Bladder Cancer – From the Basics to State-of-the-Art

One of the many ways Weill Cornell Medicine and NewYork-Presbyterian provide supportive resources to the community is by offering physician-led presentations and Q&A sessions in the Myra Mahon Patient Resource Center.

Two weeks ago, Dr. Scott Tagawa, medical oncologist and Director of the Weill Cornell Medicine Genitourinary (GU) Oncology Program, presented to and educated people in the local community about bladder cancer. His presentation was titled, “Bladder Cancer: From the Basics to State-of-the-Art.” Following the presentation, all attendees were invited to ask Dr. Tagawa questions.

Key topics from Dr. Tagawa’s presentation included the most common risk factors for bladder cancer, different types of bladder cancer (also known as clinical phases), and corresponding treatment options, research, as well as the benefits of utilizing an individualized approach to treatment, also known as precision medicine.

Highlights from Dr. Tagawa’s presentation are outlined below.

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Dr. Tagawa noted that anyone can be diagnosed with bladder cancer, however, factors such as age and exposure to cigarette smoke may increase the risk of bladder cancer from developing. Most people who are diagnosed with bladder cancer are older in age. In fact, the average age at diagnosis is 73. In addition, bladder cancer is twice as common among Caucasians as African Americans.

Clinical Phases of Bladder Cancer and Corresponding Treatment Options

BladderCancer_5Dr. Tagawa highlighted the importance of using a uniform method for developing and testing biomarkers in bladder cancer, a disease with a high incidence of recurrence and expensive clinical surveillance. He also pointed out that most bladder cancers are of a type called transitional cell, affecting the same kinds of cells (transitional cells) that are usually the cancerous cells responsible for renal pelvis, ureter as well as kidney cancers. Dr. Tagawa described the four main phases of bladder cancer.

Pre-Cancer Diagnosis

The first phase is to assess symptoms in high-risk individuals, which defines those who are likely to develop bladder cancer. The most common symptom of bladder cancer is blood in the urine and testing to include assessment for the possibility of cancer would be beneficial for a high-risk population. Risk factors include, those who are aged 65 years or older, have used tobacco and has family history of cancer.

Often, the first test in the assessment of a patient with the symptom of blood in urine (or reddish urine) is a urinalysis, which is a test to assess for the presence of blood versus other elements that may appear like blood in the urine.  Other tests may include the assessment of other urine or blood factors, including assessment for infection. One test that is more specific for bladder cancer is a urine cytology, which looks at the urine under a microscope to detect abnormal appearing cells. If these cells are seen, a cancer diagnosis may be made, as the bladder has “shed” these cells into the urine. However, this test does not detect all cases of bladder cancer. Physicians may also want to perform blood tests or scans including, CT scan, MRI and ultrasounds.

“Superficial” Non-Muscle Invasive Disease

Non-muscle invasive disease means the cancer is confined to the inner lining of the bladder with no evidence that it has spread to another part of the pelvis or other organs. It used to be referred to as “superficial” bladder cancer, but this term is confusing since this stage of cancer often does invade into the first lining of the bladder. This type of bladder cancer comprises about 70% of all cases of newly-diagnosed bladder cancer. These patients are typically managed with resection (surgical removal of the cancerous parts of the bladder using a scope/camera), sometimes followed by intravesical therapy (usually immunotherapy with bacillus calmette-guerin), a process where the physician inserts a liquid drug directly into the bladder through a catheter. The drug can affect the cells lining the bladder without having major effects in other parts of the body.

Muscle Invasive Disease

In patients with muscle invasive disease, the cancer has spread into the muscle wall of the bladder. Those with this type of bladder cancer, which comprise of approximately 40% of all bladder cancer patients, are preferentially treated with systemic neoadjuvant chemotherapy followed by surgery to remove the bladder. Dr. Tagawa explained the different types of surgery patients may undergo if they are diagnosed with muscle invasive disease. The first is transurethral bladder tumor resection (TURBT), in which the surgeon removes the tumor using a tool with a small wire loop. Another form of surgery is a radical cystectomy, the removal of the whole bladder and possibly nearby tissues and organs. In addition, lymph nodes in the pelvis area are removed for both men and women, also known as a pelvic lymph node dissection. A selected subgroup of patients may have similar outcomes with a combination of initial TURBT surgery followed by chemotherapy and radiation.

