At this year’s Chemotherapy Symposium held in New York, a standout presentation by Mark Stein, MD, showed that there is a lot of promise in the area of circulating tumor cell biomarkers for patients with prostate cancer. While this is an emerging and advancing development in research, biomarkers are not routinely used in clinical care. However, with advances in technology progressing as they are, the ability to sample cells, blood, and DNA that are in circulation are all likely to be integrated into routine care over the coming months and years, according to Stein.

The first use of circulating biomarkers in prostate cancer was to understand prognostic factors. However, isolating and characterizing circulating tumor cells is challenging, so instead, it is better to count these cells to see how many are present. By counting the circulating tumor cells, oncologists can use the count as a prognostic factor. Researchers have looked to see if these markers add anything to traditional markers such as CAT scans and prostate-specific androgen (PSA) tests. Results from the last few years have shown that biomarker assays do contribute to other tests, focusing mainly on counting the number of circulating tumor cells. Some of the newer technologies are even moving beyond this, and are looking at specific characteristics of the DNA in circulation.

Particularly when looking at some of the hormonal therapies, one of the main questions is whether there are certain predictors of response that could be sampled beforehand. If a patient has a lot of circulating tumor cells, it seems to be a rather poor prognosis factor, and can dictate the priorities of treatment. However, patients who have a decrease in the number of circulating tumor cells tend to do better, an early indicator of having a good response to treatment.

Investigators are even looking at utilizing biomarkers and counting circulating tumor cells as an endpoint in clinical trials. Typically, a trial will follow patients for survival, but this can take a long time and slow the trial down, making it more difficult to find answers to essential questions on patient treatment and care. The alternative, as studies are showing, is to use a decrease in circulating tumor cells as a clinical endpoint in a trial, rather than looking at survival. One focus is to look into whether changes in circulating tumor cells correlate so tightly with survival that, therefore, investigators can always choose it as a substitute, or a surrogate. Stein comments, “now, there are going to be additional trials going forward with circulating tumor cells being embedded into the trial, so that it is really definitively established that you can use those changes as a surrogate for overall survival, and, therefore, really expedite trial development.”

Another benefit to counting circulating tumor cells is that it can be done by taking a liquid biopsy, which requires a minimally invasive procedure that can be repeated, if necessary. This becomes especially helpful in situations where other tissues, such as bone, are not available, or could potentially cause the patient harm.

Another area of development is using changes in the androgen receptor to understand if tumors will still respond to hormonal therapies, specifically drugs like enzalutamide or abiraterone, which have become a routine part of practice for patients with castration-resistant prostate cancer. The response rate, although perhaps not zero, is present when patients have a mutation in the androgen receptor. Cells with a mutation in the androgen receptor do not respond under hormonal therapy, and potentially are an important mechanism of resistance. Identifying this mutation early would be invaluable in determining which therapy to use.

Androgen receptor mutations are the result of selective pressure, Stein explains. The receptor itself is the majority of the androgen receptor in the cell, and then under selective pressure, cells proliferate that are able to adapt to the presence of an androgen receptor inhibitor, such as enzalutamide. Stein adds, “What’s also interesting is that if you then—given the symptoms&mdash;give another treatment after, such as chemotherapy, you will see levels of the androgen receptor variants decrease, suggesting, again, that once the selective pressure is removed, that variant goes away.”

There are already commercially available tests looking at splice variants, so that is certainly something that can be useful, particularly if it becomes very difficult to understand whether a patient should go on a particular therapy or not.

So far, everything looks promising for looking at biomarkers in patients with prostate cancer, although more focused studies are always needed. “Once you have this biomarker,” comments Stein, “then you have to decide what you’re going to do with it. You certainly want direct additional therapies towards patients who might be in most need of additional treatment.”

Articles

At this year’s Chemotherapy Symposium held in New York, a standout presentation by Mark Stein, MD, showed that there is a lot of promise in the area of circulating tumor cell biomarkers for patients with prostate cancer.


The Future of Biomarkers in Prostate Cancer

It is only fitting that arguably one of the all-time great troubadours, Bob Dylan, was awarded the Nobel Prize for Literature in 2016 (although his trip to Stockholm to deliver his acceptance lecture will be delayed until 2017). The events of 2016 will certainly lay the framework for an interesting year to come. As a result of the most recent presidential election, it is a big unknown what the new administration will bring as it relates to the future of healthcare in the US. The likelihood of a complete repeal of Affordable Care Act (ACA) is unlikely. Given his lack of expertise in the area, President-Elect Trump will need to work closely with Speaker Ryan to craft a plan that has more transparency, less government regulations, and eliminates individual and employer mandates. This would be a good start, and we hope the incoming President will surround himself, and more importantly, take heed and act, with those who understand the complexities of the health care industry.

As a side note, we will be fortunate to have a urologist in Congress! My good friend, Neal Dunn, MD (R), won the 2nd congressional district in Florida. For those of you who do not know Neal, he was instrumental in getting an amendment stripped from a Florida health care bill back in 2012. Had he not led the charge at the 23rd hour, it would have set precedent for many states to follow that would have made ownership of free-standing radiation centers difficult for urology groups. Along with others, he also led the discussion to integrate groups from the panhandle of the state to the east coast. Dunn will represent us well, and we should continue to support his efforts over the next couple of years so that he can maintain presence on the Hill.

