Melanoma Surgical Practice Guidelines

Scope and Format of Guidelines

The Society of Surgical Oncology surgical practice guidelines focuson the signs and symptoms of primary cancer, timely evaluation of the symptomaticpatient, appropriate preoperative evaluation for extent of disease, androle of the surgeon in diagnosis and treatment. Separate sections on adjuvanttherapy, follow-up programs, or management of recurrent cancer have beenintentionally omitted. Where appropriate, perioperative adjuvant combined-modalitytherapy is discussed under surgical management. Each guideline is presentedin minimal outline form as a delineation of therapeutic options.

Since the development of treatment protocols was not the specific aim ofthe Society, the extensive development cycle necessary to produce evidence-basedpractice guidelines did not apply. We used the broad clinical experienceresiding in the membership of the Society, under the direction of AlfredM. Cohen, MD, Chief, Colorectal Service, Memorial Sloan-Kettering CancerCenter, to produce guidelines that were not likely to result in significantcontroversy.

Following each guideline is a brief narrative highlighting and expandingon selected sections of the guideline document, with a few relevant references.The current staging system for the site and approximate 5-year survivaldata are also included.

The Society does not suggest that these guidelines replace good medicaljudgment. That always comes first. We do believe that the family physician,as well as the health maintenance organization director, will appreciatethe provision of these guidelines as a reference for better patient care.

Societyof Surgical Oncology Practice Guidelines: Melanoma

Symptoms and Signs Early-stage disease

• Asymptomatic
• Asymmetry
• Border irregularity
• Color: variegated
• Diameter: > 6 mm
• Itching, bleeding with minor trauma

Advanced-stage disease

• Primary
• Nodularity
• Friability, bleeding
• Satellites
• Regional disease
• Patients may present with metastatic involvement of regional nodeseven with no known primary.
• Systemic disease
• Unusual for patients to present initially with visceral metastasisin the absence of a known primary

Evaluation of the Symptomatic Patient Diagnosis of the primary tumor

• Plan biopsy with definitive therapy in mind
• Incisional vs excisional biopsy
• Excision increases staging accuracy.
• Excision is not always possible (eg, lesions on digit, palm sole, face,or ear)
• For lesions on digit, palm, sole, face, ear, incisional biopsy of theclinically thickest area is appropriate.
• Shave biopsies are inappropriate.

Diagnosis of metastatic disease

• Excision
• Best if no primary known, especially for isolated node
• Fine-needle aspiration
• Sufficient to diagnose recurrence of known melanoma

Appropriate timeliness of surgical referral

• Lesions fulfilling criteria for early-stage disease (see above) shouldbe biopsied without a period of observation.

Preoperative Evaluation for Extent of Disease Complete history

• Sun exposure
• Prior moles
• Nonmelanoma skin cancers
• Family history of melanoma

Examination

• Complete dermatologic examination
• Regional and remote lymph nodes
• Regional and remote soft tissue

Laboratory studies

• CBC
• Chemistry profile

Radiology

• Chest x-ray
• CT scan—only for advanced stages
• Pelvic CT for patients with inguinal adenopathy to guide extent oflymph node dissection

Role of the Surgeon in Initial Management Evaluation of pigmented lesion Diagnosis by biopsy Surgical considerations

• Primary tumor
• Margin of excision (may vary with location):
• In situ primary: 0.5-cm margin
• < 1-mm thick primary: 1-cm margin
• 1- to 4-mm thick primary: 2-cm margin
• > 4-mm thick primary: > 2-cm margin
• Moh's surgery not appropriate
• Type of closure (variable):
• Primary
• Split-thickness skin graft
• Local rotation flap
• Free flap
• Digital amputation in highly selected patients (eg, subungual lesions)
• Regional nodes
• Intent
• Elective
• Selective with intraoperative mapping
• Therapeutic
• Palliative
• Procedures
• Neck dissection
• Axillary dissection
• Groin dissection
• Extent of lymph node dissection
• Radical vs modified radical neck dissection
• Indications for elective inguino-femoral-pelvic lymph node dissection
• In-transit metastases
• Excision
• Injection
• Laser ablation
• Hyperthermic isolated limb perfusion
• Amputation

These guidelines are copyrighted by the Society of Surgical Oncology(SSO). All rights reserved. These guidelines may not be reproduced in anyform without the express written permission of SSO. Requests for reprintsshould be sent to: James R. Slawny, Executive Director, Society of SurgicalOncology, 85 West Algonquin Road, Arlington Heights, IL 60005.

