14/03/2016

Transcription Prof. Dr Rolf-Markus Szeimies:

Dear listeners, I’d like to welcome you from the 74th American Academy of Dermatology here in Washington DC in the United States. It’s a pleasure to see you again since I already did this press coverage last year from San Francisco.

Today I’d like to start with a presentation by Dr Anthony Rossi from Sloan Kettering Cancer Center in New York. In his first session in the morning he presented non-surgical and adjuvant treatments for skin cancers.

Dr Rossi asked the question why overall there are therapies which are non-surgical. The problem is that melanoma and non-melanoma skin cancer is increasing worldwide. There are more than two million cases per year just in the United States and of course surgery is standard of care but non-surgical treatments can also be beneficial.

Of course there are patients who are non-surgical candidates. There is excessive morbidity in some cases from surgery. 

Of course cosmesis plays a role and if you have multiple lesions, so you like to treat fields or field cancerisation, I think there is also the need for an alternative to surgery. 

Of course there are some high-risk patients who also need other kinds of approaches rather than surgery.

In the first part of his talk he focused on basal cell carcinoma and looked at the different subtypes of basal cell carcinoma. There are the less aggressive growth patterns of BCC which are nodular basal cell carcinomas or superficial basal cell carcinomas. They are not that much of a problem and there are of course possible alternatives. However, for the more aggressive growth patterns like micro-nodular, infiltrative sclerosing, more fake types or basal screamers, so the mixed types of basal cell carcinomas, it’s more necessary to keep with the given standards of treatment if this is possible.

An interesting part was his presentation on BCC biopsies. He presented one clinical trial where 232 biopsy specimens were examined for their corresponding exigence to determine the correlation between the BCC subtypes in either the biopsy or the wide excision. Interestingly, 80% of those 232 lesions were performed as shave biopsies versus 12% as punch biopsies. The total specimen accuracy rate was 82% and mixed histological subtypes were present in almost half of the cases and half of them contained an aggressive subtype which means infiltrative morphic or micro-nodular variants of basal cell carcinoma and that means that there was an 80% discordance rate between the biopsy specimen, subtypes when the growth pattern was mixed.

So, to speak frankly, if you do take a shave biopsy from the surface it’s a high risk that in the underlying part there is a mixed subtype, for example, an infiltrative basal cell carcinoma, and you may miss the diagnosis and you perform a different therapy which is not suitable for this lesion. 

In 40% of the cases, aggressive subtypes were not apparent in the original biopsy and therefore this is really a matter for concern. When he looked at the treatment comparisons with five-year cure rates performing with BCC the highest cure rates were reported for most micrographic surgery: 97–98%. 

Standard excision is in the range between 90–95%, radiotherapy is in the range between 83–95%, electrodesiccation and curettage is a little bit lower 81–92%, for dynamic therapies—so far a few clinical trials have been followed up for five years—is in the five-year cure rate of 86%.  Topical five percent Imiquimod is only 69% and Cryo, which was always thought to be a nice alternative, is only in the range of 61% and this is only after a two-year follow-up study. 

Interestingly, the hedgehog pathway inhibitors also play a role.

Meanwhile, as drugs for the treatment of advanced basal cell carcinoma, 90% of the BCC have inactivating mutation, the so called patch which leads to an unregulated smoothant and those activating mutations in smoothant are however less common. 

 Interestingly, the drug which is now on the market called Vismodegib binds to smoothant and therefore inhibits the pathway so the upper regulation and the synthesis of cellular growth is blocked by the intake of Vismodegib. Since 24 July last year, 2015, Sonidegib is also approved by the FDA and also binds to smoothant.

He also covered the topic squamous cell carcinoma which is the second most common non-melanoma skin cancer in the United States. It accounts for about 20–30% of NMSC. 

The incidents appear to have increased over a year and this is not only in the US but also in Europe. 

