Skin Cancer Update
UPDATE ON PHOTOTHERAPY
February 2002
The reimbursement issue with phototherapy has been resolved, but a few other issues remain. Does narrow-band UVB work as well as PUVA phototherapy? Are you putting patients at risk for melanoma with PUVA phototherapy?
As of January 1, Medicare increased the reimbursement rate of UVB therapy and of phototherapy by 117%, thanks to work spearheaded by the National Psoriasis Foundation, which was represented by Mark Lebwohl, M.D., the chairman of dermatology at the Mount Sinai School of Medicine. The work was endorsed by the AAD. However, there are still a few other issues regarding UVB therapy and phototherapy that need to be discussed.
PUVA Versus Narrow-Band UVB
Results of earlier, small studies comparing the efficacy of narrow band UVB phototherapy to PUVA phototherapy were mixed. However, in a recent British randomized study of 100 patients, where 51 were treated with narrow-band UVB and 49 were treated with PUVA, the efficacy and duration of remission with PUVA phototherapy proved to be significantly superior to that of narrow-band UVB phototherapy.1 For this clinical trial, phototherapy was conducted for up to 16 weeks. PUVA phototherapy showed an 84% overall improvement of psoriasis as opposed to a 63% improvement seen with narrow-band UVB phototherapy. After 6 months, 35% of PUVA phototherapy patients remained in remission, while only 12% of narrow-band UVB patients stayed in remission. The results show that this is a valuable treatment for psoriasis, but do you increase melanoma risk as a result or is this a safe form of treatment?
PUVA and Melanoma Risk
Most of us are aware of the report of a U.S. 16-center PUVA cohort that demonstrated increased risk of melanoma among long-term PUVA patients.2-3 However, many are not aware of the fact that no less than 22 studies have been published world-wide specifically examining the melanoma risk of PUVA phototherapy showing no increased risk of melanoma. In fact, the U.S. 16-center study is the only cohort to date showing increased risk of melanoma with PUVA phototherapy. Among the 22-plus negative studies, the most comprehensive is a Swedish, long-term PUVA-melanoma study involving 4,799 patients of which 1,876 patients were followed for 15 to 21 years.4 When compared to the general Swedish population, neither the entire cohort nor the 1,876 patients followed for 15 to 21 years showed any increased melanoma risk. A separate analysis for the 1,876 patients was conducted specifically to determine whether the findings of the U.S. 16-center study could be replicated. The result was negative.
These diametrically opposite findings suggests that either there was a serious difference in the methodology on how the studies were conducted or that the relationship between PUVA and melanoma is much more complicated than the U.S. study suggests. There was a significant difference in the quality of the comparison group used to calculate the melanoma risk. Neither cohort had a control group. The U.S. study used the surveillance, epidemiology, and end results (SEER) data collected from hospital inpatients by the National Institute of Cancer. Many publications have criticized the use of this data as a comparison group because melanoma is often treated on an outpatient basis, not inpatient. Also, there is no legal requirement to report melanoma in the United States, so the SEER data might have underestimated the prevalence of melanoma in the general population, which automatically inflated the calculated risk of PUVA phototherapy. In contrast, both dermatologists and pathologists in Sweden are legally required to report melanoma.
Other Possible Explanations for the Discrepancy
Another possibility for the contradicting results is that increase in melanoma risk in the U.S. study is real, but simply not due to long-term exposure to PUVA phototherapy. If the increase is simply due to the fact that these patients were exposed to PUVA over that period of time, there is no way to explain the negative finding from the Swedish study. The true culprit might be more complicated in that it may have to do with how PUVA phototherapy was used or what it was used with. The discrepancy may be explained by the fact that, initially, PUVA phototherapy was conducted extremely aggressively in the U.S. 16-center study, where investigators tried to obtain visible erythema on research subjects. This protocol was later modified when it was realized that such aggressiveness was not necessary with PUVA (as opposed to UVB therapy) and often counterproductive. This aggressive protocol was never utilized in any of the other European studies. The more widespread use of bathPUVA and RePUVA in some European cohorts may also help explain the discrepancy.
In order to really understand the cause of the increased melanoma risk in the U.S. 16-center study and understand the discrepancies with all other published studies, open dialogue between the investigators is still needed. This is the only way the true nature of the risk factor(s) responsible for the melanoma risk can be elucidated.
