To Screen or Not to Screen (for Skin Cancer) – Reframing the Question

July 29, 2016
Louise M. Perkins, Ph.D.
MRA Chief Science Officer

To screen or not to screen actually isn’t the question screen

While an adaptation of Hamlet’s famous phrase may capture the headlines on whole-body skin checks, a deeper dive gets us closer to questions of life and death. In fact, there is no question that skin cancer screening is important!  The real question is when, how and for whom does skin cancer screening fit as a means to protect yourself from the deadliest of skin cancers, melanoma.

Just the facts

An independent body of medical experts called the U.S. Preventive Services Task Force (USPSTF) recently published their findings on the recommendation for whole-body skin examinations for the early detection of skin cancer. With a focus on primary care physicians and the total universe of potential patients, they concluded that there is not enough evidence to weigh the balance of benefits against possible harms in making this a universal practice.

This doesn’t mean screening is ineffective or unimportant for certain individuals – just that the jury is still out on screening for the general population.  Where a clear verdict can be delivered, is the importance of skin checks for those at higher risk for melanoma:  if you have a history of sunburns or UV exposure, family history of skin cancer, more than 50 moles, or fair skin, light eyes and/or red or blonde hair, you should discuss the benefits of regular skin exams with your doctor.  Everyone can use the ABCDE system for a monthly skin check to help identify suspicious moles and bring them to your doctor’s attention.

Here are some more details

What’s new – the 2016 USPSTF recommendation

On July 26, 2016, the USPSTF published a recommendation that there is not sufficient evidence to weigh the benefits of visual skin cancer screening by primary care providers (PCPs) against potential harms for symptom-free individuals who are not at increased risk for melanoma.

That’s a pretty dense sentence so let’s break it down a bit.

Who is the USPSTF?

The USPSTF is a volunteer panel of medical experts who are, despite the name, independent of the U.S. government and provide recommendations about prevention and evidence-based medicine to primary care physicians. This is an influential group whose determinations can have wide-ranging impact on medical practice not only by non-specialist physicians but can also affect health coverage.

What did the USPSTF study?

The task force gathered evidence from the scientific literature to measure if there is enough information of sufficient quality that related to the potential benefit and potential harms of a universal skin screening program.

What is skin screening?

Skin screening involves having a clinician examine the skin for suspicious spots.  A thorough total body exam includes looking on the scalp, between toes, and all points in between.  So, yes, you need to be out of your clothes for it, and it may take you more time to undress and dress for the exam than the exam itself!

What kind of evidence might’ve convinced USPSTF otherwise? Help me understand benefit and harms.

The USPSTF could have recommended that PCPs perform total body skin screens on everyone if robust evidence existed to support it.  A convincing study might have shown that skin screens performed on the general population by PCPs led to decreased deaths from melanoma – and there were not too many biopsies of suspicious lesions that turned out not to be skin cancer – or too much unnecessary anxiety produced by that screening.  At the present time, however, there simply is not enough evidence like this, hence the USPSTF “I” rating for insufficient evidence.

An analogy might be useful here. Broad screening would be like having your mechanic check your car once a year for rust whether or not you have a ding on its body.  With no dings, dents or scratches, the likelihood of rust is next to nil, and the regular checks become just a burden of time and resources; and for the overly anxious person – a bit of non-productive anxiety. Those would be harms. But if your car ran years and years because of this inspection, that would be a benefit. 

So, skin screening is a big waste of time and I should skip it, right?

Wrong. What the USPSTF found is that there’s just not sufficient evidence to recommend for or against PCP screening for the adult general population. However, “insufficient evidence of benefit” is different from “evidence of no benefit.” We know that when caught early, melanoma is highly treatable with surgery. But once it spreads throughout the body (metastasizes), it can be deadly. So, detecting melanoma at its earliest stages is very important. Keep in mind that adults with concerning skin symptoms or who are at higher-risk for skin cancer were not included in the USPSTF’s evaluation. Nor was screening by the skin specialists – the dermatologists – or even skin screening by individuals themselves considered (that evidence will be looked at by USPSTF later).

Um – okay.  So, when it comes to screening, what should I do?

