Toward Resolving the Ocular Melanoma Controversy conference on melanoma sponsored by the National Eye Insti¬ tute that was held on July 14 and 15, 1978, ophthalmologists working in the field of ocular malignancy joined with biometricians and authorities in other areas of oncology to review the status of our knowledge on how best to treat ocular melanomas. Attention at the meeting focused on a reappraisal by Zimmerman and associates1·2 of survi¬ val data for patients with uveal mela¬ noma; this information led them to the conclusion that (1) the mortality before enucleation is low (estimated at 1% per year), and (2) the mortality rises abruptly following enucleation, reaches a peak of about 8% during the second year after enucleation, and then drops off monotonically. Other data that were reviewed at the confer¬ ence pointed out that both cell type and tumor size at enucleation are major prognostic factors for survival after enucleation. At
a
A
POSSIBLE CAUSES OF FATALITY
Zimmerman and co-workers con¬ clude that about two thirds of the fatalities following enucleation could be attributed to the dissemination of tumor emboli at the time of surgery. They believe that the characteristics
of the tumor (its size, cell type, mitotic activity, and vascularity) are those that determine just how hazardous surgery will be. An alternative expla¬ nation for the rise in mortality follow¬ ing enucleation offered by Drs Jack¬ son Coleman, Robert Ellsworth, and others is that the growth curve of ocular melanomas, like all population growth patterns, has an initial slow growth phase that may last an unpre¬ dictably long time. At some point, however, a rapidly accelerated growth phase is usually encountered that, clinically, may produce symptoms and may account for detection. Thus, they attribute the rise in mortality follow¬ ing enucleation to the phase of growth of the tumor at the time of detection and not the therapy used (ie, enuclea¬
tion). MANAGEMENT the belief of the majority of participants in the meeting that observation (ie, no treatment) or radi¬ ation in selected situations is the most acceptable alternative to enucleation for choroidal melanomas. Other mod¬ alities may hold promise, including local resection, photocoagulation, or the therapeutic use of ultrasound; It
was
these, however, require
more
exten-
Downloaded From: http://archopht.jamanetwork.com/ by a University of Calgary User on 05/27/2015
sive evaluation. Observation alone seems particularly appropriate in the management of small melanomas (de¬ fined at the meeting as a lesion of 10 mm or less in its largest diameter, and 2 mm or less in elevation). A minority opinion was that radiation therapy might be used as a substitute for enucleation in the management of moderate-sized tumors, although radi¬ ation found more favor as an adjunc¬ tive method of treatment of large melanomas. Attention was called to European reports that postenucleation radiation therapy doubles the five-year survival rate,3·4 and to the lack of any American trials of either preenucleation or postenucleation radiation therapy. Shammas and Blodi's recent study on the treatment of orbital extension5 would indicate exenteration to be the most effective means of coping with orbital spread, although this was not the clinical impression of all the ophthalmic surgeons
present. ENUCLEATION
Regarding the potential danger of enucleation as presently performed, there does not seem to be sufficient data available to confirm or refute the contention of Zimmerman and co-
workers that this procedure may have adverse rather than a beneficial ef¬ fect with respect to the development of metastatic disease from malignant melanoma of the choroid and ciliary body. Nor do studies in progress seem likely to supply an answer to whether either avoidance of enucleation or the development of new techniques along the lines of the "no-touch" technique of Dr Frederick Fraunfelder et al" will alter the prognosis. A strongly held belief on the part of many is that it would not be advisable at the present time for the clinician to change the type of management that is routinely recommended for patients with malignant melanoma on the basis of the hypotheses presented by Dr Zimmerman and his co-workers. This routine treatment assumes care¬ ful enucleation of the eye by an expe¬ rienced operator, which would involve minimal manipulation, for mediumsized and large melanomas. Necessary preoperative diagnostic studies should also be conducted with great care and with no unnecessary trauma. an
FURTHER STUDIES NEEDED
In view of
our
present lack of
the natural his¬ a collaborative prospective study of uveal melanomas as presently treated would seem appropriate. It was the consensus of the conference participants that a central registry of reports of un¬ treated cases of melanomas of the choroid and ciliary body be established
knowledge regarding
tory of melanomas,
auspices of the American of Ophthalmology. Further examination of alternative explana¬ tions for the high frequency of death observed soon after enucleation, other than the suggestion that it represents adverse effect of enucleation, an needs to be carried out by experts in the fields of cancer research and bio-
Matthew Davis when he stressed that eventually it will be desirable to devel¬ op one or more clinical trials to evalu¬ ate clinical alternatives. Such trials may support the clinician in following currently accepted clinical practice or may provide substantial evidence that this is not in the patient's best inter¬
well. All of the biometricians at the conference and many of the ophthal¬ mologists shared the opinion that a randomized study would be the most effective method to resolve the con¬ troversy dealing with the hazards or benefits of enucleation. There was agreement that it would be useful to develop outlines of clinical trials that might be feasible at the present. In view of the small number of patients with ocular melanoma that are avail¬ able (approximately six per million
In summary, then, this recent ques¬ tion regarding the role of enucleation in the treatment of melanoma is a vital issue to all ophthalmologists, and the need for a definitive answer cannot be ignored. Daniel Albert, MD Boston
under the
Academy
statistics,
as
per year in the United States7) and the confusion regarding accepted alterna¬ tives to enucleation other than obser¬ vation alone, data from a collaborative prospective study may be helpful in defining the population and alterna¬ tive modes of treatment to be included in a randomized clinical study. Manybelieved that a possible group that might be included immediately in a randomized clinical study are older patients or patients with tumors who have a poor prognosis.
