, and failure of care coordination for sentinel lymph node biopsy (SLNB). MMS offers a safe, effective, and value-based treatment for both melanoma in situ (MIS) and invasive melanoma (IM), particularly with immunohistochemistry use on frozen sections. Compared to wide local excision, MMS treatment demonstrates similar or improved outcomes for local tumor recurrence, melanoma-specific survival, and overall survival at long-term follow-up. Tumor upstaging risk is low, and if present, alteration to clinical management is minimal. Discussion of SLNB for eligible head and neck IM cases should be done prior to MMS. Though challenging, successful multidisciplinary coordination of SLNB with MMS has been demonstrated. Herein, we provide a detailed clinical review of evidence for MMS treatment of cutaneous melanoma and offer recommendations to address current controversies surrounding the evolving paradigm of surgical management for both MIS and invasive melanoma (IM).

The use of oral benzodiazepines for patient anxiety associated with Mohs micrographic surgery: An Australian survey.

A survey of Mohs surgery specialists in Australia showed diazepam was the preferred agent and felt to be the safest oral benzodiazepine for perioperative anxiolysis.

Perspectives on oral benzodiazepine use for anxiety in Mohs micrographic surgery: A response to the Australian survey.

This letter responds to the recent Australian survey by Harris and Lee (Australas J Dermatol, 2024, doi: 10.1111/ajd.14361) on the use of oral benzodiazepines for anxiety management in Mohs micrographic surgery (MMS). While commending the authors' efforts, we provide additional perspectives on current practices, recent evidence and safety considerations. We highlight the alignment with U.S. practices, discuss a recent randomized controlled trial supporting diazepam's efficacy and emphasize the importance of non-pharmacological interventions. The letter also addresses the need for flumazenil availability and calls for standardized guidelines and further research to optimize patient care in MMS.

Comparison of Infection Rate Between Sterile and Nonsterile Gloves During Mohs Micrographic Surgery: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Mohs micrographic surgery (MMS) is a well-established technique for the removal of various types of skin cancers. While sterile gloves (SG) are commonly used in skin surgeries such as MMS, additional understanding of their effectiveness compared to nonsterile gloves (NSG) in preventing local infection is required. OBJECTIVE: We aimed to perform an updated systematic review and meta-analysis comparing the use of SG with NSG for local infection rate post-MMS and point out cost discrepancies between these 2 scenarios. METHODS: We searched MEDLINE, Embase, and Cochrane for studies published up to August 2023 comparing the use of SG with NSG during MMS that reported the outcome of wound infection. RESULTS: A total of 4 studies with 10,644 MMS were included, of which 7512 (70.6%) were performed with SG and 3132 (29.4%) were done with NSG. In the SG group, 232 out of 7512 cases (3.1%) developed infection compared to 64 out of 3132 (2.0%) in the NSG group [odds ratio (OR) 1.14; 95% confidence interval (CI) 0.85-1.52; P = .39; I2 = 0%]. Therefore, the post-MMS infection rates were not significantly different between SG and NSG groups, including in the excision (OR 0.92; 95% CI 0.48-1.79; P = .81; I2 = 0%) and reconstruction (OR 1.17; 95% CI 0.85-1.60; P = .34; I2 = 0%) subanalysis. Regarding the mean cost of the gloves, the NSG pair was $0.24, approximately 10% of the price of the SG pair ($2.27). CONCLUSION: The results support that, compared to SG, NSG are equally effective in preventing infections during MMS while offering significant cost savings without compromising patient outcomes.Protocol registration: PROSPERO, CRD42023458525.

Mohs micrographic technique in high-risk basal cell carcinoma: a 3D prediction of safety margins.

OBJECTIVE: Compared with standard excision with a two-dimensional histological examination, Mohs micrographic surgery offers a lower recurrence rate and a greater extent of healthy tissue sparing for the treatment of high-risk basal cell carcinoma (BCC). The aims of this study were to first quantify the healthy tissue spared through the micrographic technique compared to traditional surgery for high-risk tumours. Then, to speculate, through the analysis of the distal micrographic resection margin, the adequate width of safety margins for standard excision. METHOD: A cohort of patients with high-risk BCC was treated with Mohs surgery. Safety margins, tumours residual final breach and hypothetical standard excision safety margins areas were recorded. RESULTS: A total of 96 patients were included. A reduction of 27.96% (95% Confidence Interval (CI): 17.90-38.02) of healthy skin removed was observed using a micrographic method compared to the standard approach. Standard excision with a 6mm safety margin was associated with 86.46% (95% CI: 79.62-93.30) of complete excision. Greater margins were not associated with a statistically significant improvement of complete excision. CONCLUSION: Mohs surgery should be considered the gold standard operative treatment for high-risk BCC. However, if micrographic techniques are not feasible, the standard excision with a predetermined margin of 6 mm, should be considered as the best option.

