Eye conservation can be achieved in patients with uveal
melanomas by several techniques, with external beam charged particle (
proton) therapy and episcleral
radionuclide plaque
therapy being used most commonly. The probability of visual preservation and of eye retention with either technique is related to
tumor size and location. If vision is poor or absent in the fellow eye, even very large
tumors can be treated with the
proton beam, with a 75% to 80% probability of eye salvage and preservation of some degree of visual function. Local control is achieved in a large proportion of treated eyes with either technique probably because of the large doses that can be focally administered to these relatively small
tumors with those techniques. Achieving local control may also contribute to improved survival in some patients. Survival clearly has not been compromised. Useful vision is preserved in eyes with
tumors occurring in a favorable location with respect to the optic disc or macula. A dose-searching trial, aimed at improving visual outcome in patients with
tumors in unfavorable locations, has been completed and has provided data to aid in designing future trials. Successfully treating
uveal melanoma without removal of the involved eye is one of the major oncologic triumphs of the latter part of the 20th century. Very high rates of local control can be achieved with heavy charged particle external beam
radiotherapy or 125I episcleral plaque
brachytherapy, with preservation of a functionally useful eye in many patients. The excellent results in the eye
melanoma patients treated with external beam
proton therapy also demonstrate that almost all the patients can successfully cooperate in their treatment by voluntarily fixating the eye on a particular point during treatment, so that their
tumor is positioned properly in the beam during treatment.
Conservative treatment can achieve local control rates similar to or superior to those achieved with
radiation therapy alone in other commonly treated solid
tumors, including early stage
carcinomas of the breast, vocal cord, and prostate. Continued careful follow-up of conservatively treated patients will provide even better understanding of the radiation effects on uveal
melanomas and on normal ocular structures. It is also impressive that these gains have not been achieved at a cost of increased mortality: survival rates in irradiated patients are at least as good as after enucleation. Further observation will reveal whether these initial dramatic and encouraging results will be maintained. The COMS Study may provide additional data in this regard at least regarding survival after
brachytherapy relative to enucleation. It will not, however, clarify indications for the two types of
radiotherapy (
brachytherapy and charged particle
therapy) nor will it allow direct comparisons of acute and chronic ocular effects of those therapeutic modalities. The UCSF-LBL trial mentioned previously, which compared
helium ion
therapy with 125I episcleral plaque treatment, has documented the superiority of charged particle
therapy to plaque
therapy in terms of local
tumor control and eye retention. Of interest is a recent survey reporting that choice of treatment for
uveal melanoma did not seem to be associated with large differences in quality of life when assessed at long-term follow-up. The distant failures and metastatic deaths in
uveal melanoma patients, more common with larger and more anteriorly located
tumors, are most distressing. A randomized clinical trial of adjuvant systemic
therapy is clearly indicated but has not been mounted because of the relatively poor results obtained with systemic
therapy in metastatic
melanoma patients. The recent report of improved survival in cutaneous
melanoma patients at high risk for
metastasis who were treated with
interferon is encouraging, and it led to the initiation of the nonrandomized study described previously, which uses
interferon following
proton eye irradiation for patients with increased risk of
metastasis. Other trials would clearly be indicated if more effective systemic
therapies become available.