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FROM THE ASCO Reading Room
A study by the Melbourne Melanoma project defined a very low risk recurrence group of stage I-II melanoma that could be potentially followed with less intense follow ups. This group of patients was defined by the absence of adverse pathological features -- i.e., ulceration, presence of mitosis, Clark level >4 and lymph vascular invasion, and history of autoimmune disease. The researchers suggested that these patients could be followed with a less intense surveillance regimen of yearly follow-ups with full skin checks.
The presence of autoimmune disease and lymph vascular invasion in the primary tumor were found to be independent predictors of recurrence, which have not been previously used in risk stratification. The 28-gene expression profiling test is another important tool being studied for risk stratification of high-risk stage I and II melanoma and can be used to predict the risk of metastasis.
In conclusion, a risk-based surveillance strategy should be employed for follow up of early stage melanoma, and very low risk patients can be followed once a year.
Patients with stage I melanoma without adverse pathologic features have a low risk of recurrence and do not require intensive follow-up for their primary melanoma, according to a new study.
"This study uses a large prospective dataset to show that patients with stage I melanoma without adverse pathologic features -- non-ulcerated, absence of mitosis, Clark level less than 4, and absence of lymphovascular invasion -- have a very low risk of melanoma recurrence and do not require intensive follow-up," the senior author, , of Peter MacCallum Cancer Centre in Melbourne, Australia, told ľֱ.
"The study identified autoimmune disease as an independent predictor of melanoma recurrence. Also, the presence of lymphovascular invasion in the primary tumor was independently associated with recurrence. These factors are not reflected in the AJCC [American Joint Committee on Cancer] staging system."
Gyorki noted that the prognosis for patients with early-stage melanoma is generally excellent, with a 5-year survival rate of 95%. For stage II, however, the rate is 68%. Poorly understood tumor heterogeneity means that even patients with stage I disease can develop subsequent metastatic disease.
The researchers analyzed data from the Melbourne Melanoma Project to assess whether known prognostic factors associated with recurrence were predictive in a large, prospectively collected data set. The aim was to confirm known prognostic factors for recurrence and survival, identify novel predictors of recurrence, and define which patients were at low-risk for recurrence.
The study, published in in February 2017, included 1,029 patients with stage I and stage II melanoma; 123 patients developed a recurrence during follow-up of a median 2.13 years. Multivariable analysis identified ulceration, the presence of mitoses, Clark level, presence of lymphovascular invasion, and a history of autoimmune disease as factors independently associated with recurrence.
The researchers suggest that patients with stage I melanoma with very low-risk for recurrence -- no ulceration, zero mitoses, low Clark level, no lymphovascular invasion, and possibly no history of autoimmune disease -- do not require intensive follow-up, and that 12 monthly reviews and full skin checks may be appropriate.
"Patients should be counseled about their risk of recurrence based on a multitude of pathological factors," Gyorki said. "Patients with autoimmune disease should be followed more closely because of an increased risk of melanoma recurrence."
The majority of patients diagnosed with melanoma have early stage disease. "Most of these patients will not recur," he said. "Long-term follow-up for such patients should be focused on detecting new primary cancers and therefore guided by risk factors such as prior melanomas, multiple nevi, or immunosuppression -- factors that were not investigated in this study -- and not by the features of the index lesion."
The in a patient with stage I melanoma has been estimated to be $38,574, with the bulk of the cost related to follow-up appointments. A modeling study of 3,081 patients with stage I and stage II melanoma found that annual visits until 10 years after diagnosis would result in only a compared with a regimen of two visits per year for 5 years and subsequent annual visits.
"Our study demonstrates that using the routinely reported factors of tumor depth, presence of ulceration, presence of mitosis, and presence of lymphovascular invasion plus a clinical history of autoimmune disease provides a cost-effective way of identifying a cohort of patients at very low-risk for recurrence," the researchers stated.
The next step in the research, said Gyorki, is to look at patients with thick primary melanoma as well as with lymph node-positive melanoma to identify ways to improve risk stratification for these patients. Melanoma staging continues to evolve to include new prognostic markers that may stratify patients more accurately into those who are at very low risk for recurrence and those who need more aggressive surveillance, and who therefore may be candidates for more advanced adjuvant therapies.
Researchers studying a recently reported a negative predictive value of 97% and a positive predictive value of 72% for identifying stage I and stage II melanoma with 5-year metastatic disease-free survival. The GEP tool also in patients with a negative sentinel lymph node biopsy. Gene expression profiling on primary and recurrent tumor tissue to look for recurrences in low-risk patients holds promise, he said, but is an expensive method for stratifying risk.
For now, oncologists need to know that "patients with autoimmune disease diagnosed with melanoma are at higher risk of recurrence. The full pathology report, including ulceration, mitotic rate, and lymphovascular invasion, should be considered in risk stratification."
Gyorki had no disclosures.