Metastatic Disease

Patients with metastatic bladder cancer, accounting for approximately 15% of bladder cancer patients, have cancer that has extended through the bladder wall and invaded the pelvic and/or abdominal wall. Dr. Tagawa noted that while the other clinical states are treatable, if someone is going to pass away from bladder cancer, they would most likely be at the metastatic disease state. Dr. Tagawa highlighted that chemotherapy with platinum-based regimens remains the mainstay of first-line treatment for metastatic disease. He explained that if physicians combine platinum-based chemotherapy (e.g. cisplatin) with other treatments, patients will most likely benefit from positive clinical outcomes, resulting in tumor shrinkage and longer overall survival rates.

Systemic immunotherapy (administered into veins as opposed to only instillation in the bladder) is another treatment approach and one in which bladder cancer patients tend to have positive responses. The type of immunotherapy drugs given to patients with bladder cancer are known as immune checkpoint inhibitors, as they “release the brakes” on the immune system and allow immune cells to attack tumors. The first Food and Drug Administration (FDA)- approved immunotherapy drugs is tecentriq, also known as atezolizumab, which is an immune checkpoint inhibitor that selectively binds to cancer cells based on the presence of PD-L1, a protein on the tumor’s surface.  There are now five such drugs approved for bladder cancer – more than for any other cancer type.

Treatment Approaches in the Pipeline

Dr. Tagawa noted that we’ve come a long way in recent years with the most available treatment options than ever before for bladder cancer patients. He emphasized, though, that there is still room for improvement with the development of more treatments and additional treatment combinations to increase survival rates for patients. One of the ways physicians are able to do this is by utilizing precision medicine, treating each patient as an individual based on his or her own genetic makeup. For bladder cancer patients, physicians look at the different genes and whether the genetic mutations are within the tumor, or germline, to determine the best treatment options. Some of the most promising drugs for bladder cancer work best in the presence of certain altered genes. Another way clinicians are able to continue utilizing precision medicine is through clinical trials, which pave the way toward further scientific advances that could potentially find a cure for bladder cancer, in addition to other cancers. Weill Cornell Medicine and NewYork-Presbyterian offer many bladder cancer-specific trials that you can search for here.

Overall, Dr. Tagawa reinforced the benefit of working with a multidisciplinary team, which should include at least a surgeon, radiation oncologist and medical oncologist. He concluded his talk by emphasizing how clinical research has progressed over the years and what it has taught us – “we have seen translational therapy lead to real clinically relevant improvement for patients.”

Watch Dr. Tagawa’s full presentation below.

ASCO 2017: Genitourinary (GU) Oncology Highlights

ASCO Logo PhotoEach year, the American Society of Clinical Oncology (ASCO) Annual Meeting brings together more than 30,000 oncology professionals. At this year’s meeting in Chicago, physicians and scientists presented the latest research findings in an effort to bring the best cancer treatments to patients across the United States and the world. We’ve outlined some of the genitourinary (GU) oncology highlights, broken down by disease type.

At this year’s meeting, there was also some important research presented related to communication, quality of life and survival. In a study that involved patients with GU cancers, as well as those with other types of tumors, patients were randomized to two groups: 1) a control group of standard care 2) a group to utilize a web-based patient-reported outcome questionnaire between visits. Results from any answers completed in the online system were sent to the treatment team in real time. In this study, the patients that were randomized to the online questionnaire group experienced better quality of life. In addition, these patients lived longer, with a 17% improvement in survival simply by using the online tracker reporting symptoms to their treatment team between visits. While the study was only conducted at a single institution, it underscores the importance of communicating and relaying any symptoms to your treatment team members responsible for your medical care (generally physicians, nurses and advanced practitioners).

Prostate Cancer:

The results from two large phase 3 clinical trials will lead to a change in the standard of care treatment for men with advanced prostate cancer. The LATITUDE and STAMPEDE trials investigated the addition of abiraterone and low dose prednisone to standard androgen deprivation therapy (ADT) for men with advanced prostate cancer. Similar to the unprecedented results presented at ASCO in 2014 (CHAARTED) and 2015 (STAMPEDE) with the use of docetaxel chemotherapy, a major improvement in overall survival was demonstrated, improving length of life by nearly 40%. The results from these studies will provide an additional treatment option for men presenting with advanced prostate cancer.