Melanoma is now the seventh most common malignancyin the United States, and the rateat which its incidence has increased(approximately 4% per year since 1973) is higher than that for any othercancer. According to American Cancer Society estimates, approximately 38,300new cases of melanoma were diagnosed in 1996, and 7,300 deaths were attributableto this cancer.

Early melanoma often arises in the context of a preexisting nevus. Earlysigns of melanoma include the so-called ABCDs: lesion asymmetry, borderirregularity, variegated color, and diameter over 6 mm. Other, less specificsymptoms include itching or bleeding with minor trauma.

More advanced primary melanomas may present as a nodular skin lesion,which may be friable or bleeding and occasionally may have clinical satellitosis.More advanced lesions are often amelanotic.

Of patients with melanoma that is clinically metastatic to regionallymph nodes, 10% to 15% may present with regional node involvement in theabsence of a known primary. Fewer than 2% of patients with metastatic diseasepresent with visceral metastatic melanoma in the absence of a known primary.

Evaluation

The initial step in evaluating a patient with a symptomatic or suspiciouspigmented lesion is to obtain a biopsy. The biopsy should always be plannedwith definitive therapy in mind. In general, total excisional biopsy ispreferred over either incisional or shave biopsy. Excision increases thelikelihood of accurately staging the primary tumor, which is importantin planning therapy and determining prognosis.[1]

Total excision is not always possible, however, as tumors on a digit,palm of the hand, sole of the foot, face, or ear often cannot be completelyexcised without compromising plans for definitive therapy. In those cases,incisional biopsy of the clinically thickest area of the tumor is appropriate.Partial-thickness shave biopsies should be avoided, as valuable staginginformation can be lost with this technique.

In an effort to minimize the number of biopsies required for suspiciouspigmented lesions, research is being conducted on a new technique, epiluminescencemicroscopy (ELM). Although ELM is not intended to replace biopsy in thedefinitive diagnosis and staging of melanoma, it is hoped that it willincrease the accuracy of clinical diagnosis, thus minimizing the numberof biopsies of otherwise benign lesions. At present, ELM remains an investigational.

In the patient presenting with a solitary enlarged lymph node and norelevant prior history, excisional lymph node biopsy is preferred. Thisaffords the pathologist more tissue for immunohistochemical evaluationto establish the diagnosis and to differentiate between carcinoma, lymphoma,and melanoma. In the setting of recurrent disease, fine-needle aspirationof accessible disease often suffices to confirm the clinical suspicion.

With regard to the urgency of diagnosis and management, once a lesionis felt to be suspicious, little is to be gained by delaying a diagnosticbiopsy. Therapy should be undertaken as soon as all clinically relevantconcerns have been addressed, preferably within days to weeks of diagnosis.

PreoperativeEvaluation for Extent of Disease

Any patient with a newly diagnosed melanoma should undergo a completehistory and physical examination. The history should pay particular attentionto any family history of melanoma, as well as any previous melanoma, anypigmented nevi, or prior malignancy in the patient. In addition, the patient'sprevious history of sun exposure should be determined.

Physical examination should include a complete dermatologic examination,as a small proportion of patients have other dysplastic nevi or synchronousmultiple primary melanomas.[2] In addition to examination of the primarysite for evidence of clinical satellitosis, a careful examination for anyin-transit disease should be undertaken. Both regional and remote lymphnode basins should be examined, and attention should be paid to any remotesoft-tissue metastasis, particularly in patients with more advanced-stagedisease.

Blood tests are generally of low yield in screening for occult metastaticdisease in melanoma. Nonetheless, in patients at risk for metastases (eg,those with primary lesions > 1 mm), laboratory studies should includea CBC and screening chemistry profile. In particular, liver function testsshould be orderd, as an elevated lactic dehydrogenase (LDH) has been associatedwith metastatic disease to the liver.

