Extent of Groin Dissection in Melanoma

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1		Suzana Kupper	+ 2249 word(s)	2249	2021-12-17 03:33:30	\|
2	Done	Jason Zhu	Meta information modification	2249	2022-01-10 02:18:48	\|

This entry is adapted from the peer-reviewed paper 10.3390/curroncol28060452

Melanoma metastases to the groin are frequently managed by therapeutic lymph node dissection. Evidence is lacking regarding the extent of dissection required. Thus, researchers sought to describe practice patterns for the use of inguinal vs. ilioinguinal dissection, as well as the perioperative/oncologic outcomes of each procedure.

melanoma groin metastases surgery

1. Introduction

Melanoma is a common malignancy with various subtypes including cutaneous, acral, mucosal and uveal. These different subtypes exhibit unique biological and clinical behaviour with significant resultant differences in prognosis ^[1]. Cutaneous melanoma is the most common subtype and the incidence is increasing worldwide, with an estimated 7800 new cases and 1300 melanoma-related deaths in Canada in 2019 ^[2]. Traditionally, wide local excision of the primary lesion and sentinel lymph node biopsy (SLNB) in clinically node negative patients is undertaken for curative intent, with those found to have sentinel lymph node metastases managed with therapeutic lymph node dissection. More recently, data from the DeCOG-SLT trial showed no difference in survival in patients treated with completion lymph node dissection vs. observation ^[3]. Similarly, the MSLT-II trial comparing completion lymph node dissection with observation in SLNB positive patients found greater prognostic value but no difference in melanoma specific survival ^[4]. There remains a subgroup of patients, however, for whom therapeutic dissection is indicated, such as those with clinically evident disease and those who develop disease during ultrasound surveillance after a positive SLNB. For metastases in the groin, the extent of dissection can include just the superficial lymph nodes (inguinal node dissection) or a combination of the superficial lymph nodes and the deep lymph nodes along the iliac and obturator vessels in the pelvis (ilioinguinal dissection).

To date, clear evidence is lacking regarding the extent of dissection required in the presence of inguinal disease. Specifically, data is lacking on whether the addition of an ilioinguinal dissection (i.e., a deep pelvic lymph node dissection) improves patient outcomes. Given that dissection of the groin carries increased complications and rates of lymphedema compared to other nodal basins, some surgeons are choosing to forgo the more extensive dissection entirely. There is an ongoing phase III randomized controlled trial (EAGLE FM) to address the extent of dissection; however, the estimated completion date is not until 2030 ^[5]. In this era of shrinking indications for lymph node surgery in melanoma, it is important to consider whether ilioinguinal dissection adds value or whether it simply increases postoperative complications. Furthermore, it is important to consider how patients are selected for ilioinguinal dissection and whether the selection criteria in use are reasonable.

2. Study Design and Setting

A mixed-methods approach was undertaken using both a quantitative evaluation of surgical practice patterns and a qualitative approach to understanding surgeon preference and perceptions. Study approval was obtained from the institutional review boards of all institutions.

3. Surgical Practice Patterns

A retrospective review of three prospectively maintained databases (Synoptec, AB, provincial, population based datatabase) from: Saint John, NB, Canada; Sunnybrook Health Sciences Centre, Toronto, ON, Canada; and The Ottawa Hospital, Ottawa, ON, Canada. The review was performed to abstract relevant data. All patients who were diagnosed with cutaneous melanoma and underwent a groin dissection between June 2004 and May 2019 were included. Due to the significant differences in natural history and prognosis of mucosal melanomas ^[6], as well as their low representation within the study cohort, mucosal primaries were excluded. Unknown primaries were included.

Variables collected included patient demographics (age, gender, body mass index (BMI) and co-morbidities), primary disease pathology (Breslow thickness, ulceration, mitoses, lymphovascular invasion (LVI) and satellitosis) and method of diagnosis of inguinal disease (sentinel lymph node biopsy (SLNB), palpable, radiographic; initial presentation vs. recurrence). In addition, data were collected on procedure(s) performed, node dissection pathology (total nodes, positive nodes and extra-nodal extension), postoperative course (complications, length of stay (LOS), readmission and mortality), lymphedema, adjuvant therapy, recurrence, status at last follow-up and death. Lymphedema was defined as use of compression stockings beyond the immediate postoperative period or a referral to a lymphedema clinic. A primary chart review captured any variables not contained within the databases. Patients and analyses were stratified based on their presentation of disease as sentinel lymph node positive vs. clinically positive (palpable or radiologically evident) and extent of dissection (inguinal vs. ilioinguinal dissection). The majority of dissections were performed prior to the publication of MSLT-II in 2017, thus most patients in the SLNB group went on to have completion groin dissection routinely.

