Uveal melanoma: updated considerations on current management modalities

Abstract

Published data on growth rates of uveal melanomas and effects of treatment modalities raise important considerations. Dissemination from uveal melanomas starts after the tumour is larger than 7 mm diameter; growth from 7 to 10 mm diameter increases the risk of metastases incrementally to approximately 16%. Estimations of turnout doubling times indicate that metastatic death before 8 years is nearly always due to pre-therapeutic dissemination so that the impact on survival by therapy can only be assessed thereafter. Histopathology on irradiated melanomas reveals that reproductive activity has not been suppressed and the anticipated (and unfavourable) risk of metastases is not balanced by poor post-irradiation visual acuity. Also the psychological well-being of a patient with a functional fellow eye is better after primary enucleation. Conservative management is most appropriate for: small melanomas, patients with a short life expectancy, melanomas in a single functioning eye, and patients refusing enucleation.Optimum treatment of any form of neoplastic disease by modern therapeutic modalities should ideally be based on an accurate knowledge of the biological behaviour of the specific neoplastic process. With regard to ocular melanomas, there are serious gaps in knowledge concerning growth rates in situ and in the documentation of the time intervals between the presentation of the primary tumour and the appearance of metastases. The rarity of the tumour necessitates careful accumulation of data, so that an adequate analysis can be made of the claimed success of cure rates. Equally important, the side effects and the complications of treatment should be the subject of careful scrutiny. In this communication the literature on the relevant aspects of melanoma biology and current treatment modalities is critically analysed. Tumour biology Tumour doubling timeInformation on tumour doubling time of uveal melanomas was introduced in 1980 [1] and updated reviews were provided in 1987 [2] and in 1992 [3]. From this data it was possible to estimate the risk of metastatic disease in relation to the dimensions of the tumour. The application of meta analysis provided by Diener-West and associates [4] and Markowitz et al. [5] has indicated that a radical reappraisal of the current philosophy of management is required. When do uveal melanomas metastasize ?In 1984, an editorial in the American Journal of Ophthalmology stated that 'it is unclear at what stage in its course a uveal melanoma develops the capacity to metastasize ' [6]. However an analysis of the data then available in the literature provided evidence which indicated that metastatic disease does not occur until

Survival following enucleation versus plaque radiotherapy in statistically matched subgroups of patients with choroidal melanomas: results in patients treated between 1980 and 1987

“…These observations are in agreement with the results of our recently published study on an independent cohort of patients treated by cobalt-60 plaque radiotherapy or enucleation between 1976 and 1980 [5]. These observations are important because they contradict the published expectations of some advocates of enucleation [13,14]. One aspect of our results, the finding that the survival rate among plaque-treated patients who experienced local tumor relapse was substantially higher than that among plaque-treated patients who did not have local recurrence [9,16], is particularly worrisome to many clinicians.…”

Survival following enucleation versus plaque radiotherapy in statistically matched subgroups of patients with choroidal melanomas: results in patients treated between 1980 and 1987

“…These observations are in agreement with the results of our recently published study on an independent cohort of patients treated by cobalt-60 plaque radiotherapy or enucleation between 1976 and 1980 [5]. These observations are important because they contradict the published expectations of some advocates of enucleation [13,14]. One aspect of our results, the finding that the survival rate among plaque-treated patients who experienced local tumor relapse was substantially higher than that among plaque-treated patients who did not have local recurrence [9,16], is particularly worrisome to many clinicians.…”

Influence of uveal melanoma therapy on patients' quality of life: a psychological study

“…A similar result was found in a preliminary study in a sample of 240 patients with treated uveal melanoma, where patients were as likely to report fears of local tumour recurrence after enucleation as after conservative therapy (Damato 2000). This contrasts with results published by Manschot et al (1996), where patients treated with primary enucleation were found to be unaware of the potential anxiety and depression that might be caused by an intraocular malignancy that might disseminate and cause a much‐feared metastatic death. This could be due to differences in patients' points of view after primary and secondary enucleation.…”

Robotic radiosurgery for the treatment of medium and large uveal melanoma

“…Local effective therapy seems important as delay or refusal of treatment is associated with an increased incidence of metastatic disease and/or death compared with mortality rates of patients who received prompt treatment [30,31]. However, 5-year metastatic disease rates are probably not going to be favorably influenced by any treatment of the primary tumor as the interval can be long (up to 30 years) before micrometastases become clinically evident [32].…”

Survival following enucleation versus plaque radiotherapy in statistically matched subgroups of patients with choroidal melanomas: results in patients treated between 1980 and 1987

“…These observations are in agreement with the results of our recently published study on an independent cohort of patients treated by cobalt-60 plaque radiotherapy or enucleation between 1976 and 1980 [5]. These observations are important because they contradict the published expectations of some advocates of enucleation [13,14]. One aspect of our results, the finding that the survival rate among plaque-treated patients who experienced local tumor relapse was substantially higher than that among plaque-treated patients who did not have local recurrence [9,16], is particularly worrisome to many clinicians.…”

Influence of uveal melanoma therapy on patients' quality of life: a psychological study

“…A similar result was found in a preliminary study in a sample of 240 patients with treated uveal melanoma, where patients were as likely to report fears of local tumour recurrence after enucleation as after conservative therapy (Damato 2000). This contrasts with results published by Manschot et al (1996), where patients treated with primary enucleation were found to be unaware of the potential anxiety and depression that might be caused by an intraocular malignancy that might disseminate and cause a much‐feared metastatic death. This could be due to differences in patients' points of view after primary and secondary enucleation.…”

Robotic radiosurgery for the treatment of medium and large uveal melanoma

“…Local effective therapy seems important as delay or refusal of treatment is associated with an increased incidence of metastatic disease and/or death compared with mortality rates of patients who received prompt treatment [30,31]. However, 5-year metastatic disease rates are probably not going to be favorably influenced by any treatment of the primary tumor as the interval can be long (up to 30 years) before micrometastases become clinically evident [32].…”

Survival following enucleation versus plaque radiotherapy in statistically matched subgroups of patients with choroidal melanomas: results in patients treated between 1980 and 1987

“…These observations are in agreement with the results of our recently published study on an independent cohort of patients treated by cobalt-60 plaque radiotherapy or enucleation between 1976 and 1980 [5]. These observations are important because they contradict the published expectations of some advocates of enucleation [13,14]. One aspect of our results, the finding that the survival rate among plaque-treated patients who experienced local tumor relapse was substantially higher than that among plaque-treated patients who did not have local recurrence [9,16], is particularly worrisome to many clinicians.…”

Influence of uveal melanoma therapy on patients' quality of life: a psychological study

“…A similar result was found in a preliminary study in a sample of 240 patients with treated uveal melanoma, where patients were as likely to report fears of local tumour recurrence after enucleation as after conservative therapy (Damato 2000). This contrasts with results published by Manschot et al (1996), where patients treated with primary enucleation were found to be unaware of the potential anxiety and depression that might be caused by an intraocular malignancy that might disseminate and cause a much‐feared metastatic death. This could be due to differences in patients' points of view after primary and secondary enucleation.…”

Robotic radiosurgery for the treatment of medium and large uveal melanoma

“…Local effective therapy seems important as delay or refusal of treatment is associated with an increased incidence of metastatic disease and/or death compared with mortality rates of patients who received prompt treatment [30,31]. However, 5-year metastatic disease rates are probably not going to be favorably influenced by any treatment of the primary tumor as the interval can be long (up to 30 years) before micrometastases become clinically evident [32].…”