Standard radiologic evaluation should include diagnostic, high-qualitypostero-anterior and lateral chest x-rays. Extensive CT scans, MRIs, andnuclear medicine scans are generally of low yield, and multiple serieshave found these imaging studies to be unnecessary.[3] There is controversyover the extent of radiologic evaluation required for patients with thick(> 4.0 mm) cutaneous melanoma, who are at significant risk of systemicdisease.

In patients who present with clinical lymphadenopathy, a thorough physicalexamination (as detailed above) should be performed. The extent of radiologicwork-up required for such patients is controversial. In patients with inguinallymphadenopathy, pelvic CT scans have been used to assess for pelvic lymphadenopathy;such information is helpful in guiding the extent of groin dissection.[4]Laparotomy has been used for this purpose in the past, and some investigatorsare exploring the role of laparoscopy.

In patients with known systemic metastasis, the extent of the work-updepends on the intent of the proposed procedure. For procedures performedwith curative intent, (eg, in patients with remote nodal/soft tissue orpulmonary metastasis), a comprehensive evaluation for extent of diseaseis mandatory. This should include a CT scan of the head, chest, abdomen,and pelvis.

The F18 flurodeoxyglucose-enhanced total-body PET scan may be more sensitivefor evaluating systemic metastasis than are standard radiologic techniques.[5]At present, this promising imaging modality remains investigational.

For patients undergoing palliative resection of systemic metastaticdisease, a more limited radiologic evaluation for extent of disease isappropriate. In such cases, a chest x-ray should suffice for most patients.

Staging

The current American Joint Commiittee on Cancer (AJCC) staging systemreflects the fact that, for patients with localized melanoma, prognosisis most closely related to primary tumor thickness. Patients with thickcutaneous melanomas > 4 mm or invading into subcutaneous fat have ahigh risk of metastasis and death, and have been classified as stage III,together with patients who have regional disase. Within the group of patientswith regional nodal recurrence, prognosis correlates with the tumor burdenin the nodes; the number of positive nodes involved may be a better predictorof outcome than the size of the largest node involved.

The TNM staging for melanoma is shown in Table1, along with approximate 5-year survival rates by stage.

Treatment

In addition to having a prominent role in diagnosis and evaluation (asdetailed above), the surgeon plays a critical role in definitive managementof melanoma.

Primary Lesion

Wide excision of the melanoma is appropriate in virtually all cases.The excision margin required to minimize the likelihood of local recurrenceis now well established, and depends on the thickness of the tumor: Forin situ melanoma, a margin of 0.5 cm is sufficient. For melanomas <1-mm thick, a 1-cm margin is appropriate,[6] whereas for melanomas measuring1 to 4 mm in thickness, a 2-cm margin is needed.[7] For melanomas >4-mm thick, the margin necessary to minimize local recurrence is unknown,although most experts feel that it ought to be at least 3 cm.

Subungual melanomas usually require digital amputation. For subungualmelanomas of the thumb, every effort should be made to preserve the meta-carpophalangealjoint to maintain function.

Moh's chemosurgery is inappropriate, even for the management of verythin melanomas.

The type of closure depends on such factors as the margin of excisionrequired and the anatomic location of the lesion. Many excisions can beperformed with primary closure. When primary closure is impossible, localrotation flaps may be employed to optimize the cosmetic results. Split-thicknessskin graft may be required for lesions of the distal extremity. Rarely,a microvascular free flap is needed for lesions that involve extensiveportions of the weight-bearing surface of the foot.

Lymph Node Dissection

The indications for elective lymph node dissection in the setting ofclinically and radiologically negative nodes remains controversial. Inthe absence of conclusive data, the decision to proceed with elective lymphnode dissection should be made on a case-by-case basis by the patient andsurgical oncologist. Recently, the technique of intraoperative lymphaticmapping with selective lymphadenectomy of patients with a positive "sentinelnode" has been described.[8] This procedure is used to pathologicallystage patients with melanoma who are at risk for regional metastases andwho have clinically negative nodes. The value of this procedure for theindividual patient with regard to improving the cure rate over wide excisionand observation has not been demonstrated. This is currently the focusof an ongoing, prospective, randomized clinical trial.

