In Plain English: What’s New in Stage II?



There is news to report in the world of Stage II melanoma, but first, let’s review the basics of Stage II and the current treatment landscape.

Stage II is localized melanoma—there is no indication it has spread to lymph nodes or distant organs, but it has grown from the epidermis (the top layer of skin) into the dermis (the second layer). It is mainly differentiated from Stage I melanoma by having a thicker Breslow depth.

Stage II melanoma is further defined with the lettering A, B, or C. Stage IIA melanoma is either 1.01mm to 2mm in depth and ulcerated, or 2.01mm to 4mm and not ulcerated. Stage IIB is either 2.01mm to 4mm in depth and ulcerated, or greater than 4mm and not ulcerated. And Stage IIC melanoma has a depth greater than 4.0mm and ulcerated.

Treatment for Stage II melanoma for a number of years has been two-pronged and surgical: a wide local excision of the tumor site and a sentinel lymph node biopsy to check for localized spread.

Prognosis for Stage II melanoma is varied because Stage IIC is a higher risk than Stage IIA. Breslow thickness and ulceration (which basically make up your Stage) are the two most important factors in determining the prognosis for melanoma. Survival rates decline, and recurrence increases, as the tumor thickness increases. Stage II melanoma is considered intermediate to high risk (as the depth increases) for local recurrence or distant metastasis.

The interesting note is that the survival rates for Stage IIB and IIC melanoma are lower than for Stage IIIA. This fact seems counter-intuitive. Indeed, why would a higher stage of cancer have a better survival rate than a lower stage? The answer seems to be related to the depth and/or ulceration of Stage IIB and IIC cancer: It has a high risk of recurrence and that recurrence affects survival rates. The reason for this seems to be that the deeper into the skin the tumor grows, the more access it has to the blood vessels and lymph nodes that help it spread. Another thought about the lower survival rate in Stage IIB and IIC compared to IIIA may be that patients who are IIIA have access to treatment with preventative (adjuvant) treatments that are not currently approved for their equally deep counterparts in Stage IIB and IIC.

Because of the high risk for Stage IIB and IIC melanoma, there has been increased attention on adjuvant and neo-adjuvant therapy for patients in these categories. Since adjuvant therapy was approved for and has good responses to reduce recurrence and increase survival in Stage III, the question was whether adjuvant therapy might be effective for Stage II, too.

Adjuvant means “helper,” and these treatments are used in addition to the primary treatment, which in this case is surgery. In the case of adjuvant therapy, the treatment is given after surgery to remove the melanoma, and the therapy is designed to eradicate potential breakaway melanoma cells. Neo-Adjuvant therapy is given both before the surgery and after.

Currently, there are clinical trials underway in adjuvant treatment for Stage IIB and IIC to test this theory. Currently open and accruing patients is a clinical trial testing the use of pembrolizumab (Keytruda) against placebo (which is currently the standard of care following surgery for Stage II) in patients who are Stage IIB and IIC. There is also an additional adjuvant trial that will open soon in the U.S. testing the effectiveness of nivolumab (Opdivo) compared to placebo in prevention of recurrent melanoma after complete resection of Stage IIB and IIC melanoma.

In plain English: These studies are testing whether giving these drugs to Stage IIB and IIC patients will help prevent the recurrence of melanoma versus giving no drug treatment, which is the standard of care now.

Stay tuned for results of these clinical trials!