a revisit to anorectal malignant melanoma (armm) joint hospital surgical grand round 8 nov 2014 dr...
TRANSCRIPT
A Revisit to AnorectalMalignant Melanoma (ARMM)
Joint Hospital Surgical Grand Round
8 Nov 2014
Dr Jessie Chan
Pamela Youde Nethersole Eastern Hospital
Outline
Introduction Epidemiology Presentation Investigations Staging Prognosis
Treatment Surgery Adjuvant therapy
Introduction
Rare neoplasm
First reported by Moore in 1857
Distinct biological and clinical entity from cutaneous melanoma with worse prognosis
No clear etiology elucidated
Arised from melanocytes distal to dentate line and extend proximally to rectum
Arised directly from melanocytes which present rarely in the mucosal epithelium of proximal anus or distal rectum
ARMM
<1% of all malignant melanomas
<4% of anal canal malignancies
Primary
Secondary Metastasis from cutaneous melanoma (2%)
Epidemiology
Median age at presentation: 55 (range 29-92)
Reported incidence: 0.04 – 1.19%
No adequate population-based studies to draw definite conclusions for racial and gender difference
Presentation
Non-specific symptoms PR bleeding Anal pain, anal mass Tenesmus, pruritus Change in bowel habit
Symptoms of metastatic disease Most common sites of metastases: inguinal / mesenteric /
hypogastric / para-aortic lymph nodes, liver, lung, skin, brain
Weight loss, groin mass, pelvic mass, bowel obstruction
Incidental finding
Presentation
80% lack obvious pigmentation
20% histologically amelanotic
Presentation
Up to 60% with locoregional lymphatic spread (mesorectal, pelvic side wall, inguinal lymph nodes)
Up to 40% with distant metastasis
Investigations
Endoscopy and biopsy
Staging Endoscopic ultrasound: role unclear CT: regional lymphadenopathy, distant metastasis PET scan: may be helpful
Staging
Cutaneous melanoma: AJCC TNM system
ARMM Clinical staging Stage I: local disease Stage II: local disease with regional lymph nodes Stage III: distant metastatic disease
Prognosis
Poor prognosis
Overall 5-year survival 3-22%
Survival <10 months with recurrent or metastatic disease
Prognosis
Good prognostic factors Tumour thickness <2mm
Poor prognostic factors Tumour thickness >3mm Tumour site above dentate line Lymphovascular / perineural invasion Necrosis
Wanebo HJ, Woodruff JM, Farr GH, et al. Anorectal melanoma. Cancer. 1981 Apr 1; 47(7):1891-900.Brady MS, Kavolius JP, Quan SH. Anorectal melanoma. A 64-year experience at Memorial Sloan-Kettering Cancer Center. Dis Colon Rectum. 1995 Feb; 38(2):146-51.
Perez DR, Trakarnsanga A, Shia J, et al. Locoregional lymphadenectomy in the surgical management of anorectal melanoma. Ann Surg Oncol. 2013;20:2339-2344.
Treatment
Treatment
Surgery Wide local excision (WLE) Abdominoperineal resection (APR)
Regional lymph node Sentinel lymph node biopsy Lymphadenectomy
Treatment
Adjuvant therapy Systemic
Chemotherapy Biochemotherapy Interferon Vaccine / immunotherapy
Local Radiation therapy Electrochemotherapy
Surgery
Mainstay of treatment
Controversies
① APR vs local excision (LE) APR – en bloc excision with mesorectal lymph nodes ?oncological benefit
② Inguinal lymphadenectomy
Surgery
Meta-analysis by Akihisa Matsuda et al in Annals of Surgery 2014 31 studies 1006 patients APR vs LE
Overall survival Relapse-free survival Local recurrence rate
Akihisa Matsuda, Masao Miyashita, Satoshi Matsumoto, et al. Abdominoperineal Resection Provides Better Local Control But Equivalent Overall Survival to Local Excision of Anorectal Malignant Melanoma – A Systemic Review. Ann Surg. 2014; 00: 1-8.
APR vs LE
Overall survival – no difference (31 studies, N=1006)
APR vs LE
Recurrence-free survival – no difference (14 studies, N=328)
APR vs LE
Local recurrence rate – significantly lower in APR (13 studies)
Surgery
No survival benefit from APR over LE
Higher local recurrence from LE which could be managed by salvage surgery
Less complications and morbidities with LE Better body image Better urinary and sexual function Minimal impact on bowel function
Minimizing morbidities and maximizing quality of life merits consideration in such an aggressive disease
Inguinal lymphadenectomy
Locoregional lymph node metastasis – no significant prognostic implication
Perez DR, Trakarnsanga A, Shia J, et al. Locoregional lymphadenectomy in the surgical management of anorectal melanoma. Ann Surg Oncol. 2013;20:2339-2344.
Inguinal lymphadenectomy
Systemic dissemination with micrometastasis in distant organs occurs early with unfavourable prognosis
Prophylactic – no improvement in survival, increased risk of complications
Therapeutic – seems not to contribute to improvement of survival
Perez DR, Trakarnsanga A, Shia J, et al. Locoregional lymphadenectomy in the surgical management of anorectal melanoma. Ann Surg Oncol. 2013;20:2339-2344.
