Surgical excision margins for primary cutaneous melanoma.

BACKGROUND: Cutaneous melanoma accounts for 75% of skin cancer deaths. Standard treatment is surgical excision with a safety margin some distance from the borders of the primary tumour. The purpose of the safety margin is to remove both the complete primary tumour and any melanoma cells that might have spread into the surrounding skin.Excision margins are important because there could be trade-off between a better cosmetic result but poorer long-term survival if margins become too narrow. The optimal width of excision margins remains unclear. This uncertainty warrants systematic review. OBJECTIVES: To assess the effects of different excision margins for primary cutaneous melanoma. SEARCH STRATEGY: In August 2009 we searched for relevant randomised trials in the Cochrane Skin Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 3, 2009), MEDLINE, EMBASE, LILACS, and other databases including Ongoing Trials Registers. SELECTION CRITERIA: We considered all randomised controlled trials (RCTs) of surgical excision of melanoma comparing different width excision margins. DATA COLLECTION AND ANALYSIS: We assessed trial quality, and extracted and analysed data on survival and recurrence. We collected adverse effects information from included trials. MAIN RESULTS: We identified five trials. There were 1633 participants in the narrow excision margin group and 1664 in the wide excision margin group. Narrow margin definition ranged from 1 to 2 cm; wide margins ranged from 3 to 5 cm. Median follow-up ranged from 5 to 16 years. AUTHORS' CONCLUSIONS: This systematic review summarises the evidence regarding width of excision margins for primary cutaneous melanoma. None of the five published trials, nor our meta-analysis, showed a statistically significant difference in overall survival between narrow or wide excision.The summary estimate for overall survival favoured wide excision by a small degree [Hazard Ratio 1.04; 95% confidence interval 0.95 to 1.15; P = 0.40], but the result was not significantly different. This result is compatible with both a 5% relative reduction in overall mortality favouring narrower excision and a 15% relative reduction in overall mortality favouring wider excision. Therefore, a small (but potentially important) difference in overall survival between wide and narrow excision margins cannot be confidently ruled out.The summary estimate for recurrence free survival favoured wide excision [Hazard Ratio 1.13; P = 0.06; 95% confidence interval 0.99 to 1.28] but again the result did not reach statistical significance (P < 0.05 level).Current randomised trial evidence is insufficient to address optimal excision margins for primary cutaneous melanoma.

Confidence intervals in procedural dermatology: an intuitive approach to interpreting data.

BACKGROUND: Significant differences observed in therapeutic trials in procedural dermatology are typically denoted by p values of less than .05. Alternatively, significance can be conveyed by use of confidence intervals. OBJECTIVES: The purpose of this article is to clarify how confidence intervals convey the same information about outcomes as p values, albeit in a slightly different manner. METHODS: (1) Selective review of textbooks and other relevant literature and (2) presentation of a brief tutorial describing confidence interval determination for therapeutic clinical trials comparing differences between means of two groups. RESULTS: Routine use of confidence intervals is an intuitively satisfying means for conveying the statistical significance of results and can be used in combination with p values for understanding these results. Specifically, confidence intervals are a useful tool for indicating the size, spread, and direction of the observed differences. Unfortunately, dermatologic surgery trials tend to have low sample sizes, which frequently result in outcomes below the threshold of statistical significance (p > .05, or confidence intervals including 1.00). In the absence of statistical significance, neither p values nor confidence intervals yield definitive results. CONCLUSION: Confidence intervals can complement p values as a means for explaining statistical significant differences. When differences are not statistically significant but are clinically significant and approach statistical significance, neither p values nor confidence intervals can definitively establish whether the observed trends are indicative of an underlying difference. In these cases, common in procedural dermatology, larger, better designed, randomized prospective trials are needed.

Power and sample size of therapeutic trials in procedural dermatology: how many patients are enough?

BACKGROUND: Many new devices and therapeutic interventions are continually introduced in cutaneous surgery. The efficacy of these new techniques must be compared with that of preexisting standards so that patients can be appropriately counseled. OBJECTIVES: The purpose of this article is to (1) review methods for estimating sample size and power, (2) estimate the range of sample sizes sufficient to ensure that true differences are not missed in clinical trials of new procedural dermatologic therapies, and (3) consider the reasons why the sample size may be too small in procedural dermatology trials and how this problem can be addressed. METHODS: (1) Selective review of textbooks and other relevant literature, presentation of a brief tutorial describing sample size and power determination for therapeutic clinical trials comparing two groups with continuous outcomes variables; (2) implementation of standard formulae and assumptions to estimate sample size in cutaneous surgery therapeutic trials. RESULTS: Assuming that one group receives a standard surgical intervention and another group undergoes a new technique, to identify a moderate difference in efficacy between groups, at least 50 to 200 subjects will need to be enrolled if conventional strategies are used to reduce the likelihood of finding a difference that does not really exist (Type I error), as well as the likelihood of missing a true difference (Type II error). CONCLUSION: By face validity, it is apparent that most efficacy comparisons in procedural dermatology have low sample size and a concomitant risk of failing to detect actual differences between therapeutic arms. Owing to the limitations that restrict surgeons from frequently performing large randomized controlled trials in procedural dermatology, meta-analyses may be needed to pool the results of smaller studies. When it is critically important that differences between groups be accurately identified, dermatologic surgeons may consider eschewing smaller trials in favor of collaborating on larger trials with an adequate sample size.

Geographic and patient variation in receipt of surveillance procedures after local excision of cutaneous melanoma.