For men with metastatic castration-resistant prostate cancer (mCRPC), a randomized phase 2 trial demonstrated no significant differences in the efficacy, or effectiveness, of abiraterone or enzalutamide, two of the leading treatments for prostate cancer that is resistant to hormonal therapy. This research finding was consistent with most clinicians’ belief that either drug may be utilized, allowing physician and patient choice. Importantly, the study incorporated a number of interesting biomarkers using circulating tumor cell (CTC) DNA from a liquid biopsy, and the data gleaned from the DNA revealed prognostic insights about disease aggressiveness and biology. Another study showed a lack of utility to continue enzalutamide after disease progression, confirming the current practice of switching treatments after cancer growth.

Interesting data using the PARP inhibitor veliparib was presented. In a randomized phase 2 trial, the combination of veliparib and abiraterone was not better than abiraterone alone overall, but for tumors with DNA damage repair defects, there was a difference. This adds to the anticipation of results from the many ongoing randomized trials that are testing PARP inhibitors in molecularly selected patients.

Additional data was presented on genomic signatures from prostate tissue, which in combination with clinical data, are more powerful in indicating prognosis in men who receive treatment for clinically localized (low stage / early) prostate cancer.

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Dr. Himisha Beltran

Prostate cancer acquires resistance to systemic treatment as a result of tumor evolution and selection, but repeat biopsies to study how cancers evolve are challenging, invasive, and may be confounded by tumor heterogeneity. Dr. Himisha Beltran evaluated a non-invasive approach: whole exome sequencing of circulating tumor DNA in the blood. Additional data utilizing circulating tumor cell (CTC) counts as an early indicator of response may speed drug development. Clinical trials are currently evaluating measuring circulating tumor cell counts as a biomarker for whether or not treatments are working. This may be a better indicator than measuring levels of prostate specific antigen (PSA), the current indicator for response.

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Dr. Scott Tagawa presents an update on the 177Lu-PSMA-617 clinical trial for men with metastatic prostate cancer.

Dr. Scott Tagawa presented a trial-in-progress update about the clinical trial he is leading at Weill Cornell Medicine and NewYork-Presbyterian utilizing the small molecule lutetium 177Lu-PSMA-617 to target prostate-specific membrane antigen (PSMA). PSMA is a protein abundantly expressed in 85-90 percent of metastatic prostate cancer cells, and this is the first U.S. trial of its kind. Learn more about this radionuclide therapy-based clinical trial and the eligibility criteria.

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Dr. Loredana Puca

Additionally, there were many research updates presented in the area of neuroendocrine prostate cancer (NEPC), an aggressive subtype of prostate cancer that is resistant to many traditional treatment types. Dr. Loredana Puca received a Merit Award from the Conquer Cancer Foundation for her research examining the potential use of antibody-drug conjugate rovalpituzumab tesirine for treatment of NEPC. View the abstract and learn more about our open clinical trial using this antibody-drug conjugate. Dr. Himisha Beltran highlighted the significance of the loss of tumor suppressor ZFP36 in prostate cancer patients.

Prostate cancer was the first tumor type to have a cancer vaccine (sipuleucel-T) lead to longer survival, but the drug’s activity may be limited on its own. In a randomized phase 2 trial, receiving sipuleucel-T in combination with indoximod – a drug with the potential to improve immune response – kept the cancer at bay more than twice as long compared to those who received sipuleucel-T plus a placebo. This was an exciting research update showing promise for patients with prostate cancer.

New research using tumor and liquid (blood-based) biopsies demonstrated that a majority of tumors and circulating tumor cells in men with metastatic castration-resistant prostate cancer express a protein called Trop-2, justifying a targeted treatment approach. With this knowledge, we are now evaluating the safety and efficacy of IMMU-132, an immunotherapy-based drug that targets Trop-2, in an open clinical trial for men with prostate cancer.

