|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Originally published as JCO Early Release 10.1200/JCO.2004.06.921 on August 9 2004 © 2004 American Society of Clinical Oncology.
Thin Melanoma: Still "Excellent Prognosis" Disease?Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY
The American Joint Commission for Cancer (AJCC) revision of the melanoma staging system in 2002 changed the definition of "thin" melanoma from lesions The melanoma staging committee of the AJCC was formed in 1999.6 It included representation from all appropriate medical specialties from the international melanoma community. Based on a series of meetings, the committee proposed revisions to the AJCC Staging System for melanoma in 2001. In preparation for their final recommendations, the melanoma staging committee undertook an unprecedented collaboration to perform a large scale prognostic factors analysis in a combined data set of 17,600 melanoma patients derived from 13 institutions and cooperative study groups worldwide.2 The resulting final version of the staging system was published in 2002 in the sixth edition of the AJCC Cancer Staging Manual and the International Union Against Cancer (UICC) TNM classification of malignant tumors.7,8 The resulting staging system has multiple advantages over the previous version. It accomplishes many of the goals of the Melanoma Staging Committee in that it is practical, reflects the biology of the disease, and can easily be used by tumor registrants. Increasingly homogeneous subgroups that predict survival within stages have the potential to enhance the efficiency and validity of clinical trials. On the other hand, it is not clear that the committee succeeded in its lofty goal to "produce a staging system that was applicable to the diverse needs of all medical disciplines and relevant to current clinical practice." The accuracy and clinical utility of the new staging system for thin melanomas—the lion's share of newly diagnosed cases—has been repeatedly questioned.9–13 In the current issue of the Journal of Clinical Oncology, two groups offer new prognostic models for thin cutaneous melanoma. The similar approaches taken by the two groups highlight recent advances in prognostic modeling methodology. The significantly different models they propose underscore the challenges that remain in the application of prognostic modeling in clinical practice. Gimotty et al14 present a tree-structured analysis of 10-year survival from invasive thin (< 1 mm) primary melanomas, based on data from the University of Pennsylvania Pigmented Lesion database (N = 1,114). They utilize classification and regression tree (CART) analysis to produce a prognostic tree for 10-year metastatic disease that incorporates four prognostic factors: sex, growth phase, mitotic rate, and tumor infiltrating lymphocytes (TILs). The resulting prognostic tree discriminates between four groups with projected 10-year survival rates of 99.5%, 95.9%, 87.5%, and 68.9%. The authors comment that they strove to produce a model that would be adopted in clinical practice by including biologic variables that are readily obtained in routine pathology practice and by providing a simple table of risk projections that do not require calculation on the part of the end user. Construction of this model on the foundation of prevailing concepts in tumor progression lends scientific elegance and clinical credibility to the model. The notion that growth phase (tumorigenic v nontumorigenic), proliferative capacity of the tumor (presence of mitoses), and tumor recognition by the host immune system (TILs) are relevant to prognosis is more intuitive than the notion that a 0.01-mm difference in tumor thickness alone determines outcome. It may, however, be unrealistically optimistic on the part of the authors to anticipate that this biologic credibility will translate into adoption of the model in clinical practice. The prognostic utility of growth phase and TILs has been validated in multiple data sets.15–20 The consistent inclusion of these attributes in routine pathology reports, however, does not seem to be common in current clinical practice.21 Perhaps this will change if the Gimotty et al model is validated in a separate database. In a companion article, Leiter et al22 report on prognostic factors of thin cutaneous melanoma from an analysis of the central malignant melanoma registry of the German Dermatological Society. As in the Gimotty article, proportional hazard models and CART analysis were used to define prognostic groups in this large cohort (N = 12,728) derived from 80 clinical centers located throughout Germany, Austria, and Switzerland. Similar to the Gimotty model, neither ulceration nor Clark's level—the prognostic variables used in thin melanomas in the current AJCC staging system—enter the final model. Clark's level of invasion was a strong univariate predictor of outcome in the Leiter et al data set, but failed to enter the multivariate model as an independent prognostic factor. Unlike the AJCC database, ulceration was not a univariate predictor of outcome in the German registry. The authors comment that this may reflect the more recent melanoma population represented in the German registry, which therefore may be more applicable to current practice. This is supported by the overall 10-year survival rates in their study (96.5%) and in the Gimotty study (95.5%), which are significantly higher than the 87.9% and 83.1% 10-year survivals for T1a and T1b (< 1 mm) melanomas in the AJCC database. The 10-year survivals reported in the two articles in this issue are more consistent with recent SEER data and the Australian experience than are the data in the AJCC data set.1,5,11 While both the Gimotty et al and Leiter et al articles highlight some of the deficiencies of the new, and mostly improved, AJCC staging system as relates to thin melanoma, their juxtaposition underscores the greater challenges of clinically relevant prognostic modeling. The two models utilized different prognostic variables in their analyses and neither model was externally validated in different patient populations. While both groups assume that presenting data as decision trees or tables will gain acceptance in clinical practice, this premise has not yet been borne out in the literature.