Adjuvant Therapy
Chemotherapy
Role remains unclear ?Adjuvant ?Palliative
Dacarbazine, cisplatin, vinblastine, vincristine, nimustine, bacillus Calmette-Guérin, levamisole, temozolomide
Single or combination – poor results
Interferon
Interferon alpha Combination of direct activities and indirect immune-
mediated effects Parenteral route / intratumoural injection No standard regimen established Insufficient data
Biochemotherapy
Biologic agent (interferon, interleukin) + traditional cytotoxic chemotherapeutic agent
Longer disease-free and median survival in metastatic ARMM when compared with chemotherapy alone
Kim K B, Sanguino A M, Hodges C, et al. Biochemotherapy in patients with metastatic anorectal mucosal melanoma. Cancer. 2004;100:1478–1483.
Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999 Jul; 17(7):2105-16.
Biochemotherapy
Role Best available adjuvant therapy after surgery Considered in advanced or metastatic ARMM
Vaccine / Immunotherapy
Immunize against melanoma cell antigen
BRAF and cKIT mutations
Insufficient data
Area of significant research effort and may play an important part of the non-operative treatment of melanoma in the future
Radiation Therapy
Locoregional disease control Primary lesion, inguinal and pericolic lymph nodes
Utility unclear, evidence conflicting
Radiation Therapy
Ballo et al Local excision + post-op RT
Local control rate comparable with APR 5-year local control rate: 74%
No improvement in survival
Moozar et al Pre-op RT little effect on tumour burden Post-op RT did not change local recurrence No survival benefit
Moozar KL, Wong CS, Couture J. Anorectal malignant melanoma: treatment with surgery or radiation therapy, or both. Can J Surg. 2003 Oct; 46(5):345-9.
Ballo MT, Gershenwald JE, Zagars GK, et al. Sphincter-sparing local excision and adjuvant radiation for anal-rectal melanoma. J Clin Oncol. 2002 Dec 1; 20(23):4555-8.
Electrochemotherapy
Injection of chemotherapy directly into the lesions, followed by application of electric pulses using a needle electrode
Electrical stimulation to the tissues creating a transient permeabilization of the plasma membrane
Allows direct access of the chemotherapeutic agents into the cytosol of tumor cells
Known to provide effective local control for cutaneous melanoma
Electrochemotherapy
Convert APR to sphincter-preserving local excision
Overall success rate unclear
Snoj M, Rudolf Z, Cemazar M, et al. Successful sphincter-saving treatment of anorectal malignant melanoma with electrochemotherapy, local excision and adjuvant brachytherapy. Anticancer Drugs. 2005 Mar; 16(3):345-8.
Summary
ARMM is a rare and highly malignant disease
Survival predicted by status of regional and distant metastasis but not method of surgery for local control
Minimizing surgical morbidities and maximizing quality of life should be the major consideration in formulating the treatment plan
Role of all adjuvant therapies is still unclear
References
P Carcoforo, M.T Raiji, G.M Palini, et al. Primary Anorectal Melanoma: An Update. J Cancer. 2012; 3:449-453. doi:10.7150/jca.5187.
Marc Singer and Matthew G. Mutch. Anal Melanoma. Clin Colon Rectal Surg. May 2006; 19(2): 78–87.
Akihisa Matsuda, Masao Miyashita, Satoshi Matsumoto, et al. Abdominoperineal Resection Provides Better Local Control But Equivalent Overall Survival to Local Excision of Anorectal Malignant Melanoma – A Systemic Review. Ann Surg. 2014; 00: 1-8.
Perez DR, Trakarnsanga A, Shia J, et al. Locoregional lymphadenectomy in the surgical management of anorectal melanoma. Ann Surg Oncol. 2013;20:2339-2344.
Wanebo HJ, Woodruff JM, Farr GH, et al. Anorectal melanoma. Cancer. 1981 Apr 1; 47(7):1891-900.
Brady MS, Kavolius JP, Quan SH. Anorectal melanoma. A 64-year experience at Memorial Sloan-Kettering Cancer Center. Dis Colon Rectum. 1995 Feb; 38(2):146-51.
References
Kim K B, Sanguino A M, Hodges C, et al. Biochemotherapy in patients with metastatic anorectal mucosal melanoma. Cancer. 2004;100:1478–1483.
Ulmer A, Metzger S, Fierlbeck G. Successful palliation of stenosing anorectal melanoma by intratumoral injections with natural interferon-β. Melanoma Res. 2002;12:395–398.
Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999 Jul; 17(7):2105-16.
Snoj M, Rudolf Z, Cemazar M, et al. Successful sphincter-saving treatment of anorectal malignant melanoma with electrochemotherapy, local excision and adjuvant brachytherapy. Anticancer Drugs. 2005 Mar; 16(3):345-8.
Ballo MT, Gershenwald JE, Zagars GK, et al. Sphincter-sparing local excision and adjuvant radiation for anal-rectal melanoma. J Clin Oncol. 2002 Dec 1; 20(23):4555-8.
Moozar KL, Wong CS, Couture J. Anorectal malignant melanoma: treatment with surgery or radiation therapy, or both. Can J Surg. 2003 Oct; 46(5):345-9.
Thank You