**7. Treatment**

The main treatment options for AM are surgery, chemotherapy, radiation therapy and targeted therapies. According to a study which analyzed data of 1333 AM patients from National Cancer Database from 2004 to 2015, the authors found that surgery alone (48.7%) was the most common treatment given to the AM patients [6]. The use of chemotherapy and radiotherapy was similar throughout the study period but there has been a rapid increase in the use of targeted therapies for AM in the last few years. In **Figure 7**, we have provided an overview of the management of patients with AM.

#### **7.1 Surgery**

Surgery remains the mainstay of treatment. Most of the previous studies recommend surgical excision for Stage I and II AM. However, the benefit of lymph node

**57**

*Anorectal Melanoma*

*DOI: http://dx.doi.org/10.5772/intechopen.93759*

tasis, then APR should be considered [39].

**7.2 Chemotherapy**

**7.3 Radiation therapy**

OS was only 30% [57].

**7.4 Targeted therapies**

dissection in AM has not been established. Unlike rectal adenocarcinoma and CM, lymph nodal metastasis has no significant impact on the long-term survival [41, 42]. The systemic dissemination of the disease occurs early in the course of the disease even before lymph nodal metastasis [43]. The 2020 UK National guidelines recommend R0 surgical resection in the least radical fashion [44]. Lymphadenectomy

The main procedures for AM include: (1) function-preserving procedures such as endoscopic mucosal resection (EMR), wide local excision (WLE); (2) radical procedures such as low anterior resection (LR), abdominoperineal resection (APR). In a meta-analysis of 31 studies [43], 7 studies found APR to be superior to WLE [45–47], 11 studies found WLE to be better than APR [41, 48, 49] while 10 studies reported similar survival outcomes between the two procedures [42, 50, 51]. However, the local recurrence rate was significantly higher in WLE group (57% vs. 21.6%). The most recent study of 305 AM patients treated from 2004 to 2015 found no difference in overall survival (OS) between local and transabdominal resection (2.54 vs. 1.86 years, p = 0.77) [52]. Another recent meta-analysis found no significant difference in OS, disease-free survival (DFS) and local recurrence rates between WLE and APR on analyzing of data from 23, 7 and 19 studies, respectively [53]. So, we believe that WLE with regular surveillance should be the preferred approach. If WLE is not feasible or there is local recurrence without distant metas-

There is no standard chemotherapy regimen for AM due to the rarity of the disease. However, dacarbazine in combination with high-dose interferon and interleukin-2 was found to be effective in 10–20% cases of mucosal melanomas [54]. In a Turkish study of 6 AM patients, all patients received APR followed by adjuvant chemo- and radiotherapy [55]. The adjuvant chemotherapy included dacarbazine and temozolomide. In addition, two patients received ipilimumab, and one patient received interferon therapy. At the mean postoperative follow up of 12.5 months (6–26 months), 4 patients died due to extensive distant metastases while two patients were disease free [55]. In another study of 22 patients with metastatic AM, six patients received dacarbazine while one patient received temozolomide and

Radiation therapy has been used for palliation or in the adjuvant setting after organ preserving surgery such as wide local excision to reduce the chances of local recurrence. A study by Kelly et al. of 54 patients treated by WLE followed by hypofractionated radiotherapy reported good local control in 82% cases but the 5-year

Immune checkpoint inhibitors have become the standard of care in the treatment of metastatic CM. However, their role in MM is still under investigation. Cytotoxic T-lymphocyte-associated antigen (CTLA-4) and programmed-death (PD1) protein are the most common immune checkpoint targets expressed on activated T-cells with immunosuppressive effects. Ipilimumab is a fully human monoclonal that blocks the binding of CTLA4 with CD80 and CD86 ligands. It was the first agent approved for the treatment of advanced melanoma. It has an indirect

thalidomide. The median survival in these patients was 9 months [56].

should be performed in cases with metastatic regional lymph nodes.

#### **Figure 7.**

*A suggested algorithm for the management of anorectal melanoma. (WLE—Wide local excision, APR—Abdominoperineal resection, systemic therapy—Chemotherapy, targeted therapies).*

#### *Anorectal Melanoma DOI: http://dx.doi.org/10.5772/intechopen.93759*

*Melanoma*

**6. Diagnosis and staging**

of the tissue sample [36].

**7. Treatment**

**7.1 Surgery**

prognosticate the disease in patients with AM.

As CM and MM are known for early hematogenous spread, secondary gastrointestinal melanomas are not rare. Hence, for differentiation between primary and secondary melanoma, the following criteria must be satisfied: absence of melanoma at any other cutaneous or mucosal sites confirmed by thorough clinical including genital, oropharyngeal, ophthalmological and endoscopic examination; no past history of melanoma and presence of atypical melanocytes in the basal epithelium

There is no formal staging system for AM. However, the most commonly described system for AM in previous studies is the Ballantye clinical system which has three stages as follows: Stage I – localized disease, Stage II – presence of inguinal or pelvic lymph nodes and stage III – distant metastasis [37–39]. Interestingly, a recent study by Nagarajan et al. involving 160 AM patients found that the clinical American Joint Cancer Committee (AJCC) staging system (8th edition) for CM significantly stratified disease-specific survival of AM patients. Moreover, the authors recommended slight modifications in the AJCC 'T' category criteria of staging for better stratification [40]. Hence, either of the two staging systems can be used to

The main treatment options for AM are surgery, chemotherapy, radiation therapy and targeted therapies. According to a study which analyzed data of 1333 AM patients from National Cancer Database from 2004 to 2015, the authors found that surgery alone (48.7%) was the most common treatment given to the AM patients [6]. The use of chemotherapy and radiotherapy was similar throughout the study period but there has been a rapid increase in the use of targeted therapies for AM in the last few years. In **Figure 7**, we have provided an overview of the management of patients with AM.

Surgery remains the mainstay of treatment. Most of the previous studies recommend surgical excision for Stage I and II AM. However, the benefit of lymph node

**56**

**Figure 7.**

*A suggested algorithm for the management of anorectal melanoma. (WLE—Wide local excision, APR—Abdominoperineal resection, systemic therapy—Chemotherapy, targeted therapies).*

dissection in AM has not been established. Unlike rectal adenocarcinoma and CM, lymph nodal metastasis has no significant impact on the long-term survival [41, 42]. The systemic dissemination of the disease occurs early in the course of the disease even before lymph nodal metastasis [43]. The 2020 UK National guidelines recommend R0 surgical resection in the least radical fashion [44]. Lymphadenectomy should be performed in cases with metastatic regional lymph nodes.

The main procedures for AM include: (1) function-preserving procedures such as endoscopic mucosal resection (EMR), wide local excision (WLE); (2) radical procedures such as low anterior resection (LR), abdominoperineal resection (APR). In a meta-analysis of 31 studies [43], 7 studies found APR to be superior to WLE [45–47], 11 studies found WLE to be better than APR [41, 48, 49] while 10 studies reported similar survival outcomes between the two procedures [42, 50, 51]. However, the local recurrence rate was significantly higher in WLE group (57% vs. 21.6%). The most recent study of 305 AM patients treated from 2004 to 2015 found no difference in overall survival (OS) between local and transabdominal resection (2.54 vs. 1.86 years, p = 0.77) [52]. Another recent meta-analysis found no significant difference in OS, disease-free survival (DFS) and local recurrence rates between WLE and APR on analyzing of data from 23, 7 and 19 studies, respectively [53]. So, we believe that WLE with regular surveillance should be the preferred approach. If WLE is not feasible or there is local recurrence without distant metastasis, then APR should be considered [39].