First of all, everyone should check their own skin monthly using the ABCLayout 1DE system. If you’re at higher risk for melanoma, discuss the benefits of regular skin exams with your doctor.  How do you know if you’re at risk? Risk factors include:

  • Fair skin
  • Red or blonde hair
  • Light eyes
  • More than 50 moles
  • History of sunburn or excessive UV exposure
  • Personal or family history of skin cancer
  • Weakened immune system

About half of melanomas are found initially by the patient themselves.  So, for now, take charge of your own skin using the ABCDEs.

If you have something on your skin that looks suspicious, bring it to your doctor’s attention and s/he may refer you for further testing.

What is MRA doing?

The USPSTF conclusion on skin screening means that more research needs to be done on the benefits and potential harms of skin cancer screening. In 2014, MRA funded an interdisciplinary team of researchers to study melanoma skin screening in the primary care setting.  That work is just starting to yield results with a paper published recently.  One of the key components of their approach is a training system that MRA funded in 2009 called INFORMED and is used to teach PCPs skin screening.  We’ve worked with numerous allies to advocate for melanoma awareness and to spread the word that exposure to ultraviolet light (UV) from the sun and tanning beds is the most preventable risk factor for melanoma.

So, learn as much as you can, avoid tanning beds, use sun-safe practices and check your skin and you can decrease your risk of this deadly disease.

Highlights from the National Cancer Moonshot Summit

By Louise Perkins, PhD – MRA Chief Science Officer

National Cancer Moonshot Summit
June 28, 2016
Washington, DC

cancer moonshotThe National Cancer Moonshot was announced by President Obama in his State of the Union Address in January 2016 and VP Biden was charged with spearheading the effort. Few would disagree with Mr. Biden’s selection as leader given the personal experience he and his family endured with the loss of their son, Beau, to cancer. After seeing him speak on the subject at the American Society for Clinical Oncology
meeting, his passion for defeating cancer is very evident as genuine and inspiring. VP Biden continued to convey his passion at the National Cancer Moonshot Summit held two weeks ago in Washington, DC.

This passion is important and widely shared. What’s been gratifying to see is that Mr. Biden has brought in others that share the personal impact, experience, and drive to make a difference.  Greg Simon, the executive director of the Moonshot, was a member of MRA’s Board of Directors, and is a cancer patient himself.  Between the two of them and the Task Force of advisors assembled, the opportunity to propel cancer research forward in new ways is tantalizing.

But passion alone is not enough to exploit available treatments and technology, the potential resources the Moonshot offers, and, importantly, the will to come together to do something different.  Defining the goals of the National Cancer Moonshot and how those will be achieved is critical.

Towards this objective, VP Biden assembled around 300 leaders from around the country to attend the National Cancer Moonshot Summit on June 28 at Howard University in Washington, DC.  It was a privilege to be invited with patients as well as participants from academia, corporations, government and non-profits Hearing the VP and other thoughtful speakers, including emcee Carol Burnett, was a truly inspiring experience.

The overarching objective of the Moonshot is to achieve the work of 10-years in a 5-year timeframe. But how do we get there? 

Moderated working groups were assembled from the Summit participants and tasked to identify the challenges and solutions on topics ranging from improved sharing and harvesting of patient data to increasing the participation of patients in cancer clinical studies. The ideas submitted along with those collected in an online submission tool are to be evaluated by the Task Force as part of the ongoing prioritization of activities to achieve the objective.

What’s next?

We look forward to learning more and participating on behalf of melanoma and all cancer patients to drive towards ever better solutions that speed progress towards improved outcomes.

The Cancer Moonshot is a mission, and all of us #CanServe.

Understanding Immunotherapy Part 3: CTLA-4

By Amrita Bhatt, MRA Intern

Now that you’ve read our background on immunotherapy and learned about PD-1, it’s time to focus on another protein that plays a key role in cancer development, CTLA-4.

What is CTLA-4?

In addition to displaying PD-1 on the cell surface, T cells also display CTLA-4. This protein will bind to its partner, B7, causing the T cell to be turned off. Consequently, the immune response is impaired. As with the PD-1/PD-L1 interaction, this is a normal negative control of the immune response. Unfortunately, melanoma cells can take advantage of this, allowing the cancer cells to flourish.

What anti-CTLA-4 drugs are available now?