The reimbursement issue with phototherapy has been resolved, but a few other issues remain. Does narrow-band UVB work as well as PUVA phototherapy? Are you putting patients at risk for melanoma with PUVA phototherapy?
As of January 1, Medicare increased the reimbursement rate of UVB therapy and of phototherapy by 117%, thanks to work spearheaded by the National Psoriasis Foundation, which was represented by Mark Lebwohl, M.D., the chairman of dermatology at the Mount Sinai School of Medicine. The work was endorsed by the AAD. However, there are still a few other issues regarding UVB therapy and phototherapy that need to be discussed.
PUVA Versus Narrow-Band UVB
Results of earlier, small studies comparing the efficacy of narrow band UVB phototherapy to PUVA phototherapy were mixed. However, in a recent British randomized study of 100 patients, where 51 were treated with narrow-band UVB and 49 were treated with PUVA, the efficacy and duration of remission with PUVA phototherapy proved to be significantly superior to that of narrow-band UVB phototherapy.1 For this clinical trial, phototherapy was conducted for up to 16 weeks. PUVA phototherapy showed an 84% overall improvement of psoriasis as opposed to a 63% improvement seen with narrow-band UVB phototherapy. After 6 months, 35% of PUVA phototherapy patients remained in remission, while only 12% of narrow-band UVB patients stayed in remission. The results show that this is a valuable treatment for psoriasis, but do you increase melanoma risk as a result or is this a safe form of treatment?
PUVA and Melanoma Risk
Most of us are aware of the report of a U.S. 16-center PUVA cohort that demonstrated increased risk of melanoma among long-term PUVA patients.2-3 However, many are not aware of the fact that no less than 22 studies have been published world-wide specifically examining the melanoma risk of PUVA phototherapy showing no increased risk of melanoma. In fact, the U.S. 16-center study is the only cohort to date showing increased risk of melanoma with PUVA phototherapy. Among the 22-plus negative studies, the most comprehensive is a Swedish, long-term PUVA-melanoma study involving 4,799 patients of which 1,876 patients were followed for 15 to 21 years.4 When compared to the general Swedish population, neither the entire cohort nor the 1,876 patients followed for 15 to 21 years showed any increased melanoma risk. A separate analysis for the 1,876 patients was conducted specifically to determine whether the findings of the U.S. 16-center study could be replicated. The result was negative.
These diametrically opposite findings suggests that either there was a serious difference in the methodology on how the studies were conducted or that the relationship between PUVA and melanoma is much more complicated than the U.S. study suggests. There was a significant difference in the quality of the comparison group used to calculate the melanoma risk. Neither cohort had a control group. The U.S. study used the surveillance, epidemiology, and end results (SEER) data collected from hospital inpatients by the National Institute of Cancer. Many publications have criticized the use of this data as a comparison group because melanoma is often treated on an outpatient basis, not inpatient. Also, there is no legal requirement to report melanoma in the United States, so the SEER data might have underestimated the prevalence of melanoma in the general population, which automatically inflated the calculated risk of PUVA phototherapy. In contrast, both dermatologists and pathologists in Sweden are legally required to report melanoma.
Other Possible Explanations for the Discrepancy
Another possibility for the contradicting results is that increase in melanoma risk in the U.S. study is real, but simply not due to long-term exposure to PUVA phototherapy. If the increase is simply due to the fact that these patients were exposed to PUVA over that period of time, there is no way to explain the negative finding from the Swedish study. The true culprit might be more complicated in that it may have to do with how PUVA phototherapy was used or what it was used with. The discrepancy may be explained by the fact that, initially, PUVA phototherapy was conducted extremely aggressively in the U.S. 16-center study, where investigators tried to obtain visible erythema on research subjects. This protocol was later modified when it was realized that such aggressiveness was not necessary with PUVA (as opposed to UVB therapy) and often counterproductive. This aggressive protocol was never utilized in any of the other European studies. The more widespread use of bathPUVA and RePUVA in some European cohorts may also help explain the discrepancy.
In order to really understand the cause of the increased melanoma risk in the U.S. 16-center study and understand the discrepancies with all other published studies, open dialogue between the investigators is still needed. This is the only way the true nature of the risk factor(s) responsible for the melanoma risk can be elucidated.
