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Roughly 13% of high-risk melanoma patients experienced disease recurrence within 2 years, but in patients who develop metastatic disease, time to recurrence appeared to be a poor surrogate for predicting survival, researchers said.

In an that characterized recurrence in high-risk primary melanoma at 2 years, 29.8% of patients whose melanoma recurred had distant spread, while the rest experienced locoregional recurrence, reported Lena von Schuckmann, MBBS, MPH, of Berghofer Medical Research Institute in Herston, Australia, and colleagues.

Meanwhile, in a , time to recurrence of metastatic melanoma poorly correlated with progression-free survival (PFS) and overall survival (OS), Anaïs Vallet, MD, of Hôpital St-Louis in Paris, and colleagues reported.

Both studies appeared in JAMA Dermatology.

Predictors of Recurrence

The Australian study also examined patterns of recurrence within 2 years for patients with high-risk primary melanoma. Along with advanced disease stage, the following were significantly associated with disease recurrence:

• Ulceration (HR 1.55, 95% CI 1.00-2.41)
• Head or neck tumors (HR 1.67, 95% CI 1.01-2.76)
• Unclassified tumor histology (HR 1.84, 95% CI 1.04-3.25)
• Higher mitotic index, rate >3/mm² (HR 2.36, 95% CI 1.19-4.71)

"Although there are no universal follow-up guidelines for primary melanoma survivors, the general consensus is that regular examinations of skin and lymph nodes are required for early detection of disease recurrence or subsequent new primary tumors," von Schuckmann and colleagues wrote. "With the introduction of targeted and immune therapies for treatment of metastatic melanoma, including possible adjuvant therapy, a detailed understanding of the risk of melanoma recurrence may assist clinicians to advise patients with a primary tumor at high risk of disease metastasis."

The investigators evaluated 700 high-risk primary melanoma patients (mean age 62.2 years, 58.6% men) from Queensland, Australia, with newly diagnosed and histologically verified T1b to T4b melanoma. Among 64 patients who underwent surgery for locoregional disease, 10.9% developed a new locoregional recurrence at 2 years, 57.8% stayed disease free, and 31.3% developed distant disease.

In all, sentinel lymph node biopsy (SLNB) was not performed on 442 patients, 213 had SLNB but the result was negative, while 38 were found to have stage IIIa disease following a positive SLNB. Patients with T2a or T4a melanoma who didn't undergo SLNB had worse 2-year disease-free survival than those who did and had a negative SLNB:

• T2a: 91.1% versus 96.9%, respectively
• T4a: 78.8% versus 83.3%

Patients self-reported instances of recurrence by completing follow-up questionnaires every 6 months, which were verified using imaging and histologic findings. Using the Cox proportional hazard regression analysis, the researchers assessed relationships between melanoma recurrence and patient and tumor factors. Disease-free survival based on melanoma tumor category was assessed using the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging manual.

Comparing AJCC 7 and AJCC8, 2-year disease-free survival were similar for T1b (~93% for both) and T4b melanoma (68% for both).

In an that accompanied the study, Daniel Coit, MD, of Memorial Sloan Kettering Cancer Center in New York City, said that the "biggest challenge in interpreting the significance of this study is the heterogeneity of the patient data set," which recalled the heterogeneity "of the AJCC7 data set, where pathologic staging of clinically localized melanomas was not required."

He noted that AJCC8 included over 10,000 patients with pathologic T1b to T4b melanoma and "addressed this shortcoming" by restricting inclusion to melanoma patients who had undergone SLNB. Coit also noted that while a 2-year interval may be practical for a prospective study, it may not be reflected in the true biology of the study cohort as AJCC8 demonstrated that most recurrences "are expected to occur after the 2-year threshold."

Time to Recurrence, a Poor Surrogate for Survival

Evaluating unresectable stage III or IV melanoma patients in the MelBase cohort, French researchers found no evidence of a relationship between time to disease recurrence and PFS:

• 12 to 24 months (HR 0.75, 95% CI 0.56-1.02)
• >24 months (HR 0.62, 95% CI 0.47-1.01)
• Continuous variable (HR 0.99, 95% CI 0.99-1.01)

Similarly there were no apparent relationships between time to recurrence and OS

• 12 to 24 months (HR 0.76, 95% CI 0.54-1.07)
• >24 months (HR 0.61, 95% CI 0.54-1.03)
• Continuous variable (HR 0.99, 95% CI 0.98-1.02)

"Although the kinetics of metastatic disease seem to be correlated with patient survival, the first relapse is not predictable, and data from the literature on the topic are controversial," Vallet's group wrote. "We hypothesized that the progression of the metastatic disease would be associated with the time from primary excision to the first distant recurrence of melanoma."

The study verifies more recent information on the unpredictable nature of cancer relapse, they said.

Although the current investigation does not provide a definitive answer, it underscores the need for further research into prognostic variables, Rajani Katta, MD, of McGovern Medical School at UTHealth in Houston, told 番茄社区.

She noted that based on this cohort, knowing whether recurrence happens sooner or later does not provide clinicians with any predictive information regarding OS. "Given conflicting results in studies of other cohorts, this question has not been answered definitively," said Katta, who was not involved in either of the studies.

Vallet's group assessed 638 patients (median age 64 years, 42.6% women). Patients had unresectable stage III or IV melanoma and were treated with chemotherapy (n=52), targeted therapies (n=180), first-line immunotherapies (n=274), or were enrolled in open clinical trials (n=132). Patients with de novo or unknown primary metastatic melanoma were not included. Median time from primary excision to first distant recurrence was 25 months.

Limitations cited by the authors included the retrospective collection of excision and recurrence data. "Moreover, in most patients, we lack the estimation of the start of disease from the patient's point of view," they continued.