Squamous cell carcinoma in situ is very easy to be treated with other therapies rather than surgery so topical treatments play a very important role. Only 3% however up to 26% of cases may develop invasive squamous cell carcinoma.  

He also talked about SCC high-risk features. So the increasing depth of invasion leads to an increased risk of local recurrence in nodal metastasis and therefore the rate of survival decreases. 

 If the depth of the tumour is less than two millimetres, it’s not really likely that it will metastasise so I think also the follow-up procedures can be followed in a little less aggressive mode.

However, if the depth of invasion is in a range between 2–4 mm then there is an historical recurrence rate of 5.3% and a metastasis rate of already 6.7%. The survival rate in cases less than 2 mm is 95%, between 2 and 9 millimetres it drops to 80% and if a tumour of an SCC is thicker than 9 mm, the survival rate is only 65%.

He also covered a new interesting drug which is actually an old drug: oral nicotinamide. There was a supplemental report in the JCO by Martin. He presented a phase III, double-blind, randomized trial with more than 380 immune competent participants who had more than two histologically confirmed non-melanoma skin cancers in the past five years. They received oral nicotinamide 500 mg twice a day or placebo for one year. The primary endpoint was measured as the new NMSCs in this 12 month follow-up period. The average NMSC rate was significantly lower for the oral nicotinamide group; 1.77 compared to the placebo group where it was 2.42. The relative rate reduction was 0.23 with a confidence interval between 0.04–0.38 and adjusted for centre and NMSC history this was almost in this range. 

For BCC the relative risk rate was 0.2 whereas for SCC it was 0.3. Actinic keratosis counts were also reduced by 11% after 3 months, 14% after half a year and 20% after 9 months so this was also quite interesting and as well 13% after one year and this was also of high statistical significance compared to the control group.

Finally, he also covered lentigo maligna melanoma; 4–15% of the cutaneous cases are of this origin and actually we all know that they may evolve for decades before they invade papillary dermis so they stay on top. 

However, sometimes it’s quite difficult to diagnose this in really sun-damaged skin because it also looks quite equal to other benign pigmented lesions. So, probably it’s necessary to do a series of multiple biopsies before you really can get the diagnosis.

When you look at the five-year survival rates for the different melanoma types, nothing has changed so much. Superficial spreading melanoma, one of the most common melanoma types, has a five-year survival rate of 95.8%, lentigo maligna melanoma 96.3% and it then drops dramatically to the nodular melanoma which is roughly in the range of 69%. A little bit better are the acral lentiginous and subungual melanomas with 81% of cases.

Interestingly, the melanoma biopsy has also been studied. He presented a paper by Johnson, who studied the impact of an incisional biopsy on melanoma micro staging and when you perform a shave biopsy, this significantly increases the odds of upstaging after the excision of the residual lesion compared to the use of a punch biopsy. So, therefore, also for melanoma diagnostics it’s always recommended to perform a punch biopsy. The shave biopsies increased in the odds of upstaging by 2.3 compared with the punch biopsies in this trial.

Sometimes it’s really difficult to differentiate between severely sun-damaged skin and melanoma in situ and therefore a nice approach could be to perform controlled biopsies, which means that you select an equally sun-damaged skin area and you take a number of biopsies. Then you can look at the numbers of atypical melanocytes in the background skin compared to that of the lesion of interest.

Occult invasion, so those called  , in a range of 0.1–0.75 mm have been identified in 15–40% of pathologically diagnosed lentigo maligna cases when you perform a complete excision. So far, this invasive pattern in respect of risk is undefined but recurrence rates for standard excision of lentigo maligna range in the area of between 6–20%.

So, it’s obvious that sometimes you may need a greater range than the five millimetre margins and in this observation it was roughly 60% of cases which required these greater margins. The recurrence rates for stage excision ranged between 0–5% when it is performed like this and this was the final presentation from Dr Rossi. Thank you very much for your attention.

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