Testing & Prognosis

Introduction

Prognostic indicators are still not that well understood for OM although there are several predictive factors discussed in medical literature. Several factors have been identified, though, as being associated with a higher risk of developing metastatic ocular melanoma include:

  • Large tumor size
  • Ciliary body involvement (this is a highly vascularized area, meaning it has a lot of blood vessels, so the cancer cells can get to other areas of the body, such as the liver, more easily)
  • Presence of orange pigment overlying the tumor
  • Age at diagnosis
Pathological findings such as epithelioid (versus spindle) morphology is also associated with higher risk of metastasis.

Unlike melanomas of the skin, a tumor staging system is not widely used by ocular oncologists.

OM rarely spreads through the lymph system, instead it is more likely to spread hemotogenously, or through the blood. This is one of the reasons you are likely to see metasteses ("mets") appear in the liver first and also why ciliary body involvement is a likely indicator of future metastatic disease.

Chromosomal Abnormality

The genetic makeup of the tumor is also becoming a much more useful prognostic indicator.

Recent molecular genetic research has shed light on chromosomal alterations, gene expression patterns and the relationship between these patterns and overall prognosis. The most widely used predictor of metastatic disease is the detection of monosomy 3. A monosomy is any form of aneuploidy (chromosomal abnormality) with the presence of only one chromosome (instead of the typical two in humans) from a pair.

The majority of tumors with the monosomy 3 abnormality have a poor prognosis (i.e. result in metastatic disease) versus less than 5% of tumors that have not had chromosome 3 deleted. Put another way, most of the patients missing one of their chromosome 3 pairs exhibited metastatic disease.

Here is the link to a paper that states 66% of metastasizing OM tumors with the monosomy 3 abnormality have a poor prognosis: "Monosomy 3 Predicts Death but Not Time until Death in Choroidal Melanoma"

It is believed that gains on chromosomes 6 and 8 can increase the predictive value of monosomy 3 (source: Melanoma Research Foundation). A gain of 6p indicates a better prognosis and a gain of 8q indicates a worse prognosis. This information can help predict risk of developing metastatic disease and can be obtained from a fine needle biopsy at the time of treatment of the primary eye tumor, but not after brachytherapy.

New Gene Mutation Discovered: BAP1

Another exicting advancement in the field is the work around BAP1. The loss of chromosome 3 has been recently linked to BAP1 (BRCA associated protein 1) being mutated or inactivated in a tumor and is often found in tumors with a higher risk of metastasis.

Dr. Bill Harbour at Washington University, St. Louis has been leading this research and research is currently ongoing to understand the relationship with effective uveal melanoma treatments.

Read more: http://www.sciencemag.org/content/330/6009/1410 and http://www.medicalnewstoday.com/articles/233508.php

This mutation has also been identified in a cancer called mesothelioma (a cancer linked to asbestos exposure) and researchers in both fields are coming together to learn more about the BAP1 mutation.

Gene Expression Patterns

Gene expression patterns of the tumor biopsy can also be used to predict prognosis.

Around half of ocular melanomas are shown to be “class 1” tumors and these tumors exhibit a distinct gene expression pattern, most often have chromosome 3, and thus have a low risk of metastasis. The other half of ocular melanomas, though, fall into the “class 2” category. These exhibit a different gene expression pattern, usually have lost one copy of chromosome 3, and have a relatively high risk of metastasis.

Please talk to your ophthalmologist or oncologist as early in your treatment process as possible about having the genetic makeup of your tumor tested. This is very important - knowledge is power, after all - and should be done before you have any plaque therapy.

Oncologic Follow-up

It cannot be stressed enough that you see an experienced medical oncologist and then follow up with them regularly. Hopefully, good follow-up for you will be like good insurance - you won't ever really need it, but it is there just in case.

Unfortunately, there are no approved guidelines for specific follow-up, but it would likely be comprised of blood work and scans at some sort of regular interval such as every six to nine months (likely guided by some of the factors outlined above, if known).

Some patients have reported having an ultrasound or MRI of the liver 1-2x/year for at least the first 1-5 years following plaque treatment (the liver is the first site of metastasis in 80%-90% of OM patients) with blood work and then possibly 1x/year thereafter. And again, make sure it is a trusted oncologist following these scans and not just your ophthalmologist.

Additionally, there are studies being conducted at various institutions around the country offering adjuvant treatment to people with high risk factors and without metastatic disease.

As with any education and treatment regimen, you are your own best advocate. You need to talk to as many doctors as possible and find a good medical oncologist who you trust and who is knowledgeable about OM. Ask them how many cases they see per year if you’re unsure.

Other Resources

DecisionDx-UM Genetic Test

The DecisionDx-UM test, developed by Bill Harbour, MD of Bascom Palmer Eye Institute, is a more advanced test to better understand genetic makeup. A gene expression profile (GEP) test, it can determine Class 1A (very low risk), Class 1B (low risk; 21% chance of metastasis over 5 years) and Class 2 (high risk of metastasis; 72% chance of metastasis over 5 years).

Learn more >