Currently, two anti-CTLA-4 drugs have been approved by the FDA – Ipilimumab (Yervoy®) and a combination therapy, Nivolumab + Ipilimumab (Opdivo® + Yervoy®). Yervoy is a checkpoint inhibitor that boosts your immune system in order to attack cancer cells. Specifically, it promotes the function and growth of T-cells, which are part of the immune response. When used in combination, Nivolumab and Ipilimumab help build your immunological “memory,” meaning that your immune system may continue attacking melanoma cells even after treatment. A phase II clinical trial in 2015 indicated that using the two in combination showed a higher response rate than just using ipilimumab alone.

Watch Dr. Evan J. Lipson of Johns Hopkins Medicine discuss more on the benefits of combination therapy.

What type of CTLA-4 research has MRA funded?

Anti-CTLA-4 therapy is a promising agent for the treatment of cancer patients and research funded by MRA plays a crucial role in advancing the field. MRA is currently funding the melanoma supplement of the SU2C-CRI Immunology Dream Team co-led by Drs. James Allison and Antoni Ribas. Their studies aim to identify biomarkers of response in patients treated with ipilimumab, nivolumab, and a combination of the two.

In 2008, MRA funding helped Dr. Jedd Wolchok of Memorial Sloan Kettering Cancer Center and Dr. Padmanee Sharma of MD Anderson Cancer Center work on research projects focused on biomarkers for ipilimumab. Biomarkers are biological substances that can be indicative of a certain disease – in this case, melanoma. Additionally, Dr. Frank Hodi of the Dana-Farber Cancer Institute worked on two funded projects that investigated combination therapy involving ipilimumab.

What’s Next?

Immunotherapy provides hope to not only melanoma patients, but patients of all cancer types. Recent clinical trials have shown that ipilimumab allows for greater survival compared to a vaccine. Additionally, ipilimumab can be used as adjuvant therapy in cases of high-risk melanoma. In these situations, ipilimumab is given in addition to the primary treatment, which is usually surgery. High-risk patients undergoing adjuvant therapy are able to experience a longer relapse-free survival. As we continue to learn more about immunotherapy, and CTLA-4 in particular, MRA is committed to accelerating research in order to benefit even more patients.

We hope you enjoyed and learned more through mini-series on immunotherapy!

Learn more about the promise of immunotherapy:

Trena’s Story: An African-American Retiree’s Journey with Melanoma

“Trena, you have melanoma and you are going to lose your toe. “  WHAT?!?!

I am a Black woman in her sixties—that is crazy!!

TB and Boyfriend

Trena with her boyfriend, Maceo.

My name is Trena Brown. Retired from corporate life, I was in the process of travelling to places on my bucket list when in March 2013, I learned that the “blister” on my great right toe was not a blister. It revealed its ugly bubble near the toenail, near a spot that had previously been excised in 2011 because of severely darkened skin in an irregular pattern.  However, the biopsy results were benign and the margins were clear so “I’m good!” So how is it possible that I had melanoma?  My doctor was explaining it all to me but I was not hearing anything except my own wild sobs and screaming.

Two weeks later with a cast up to my knee I am grateful for my family, neighbors and friends who are helping me literally get back on my feet. Some people had no clue what the word melanoma meant and thought I had an amputation due to diabetes. Others thought that melanin not only beautifies skin, but protects it. So why would this happen to any of us with lots of melanin?

TB Group

Trena (center) with her family.

After the amputation, my doctor had used the same words again…”the margins were clear”….and this time surely they were, since I no longer had a big toe.  I relegated myself to visiting my reconstructive surgeon, my dermatologist, and my oncologist every three months. In six months, I was able to take a pre-scheduled trip to China, and in a year, I was back in my Zumba class, seeing my trainer at the gym, and enjoying dancing at parties again. “I’m good!”

In December of 2015, I told my PCP that sometimes when I was outside, I seemed to have labored breathing.  He suggested I stop downstairs on my way out and get a chest x-ray. In the following days, my doctor told me I needed both a CT scan and lung biopsy.

In 48 hours after the biopsy, I got a message from MyChart, saying I had “test results.”  With my brother and sister-in-law on the phone for support, I opened the results to see the entire page filled with print, but my eyes focus on the line in the center that had two words in bold print:  Metastatic Melanoma.  My brother was talking to me but all I could hear were my own wild sobs and screaming.