Bladder Cancer and Other Urothelial Cancers:

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Dr. Bishoy Faltas presents on “Unlocking the Genome: Insights Into Risk and Response in Bladder Cancer” at the ASCO 2017 Clinical Science Symposium.

Dr. Bishoy Faltas was invited to present at the ASCO Clinical Science Symposium entitled “Expanding the Actionable Landscape: Bladder Cancer Genomics — Unlocking the Genome: Insights Into Risk and Response in Bladder Cancer.”

During this session, Dr. Faltas discussed the genomics of urothelial cancer, and highlighted the latest research describing new data on the frequency of inherited (germline) mutations as well as tumor (somatic) genomics and relationship to response to chemotherapy and immunotherapy. Patients with “upper tract” urothelial cancer (tumors arising in the kidney or ureter) in particular have a higher chance of harboring an inherited mutation. Different genomic alterations in the tumors may be separated into groups that are associated with better responses to chemotherapy and immunotherapy. This is becoming more clinically relevant as we can test for these genes and the number of treatment options is expanding.

Additionally, updated results of the KEYNOTE-045 study confirmed the overall survival benefit of the anti-PD1 immune checkpoint inhibitor pembrolizumab (Keytruda) compared to second-line chemotherapy in patients with prior platinum-based chemotherapy. Importantly, this was the first head-to-head trial to demonstrate the superiority of immunotherapy over chemotherapy in urothelial cancer.

Dr. Scott Tagawa contributed to the investigation of a novel oral targeted chemotherapeutic agent called RX-3117 in advanced bladder cancer patients. Learn more about our open clinical trial with RX-3117.

Kidney Cancer (Renal Cell Carcinoma):

Several different combination studies for the treatment of advanced renal cell carcinoma (RCC) were presented at the 2017 ASCO Annual Meeting. While some studies demonstrated promising response data, significant toxicity of some combinations underscored the importance of clinical trials and the recommendation to avoid combinations outside of the research setting, which is regulated and in which these types of side effects can be monitored. Several randomized phase III trials testing combination therapy are ongoing with results anticipated to lead to changes in standard of care.

Unfortunately, despite imaging that indicates no evidence of cancer metastases (spread), many patients are not cured with surgery alone. Treatment of many cancers incorporate the use of systemic (medical) therapy in addition to surgery to increase cure rates. For the most part, this strategy has not been overwhelmingly successful in the setting of renal cell carcinoma (RCC). Unfortunately, another “negative” phase III trial showed that the addition of pazopanib (Votrient) to surgery did not improve cure rates for patients with RCC. Additional data was presented utilizing either clinical or genomic biomarkers that may assist physicians in choosing patients that might benefit from the addition of the oral drugs following surgery. We continue to await the results of additional completed studies and some currently enrolling studies utilizing immunotherapy before/after surgery.

AACR 2017

AACR 2017April brings more than just showers – the month kicks off with a very important cancer research conference. Tomorrow we are headed to Washington, DC for the American Association for Cancer Research (AACR) annual meeting held April 1-5, 2017.

Our team will be joining approximately 20,000 cancer researchers from across the country and around the world for this important meeting. Several physicians and scientists from Weill Cornell Medicine, NewYork-Presbyterian, and the Meyer Cancer Center again served on the scientific program committee, including our own Dr. Scott Tagawa.

We’re also proud that Dr. Bishoy Faltas was selected as an AACR NextGen Star, a competitive award that supports professional development and advancement for scientists who are early in their career. Dr. Faltas will be presenting important updates related to bladder cancer, and his NextGen Star talk will take place on Wednesday, April 5, and is titled Genomic dissection of the clonal evolution dynamics of chemotherapy-resistant urothelial carcinoma.

We have a lot to share at AACR 2017, so please check back frequently as we’ll be updating the blog regularly throughout the week.

Here are some additional highlights of what’s to come:

  • Updates regarding circulating tumor cells (CTCs) and the role of biomarkers in non-invasive diagnostics and treatments
  • How organoids may help us better treat neuroendocrine prostate cancer (NEPC)
  • The different types of radiation used to treat prostate cancer and how we’re targeting PSMA – a marker on the surface of most prostate cancer cells – with radioimmunotherapy to kill cancer cells
  • The latest updates in bladder cancer research, including updates in genomics and targeting molecular pathways