Porocarcinoma: Clinical and Histological Features, Immunohistochemistry and Outcomes: A Systematic Review.

Porocarcinoma (PC) is a rare adnexal tumor, mainly found in the elderly. The tumor arises from the acrosyringium of eccrine sweat glands. The risk of lymph node and distant metastasis is high. Differential diagnosis with squamous cell carcinoma is difficult, although NUT expression and YAP1 fusion products can be very useful for diagnosis. Currently, wide local excision is the main surgical treatment, although Mohs micrographic surgery is promising. To date, there is no consensus regarding the role of sentinel lymph node biopsy and consequential lymph node dissection. No guidelines exist for radiotherapy, which is mostly performed based on tumor characteristics and excision margins. Only a few studies report systemic treatment for advanced PC, although therapy with pembrolizumab and EGFR inhibitors show promise. In this review, we discuss epidemiology, clinical features, histopathological features, immunohistochemistry and fusion products, surgical management and survival outcomes according to stage, surgical management, radiotherapy and systemic therapy.

Risk factors for developing depressive symptoms in the immediate postoperative period after Mohs micrographic surgery.

PURPOSE: Mohs micrographic surgery (MMS) is a highly efficacious, tissue sparing method of skin cancer removal. Nevertheless, in the months to years after MMS, psychosocial distress has been described. The present study addressed the immediate period after MMS and assessed the frequency and risk factors for development of depressive symptoms. METHODS: Subjects undergoing MMS at two physician practices (JL, FS) were included in this prospective cohort study. Preoperatively, a standardized depression screening, the Patient Health Questionnaire-8 (PHQ-8), was administered. After MMS, the PHQ-8 was readministered at weeks 1, 2, 4, 6, and 12. Average PHQ-8 score by week and change from baseline PHQ-8 score were the primary outcomes. RESULTS: Sixty-three subjects were included of which 49 (78%) had a facial site. Twenty-two subjects (35%) had some increase in score during the 12-week follow-up period, of which 18 had a facial site. The oldest subjects (83-99 years, n = 14) had significantly higher PHQ-8 scores at week 4 (p < 0.01) and week 6 (p = 0.02) than all other age groups. There were no differences in scores between location groups. CONCLUSIONS: One-third of subjects had some increase in score during the follow-up period. Those in the oldest age cohort were at highest risk of increased score. In contrast to prior literature, those with facial sites were not at higher risk. This difference may be explained by increased masking during the ongoing COVID-19 pandemic. Ultimately, consideration of patients' psychologic status in the immediate postoperative period after MMS, particularly in the elderly population, may enhance perceived patient outcomes.

Mohs surgery for female genital Paget's disease: a prospective observational trial.

BACKGROUND: Extramammary Paget's disease recurs often after traditional surgical excision. Margin-controlled surgery improves the recurrence rate for male genital disease but is less studied for female anatomy. OBJECTIVE: This study aimed to compare surgical and oncologic outcomes of margin-controlled surgery vs traditional surgical excision for female genital Paget's disease. STUDY DESIGN: We conducted a prospective observational trial of patients with vulvar or perianal Paget's disease treated with surgical excision guided by Mohs micrographic surgery between 2018 and 2022. The multidisciplinary protocol consisted of office-based scouting biopsies and modified Mohs surgery followed by surgical excision with wound closure under general anesthesia. Modified Mohs surgery cleared peripheral disease margins using a moat technique with cytokeratin 7 staining. Medial disease margins (the clitoris, urethra, vagina, and anus) were assessed using a hybrid of Mohs surgery and intraoperative frozen sections. Surgical and oncologic outcomes were compared with the outcomes of a retrospective cohort of patients who underwent traditional surgical excision. The primary outcome was 3-year recurrence-free survival. RESULTS: Three-year recurrence-free survival was 93.3% for Mohs-guided excision (n=24; 95% confidence interval, 81.5%-100.0%) compared to 65.9% for traditional excision (n=63; 95% confidence interval, 54.2%-80.0%) (P=.04). The maximum diameter of the excisional specimen was similar between groups (median, 11.3 vs 9.5 cm; P=.17), but complex reconstructive procedures were more common with the Mohs-guided approach (66.7% vs 30.2%; P<.01). Peripheral margin clearance was universally achieved with modified Mohs surgery, but positive medial margins were noted in 9 patients. Reasons included intentional organ sparing and poor performance of intraoperative hematoxylin and eosin frozen sections without cytokeratin 7. Grade 3 or higher postoperative complications were rare (0.0% for Mohs-guided excision vs 2.4% for traditional excision; P=.99). CONCLUSION: Margin control with modified Mohs surgery significantly improved short-term recurrence-free survival after surgical excision for female genital Paget's disease. Use on medial anatomic structures (the clitoris, urethra, vagina, and anus) is challenging, and further optimization is needed for margin control in these areas. Mohs-guided surgical excision requires specialized, collaborative care and may be best accomplished at designated referral centers.