TB Sister

Trena (R) with her sister-in-law, Aileen.

Three years ago, there was no cure. Surely God put angels on my shoulders because now, as I started telling friends and family about my condition and my oncologist’s recommendation for immunotherapy, I found that there were quite a few people in the clinical trials who had amazing success.  A friend introduced me via e-mail to Louise Perkins who invited me to a Melanoma Research Alliance reception in Washington DC where I had the opportunity to meet several survivors.  I also talked to several doctors about their interest in melanoma and what they hoped to see in the coming years.  It was a very uplifting experience that helped me focus through the Yervoy/Opdivo drips and envision a positive outcome where “I’m going to be good.”

In May of 2016, I had CT scans to determine my progress after starting immunotherapy in February. Because I had not experienced any symptoms throughout my immunotherapy, I always considered that I was improving. If President Carter could beat this at his age then I surely should be able to.  Later that day, I finally get a call from the doctor with words I actually can hear:

“Trena, you have had outstanding results from your immunotherapy!  The nodules have shrunk to be miniscule and the swollen lymph node is a normal size”. 

YES!!!  No screaming, no sobs, just tears of joy!

So now I am in Phase Two—maintenance.  I continue to let people know that African-Americans can get melanoma I encourage people to check out any abnormalities on their skin, wear sunscreen, and see dermatologists.  I am only one person, but hopefully one person who can help educate my community on melanoma, and as well as the advances that are being made.

I truly believe my best days are yet to come.

Insider’s Tips for Melanoma Prevention: Make Every Day Don’t Fry Day

Don'tFryDay_logo_v2The Friday before Memorial Day weekend in the U.S. is Don’t Fry Day – a day to remember to keep your skin safe as we launch into the summer season here in the northern hemisphere.

Why you should care – the case for every day as Don’t Fry Day

Most people want to avoid getting cancer, right? How many people do you know who say, “Sure, I want to set myself up for costly visits to the doctor, scars from surgery and needing drugs that may or may not save my life and have uncertain side-effects.”

And even if you’re one of those folks who want to take the risk because it might not happen to you, you don’t want your kids, family, and friends to go through that.

Stay Shady My Friends

Melanoma is one of the most preventable cancers under the sun – pun intended. Why? Because in the vast majority of melanomas from many different patients, scientists can see that ultraviolet (UV) light caused DNA damage, and DNA damage is the number one pre-disposing factor behind cancer. Very rarely, melanomas occur without an obvious amount of UV-caused DNA damage. But that doesn’t mean that UV isn’t a major culprit in causing most melanomas. It is. And, UV rays come from two major sources in our world – sunlight and tanning beds.

In a recent article in Chicago Health magazine, Jason J Luke, MD, who treats melanoma talks about the benefits of new therapies, which while good are by no means perfect. Still an ounce of prevention is worth a pound of cure. And for skin cancer and melanoma in particular, a little effort may mean you never get a bad melanoma in the first place.

Here are some tips for protecting your skin and preventing melanoma:
• Stay in the shade whenever possible
• Avoid the sun in the middle of the day when rays are strongest
• Wear a wide-brimmed hat and other protective clothing
• Use and reapply a broad-spectrum SPF 30+ sunscreen every 2 hours, and/or after swimming or excessive sweating
• Avoid tanning beds

Protect your skin – make every day Don’t Fry Day – and share with your friends and family. You could literally save a life!

Learn more about Don’t Fry Day here.

MRA Partner Feature: Neiman Marcus

By Regina Campbell

This week, we’re featuring a guest post from Regina Campbell, who is Director of Social Media for Neiman Marcus. Read more.

For some, skincare can be an afterthought. Of all the items on our to-do lists, applying SPF may not be at the top. The chaos of life often distracts us from the one thing we at Neiman Marcus consider most important—our personal health. Cancer has affected many of us in one way or another, and it’s up to us to protect ourselves as best we can.

Recently there have been tremendous advances in melanoma research, from increased attention to the disease to improved treatment options. Neiman Marcus is honored to be a part of this process, having partnered with the Melanoma Research Alliance (MRA) to increase awareness and fund research to help reduce the risk of melanoma.

