The Zimmerman-McLean-Foster hypothesis: 25 years later

Abstract

It is now 25 years since the publication of the landmark article by Zimmerman, McLean, and Foster, in which they cast doubts on the benefit of enucleation, which was the prevailing management of choroidal melanoma at that time. Over the past 25 years several advances have been made in the management of uveal melanoma. Research in the pathobiology of cancer metastasis in general and uveal melanoma in particular has also provided new insights. In this review, the Zimmerman-McLean-Foster hypothesis is explored in the light of current clinical, epidemiological, statistical, and experimental evidence.

Figure 1

Annual melanoma specific mortality rate following enucleation. Reproduced with permission from Zimmerman et al.

Figure 2

Observed and hypothetical survival curves following enucleation for uveal melanoma. E indicates the time of enucleation. EP is observed survival curve. EA, EC, and ED are hypothetical survival curves of untreated patients. EA represents the survival curve with low and steady mortality rate of 1%. EC represents survival with moderately increased mortality rate. ED represents survival with markedly increased mortality rate. Reproduced with permission from Zimmerman et al.

Figure 3

Five year relative survival rate with uveal melanoma and proportion of cases treated with surgery and radiotherapy. Reproduced with permission from Singh et al.

Figure 4

Relative survival rates (with 95% confidence intervals) in uveal melanoma patients with regard to year at diagnosis. Reproduced with permission from Bergman et al.

Figure 5

Annual all-cause mortality rate following enucleation for medium sized melanoma. Data derived from Diener-West et al.

Figure 6

Annual all-cause mortality rate following plaque therapy for medium sized melanoma. Derived from Collaborative Ocular Melanoma Study. Data derived from Diener-West et al.

Figure 7

Annual all-cause mortality rate following proton beam therapy. Data derived from Seddon et al.

Figure 8

Inferred growth of primary (solid line) and metastatic uveal melanoma (broken line) based on tumour doubling times. It takes 2.2 years after the diagnosis of primary tumour (point B) for the metastases to be clinically detected, point C. At the time of metastasis (point A), the primary tumour is estimated to be 7 mm³ and the metastases are subclinical. Reproduced with permission from Eskelin et al.