There is significant room for improvement in our ability to predict outcome from thin primary melanoma. Improved prognostic prediction has implications for patient counseling, therapeutic decision-making, the design and interpretation of clinical trials and quality assessment of health outcomes. In the case of thicker melanomas, sentinel lymph node biopsy (SLNB) has become a standard tool for assessing prognosis despite its associated morbidity, expense, and lack of proven clinical utility.23,24 As in the case of growth phase, the biologic plausibility of the prognostic importance of lymph node metastases lends SLNB significant clinical credibility. It has not, however, been established that the staging information obtained from SLNB is clinically more accurate or relevant than that which can be obtained from multivariate, noninvasive staging. Nonetheless, there has been a persistent extension of the application of this technique to thinner and thinner melanomas. It is currently common practice in many settings to perform SLNB in all melanomas that are T1B or higher stage (greater than 1 mm or < 1 mm with Clark level Much progress has been made in our ability to predict prognosis for primary cutaneous melanoma. In order to ensure continued progress, it is critical that pathology reporting in tumor registries and academic data sets include all prognostic elements of proven prognostic importance.28 Mechanisms need to be developed to help insure the external validation of promising prognostic models. It must be recognized that the utility of prognostic models and staging systems should be formally assessed. These assessments must consider the context in which the models are being utilized. The advantages of homogenous patient populations for clinical trials are readily apparent and can be assessed mathematically based on the statistical performance of the model. Utility in clinical practice is another matter. Much work is still needed to determine what constitutes a clinically relevant difference in predicted survival and the optimal way to convey such information to both physicians and patients. As newer models are developed to incorporate ongoing advances in gene expression profiling of tumors, attention to these fundamental questions in prognostic modeling will become increasingly important. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Balch CM, Buzaid AC, Soong SJ, et al: Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19:3635–3648, 2001
2. Balch CM, Soong SJ, Gershenwald JE, et al: Prognostic factors analysis of 17,600 melanoma patients: Validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 19:3622–3634, 2001 3. Freedberg IM, Eisen AZ, Wolff K, et al: Fitzpatrick's Dermatology in General Medicine (ed 6). New York, NY, McGraw-Hill, 2003 4. American Cancer Society, Cancer Facts and Figures 2004. New York, NY, American Cancer Society, 2004 5. Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER 9 Regs, Nov 2002 Sub (1973-2000), (ed April 2003, based on the November 2002 submission.), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, 2003 6. Balch CM, Buzaid AC, Soong SJ, et al: New TNM melanoma staging system: Linking biology and natural history to clinical outcomes. Semin Surg Oncol 21:43–52, 2003[CrossRef][Medline] 7. Sobin L, Wittekind C: TNM Classification of Malignant Tumors, 6th Edition. New York, Wiley, 2002 8. Greene F, Page D, Fleming I, et al: AJCC Cancer Staging Manual 6th Edition. New York, Springer Verlag, 2002