For those who attended the annual Large Urology Group Practice Association (LUGPA) meeting this past November, a major concern that was voiced repeatedly by many of the speakers was the runaway costs of prescriptions drugs in the US. This is of great concern for those readers who manage genitourinary malignancies, where the constant wave of new therapies, especially the immuno-oncology (IO) agents, are being approved in waves. There is no question that our more thorough understanding of the molecular drivers of cancer progression, regardless of the organ of origin, has led to better targeted-boutique drugs that will slow the disease progression and prolong survival without sacrificing quality of life. The cost to develop these drugs is in the billions of dollars. As many of you are fully aware, outside the United States, the reimbursement is from a single payer in most countries, namely the government. Thus, the US is the only market where pharma can recoup some of the research and development costs. As providers, we and our patients, for the most part, have access to most of these agents once they get fast-tracked by the FDA. However, in this age of budget neutrality, the trajectory is unsustainable.

Compounding on the rising costs of the drugs is the lack of financial assistance available to our patients, as well as drug shortages. Taken together, this represents a serious threat to our cancer patients. As we are all aware, the Office of the Inspector General (OIG) this past year has been looking into the legality of patient assistance foundations and the funds once available to help our patients are now quite limited. With the exorbitant costs of therapies, regardless of the mode of delivery, in patients often on fixed income, many are now going without treatment. Unfortunately, there appears to be no relief in the immediate future.

This past week, Sanofi has just announced that it will no longer be manufacturing BCG. For the thousands of patients with high-grade non-muscle invasive bladder cancer (NMIBC), this can only result in worsening outcomes for our patients, and many will progress to muscle invasive disease (MIBC), given the lack of therapeutic options with proven efficacy. There are other companies that produce BCG. However, the ability to meet worldwide demands is dubious. We remain hopeful that newer agents and delivery systems, especially IOs, can come to market quickly and be more efficacious.

With all due respect to the Nobel Laureate Bob Dylan, I am offering my adaptation of his words:

Come senators, congressmen Please heed the call

Don’t stand in the doorway Don’t block up the hall

It’ll soon shake your windows and rattle your walls For the times they are a-changing

As a result of the most recent presidential election, it is a big unknown what the new administration will bring as it relates to the future of healthcare in the US.


The Times They Are a Changin'

The tail-end of this year saw 2 annual conferences occurring at the same time: the 2016 Large Urology Group Practice Association (LUGPA) annual meeting in Chicago, and the 15th annual International Kidney Cancer Symposium (IKCS) in Miami. Both are covered in this issue’s Conference Highlights section, featuring key stories and landmark research in their respective fields.

From the LUGPA meeting, we focus on emerging therapies and diagnostic tools for bladder cancer. Geoffrey Sklar, MD, met with 

 for an interview on the potential for neoadjuvant immunotherapy in bladder cancer. The current focus is on PD-L1 inhibitors, but we still don’t have effective therapies for high-grade, non-muscle invasive bladder cancer (NMIBC). Nivolumab is showing a lot of promise for patients with advanced disease, but immunotherapy tends to work best with low-volume disease and earlier intervention, says Sklar, and there are areas that need “major improvement.”

In response to this call for improvement, there are novel immunotherapies being offered for NMIBC. Several studies have been conducted, and more are on the way, with researchers looking into intravesical gene therapy and various drug combinations.

Of course, there is no substitute for early detection, accurate diagnosis, and effective monitoring. Bladder cancer biomarkers could be essential to bringing beneficial care and improving tumor detection. In particular, new assays like the BTA/BTA Stat, NMP22 (BladderChek), UroVysion’s post-BCG FISH test, ImmunoCyt, and Cxbladder are emerging to accomplish these very goals. We discuss the benefits and drawbacks of these tests, with valuable input from Badrinath Konety, MD, MBA.

Several treatments options are on the rise for kidney cancer. In an interview with Toni K. Choueiri, MD, it becomes clear that no single therapy can be the end-all, be-all in treating renal cell carcinoma (RCC), but instead, combination therapies and targeted agents make better treatment options. Choueiri points specifically to the MET inhibitor volitinib, which is undergoing study in a phase II trial, as a promising treatment option alongside other MET inhibitors and recently approved drugs.

However, immunotherapy is still considered by experts to be integral to optimizing adjuvant care. In fact, an expert panel that gathered at IKCS projected that immunotherapy will be critical to optimizing outcomes in the adjuvant setting for patients with RCC. More pointedly, the panelists agreed upon the importance of investigating prognostic markers in order to prevent overtreatment or incorrect treatment of RCC, which is a rising issue of the last few years.

And finally, lenvantinib and everolimus combination regimens are emerging as essential second-line treatment options in advanced RCC, and research to move the regimen into frontline settings is underway. Thomas E. Hutson, DO, PharmD, strongly advocates for this combination, discussing its unique success in Study 205. All these stories sum up to a hopeful future, with much progress to come.

The tail-end of this year saw 2 annual conferences occurring at the same time: the 2016 Large Urology Group Practice Association annual meeting in Chicago, and the 15th annual International Kidney Cancer Symposium in Miami. Both are covered in this issue’s Conference Highlights section, featuring key stories and landmark research in their respective fields.


December 2016 | Oncology Live Urologists in Cancer Care®

The Future of Biomarkers in Prostate Cancer

The Times They Are a Changin'

Two Landmark Conferences Contribute to Progress in Kidney and Bladder Cancers