Melanoma during pregnancy: level of evidence and principles of precaution

Kiarash Khosrotehrani1,2,3, Catherine M Olsen4,5, Lisa Byrom1, Adele C Green4,6

1The University of Queensland, UQ Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia

2 The University of Queensland, UQ Centre for Clinical Research, Experimental Dermatology Group, Brisbane, QLD, Australia

3 The Princess Alexandra Hospital, Department of Dermatology, Brisbane, QLD, Australia

4QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia

5 The University of Queensland, School of Public Health, Brisbane, QLD, Australia

6 CRUK Manchester Institute and Institute of Inflammation and Repair, University of Manchester, Manchester, UK

Corresponding Author:

Kiarash Khosrotehrani, MD PhD FACD

The University of Queensland Diamantina Institute

Translational Research Institute, 37 Kent Street,

Woolloongabba, QLD Australia

Tel: +61733466077, Fax:+61733465598

Email:

Conflict of Interest Disclosure: None Declared

To the editor,

For many years, the outcome ofmelanoma during pregnancy has been the subject of debate. This is an ever-increasing medical issue as melanoma ranks first among malignancies discovered during pregnancy and post-partum in many parts of the world1, 2.A major discussion point has been whether analysis of the association with mortality adjusted for tumour thickness, a major prognostic factor, is appropriate, since some large population cohortshave observed that melanomas during pregnancy and the first year post-partum are significantly thicker3, 4. However whether or not pregnancy-associated melanoma is an independent criterion for poor prognosis, it remains obvious that due to the increased thickness of their melanomas these patients diagnosed during pregnancy are worse off. In other studies, despite adjusting for melanoma thickness, women with pregnancy-associated melanomas were at increased odds of mortality2, 5. In a recent systematic review with strict inclusion and exclusion criteria taking into account all available evidence after adjustment that could be pooled for meta-analysis, we reported that pregnancy-associated melanoma conferred a significant 56% increased risk of mortality6-8. This epidemiological evidence is further supported by an array of pre-clinical and basic science experiments suggesting that pregnancy results in reduced anti-tumourimmunity9and increasedtumourlymphangiogenesis among other hormonal theories10, 11.

In their study Tellez et al. add another piece to the available evidence suggesting that pregnancy significantly affects melanoma outcome12. This is a single institution study with small numbers of cases (41 pregnancy-associated melanoma) and understandably has substantiallimitations regarding design and analysis, as pointed out by Martires et al in their letter to the editor13. We also contend that given the persistent debate on statistical methodology and adjustment for different variables, it is important to conduct large population-level studies which allow comparing mortality of pregnancy-associated melanomas to melanomas in other women from the same age group without the need for adjustment and therefore reflecting the reality of the disease course.Indeed, including the study of Tellez et al.12 along with others fulfilling the criteria for our meta-analysis2, 3, 5, 12, 14, gives the most up-to-date estimate of 1.64 [1.30-2.08] (Figure 1), showing that pregnancy remainsan independent hazard for death basedon all relevant evidence.We therefore strongly differ from Martires et al. intheir dismissal of the evidence and suggesting that “alarm bells” should not be triggered yet. It is a concern that principles of precaution do not seem to prevail and drive management given the pooledevidence.We believe until our current knowledge becomes more complete,these data suggesting a worse prognosis should indeed trigger alarm bells of precaution and drive more extensive efforts during pregnancy and immediate post-partum to identify primary tumors, regular mapping of pigmented lesions for patients at risk and possibly more aggressive management especially in thosewomen with thicker primary tumors regarding sentinel node biopsy and imaging technology for staging. This increased awareness would in our view expedite improvement in outcomes (although this needs strict evaluation) in this category of patients without compromising the joys and experience of pregnancy in the large population of women at risk of melanoma.

Figure 1

Figure 1: Pooled effect estimate of melanoma death in pregnancy-associated melanomas: Increased risk of melanoma death in pregnant group

References

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14. Lens MB, Rosdahl I, Ahlbom A, Farahmand BY, Synnerstad I, Boeryd B et al. Effect of pregnancy on survival in women with cutaneous malignant melanoma. JClinOncol 2004;22:4369-75.

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