Although genetics and increasing age can be risk factors for melanoma, exposure to ultraviolet (UV) rays is a major risk factor for the disease. According to the MRA, melanoma is the most common cancer diagnosis in women ages 25-29 years old.

Neiman Marcus’ wide assortment of products includes many brands that strive to incorporate agents that help protect the skin from the sun for women of all ages. In fact, during June we are partnering with companies that are generously donating 10% of net proceeds of select suncare product sales to support the MRA.

But it’s not just beauty products that help shield the sun. Swimwear brand Cover addresses the need for fashionable and protective T-shirts and cover-ups for women to wear in the sun. Founder Lisa Moore launched Cover in 2008, just two years before her 22-year-old sister was diagnosed with melanoma. Since then, the line has made health a priority.

It’s increasingly important for women of all ages to understand their family history with cancer, be persistent with regular health exams, and help protect one’s skin from external harm such as the sun.

Despite the advancements made in fighting melanoma, we must still acknowledge the long road ahead. Many still downplay the seriousness of the disease with the assumption that it’s easy to treat. As someone who has a family history of skin cancer, I’m vigilant about making frequent visits to the dermatologist. Considering my personal experience with the disease, I urge all women to do the same.

Whither melanoma and whither cancer research? 

By Louise M. Perkins, PhD
Chief Science Officer, Melanoma Research Alliance

There is no doubt that the last few years have seen incredible progress for melanoma patients with 11 treatments approved since MRA’s founding in 2007: personalized medicine, targeted therapy, immunotherapy. What remains to be done for melanoma and other cancers? How are the successes in melanoma and other research areas converging on even greater progress for patients?

The answers to these questions were touched on at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans in late April.

First – a quick comment on the AACR Annual Meeting itself. It is the largest meeting of cancer researchers from around the world and takes place during half a week.  In that time, there are many and various presentations covering basic cancer biology, translational research and clinical outcomes.

Image courtesy of AACR twitter account.

Vice President Joe Biden speaking at the 2016 AACR Annual Meeting. Image courtesy of AACR twitter account.

Starting with the opening plenary session (featuring two MRA-funded researchers) and throughout the meeting, one couldn’t help but notice how melanoma remains as the premier case study for immunotherapy – treatment that is benefiting not only melanoma patients, but also lung, kidney and blood cancer patients.  There is continuous forward progress in building beyond the status quo to expand the benefit of these new treatments to many. Meanwhile, data at the meeting revealed that 1 of 3 melanoma patients who received nivolumab were alive at 5 years. Similarly, the news was good for combination immunotherapy with early data showing that two-thirds of patients treated with the nivolumab-ipilimumab combination regimen were alive after 2 years. This is amazing!

But challenges remain. With the increased side-effects of the combination, which patients should get single-agent vs combination therapy? And what new treatments can be brought forward for those who either never benefit or whose tumors progress despite treatment whether they have melanoma or a different cancer?  Radiation therapy, new immunotherapies, different timing of treatments, new targeted therapies, biomarkers that match patients to treatments  – all of these are under study to further improve outcomes for patients.

One last note. Treating cancer is one thing, but doesn’t it sound better to never get cancer in the first place? Unfortunately, most cancers really can’t be prevented. Outcomes are improved by early diagnosis as is the case for breast and colon cancer, but we still can’t prevent most cancers (cervical cancer is a notable exception with HPV-vaccination, by the way).  But melanoma is different and this is incredibly relevant for Melanoma Awareness month. The evidence is clear: ultraviolet light causes DNA damage leading to mutations. And melanoma tumors have the most mutations of any cancer. The pattern of the melanoma mutations is clearly due to UV exposure. Further, in mouse models predisposed to melanoma, broad spectrum sunscreen profoundly decreases the number of melanomas those animals develop. And in the absence of UV light, they get very few tumors.

In practical terms, what does this mean? Basically, use UV-safe practices! Cover up, use sunscreen liberally and avoid UV light whether from the sun or tanning beds.

To paraphrase the most interesting man in the world, “Stay shady, my friends.”

About the Author

Louise M. Perkins, Ph.D., joined the Melanoma Research Alliance (MRA) as Chief Science Officer in 2013 where she is responsible for the development and implementation of MRA’s scientific strategy.