Little is known about variation in surveillance practices following the diagnosis of invasive melanoma. The objective of this study was to characterize geographic, patient, and tumor variation in the use of follow-up surveillance testing in patients with local or regional stage melanoma. A cohort of Medicare beneficiaries > or =65 y diagnosed with invasive melanoma during 1992 to 1996 living in a Surveillance, Epidemiology, and End Results registry area was studied. Outpatient and inpatient Medicare claims 3 mo following diagnosis were examined for up to 2 y for surveillance procedures of interest. Use of chest X-ray, chest computed tomography scan, abdominal and/or pelvic computed tomography scan, abdominal ultrasound, head computed tomography scan, head magnetic resonance imaging, laboratory testing, and skin examinations were compared between patient groups and geographic regions. A total of 3389 patients were identified for the analysis. Surveillance testing was relatively common, ranging from 13% for abdominal ultrasound to 80% for laboratory testing. Follow-up skin examinations were performed in 70% to 90% of patients. The use of most surveillance procedures was associated (p<0.01) with younger age, male gender, regional stage tumors, and geographical area, with up to 2-fold differences observed. In contrast, there was much less variability in the receipt of skin examinations. Further studies are needed to determine the etiology and impact of such disparities, and the influence of surveillance procedures on morbidity and mortality.

The sensitivity of Medicare data for identifying incident cases of invasive melanoma (United States).

BACKGROUND: The completeness of Medicare claims for identifying patients with melanoma for purposes of conducting population-based studies of melanoma is unknown. METHODS: Using a linked Surveillance, Epidemiology, and End Result (SEER) tumor registry-Medicare database, the sensitivity of Medicare claims for identifying 5372 patients age > or =65 years diagnosed with invasive melanoma between 1992 and 1996 was determined. Sensitivity was calculated as the proportion of incident cases of melanoma reported by SEER that was also captured by Medicare claim diagnostic codes. RESULTS: The overall sensitivity of combined Part A and Part B Medicare for incident cases of melanoma was 90.1%. Part B Medicare and Part A Medicare alone had 89.5% and 16.5% sensitivity respectively. Sensitivity was lower for patients with unrecorded Breslow depth and for patients with unstaged or distant stage melanoma. CONCLUSIONS: Medicare Part B claims have a high sensitivity for detecting melanoma incidence; Medicare Part A has low sensitivity. This sharply contrasts with published studies of other cancers, for whom Part A rather than Part B Medicare captures the predominant portion of incident cases. Medicare Part B or combined Part A and Part B administrative data is a potentially valuable resource for population-based melanoma research in the elderly. Further research characterizing the specificity and predictive value of Medicare data is needed to assess the potential implications of false positive melanoma diagnostic codes.

The potential impact on melanoma mortality of reducing rates of suboptimal excision margins.

We estimated the potential benefit of reducing rates of inadequate excision margins in the treatment of localized invasive melanoma. A computer-simulated Markov decision analytic model was created to follow until death a hypothetical cohort of 55 y old Caucasians, newly diagnosed in a community setting with localized invasive melanoma. We considered two scenarios: usual care, and a hypothetical intervention. Markov states included well without local recurrence, local recurrence, cured, and dead. Published population-based data were used for rates of optimal excision margins, local recurrence, and mortality. Two outcome measures were employed: melanoma-related mortality and life expectancy. Major assumptions included: local recurrence occurs within 10 y of diagnosis, and patients revert to general population mortality rates 10 y following melanoma excision or subsequent local recurrence. For usual care, the model estimated 8.17% melanoma-related mortality. Modeling intervention with 100% optimal excision margins reduced this rate to 6.15%, a 25% relative reduction in mortality. This increased average life expectancy by 0.437 y, which equates to approximately 11 additional years in the 4% who would not experience a local recurrence due to improved excision margins. Increasing the percentage of optimal excision margins to 80% would still yield substantial improvement, with 6.83% melanoma-related mortality, saving 0.29 life-years compared with baseline. Results were insensitive to moderate changes in the parameter values. Suboptimal excision margins may account for approximately one-fourth of all melanoma-related mortality for localized invasive melanoma. If intervention can achieve even modest adherence to optimal excision margins, it might substantially reduce mortality.

Evaluating invasive cutaneous melanoma: is the initial biopsy representative of the final depth?

BACKGROUND: An accurate initial biopsy of the deepest portion of the melanoma is vital to the management of patients with melanomas. OBJECTIVE: Our goal was to evaluate the accuracy of preliminary biopsies performed by a group of predominantly experienced dermatologists (n = 46/72). METHODS: A total of 145 cases of cutaneous melanoma were examined retrospectively. We compared Breslow depth on preliminary biopsy with Breslow depth on subsequent excision. Was the initial diagnostic biopsy performed on the deepest part of the melanoma? RESULTS: Of nonexcisional initial shave and punch biopsies, 88% were accurate, with Breslow depth greater than or equal to subsequent excision Breslow depth. Both superficial and deep shave biopsies were more accurate than punch biopsy for melanomas less than 1 mm. Excisional biopsy was found to be the most accurate method of biopsy. CONCLUSIONS: Deep shave biopsy is preferable to superficial shave or punch biopsy for thin and intermediate depth (<2 mm) melanomas when an initial sample is taken for diagnosis instead of complete excision. We found that a group of predominantly experienced dermatologists accurately assessed the depth of invasive melanoma by use of a variety of initial biopsy types.