A study found multiple factors that contributed to invasive melanoma tumor upstaging as well as higher mortality rates among patients with upstaged tumors, one of which is medical management.
According to a study conducted by Amanda Rosenthal, MD, a micrographic surgery and dermatologic oncology fellow at Cedars-Sinai Medical Center and Kaiser Permanente Los Angeles Medical Center, and colleagues, the clinical implication and prognostic outcomes associated with tumor upstaging in invasive melanoma are worse than clinicians previously thought.
"Our study found higher rates of tumor upstaging compared to the two most recently published studies on this topic, which documented rates of 3.9% and 5.2%," she told Healio. "Both of these studies, however, included melanoma in situ in their analysis which skewed their results. In our study, we focused only on invasive tumors, as we know that melanoma in situ and invasive melanomas behave very differently."
Their study, which analyzed 4,391 cases of invasive melanoma, showed a 9.4% upstaged rate and identified significant risk factors including older age, male sex, non-White race, location on the head or neck, larger clinical size, incisional or punch biopsy method and increasing time from the biopsy to the surgical excision.
The study found that patients with upstaged tumors experienced an overall and melanoma-specific mortality rate of 36% and 9%, respectively, compared with 19.5% and 2.9% among patients with non-upstaged tumors (P = .001 for both).
"The marked difference in mortality between upstaged and non-upstaged melanomas was the most clinically impactful finding of our study," Rosenthal said. "While conceptually it is not surprising that upstaged melanomas have higher mortality risk than their non-upstaged counterparts, it reinforces the concept that patients with upstaged melanomas need to be thoroughly counseled and very closely monitored."
After adjusting for all other variables, two significant risk factors stood out among the rest: head and neck location and higher pathologic T stage.
Upstaged tumors were located on the head and neck in 41.1% of cases making it the most likely location for upstaged tumors compared with other body sites (P < .001). Except for T2b and T4a, all pathological T stages above T1a saw higher overall mortality rates vs. non-upstaged comparers.
The time from biopsy to surgical excision was also longer in upstaged cases compared with non-upstaged cases (40.4 vs. 32.9 days; P < .0001). However, according to Rosenthal, this does not pose a problem for patients because a surgical delay only impacts clinical outcomes for early-stage melanomas but not any other stage.
"This is important to note because as dermatologists, we are comfortably excising T1a melanomas in clinic, but often refer patients to surgical oncology for T1b melanomas and higher," she said. "This means that we can control the scheduling of surgical excision for early-stage melanomas (ideally within 30 days). It also means that when we refer patients to surgical oncology, we can offer reassurance that even if the patient can't get an appointment for 6 to 8 weeks, it's okay."
On the other hand, the study also found that while tumor upstaging dictated a change in clinical management in more than 50% of cases, only 37.4% were given additional treatment. In fact, of the 72 upstaged tumors that met the criteria for re-excision with wider margins based on the American Joint Committee on Cancer guidelines, only 20.83% (n = 15) underwent that additional surgery.
"While our sample size is low, our data suggest that incomplete medical and surgical management may contribute to the worse prognosis appreciated among upstaged melanomas," Rosenthal told Healio. "This underscores the need for appropriate patient counseling and follow-up to ensure upstaged melanomas are managed according to their updated American Joint Committee on Cancer guidelines."