Tag: Cancer Treatment

Matters of the Bladder: 9 Facts about Bladder Cancer

Bladder_ImageThe bladder is an organ comprised of several layers of cells, and its main job is to store urine. When it’s full, it lets you know. But, chances are there are many other things about the bladder that you may not know. In honor of bladder cancer awareness month in May, here are 9 facts:

  1. There are different types of bladder cancer. Tumors typically form within the different cell layers of the bladder. The name of the specific type of bladder cancer refers to where the cancer started. That’s why bladder cancer is sometimes referred to as urothelial (one of the layers) carcinoma (a fancy word for cancer).
  2. Blood in the urine is a red flag. The most common sign of bladder cancer is blood in the urine (also called hematuria) that can be seen by the naked eye. Usually it is painless. But, bladder cancer isn’t the only culprit for blood in the urine. It can also be caused by an infection or kidney stones. Blood in the urine requires evaluation by a healthcare professional.
  3. It’s common. Bladder cancer is the fifth most commonly diagnosed cancer in the U.S. The National Cancer Institute (NCI) estimates 76,960 new cases of bladder cancer and 16,390 deaths from the disease in 2016.
  4. But lacks funding for research. It is through research that we are able to develop new treatments and ultimately cures. Despite being the fifth most commonly diagnosed cancer in the U.S., bladder cancer ranks 23rd in terms of federal funding.
  5. Some people are at increased risk. Smoking is the greatest risk factor. The good news is you can reduce your risk if you quit. We even have a program to help you get started. Bladder cancer is 3x more common in men than in women, and Caucasians are 2x as likely to develop bladder cancer than African Americans or Hispanics. Risk also increases as you get older and if you have a family history. Visit the Bladder Cancer Advocacy Network to learn more about additional risk factors.
  6. It is diagnosed through different tests. These typically include imaging tests such as ultrasounds, MRIs or CT scans to better see your bladder, urine testing to determine the presence of cancer cells and a biopsy to remove a sample if an area contains cells that appear suspicious.
  7. Treatment will depend on the type of bladder cancer and how advanced and aggressive it is. Treatments vary by stage and include surgery, chemotherapy and immunotherapy.
  8. Immunotherapy offers promise. Immunotherapy is a very encouraging approach for treating bladder cancers and other tumors arising from the renal pelvis and ureters. There are a number of different types currently in clinical trials and the FDA just approved a new treatment called atezolizumab (brand name: Tecentriq). Our team recently presented and published our findings on another form of immunotherapy for bladder cancer, an antibody drug conjugate called IMMU-132.
  9. We are dedicated to and on the forefront of bladder cancer research. At Weill Cornell Medicine, we are committed to research in order to improve outcomes for patients with this disease. The newest member of our Genitourinary Oncology team, Dr. Bishoy Faltas, is dedicated to understanding the genetic makeup of bladder cancer. He’s currently focusing on the genomic changes that happen as the tumors become resistant to chemotherapy. We’re also trying to understand why some patients respond well to immunotherapy, while others do not.

FDA Approves New Immunotherapy for Bladder Cancer

Cancer LabFor the first time in more than 20 years, today the FDA granted approval to a new treatment for urothelial carcinoma, the most common form of bladder cancer.

Tecentriq, also known as atezolizumab, is an immune checkpoint blockade or inhibitor that selectively binds to cancer cells based on the presence of PD-L1, a protein on the tumor surface. This is the first PD-L1 inhibitor that has been approved by the FDA for any disease.

PD-L1 is more strongly expressed on certain types of tumors, including urothelial cancers arising from the bladder, renal pelvis, and ureters. PD-L1 prevents the body’s immune system from being able to recognize the cancer and attack it, but PD-L1 inhibitors help the body to “see” the cancer and use the immune system to fight it.

This treatment has shown promise for platinum-resistant metastatic urothelial carcinoma – an advanced cancer that does not respond to traditional chemotherapies and which so far has very few other effective therapies.

In the study that ultimately led to atezolizumab’s approval by the FDA, it was shown to be effective at helping unleash the power of the immune system to recognize and attack these tumor cells.

The patients who responded positively to this treatment can do well on it for a long time. This is sometimes referred to as having a “durable response.” Few side effects were seen with this drug and they were mild. Severe side effects were rare and tied to too much immune activity. These study results first led to the FDA granting atezolizumab priority review designation in March 2016 to put it on the fast track for full FDA approval.