CONCLUSION
The consensus of the members at the conference was summarized by Dr
Downloaded From: http://archopht.jamanetwork.com/ by a University of Calgary User on 05/27/2015
est.
References 1. Zimmerman LE, McLean IW, Foster WD: Does enucleation of the eye containing a malig¬ nant melanoma prevent or accelerate the dissem¬ ination of tumor cells? Br J Ophthalmol 62:420425, 1978. 2. Zimmerman LE, McLean IW: An evaluation of enucleation in the management of uveal mela¬ nomas. Am J Ophthalmol, to be published. 3. Lommatzch P, Dietrich B: The effect of orbital irradiation on the survival rate of patients with choroidal melanoma. Acta Ophthalmol 173:49-52, 1976. 4. Sobanski J, Zeydler-Grzebzielewska L, Szusterowska-Martinowa E: Decreased mortality of patients with intranuclear malignant melanoma after enucleation of the eyeball, followed by orbit x-ray irradiation. Polish Med J 11:1512-1516, 1972. 5. Shammas HF, Blodi FC: Orbital extension of choroidal and ciliary body melanomas. Arch Ophthalmol 95:2002-2005, 1977. 6. Fraunfelder FT, Boozman FW III, Wilson RS, et al: No-touch technique for intraocular malignant melanomas. Arch Ophthalmol 95:16161620, 1977. 7. Cuter SJ, Young JL (eds): Third national cancer survey: Incidence data. Nati Cancer Inst Monagr 41:1-454, 1975.
a
A
POSSIBLE CAUSES OF FATALITY
Zimmerman and co-workers con¬ clude that about two thirds of the fatalities following enucleation could be attributed to the dissemination of tumor emboli at the time of surgery. They believe that the characteristics
of the tumor (its size, cell type, mitotic activity, and vascularity) are those that determine just how hazardous surgery will be. An alternative expla¬ nation for the rise in mortality follow¬ ing enucleation offered by Drs Jack¬ son Coleman, Robert Ellsworth, and others is that the growth curve of ocular melanomas, like all population growth patterns, has an initial slow growth phase that may last an unpre¬ dictably long time. At some point, however, a rapidly accelerated growth phase is usually encountered that, clinically, may produce symptoms and may account for detection. Thus, they attribute the rise in mortality follow¬ ing enucleation to the phase of growth of the tumor at the time of detection and not the therapy used (ie, enuclea¬
tion). MANAGEMENT the belief of the majority of participants in the meeting that observation (ie, no treatment) or radi¬ ation in selected situations is the most acceptable alternative to enucleation for choroidal melanomas. Other mod¬ alities may hold promise, including local resection, photocoagulation, or the therapeutic use of ultrasound; It
was
these, however, require
more
exten-
Downloaded From: http://archopht.jamanetwork.com/ by a University of Calgary User on 05/27/2015
sive evaluation. Observation alone seems particularly appropriate in the management of small melanomas (de¬ fined at the meeting as a lesion of 10 mm or less in its largest diameter, and 2 mm or less in elevation). A minority opinion was that radiation therapy might be used as a substitute for enucleation in the management of moderate-sized tumors, although radi¬ ation found more favor as an adjunc¬ tive method of treatment of large melanomas. Attention was called to European reports that postenucleation radiation therapy doubles the five-year survival rate,3·4 and to the lack of any American trials of either preenucleation or postenucleation radiation therapy. Shammas and Blodi's recent study on the treatment of orbital extension5 would indicate exenteration to be the most effective means of coping with orbital spread, although this was not the clinical impression of all the ophthalmic surgeons
present. ENUCLEATION
Regarding the potential danger of enucleation as presently performed, there does not seem to be sufficient data available to confirm or refute the contention of Zimmerman and co-