9. Ruiter DJ, Testori A, Eggermont AM, et al: The AJCC staging proposal for cutaneous melanoma: Comments by the EORTC Melanoma Group. Ann Oncol 12:9–11, 2001 10. Garbe C, Ellwanger U, Tronnier M, et al: The New American Joint Committee on Cancer staging system for cutaneous melanoma: A critical analysis based on data of the German Central Malignant Melanoma Registry. Cancer 94:2305–2307, 2002[CrossRef][Medline] 11. McKinnon JG, Yu XQ, McCarthy WH, et al: Prognosis for patients with thin cutaneous melanoma: Long-term survival data from New South Wales Central Cancer Registry and the Sydney Melanoma Unit. Cancer 98:1223–1231, 2003[CrossRef][Medline] 12. Kalady MF, White RR, Johnson JL, et al: Thin melanomas: Predictive lethal characteristics from a 30-year clinical experience. Ann Surg 238:528–535, 2003[Medline] 13. Owen SA, Sanders LL, Edwards LJ, et al: Identification of higher risk thin melanomas should be based on Breslow depth not Clark level IV. Cancer 91:983–991, 2001[CrossRef][Medline]
14. Gimotty PA, Guerry D, Ming ME, et al: Thin primary cutaneous malignant melanoma: A prognostic tree for 10-year metastasis is more accurate than American Joint Committee on Cancer Staging. J Clin Oncol 22:3668–3676, 2004 15. Lefevre M, Vergier B, Balme B, et al: Relevance of vertical growth pattern in thin level II cutaneous superficial spreading melanomas. Am J Surg Pathol 27:717–724, 2003[CrossRef][Medline] 16. Oliveira Filho RS, Ferreira LM, Biasi LJ, et al: Vertical growth phase and positive sentinel node in thin melanoma. Braz J Med Biol Res 36:347–350, 2003[Medline] 17. Bedrosian I, Faries MB, Guerry Dt, et al: Incidence of sentinel node metastasis in patients with thin primary melanoma (< or = 1 mm) with vertical growth phase. Ann Surg Oncol 7:262–267, 2000[CrossRef][Medline]
18. Clark WH Jr, Elder DE, Guerry D 4th, et al: Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst 81:1893–1904, 1989
19. Tuthill RJ, Unger JM, Liu PY, et al: Risk assessment in localized primary cutaneous melanoma: A Southwest Oncology Group study evaluating nine factors and a test of the Clark logistic regression prediction model. Am J Clin Pathol 118:504–511, 2002 20. Clemente CG, Mihm MC Jr, Bufalino R, et al: Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 77:1303–1310, 1996[CrossRef][Medline]
21. Schuchter L, Schultz DJ, Synnestvedt M, et al: A prognostic model for predicting 10-year survival in patients with primary melanoma: The Pigmented Lesion Group. Ann Intern Med 125:369–375, 1996
22. Leiter U, Buettner PG, Eigentler TK, et al: Prognostic Factors of Thin Cutaneous Melanoma: An Analysis of the Central Malignant Melanoma Registry of the German Dermatological Society. J Clin Oncol 22:3660–3667, 2004 23. Dessureault S, Soong SJ, Ross MI, et al: Improved staging of node-negative patients with intermediate to thick melanomas (> 1 mm) with the use of lymphatic mapping and sentinel lymph node biopsy. Ann Surg Oncol 8:766–770, 2001[Medline] 24. Queirolo P, Taveggia P, Gipponi M, et al: Sentinel lymph node biopsy in melanoma patients: The medical oncologist's perspective. J Surg Oncol 85:162–165, 2004[CrossRef][Medline] 25. Jacobs IA, Chang CK, DasGupta TK, et al: Role of sentinel lymph node biopsy in patients with thin (< 1 mm) primary melanoma. Ann Surg Oncol 10:558–561, 2003[CrossRef][Medline] 26. Corsetti RL, Allen HM, Wanebo HJ: Thin < or = 1 mm level III and IV melanomas are higher risk lesions for regional failure and warrant sentinel lymph node biopsy. Ann Surg Oncol 7:456–460, 2000[CrossRef][Medline] 27. Agnese DM, Abdessalam SF, Burak WE Jr, et al: Cost-effectiveness of sentinel lymph node biopsy in thin melanomas. Surgery. 134:542–558, 2003[CrossRef][Medline] 28. Compton CC, Barnhill R, Wick MR, et al: Protocol for the examination of specimens from patients with melanoma of the skin. Arch Pathol Lab Med 127:1253–1262, 2003[Medline]
Related Articles
This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
0.76 mm to lesions 
IV and/or ulceration (stage Ib) and those without these negative prognostic attributes (stage Ia). The 10-year survival from thin primary melanomas in the AJCC data set is 87.9% for stage Ia and 83.1% for stage Ib.