Additionally, in this study the investigators identified a correlation between mutational load and response to the drug. This means that when there was a higher concentration of proteins that could be recognized by the body, there was more sensitivity to this immunotherapy.

At Weill Cornell Medicine, we have been involved in the development of several types of immunotherapy and are at the forefront of developing ways to better determine which patients are most likely to respond to treatment. We are conducting research on how mutations and the “mutational load” can lead to the formation of neoantigens and the impact these neoantigens have on immunotherapy response in order to identify the patients most likely to benefit from this therapy.

We’re very excited to be able to offer Tecentriq/atezolizumab to our patients and encourage you to inquire about whether it’s a good fit for you. Additionally, we continue our research with immunotherapy and monoclonal antibodies for patients with urothelial cancer. One open clinical trial is testing whether a single checkpoint inhibitor (targeted at PD-L1) or dual checkpoint inhibitor (targeted at both PD-L1 and CTLA4 – a protein on the T-cell) is more effective against tumors compared with chemotherapy.

Cancer Alliances: Making an Impact

Beltran_Alliance Meeting 2016_1Dr. Himisha Beltran is a core member of the genitourinary (GU) correlative sciences committee and serves on the GU committee of the Alliance for Clinical Trials in Oncology, one of the five main National Cancer Institute (NCI)-sponsored cooperative groups.

Last year, she was awarded an Alliance Scholar Award in honor of Dr. Emil “Tom” Frei for her proposal to examine molecular data in samples from CALGB 90203. This clinical trial is also known as “PUNCH” = Preoperative Use of Neoadjuvant ChemoHormonal Therapy.

This clinical trial enrolled 788 men with high-risk prostate cancer who were randomized to undergo either surgery alone or in conjunction with 6 cycles of docetaxel chemotherapy and androgen deprivation therapy. Neoadjuvant refers to giving patients chemotherapy or another intervention to first try to shrink a tumor before the main treatment, which in this clinical trial was surgery to remove the prostate. This docetaxel (taxane) chemotherapy combination has demonstrated unprecedented survival advantages when these drugs are used early on in treatment. Large clinical trials, commonly referred to as CHAARTED and STAMPEDE, have shown a much larger improvement in prostate cancer survival using this approach compared with any other treatment that has been studied in the modern era.

We are still awaiting the overall PUNCH clinical trial results based on the main endpoint or outcome (in this study it was the relapse of PSA levels). But, regardless of the results, this study serves as an invaluable resource to analyze biology and mechanisms of response and resistance to chemohormonal therapy because all patients on the study had tissue samples sent for research after prostatectomy.

It is through the commitment of these men and their willingness to further the field of research in the search for a prostate cancer cure that we are able to determine which men had an especially aggressive type of non-androgen receptor (AR) driven prostate cancer. We often refer to this as neuroendocrine prostate cancer or NEPC. We at Weill Cornell Medicine, our Alliance partners and other institutions have already published a wealth of data from men with advanced NEPC. However, some of the molecular changes that make the prostate cancer so aggressive may happen much earlier in the disease spectrum than was previously realized.

At this year’s annual Alliance meeting from May 12-14, Dr. Beltran and collaborators presented on the use of novel technology to analyze gene expression pre- and post-treatment using tissue samples from patients treated on the PUNCH clinical trial.

This technology is called Nanostring and allows us to use a targeted panel of ribonucleic acid (RNA) and get reliable results using samples that have not been processed in any special way (for example, frozen or exposed to specific chemicals). It also allows us to glean insights from tissues that only have a very small amount of tumor left after treatment. In the past this had only been possible using DNA.

DNA and RNA tell us different types of information. DNA offers a biological instruction manual for the body and creates RNA. RNA helps carry out these instructions and creates proteins. The RNA (or transcriptome) is what is actually expressed by genes, so while it is harder to use, it can tell us more information about what is happening at that time. Both DNA and RNA can change after treatment, so the largest amount of information about a specific tumor is gained by combining the information we glean from each of these sources. We can go even deeper in our search for information with additional analyses at the level of the epigenome or metabolome.

In addition to proving that this approach is feasible using very small tissue samples, Dr. Beltran showed that gene expression clustered into different groups based upon AR signaling and neuroendocrine genes. This lends insight into the early development of resistance and offers a window into the mechanisms behind the resistance. Based upon these impressive results, the committee has granted approval to expand the analysis dataset with an additional 100 patient samples and an increased number of genes.

We look forward to continuing to update you on this important research project and keeping you apprised of the results.