A single-institutional cohort study found that in patients with melanoma, regressive status could be used as a valuable predictive marker of prognosis and response to systemic therapy.
Patients with regressive cutaneous melanoma who were eligible for sentinel lymph node biopsy (SLNB) were linked to better prognostic outcomes. These benefits were also observed in patients with uresectable disease who were administered immune checkpoint inhibitors (ICIs), according to a recent study published in Journal of the American Academy of Dermatology.
Previous research argues that histopathologic regression can be an indicator of immune responses to tumors in patients with melanoma; however, the impact of this regression on patient prognosis remains unclear. While the presence of regression can be interpreted as a beneficial sign, it has also been interpreted negatively. The authors of the present study point to past studies suggesting that this process signals the start of metastasis while, controversially, others attribute these unfavorable outcomes to factors like diagnostic delays.
Cases of thin melanomas exhibiting regression have additionally justified SLNB in affected patients. Due to this suggestion, the researchers embarked on a study to assess the influence of regression on outcomes in patients with melanoma who underwent SLNB.
Between January 1, 2010, and December 31, 2015, data were collected from the Department of Dermatology of University Hospital Tuebingen, Germany, on patients with cutaneous melanoma undergoing SLNB and local wide excision. A total of 1179 patients were eligible for study.
Throughout the study, 222 (18.8%) patients exhibited regression. Compared with patients without regressive melanoma, those who had regression were more likely male (64.9% vs 52.7%; P = .0013), older (mean age, 64.1 vs 60.6 years; P = .0063), to have lower Breslow tumor thickness (mean, 1.88 vs 2.73 mm; P < .001), to have a superficial spreading subtype of melanoma (80.6% vs 46.7%; P < .0001), and to be without ulceration (presence of ulceration, 23.0% vs 32.7%; P = .018). The authors added that significant associations with regression were also observed in cases of preexisting melanocytic nevus (22.5% vs 11.4%; P < .0001) and where tumors were localized on the trunk (59.5% vs 37.2%; P < .0001).
SLNB was successfully performed in 1127 patients. A total of 140 patients (12.4%) had positive SLN statuses; these patients demonstrated significantly less frequent histopathologic regression compared with those with negative statuses (10.7% v 20.0%; P = .0077).
Patients with regressive melanomas who underwent SLNB also experienced significantly lower risks for recurrence of their disease compared with individuals enduring nonregressive melanomas (11.9% vs 24.6%; OR, 0.46; 95% CI, 0.31-0.67; P < .0001). The researchers saw that regression was also significantly linked to melanoma-specific survival (HR, 0.35; 95% CI, 0.20-0.64; P = .00053), distant metastasis-free survival (HR, 0.56; 95% CI, 0.39-0.81; P = .002), and favorable relapse-free survival (HR, 0.52; 95% CI, 0.38-0.73; P = .00013).
There were 351 patients who experienced a relapse and their disease progressed to the unresectable stage, with 224 needing systemic therapy with ICIs, targeted therapy (TT), or chemotherapy. Of these patients, regression was linked to favorable outcomes in progression-free survival when they received ICIs (HR, 0.43; 95% CI, 0.20-0.92; P = .031). These favorable outcomes were not observed in patients receiving TT (HR, 1.14; 95% CI, 0.54-2.40; P = .73) or chemotherapy (HR, 3.65; 95% CI, 1.37-9.68; P = .0095).
The authors conclude by highlighting the promising benefits of their findings. Their results indicate that a patient’s regression status could be a valuable marker for predicting responses to systemic immunotherapy. Additionally, as research grows on this subject, they comment that their data could be useful for improving risk stratification in candidates for SLNB.
Reference
Wagner NB, Knierim SK, Luttermann F, et al. Histopathologic regression in patients with primary cutaneous melanoma undergoing sentinel lymph node biopsy is associated with favorable survival and, after metastasis, with improved progression-free survival on immune checkpoint inhibitor therapy: a single-institutional cohort study. J Am Acad Dermatol. 2023;S0190-9622(23)03250-4. doi:10.1016/j.jaad.2023.11.040
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