Melanoma affects persons of all ages, causing more years of lost life than any other cancer except leukemia. The American Cancer Society estimates that about 68,720 new melanomas will be diagnosed in the US in 2009, with more than 8,650 deaths, and an estimated lifetime risk of 1 in 50 for whites, 1 in 200 for Hispanics, and 1 in 1,000 for blacks.
Skin Cancer (Nonmelanoma)
Annually, about 8,000 patients are found to have metastatic melanoma presenting as recurrence of an earlier primary melanoma, and this number closely approximates the annual number of deaths from the disease. This statistic illustrates the lack of progress that has been made in the treatment of stage IV melanoma over the past several decades.
The article by Bhatia and colleagues focuses on the treatment of patients with metastatic melanoma using standard therapies, but it also includes a brief outline of recent treatment approaches using investigational agents. In addition, the authors describe prognostic factors for metastatic melanoma, highlighting the impact of the extent of tumor and the site of metastasis (eg, soft-tissue vs visceral metastases) on survival.
Reviewing treatment modalities for melanoma provides many sobering reminders that advances in our scientific understanding have not yet translated into meaningful clinical benefit. As clearly delineated by the authors, the “standard” treatment of dacarbazine chemotherapy has a poor response rate and lacks durability.
Metastatic melanoma continues to be a challenging disease to treat, with an estimated 8,420 related deaths in the United States in 2008. The 10- year survival rate for patients with metastatic melanoma is less than 10%. More than 3 decades after its initial approval by the US Food and Drug Administration (FDA) in 1975, dacarbazine continues to be the standard of care for most patients with this disease. High-dose interleukin-2 (HD IL-2 [Proleukin]), approved by the FDA in 1998 for metastatic melanoma, benefits a small subset of patients.
The recommendation to minimize sun exposure to prevent skin cancer has produced a pandemic of vitamin D deficiency. Vitamin D has generated considerable interest in the past decade, as accumulating evidence from both retrospective and prospective epidemiologic studies suggests an association between vitamin D deficiency and increased risk of autoimmune, infectious, and cardiovascular diseases, as well as cancer.
Along with various imaging modalities, serologic tumor markers such as CA 15-3 and CA 27.29 have been used for decades to monitor treatment response in patients with metastatic breast cancer (MBC). Despite the frequent use of these markers, they lack high sensitivity and specificity for breast cancer progression. The prognostic significance of these markers remains indeterminate because of the conflicting outcome of many clinical trials. The circulating tumor cell (CTC) test has recently been studied in clinical trials in patients with MBC. Some of the studies showed that high levels of CTCs are correlated with poor survival in MBC. An intergroup trial is underway to determine the implication of changing treatment based on the CTC level. This article will discuss the current data on these markers, with special emphasis on the CTC test. The potential clinical utility of these markers will also be discussed.
Mohs surgery has been well-established as the gold standard for the treatment of BCCs and SCCs. And, as described in this article, preliminary reports suggest that it may play an equally important role in the management of several other cutaneous malignancies.
The relationship between age and
melanoma prognosis is growing
more apparent and presents
interesting scientific and social questions.
My colleagues and I published
two papers analyzing melanoma patients
from our institution. Our first
paper examined a population of 620
patients during a 26-year period, and
our most recent paper analyzed 1,018
melanoma patients over 30 years.[1,2]
In both of these studies, age remained
an important prognostic predictor of
disease-free and disease-specific survival
based on multivariate analysis
(Cox proportional hazard). We also
applied a novel classification and regression
tree (CART) evaluation of
the data that showed age maintaining
a significant influence on disease-free
survival. Age maintained importance
in disease-specific survival when gender
was used as the first parameter to
segregate the entire patient population
before applying tree-structured
The use of radiation as adjuvant therapy for patients with cutaneous
malignant melanoma has been hindered by the unsubstantiated
belief that melanoma cells are radioresistant. An abundance of literature
has now demonstrated that locoregional relapse of melanoma is
common after surgery alone when certain clinicopathologic features
are present. Features associated with a high risk of primary tumor recurrence
include desmoplastic subtype, positive microscopic margins,
recurrent disease, and thick primary lesions with ulceration or satellitosis.
Features associated with a high risk of nodal relapse include extracapsular
extension, involvement of four or more lymph nodes, lymph
nodes measuring at least 3 cm, cervical lymph node location, and recurrent
disease. Numerous studies support the efficacy of adjuvant irradiation
in these clinical situations. Although data in the literature
remain sparse, evidence also indicates that elective irradiation is effective
in eradicating subclinical nodal metastases after removal of the
primary melanoma. Consequently, there may be an opportunity to integrate
radiotherapy into the multimodality treatment of patients at high
risk of subclinical nodal disease, particularly those with an involved
sentinel lymph node. Such patients are known to have a low rate of
additional lymph node involvement, and thus in this group, a short
course of radiotherapy may be an adequate substitute for regional lymph
node dissection. This will be the topic of future research.