Unknown primary melanoma looks a lot like known

Stage IV melanoma of unknown primary (MUP) origin, in which a primary tumor has either resolved or remains undiscovered, shares similar outcomes and prognostic factors to melanoma of known primary (MKP) origin, according to a new analysis of the nationwide Surveillance, Epidemiology, and End Results (SEER)-18 registries spanning from 1973 to 2014.

Previous studies of MUP have been single institutional or multi-institutional studies. The current work is the first population-level study.

MUP is uncommon, representing 2.5-5% of melanoma cases. As with MKP, worse survival of MUP patients was tied to age greater than 50 years and not undergoing a surgical procedure. The researchers did find a slight advantage in one-year survival for MUP patients compared to MKP, which could be because many of the MUP patients had experienced an immune response that eliminated the primary tumor.

“You could imagine that if the body attacks the primary tumor and it goes away, you’re set up to fight off the metastatic melanoma better,” said lead study author Jeffrey Scott, MD, a micrographic surgery and dermatologic oncology fellow at University Hospitals Cleveland Medical Center, Case Western Reserve University.

The study appeared online March 23 in the Journal of the American Academy of Dermatology.

The researchers analyzed 322 stage IV MUP cases and 12,796 stage IV MKP cases. The incidence of stage IV MUP increased over time, from 1.52 per 100,000 between 1973 and 1984, to 5.83 per 100,000 from 2005 to 2014. MUP patients were more likely to be recommended for surgery than MKP patients (surgery not recommended for 47.7% of MKP cases, compared to 37.7% of MUP cases), and they had better 1-year survival rates compared to the general U.S. population than did MKP patients (0.54, 95% CI, 0.48-0.60 versus 0.41, 95% CI 0.39-0.42). The improved survival of MUP over MKP remained steady at each measured time point out to 5 years.

However, there was no difference in 5-year disease-specific survival (DSS) in MUP versus MKP (HR, 0.91; 95% CI, 0.79-1.04; P =.16), or in the 5-year DSS Kaplan-Meier curve after adjustment for year of diagnosis, age, sex, race, and surgical treatment (log-rank P = .93).

A multivariate analysis showed increased 5-year DSS among patients who received surgery (HR, 0.41; 95% CI, 0.30-0.56; P less than .001) and decreased 5-year DSS among patients over 50 (HR 3.27, 95% CI, 1.17-9.17; P = .02 for age 50-59).

“The prognostic factors are very similar, so you should treat these patients (with MUP) similarly to patients with melanoma of known primary, the same treatments, the same clinical trials,” Dr. Scott and associates said.

The results also raise the possibility of gaining a better understanding of how immune response affects the course of metastatic melanoma.

“If MUP is due to the fact that your immune system is attacking the primary tumor, then what characteristics of the person would cause that to happen? Are younger patients (exhibiting) a more robust immune response? Could that explain why their prognosis is better? More molecular studies of the actual tumors and the immune characteristics of these patients would help us answer that,” they added.

A resolved primary tumor isn’t the only explanation for MUP, however. It’s also possible that melanocytes are found in unexpected sites, perhaps because they did not complete their migration during development. “They could give rise to melanoma that would present (as MUP). Maybe there never was a skin tumor,” the authors wrote.

The investigators recommend a thorough search for a primary tumor, employing ophthalmologists, gynecologists, and other specialists if necessary. “You could argue that once you have metastatic disease, what’s the point of finding the primary tumor? But it’s important to correctly classify these patients, in terms of what clinical trials and treatments they may be eligible for,” Dr. Scott and associates said.

SOURCE: Scott JF et al. J Am Acad Dermatol. 2018 Mar 23. doi: 10.1016/j.jaad.2018.03.021.

Stage IV melanoma of unknown primary (MUP) origin, in which a primary tumor has either resolved or remains undiscovered, shares similar outcomes and prognostic factors to melanoma of known primary (MKP) origin, according to a new analysis of the nationwide Surveillance, Epidemiology, and End Results (SEER)-18 registries spanning from 1973 to 2014.

Previous studies of MUP have been single institutional or multi-institutional studies. The current work is the first population-level study.

MUP is uncommon, representing 2.5-5% of melanoma cases. As with MKP, worse survival of MUP patients was tied to age greater than 50 years and not undergoing a surgical procedure. The researchers did find a slight advantage in one-year survival for MUP patients compared to MKP, which could be because many of the MUP patients had experienced an immune response that eliminated the primary tumor.

“You could imagine that if the body attacks the primary tumor and it goes away, you’re set up to fight off the metastatic melanoma better,” said lead study author Jeffrey Scott, MD, a micrographic surgery and dermatologic oncology fellow at University Hospitals Cleveland Medical Center, Case Western Reserve University.

The study appeared online March 23 in the Journal of the American Academy of Dermatology.

The researchers analyzed 322 stage IV MUP cases and 12,796 stage IV MKP cases. The incidence of stage IV MUP increased over time, from 1.52 per 100,000 between 1973 and 1984, to 5.83 per 100,000 from 2005 to 2014. MUP patients were more likely to be recommended for surgery than MKP patients (surgery not recommended for 47.7% of MKP cases, compared to 37.7% of MUP cases), and they had better 1-year survival rates compared to the general U.S. population than did MKP patients (0.54, 95% CI, 0.48-0.60 versus 0.41, 95% CI 0.39-0.42). The improved survival of MUP over MKP remained steady at each measured time point out to 5 years.