Patients with clinically positive nodes should undergo a thorough therapeuticlymphadenectomy in the absence of systemic metastases. In the presenceof metastatic disease, palliative lymphadenectomy should be undertakento avoid sequelae of unrestrained growth of tumor in the regional nodalbasin.

Lymph node dissections in the neck, axilla, and groin have been standardizedand are well described.[9] The extent of lymphadenectomy may be modifiedto suit the individual needs of the patient, with the goals of preservingoptimal cosmetic and functional results while minimizing the likelihoodof regional recurrence.

Metastatic Disease

In-transit metastatic disease may be managed by local excision or carbondioxide laser ablation,[10] with the expectation of further recurrencein the majority of patients. Local injection of smaller dermal in-transitmetastasis with dinitrochlorobenzene (DNCB) has led to completeregression of both injected and noninjected lesions.

In patients with extensive metastatic in-transit melanoma, hyperthermicisolated limb perfusion has produced objective response rates ranging from20% to 100%, depending on the agents used.[11] Only a fraction of the overallresponses are complete, however, and not all complete responses are durable.Several ongoing clinical trials are attempting to define the role of hyperthermicisolated limb perfusion in the management of patients with regionally recurrentmelanoma. In the past, major limb amputation was used in these patients,although, with the advent of limb perfusion, the indications for this procedureare exceedingly rare.[12]

Since patients with remote nodal and soft-tissue metastases fare bestafter complete resection, this should be attempted when possible. Noncurativeresection of symptomatic remote nodal/soft-tissue metastases in the settingof known visceral metastases can yield significant palliation in selectedpatients. Curative resection of isolated visceral metastatic disease canresult in long-term disease-free survival in highly selected patients.The best results are obtained after resection of a solitary pulmonary metastasis.Resection of brain and gastrointestinal tract metastases is usually performedwith palliative intent, with very few long-term survivors.[13]

References:

1. Lees VC, Briggs JC: Effect of initial biopsy procedure on prognosisin stage 1 invasive cutaneous malignant melanoma—review of 1086 patients.Br J Surg 78:1108-1110, 1991.

2. Slingluff CL, Vollmer RT, Siegler HF: Multiple primary melanomas—incidenceand risk factors in 283 patients. Surgery 113(3):330-339, 1993.

3. Buzaid AC, Sandler AB, Mani S, et al: Role of computed tomographyin the staging of primary melanoma. J Clin Oncol 11(4):638-643,1993.

4. Coit DG, Brennan MF: Extent of lymph node dissection in melanomaof the trunk or lower extremity. Arch Surg 124(2):162-166, 1989.

5. Kirgan D, Guenther J, Bhattathiry M, et al: The importance of wholebody PET scans in the management of metastatic malignant melanoma. ProcAm Soc Clin Oncol 13:396, 1994.

6. Veronesi U, Cascinelli N: Narrow excision
(1-cm margin): A safe procedure for thin cutaneous melanoma. Arch Surg126:438-441, 1991.

7. Balch CM, Urist MM, Karakousis CP, et al: Efficacy of 2-cm surgicalmargins for intermediate thickness melanomas (1 to 4 mm)—results of a multi-institutionalrandomized surgical trial. Ann Surg 218(3):262-269, 1993.

8. Morton DL, Wen DR, Wong JH, et al: Technical details of intraoperativelymphatic mapping for early stage melanoma. Arch Surg 127:392-399,1992.

9. Karakousis CP: The technique of lymphadenectomy for melanoma. SurgOncol Clin North Am 1(2):157-193, 1992.

10. Hill S, Thomas JM: Treatment of cutaneous metastases from malignantmelanoma using the CO2 laser. Eur J Surg Oncol 19:173-177, 1993.

11. Coit DG: Hyperthermic isolation limb perfusion—a review. CancerInvest 10(4):277-284, 1992.

12. Jaques DP, Coit DG, Brennan MF: Major amputation for advanced malignantmelanoma. Surg Gynecol Obstet 169(1):1-6, 1989.

13. Coit DG: Role of surgery for metastatic malignant melanoma: A review.Semin Surg
Oncol 9:239-245, 1993.