Appearance-related psychosocial distress after facial non-melanoma skin cancer surgery: A 1-year prospective study.

OBJECTIVE: Patients undergoing Mohs Micrographic Surgery (MMS) for facial non-melanoma skin cancer (NMSC) experience appearance-related psychosocial distress due to its post-surgical esthetic changes. However, little is known about its development over a longer follow-up period. This study prospectively assessed appearance-related psychosocial distress in patients undergoing MMS for facial NMSC over a 1-year follow up period. METHODS: Patients who had MMS for facial NMSC between September 2020 and October 2021 were invited to answer the FACE-Q Skin Cancer - appearance-related psychosocial distress scale preoperatively, 2 weeks, 6 months, and 1 year after surgery. RESULTS: A total of 217 patients completed the questionnaire at baseline. In addition, 158 (72.8%), 139 (64.1%), and 120 (55.3%) questionnaires were successfully answered 2 weeks, 6 months, and 1 year after surgery, respectively. Patients with a peripheral lesion presented higher appearance-related psychosocial distress scores at baseline than patients with a central lesion (p = 0.02). There was a decreasing trend in appearance-related psychosocial distress over time, but without a significant result (baseline-2-week; p = 0.73, 2-week-6-month; p = 0.80, 6-month-1-year; p = 0.17, baseline-1-year; p = 0.23). Patients with secondary intention healing and graft reconstruction methods experienced more appearance-related psychosocial distress over time than patients with primary wound closures (p = 0.03). CONCLUSIONS: Patients still experience appearance-related psychosocial distress 1 year after MMS. These patients may benefit from targeted counseling. Additionally, predictors of more appearance-related psychosocial distress, such as secondary intention healing and graft reconstruction methods, may benefit from additional psychological care.

Surgical management of dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon, locally aggressive cutaneous malignancy. Complete resection is the primary treatment but there is debate over the optimal method. Wide local excision was traditionally the standard of care; however, National Comprehensive Cancer Network guidelines now recommend Mohs micrographic surgery as the preferred approach. Medical therapy with imatinib can be used in advanced or unresectable disease. This review will discuss the current management of DFSP, focusing on optimal surgical approach.

Differences in sentinel lymph node biopsy utilization in eligible melanoma patients treated with Mohs micrographic surgery or wide local excision: A population-based logistic regression model and survival analysis.

BACKGROUND: Primary melanoma management relies on tumor extirpation and staging sentinel lymph node biopsy (SLNB) in eligible patients. This study compares SLNB utilization in patients undergoing wide local excision (WLE) or Mohs micrographic surgery (MMS). METHODS: American Joint Committee on Cancer seventh edition ≥ patients with T1b melanoma undergoing WLE or MMS in the Surveillance, Epidemiology, and End Results program were included. Propensity score matching was performed to compare patients who underwent MMS or WLE. Kaplan-Meier analysis and Fine-Gray cumulative incidence functions were used for overall and melanoma-specific survival. RESULTS: Eight hundred twenty-five MMS cases and 38,760 WLE cases were identified. SLNB was performed in 32.61% of MMS patients and 61.77% of WLE patients with positive rates of 12.5% and 14.82%, respectively. Multiple logistic regression of factors associated with SLNB utilization revealed that WLE, male gender, younger age, extremity location, and nodular and rare melanoma subtypes were significantly associated with increased odds of receiving SLNB whereas head and neck location and lentigo maligna melanoma subtype were significantly less likely to receive SLNB. LIMITATIONS: Potential selection bias from a retrospective data set. CONCLUSION: Patients receiving WLE for ≥ T1b melanoma are more likely to receive a SLNB than patients undergoing MMS.

Limitations in the literature regarding Mohs surgery and staged excision for melanoma: A critical review of quality and data reporting.

BACKGROUND AND OBJECTIVES: The literature supporting Mohs micrographic surgery and staged excision in treating primary cutaneous melanoma is growing but has not been critically reviewed for bias. METHODS: Articles concerning Mohs micrographic surgery and staged excision for melanoma were assessed using modified "Risk of Bias in Non-randomized Studies of Interventions" (ROBINS-I) criteria, which measures bias in 7 categories. RESULTS: Forty-seven of 48 (97.9%) studies reviewed had serious or critical bias. None were randomized controlled trials. The most frequent cause of critical bias was poorly defined outcomes. The least frequent form of bias observed was change in intervention. LIMITATIONS: The modified ROBINS-I criteria cannot account for all study limitations. Modification of the criteria leads to some degree of subjectivity. CONCLUSION: The current body of literature suffers from limitations due to serious or critical bias in 1 or more ROBINS-I criteria. Local recurrence rate definitions are often poorly defined or not defined at all. Longer follow-up times, clear tumor classifications, and prospective, randomized study designs are necessary to improve the quality of future research.