However, there was no difference in 5-year disease-specific survival (DSS) in MUP versus MKP (HR, 0.91; 95% CI, 0.79-1.04; P =.16), or in the 5-year DSS Kaplan-Meier curve after adjustment for year of diagnosis, age, sex, race, and surgical treatment (log-rank P = .93).

A multivariate analysis showed increased 5-year DSS among patients who received surgery (HR, 0.41; 95% CI, 0.30-0.56; P less than .001) and decreased 5-year DSS among patients over 50 (HR 3.27, 95% CI, 1.17-9.17; P = .02 for age 50-59).

“The prognostic factors are very similar, so you should treat these patients (with MUP) similarly to patients with melanoma of known primary, the same treatments, the same clinical trials,” Dr. Scott and associates said.

The results also raise the possibility of gaining a better understanding of how immune response affects the course of metastatic melanoma.

“If MUP is due to the fact that your immune system is attacking the primary tumor, then what characteristics of the person would cause that to happen? Are younger patients (exhibiting) a more robust immune response? Could that explain why their prognosis is better? More molecular studies of the actual tumors and the immune characteristics of these patients would help us answer that,” they added.

A resolved primary tumor isn’t the only explanation for MUP, however. It’s also possible that melanocytes are found in unexpected sites, perhaps because they did not complete their migration during development. “They could give rise to melanoma that would present (as MUP). Maybe there never was a skin tumor,” the authors wrote.

The investigators recommend a thorough search for a primary tumor, employing ophthalmologists, gynecologists, and other specialists if necessary. “You could argue that once you have metastatic disease, what’s the point of finding the primary tumor? But it’s important to correctly classify these patients, in terms of what clinical trials and treatments they may be eligible for,” Dr. Scott and associates said.

SOURCE: Scott JF et al. J Am Acad Dermatol. 2018 Mar 23. doi: 10.1016/j.jaad.2018.03.021.

Stage IV melanoma of unknown primary (MUP) origin, in which a primary tumor has either resolved or remains undiscovered, shares similar outcomes and prognostic factors to melanoma of known primary (MKP) origin, according to a new analysis of the nationwide Surveillance, Epidemiology, and End Results (SEER)-18 registries spanning from 1973 to 2014.

Previous studies of MUP have been single institutional or multi-institutional studies. The current work is the first population-level study.

MUP is uncommon, representing 2.5-5% of melanoma cases. As with MKP, worse survival of MUP patients was tied to age greater than 50 years and not undergoing a surgical procedure. The researchers did find a slight advantage in one-year survival for MUP patients compared to MKP, which could be because many of the MUP patients had experienced an immune response that eliminated the primary tumor.

“You could imagine that if the body attacks the primary tumor and it goes away, you’re set up to fight off the metastatic melanoma better,” said lead study author Jeffrey Scott, MD, a micrographic surgery and dermatologic oncology fellow at University Hospitals Cleveland Medical Center, Case Western Reserve University.

The study appeared online March 23 in the Journal of the American Academy of Dermatology.

The researchers analyzed 322 stage IV MUP cases and 12,796 stage IV MKP cases. The incidence of stage IV MUP increased over time, from 1.52 per 100,000 between 1973 and 1984, to 5.83 per 100,000 from 2005 to 2014. MUP patients were more likely to be recommended for surgery than MKP patients (surgery not recommended for 47.7% of MKP cases, compared to 37.7% of MUP cases), and they had better 1-year survival rates compared to the general U.S. population than did MKP patients (0.54, 95% CI, 0.48-0.60 versus 0.41, 95% CI 0.39-0.42). The improved survival of MUP over MKP remained steady at each measured time point out to 5 years.

However, there was no difference in 5-year disease-specific survival (DSS) in MUP versus MKP (HR, 0.91; 95% CI, 0.79-1.04; P =.16), or in the 5-year DSS Kaplan-Meier curve after adjustment for year of diagnosis, age, sex, race, and surgical treatment (log-rank P = .93).

A multivariate analysis showed increased 5-year DSS among patients who received surgery (HR, 0.41; 95% CI, 0.30-0.56; P less than .001) and decreased 5-year DSS among patients over 50 (HR 3.27, 95% CI, 1.17-9.17; P = .02 for age 50-59).

“The prognostic factors are very similar, so you should treat these patients (with MUP) similarly to patients with melanoma of known primary, the same treatments, the same clinical trials,” Dr. Scott and associates said.

The results also raise the possibility of gaining a better understanding of how immune response affects the course of metastatic melanoma.

“If MUP is due to the fact that your immune system is attacking the primary tumor, then what characteristics of the person would cause that to happen? Are younger patients (exhibiting) a more robust immune response? Could that explain why their prognosis is better? More molecular studies of the actual tumors and the immune characteristics of these patients would help us answer that,” they added.

A resolved primary tumor isn’t the only explanation for MUP, however. It’s also possible that melanocytes are found in unexpected sites, perhaps because they did not complete their migration during development. “They could give rise to melanoma that would present (as MUP). Maybe there never was a skin tumor,” the authors wrote.

The investigators recommend a thorough search for a primary tumor, employing ophthalmologists, gynecologists, and other specialists if necessary. “You could argue that once you have metastatic disease, what’s the point of finding the primary tumor? But it’s important to correctly classify these patients, in terms of what clinical trials and treatments they may be eligible for,” Dr. Scott and associates said.

SOURCE: Scott JF et al. J Am Acad Dermatol. 2018 Mar 23. doi: 10.1016/j.jaad.2018.03.021.