The reimbursement issue with phototherapy has been resolved, but a few other issues remain. Does narrow-band UVB work as well as PUVA phototherapy? Are you putting patients at risk for melanoma with PUVA phototherapy?
As of January 1, Medicare increased the reimbursement rate of UVB therapy and of phototherapy by 117%, thanks to work spearheaded by the National Psoriasis Foundation, which was represented by Mark Lebwohl, M.D., the chairman of dermatology at the Mount Sinai School of Medicine. The work was endorsed by the AAD. However, there are still a few other issues regarding UVB therapy and phototherapy that need to be discussed.
PUVA Versus Narrow-Band UVB
Results of earlier, small studies comparing the efficacy of narrow band UVB phototherapy to PUVA phototherapy were mixed. However, in a recent British randomized study of 100 patients, where 51 were treated with narrow-band UVB and 49 were treated with PUVA, the efficacy and duration of remission with PUVA phototherapy proved to be significantly superior to that of narrow-band UVB phototherapy.1 For this clinical trial, phototherapy was conducted for up to 16 weeks. PUVA phototherapy showed an 84% overall improvement of psoriasis as opposed to a 63% improvement seen with narrow-band UVB phototherapy. After 6 months, 35% of PUVA phototherapy patients remained in remission, while only 12% of narrow-band UVB patients stayed in remission. The results show that this is a valuable treatment for psoriasis, but do you increase melanoma risk as a result or is this a safe form of treatment?
PUVA and Melanoma Risk
Most of us are aware of the report of a U.S. 16-center PUVA cohort that demonstrated increased risk of melanoma among long-term PUVA patients.2-3 However, many are not aware of the fact that no less than 22 studies have been published world-wide specifically examining the melanoma risk of PUVA phototherapy showing no increased risk of melanoma. In fact, the U.S. 16-center study is the only cohort to date showing increased risk of melanoma with PUVA phototherapy. Among the 22-plus negative studies, the most comprehensive is a Swedish, long-term PUVA-melanoma study involving 4,799 patients of which 1,876 patients were followed for 15 to 21 years.4 When compared to the general Swedish population, neither the entire cohort nor the 1,876 patients followed for 15 to 21 years showed any increased melanoma risk. A separate analysis for the 1,876 patients was conducted specifically to determine whether the findings of the U.S. 16-center study could be replicated. The result was negative.
These diametrically opposite findings suggests that either there was a serious difference in the methodology on how the studies were conducted or that the relationship between PUVA and melanoma is much more complicated than the U.S. study suggests. There was a significant difference in the quality of the comparison group used to calculate the melanoma risk. Neither cohort had a control group. The U.S. study used the surveillance, epidemiology, and end results (SEER) data collected from hospital inpatients by the National Institute of Cancer. Many publications have criticized the use of this data as a comparison group because melanoma is often treated on an outpatient basis, not inpatient. Also, there is no legal requirement to report melanoma in the United States, so the SEER data might have underestimated the prevalence of melanoma in the general population, which automatically inflated the calculated risk of PUVA phototherapy. In contrast, both dermatologists and pathologists in Sweden are legally required to report melanoma.
Other Possible Explanations for the Discrepancy
Another possibility for the contradicting results is that increase in melanoma risk in the U.S. study is real, but simply not due to long-term exposure to PUVA phototherapy. If the increase is simply due to the fact that these patients were exposed to PUVA over that period of time, there is no way to explain the negative finding from the Swedish study. The true culprit might be more complicated in that it may have to do with how PUVA phototherapy was used or what it was used with. The discrepancy may be explained by the fact that, initially, PUVA phototherapy was conducted extremely aggressively in the U.S. 16-center study, where investigators tried to obtain visible erythema on research subjects. This protocol was later modified when it was realized that such aggressiveness was not necessary with PUVA (as opposed to UVB therapy) and often counterproductive. This aggressive protocol was never utilized in any of the other European studies. The more widespread use of bathPUVA and RePUVA in some European cohorts may also help explain the discrepancy.
In order to really understand the cause of the increased melanoma risk in the U.S. 16-center study and understand the discrepancies with all other published studies, open dialogue between the investigators is still needed. This is the only way the true nature of the risk factor(s) responsible for the melanoma risk can be elucidated.
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