workers that this procedure may have adverse rather than a beneficial ef¬ fect with respect to the development of metastatic disease from malignant melanoma of the choroid and ciliary body. Nor do studies in progress seem likely to supply an answer to whether either avoidance of enucleation or the development of new techniques along the lines of the "no-touch" technique of Dr Frederick Fraunfelder et al" will alter the prognosis. A strongly held belief on the part of many is that it would not be advisable at the present time for the clinician to change the type of management that is routinely recommended for patients with malignant melanoma on the basis of the hypotheses presented by Dr Zimmerman and his co-workers. This routine treatment assumes care¬ ful enucleation of the eye by an expe¬ rienced operator, which would involve minimal manipulation, for mediumsized and large melanomas. Necessary preoperative diagnostic studies should also be conducted with great care and with no unnecessary trauma. an
FURTHER STUDIES NEEDED
In view of
our
present lack of
the natural his¬ a collaborative prospective study of uveal melanomas as presently treated would seem appropriate. It was the consensus of the conference participants that a central registry of reports of un¬ treated cases of melanomas of the choroid and ciliary body be established
knowledge regarding
tory of melanomas,
auspices of the American of Ophthalmology. Further examination of alternative explana¬ tions for the high frequency of death observed soon after enucleation, other than the suggestion that it represents adverse effect of enucleation, an needs to be carried out by experts in the fields of cancer research and bio-
Matthew Davis when he stressed that eventually it will be desirable to devel¬ op one or more clinical trials to evalu¬ ate clinical alternatives. Such trials may support the clinician in following currently accepted clinical practice or may provide substantial evidence that this is not in the patient's best inter¬
well. All of the biometricians at the conference and many of the ophthal¬ mologists shared the opinion that a randomized study would be the most effective method to resolve the con¬ troversy dealing with the hazards or benefits of enucleation. There was agreement that it would be useful to develop outlines of clinical trials that might be feasible at the present. In view of the small number of patients with ocular melanoma that are avail¬ able (approximately six per million
In summary, then, this recent ques¬ tion regarding the role of enucleation in the treatment of melanoma is a vital issue to all ophthalmologists, and the need for a definitive answer cannot be ignored. Daniel Albert, MD Boston
under the
Academy
statistics,
as
per year in the United States7) and the confusion regarding accepted alterna¬ tives to enucleation other than obser¬ vation alone, data from a collaborative prospective study may be helpful in defining the population and alterna¬ tive modes of treatment to be included in a randomized clinical study. Manybelieved that a possible group that might be included immediately in a randomized clinical study are older patients or patients with tumors who have a poor prognosis.
CONCLUSION
The consensus of the members at the conference was summarized by Dr
Downloaded From: http://archopht.jamanetwork.com/ by a University of Calgary User on 05/27/2015
est.
References 1. Zimmerman LE, McLean IW, Foster WD: Does enucleation of the eye containing a malig¬ nant melanoma prevent or accelerate the dissem¬ ination of tumor cells? Br J Ophthalmol 62:420425, 1978. 2. Zimmerman LE, McLean IW: An evaluation of enucleation in the management of uveal mela¬ nomas. Am J Ophthalmol, to be published. 3. Lommatzch P, Dietrich B: The effect of orbital irradiation on the survival rate of patients with choroidal melanoma. Acta Ophthalmol 173:49-52, 1976. 4. Sobanski J, Zeydler-Grzebzielewska L, Szusterowska-Martinowa E: Decreased mortality of patients with intranuclear malignant melanoma after enucleation of the eyeball, followed by orbit x-ray irradiation. Polish Med J 11:1512-1516, 1972. 5. Shammas HF, Blodi FC: Orbital extension of choroidal and ciliary body melanomas. Arch Ophthalmol 95:2002-2005, 1977. 6. Fraunfelder FT, Boozman FW III, Wilson RS, et al: No-touch technique for intraocular malignant melanomas. Arch Ophthalmol 95:16161620, 1977. 7. Cuter SJ, Young JL (eds): Third national cancer survey: Incidence data. Nati Cancer Inst Monagr 41:1-454, 1975.