4. Statistical Methods

Descriptive statistics were used to present patient demographics and practice patterns. Median and interquartile range (IQR) were reported for continuous variables; frequencies and proportions were reported for categorical variables. Missing data were not replaced or estimated. The Mann–Whitney U-Test was utilized to compare continuous values. Categorical variables were compared using Pearson’s chi-squared test or Fisher exact test where appropriate. Kaplan–Meier survival analysis was used to display overall, recurrence free survival and cancer-specific survival (OS, RFS and CSS, respectively). Factors affecting survival were identified using multivariate Cox regression models. A two-sided p-value < 0.05 was used for statistical significance. Statistics were performed using SAS v.9.4 (SAS Institute, Cary, NC, USA). OS and RFS were calculated from the date of surgery to date of death or first recurrence of any kind (either local or distant), respectively. Time was censored at the date of last follow up for patients who were still alive or free from recurrence.

5. Patient Selection and Deep Positivity Rate

Current study showed that almost 40% of patients undergoing groin dissection for melanoma received an ilioinguinal dissection, the majority of whom (78.8%) presented with clinically evident disease (either palpable or evident on imaging). All surgeons interviewed reported using a selective approach to ilioinguinal dissections with the main indications for deep dissection being clinically evident disease and radiographic evidence of deep nodal disease. Notably absent from the interview results was any mention of the use of Cloquet’s node. In the literature, the deep node positivity rate ranges from 9.3% with microscopically identified disease (i.e., positive sentinel node biopsy) to 55% with macroscopically identified disease (i.e., clinically evident disease) ^[7]^[8]^[9]^[10]^[11]^[12].

The selective approach used by the surgeons in this study produced a deep nodal positivity rate of 40.9%. This rate is at the higher end of the range reported in the literature, which is appropriate given that surgeons were predominantly performing deep dissections on patients with macroscopic disease. In addition, the deep nodal positivity rate found in this study was well above the a priori threshold (that would prompt the inclusion of a deep dissection) stated by all interviewed surgeons. This suggests that the indications for ilioinguinal dissection currently in use are reasonable. As described above, radiographic evidence was a key indication for ilioinguinal dissection for nearly all surgeons. However, preoperative CT has been shown to have poor accuracy for pelvic node involvement, with a reported sensitivity of approximately 60% ^[13]. While PET/CT is quite accurate for superficial groin metastases (sensitivity 97%), it does not perform much better than CT for deep groin metastases with a sensitivity of 67% and a false negative rate of 33% ^[14]. This suggests that while radiologic studies may be helpful in selecting patients for ilioinguinal groin dissection, they should not be the exclusive determinant of the extent of surgery.

6. Perioperative Outcomes

The median length of stay was similar across groups and subgroups in this study. In addition, there was no difference in complication rates between any of the groups, with the exception of a small increase in minor complications (Clavien–Dindo grade I–II) in the SNLB-ilioinguinal dissection subgroup (vs. the SNLB-inguinal dissection subgroup). While grade I and II complications are typically both underestimated and underreported, presumably this would have occurred to a similar extent in both groups. Other studies have echoed these findings, showing no difference in complications with the addition of a deep dissection ^[7]^[12]. There was no significant difference in lymphedema between groups, either by mode of presentation (SLNB-positive vs. clinically positive) or by extent of dissection (inguinal vs. ilioinguinal dissection). This finding is rendered more noteworthy by the fact that significantly more patients undergoing an ilioinguinal dissection received adjuvant radiotherapy, a known risk factor for lymphedema ^[15]. Although limited, the published data directly comparing the rate of lymphedema between the inguinal and ilioinguinal cohorts have not shown a significant difference ^[7]^[12]. Nearly all surgeons surveyed felt that the inclusion of a deep dissection did not add significant morbidity and certainly, this impression is supported by current results.

