Mode of presentation and time to treatment of uveal melanoma in Finland.

AIMS: To investigate the current referral pattern and delays in treatment of patients with primary uveal melanoma. METHODS: 184 consecutive Finnish patients with uveal melanoma diagnosed between July 1994 and June 1999 were eligible, and 159 were enrolled (inclusion rate, 86%). Their mean age was 60 years (range 14-87). The dates of visits to dispensing optician, physician, ophthalmologist and ocular oncologist, the presence of symptoms, and reason for consultation were determined by structured telephone interview. Time intervals to treatment planning and treatment were calculated. RESULTS: 139 patients (87%) had symptoms at presentation and 44 patients (28%) had been seen by an ophthalmologist less than 2 years previously. The median height of the tumour was 6 mm (range, 1.0-17.0) and its largest basal diameter 11 mm (range 2.5-22.0) at diagnosis. Melanoma developed from a previously detected presumed naevus in 13 patients (8%). When the first contact was a dispensing optician (15%) the median time to treatment planning was 22 days (range 1-1156). When a physician other than an ophthalmologist (19%) was contacted the delay was 68 days (range 0-1283) and when an ophthalmologist (65%) was seen it was 34 days (range 1-1426). These differences were not significant (p=0.32). The chance of being referred at first visit was 89%. Median time to treatment was not associated with symptoms (p=0.16) and tumour volume (p=0.29), but it was significantly different between patients who were and were not referred at first visit (140 days v 34 days; p<0.001) and between those treated by ruthenium and iodine brachytherapy (59 days v 33 days; p=0.009). CONCLUSIONS: Analysis of delays in management indicates that earlier treatment could be achieved if dilated fundus examinations were performed without exceptions, all suspicious naevi were referred for a second opinion, and if the patients with melanoma were referred to the ocular oncology service concurrently with staging examinations done at the regional hospital.

Exudative retinal detachment from malignant uveal melanoma: predictors and prognostic significance.

PURPOSE: To determine independent predictors of exudative retinal detachment (RD) in eyes with uveal melanoma and the significance of RD in melanoma-specific survival. METHODS: The extent of exudative RD was recorded retrospectively in a population-based cohort of 167 consecutive patients with eyes enucleated from 1972 through 1981 because of choroidal and ciliary body melanoma, representing all melanomas treated during that period. Histopathologic features including microvascular loops and networks, microvascular density (MVD), and tumor-infiltrating macrophages were determined. Clinical and histologic predictors of RD were modeled by multiple logistic regression with a split-sample, cross-validation design. Survival was assessed by Kaplan-Meier analysis and adjusted for the effect of competing predictors by Cox proportional hazards regression. RESULTS: Of 142 (85%) eyes with adequate data, 25% had no RD, 16% had subretinal fluid around the tumor, 43% had clinical RD in one to two quadrants, and 16% had RD in three to four quadrants. The RD was more extensive if the tumor was large (P < 0.0001) and had microvascular loops and networks (P = 0.0094) and less extensive if it involved ciliary body (P = 0.011). High MVD (P = 0.054) and ruptured Bruch's membrane (P = 0.065) tended to be associated with RD. Multiple logistic regression showed largest basal diameter (odds ratio [OR] 1.43 for each 1-mm change, P < 0.0001), microvascular loops and networks (OR 1.95 for each category change, P = 0.0095), and ciliary body involvement (OR 0.20, P = 0.0039) to be independently associated with RD; ruptured Bruch's membrane (P = 0.96) and MVD (P = 0.87) were not associated. Clinical RD predicted poor survival (0.59 vs. 0.37 at 20 years; P = 0.029) by Kaplan-Meier analysis, but not after adjusting for other prognostic factors by Cox regression (hazard ratio [HR] 1.00, P = 1.0). CONCLUSIONS: Tumor size, which may be a surrogate measure for total vascular content and decompensation of choriocapillaris and retinal pigment epithelium, is a strong predictor of exudative RD. Microvascular loops and networks are likewise associated with exudative RD. Exudative RD is not associated with survival after adjusting for tumor size and microvascular loops and networks.

Tumor doubling times in metastatic malignant melanoma of the uvea: tumor progression before and after treatment.

OBJECTIVE: To obtain estimates of growth rate of metastatic uveal melanoma to infer appropriate follow-up programs and to assess the impact of current chemoimmunotherapy regimens. DESIGN: Retrospective case series. PARTICIPANTS: Of 70 consecutive patients diagnosed with metastatic uveal melanoma from 1986 through 1998, 37 patients who attended regular follow-up and had measurable metastases were eligible for this study. METHODS: Tumor doubling time (DT) was calculated by the Schwartz formula using three presumed sizes of metastasis at last negative follow-up. DT was compared according to tumor characteristics, and time of micrometastasis was estimated. MAIN OUTCOME MEASURES: Doubling time of untreated and treated metastases. RESULTS: Doubling time of untreated metastases ranged from 34 to 220 days (median, 63 days). Regardless of the presumed size of metastasis at last screening, two thirds of the metastases had a DT between 30 and 80 days. No significant correlation between DT and the observed disease-free interval was detected. Assuming constant growth rate, most metastases had predictably initiated within 5 years before primary treatment. Mean DT during active treatment of metastases in 18 patients who did not show an objective response ranged from 25 to 2619 days (median, 255 days). CONCLUSIONS: Based on the estimated growth rates, a rational follow-up interval to detect metastatic uveal melanoma would be 4 to 6 months. Primary uveal melanomas that develop clinically detectable metastasis after conservative therapy may micrometastasize several years before treatment. These estimates are rough and must be confirmed by prospective studies. Current chemoimmunotherapy regimens slow down the growth rate of metastases even if objective response is not obtained.

Screening for metastatic malignant melanoma of the uvea revisited.

BACKGROUND: The purpose of the current study was to assess the value of routine imaging and liver function tests in detecting metastases from malignant melanoma of the uvea. METHODS: Forty-six consecutive patients diagnosed with metastatic uveal melanoma between 1985 and 1996 who had participated in a screening program that included annual liver function tests (LFT), chest X-ray, and abdominal ultrasonography (US) were eligible for this retrospective cohort study. Main outcome measures were the sensitivity of screening tests, presence of symptoms, recurrence free interval, and metastatic burden. RESULTS: Metastases were diagnosed in 74% of patients (95% confidence interval [95% CI], 59-86) at screening and in 26% (95% CI, 14-41) when the patient consulted a physician because of symptoms that developed before the next scheduled visit. Of all the patients, 59% (95% CI, 43-73) were asymptomatic, and 80% (95% CI, 66-91) had only hepatic metastases. The median recurrence free interval, greatest dimension of the largest metastasis, and metastatic burden of the two groups did not differ. US was diagnostic in 78% (95% CI, 64-89), at least 1 LFT test was abnormal in 70% of patients (95% CI, 54-82), and a chest X-ray was abnormal in 2% of patients (95% CI, 0-12). LFTs and US did not reveal hepatic metastases in 33% and 4% of patients, respectively. The sensitivity of individual LFTs ranged from 0.27 to 0.67, and their specificity from 0.90 to 0.96, with lactate dehydrogenase being the most sensitive LFT used. CONCLUSIONS: The authors believe that annual screening with LFTs and abdominal US will identify 59% of patients while they are still asymptomatic and that semiannual screening will detect >95% of such patients. Chest X-ray has a very low yield and is recommended only at baseline to exclude metastatic disease to the eye and if pulmonary symptoms develop.