7. Oncologic Outcomes

Approximately half of all patients experienced a recurrence after groin dissection, which was similar regardless of extent of dissection. Patients in the clinically positive group recurred more frequently, earlier and had more distant events than the patients in the SLNB-positive group. This pattern of recurrences is consistent with previously published studies ^[16]^[17], and likely reflects the biology of the primary disease, as the clinically positive group had significantly higher risk pathology and higher stage disease compared to the SLNB-positive group. Within both the clinically positive and SLNB-positive groups, there was no difference in recurrence frequency or pattern with extent of dissection, although there was a trend towards increased isolated deep node recurrence with inguinal dissection. Looking at all patients undergoing an ilioinguinal dissection vs. an inguinal dissection, the difference in isolated deep node recurrence was significant (2.9% vs. 8.6%, p = 0.0011, respectively). This finding suggests that utilizing ilioinguinal dissection may improve regional control. Regional control, however, is also impacted by the delivery of adjuvant therapy, and there were significantly more patients receiving an ilioinguinal dissection who also received adjuvant radiation. In addition, more patients receiving ilioinguinal dissection received adjuvant systemic therapy, which also reduces locoregional recurrence ^[18]. This makes it difficult to determine the true impact of surgery on regional control. Few studies have directly assessed the impact of ilioinguinal dissection on deep node recurrence alone. Van der Ploeg et al. looked at 169 patients undergoing groin dissection for palpable metastases and did not find a difference in the pelvic node recurrence rate ^[7]. In a study by Egger et al., the rate of deep node recurrence was 11% in the cohort receiving a superficial-only dissection and 5% in the cohort receiving a combined dissection. While this difference did not reach statistical significance, the authors themselves note that their sample size was small (only 34 combined dissections) and there may well be a trend towards increased pelvic node recurrences in the superficial only group ^[12].

Another factor known to influence locoregional control is the quality of surgery performed. For instance, quality indicators such as lymph node yield and completeness of mesorectal excision have been well established in colorectal cancer surgery ^[19]. Quality indicators are less well established for melanoma surgery and this was not an area that was actively investigated in this study. However, the vast majority of the procedures included in this study were performed in a tertiary centre by a high volume of melanoma surgeons. The relationship between high volumes and improved outcomes is well documented in other solid tumours and similarly, there is evidence to support this association in melanoma treatment as well ^[20]^[21].

After adjusting for known confounders, the only significant factor associated with survival on multivariate analysis was presented, with patients diagnosed by SLNB (vs. clinical exam/imaging) significantly associated with improved OS, RFS and CSS. Specifically, extent of procedure had no significant impact on survival. This finding is mirrored in several other studies that did not show an association between extent of surgery and survival ^[16]^[22]. This finding is reflected in current qualitative results, where nearly all surgeons felt that the primary benefit of a deep dissection was regional control rather than improved survival. However, almost half of surgeons felt that there was a small possibility of improving overall survival as well. Looking closer at the data, this notion is also supported by evidence. Historically, the 10-year survival of patients with positive deep nodes is approximately 20% ^[9]^[17]. These numbers are derived from data that preceded effective systemic therapy, indicating that a reasonable proportion of patients with deep pelvic disease are cured by surgery alone. In this study, patients with positive deep nodes had a 5-year CSS, OS and RFS of 57.1%, 50% and 21.4%, respectively. For select patients, particularly given the lack of significant additional morbidity, outcomes may be improved by the addition of a deep dissection.

8. Limitations & Generalisability

This study cohort is comprised of patients who were selected to undergo groin dissection for a variety of reasons. Importantly, the majority of patients were treated prior to the publication of MSLT-II, therefore there are many SNLB positive patients who proceeded directly to groin dissection rather than ultrasound surveillance. This may have affected current results as these patients would typically have a lower burden of disease. However, more than half of the patients in this study presented with clinically positive disease. These patients would have proceeded directly to therapeutic lymph node dissection in the post-MSLT II era as well. Therefore, the data remains relevant and applicable to current melanoma patients. While multivariable analysis does control for known confounders, selection bias is impossible to remove entirely and other unmeasured variables may influence findings. Nonetheless, the qualitative component of the study strengthens current results by providing information that is generally unavailable retrospectively, namely preoperative rationale, method of patient selection and intent of surgery. It is one of the largest studies to date looking at this type of cohort and includes a broad sample of patients from multiple institutions across multiple regions. Thus, current conclusions are broadly generalizable to other patient populations. In addition, this study is one of the few to look at both perioperative and oncologic outcomes. This allows us to determine a true risk/benefit assessment of deep dissection, which is the most important assessment from a patient and provider perspective.

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