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Memorial Sloan Kettering Bladder Cancer

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Prof Jonathan Rosenberg speaks to ecancer in an online interview for ASCO GU 2022 about the BAYOU trial: A phase II, randomised, multicentre, double-blind study of durvalumab in combination with olaparib for first-line treatment of platinum ineligible patients with unresectable, stage IV urothelial carcinoma.He begins by giving some background to the study, explaining that these patients generally have a poor prognosis and elaborating on the rationale for the trail. He goes on to describe the methods used in the study.Prof Rosenberg concludes by saying that while this trial did not meet its primary endpoint, there may still be a role for combination therapies using olaparib or other PARP inhibitors in treating urothelial cancer in select patient populations.

Squamous Cell Carcinoma Of The Bladder

Squamous cell carcinoma is the second most common type of bladder cancer. It accounts for about 5 percent of bladder cancers in North America and Europe. This cancer begins in the thin, flat squamous cells that may form in the bladder after chronic inflammation and infection. Squamous cell carcinoma is most often found in parts of the world where a parasitic infection called schistosomiasis is widespread, such as the Middle East.

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Immunotherapy After Bladder Cancer Surgery May Reduce Recurrence Study Shows

New research found that using nivolumab reduced bladder cancer recurrence after surgery compared to patients who received placebo

Newswise NEW YORK CITY, June 2, 2021 New research from Memorial Sloan Kettering Cancer Center medical oncologist Dean Bajorin, MD, and colleagues found that patients who received nivolumab after bladder cancer surgery reduced their overall risk for high-grade bladder cancer recurrence. This research was published today in the New England Journal of Medicine.

In this phase III randomized study, Dr. Bajorin and a team of investigators evaluated 709 patients who were at high risk for recurrence of urothelial cancer after removal of their bladder, ureter, or kidney for high-grade cancer. To evaluate for benefit, patients were randomized to receive either nivolumab or a placebo every two weeks for one year. Patients and physicians were blinded to the treatment. Both safety and quality of life were evaluated.

We are very encouraged by the data and the results of the study, said Dr. Bajorin, first and corresponding author of the study. Despite available therapies for advanced metastatic bladder cancer, new options are needed to improve long-term disease control and patient survival. These findings have the potential to change the standard of care for bladder cancer.

Making Pioneering Advances for Bladder Cancer Patients

This trial was sponsored by Bristol Myers Squibb, Checkmate 274.

What Are The Risk Factors For Bladder Cancer

Radiation Therapy for Bladder Cancer

Tobacco use is by far the biggest risk factor for developing bladder cancer. People who smoke cigarettes are up to four times more likely than nonsmokers to develop the disease. Studies have shown that smoking is responsible for approximately 50 percent of bladder cancers.

People who work in the textile, dye, rubber, leather, paint, or printing industries may also be at an increased risk of bladder cancer.

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Small Cell Carcinoma Of The Bladder

This aggressive form of the disease begins in small nerve-like cells in the bladder called neuroendocrine cells. Small cell carcinoma makes up about 1 percent of bladder cancers. It is often detected at an advanced stage, after it has spread to other parts of the body. It usually requires a combination of treatments, including chemotherapy, surgery, and radiation therapy.

Ial Cystectomy After Neoadjuvant Chemotherapy: Memorial Sloan Kettering Cancer Center Contemporary Experience

Harry W. Herr

1 The Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA

Abstract

1. Introduction

In 2014, it is estimated that there are 608,620 bladder cancer survivors living in the United States, and an additional 74,690 cases will be diagnosed . Neoadjuvant chemotherapy followed by radical cystectomy is now considered the standard of care for muscle-invasive bladder cancer after numerous trials demonstrated a survival benefit, most notably in patients with advanced pathologic stage disease .

For highly selected patients, bladder-sparing surgery such as transurethral resection of bladder tumor or partial cystectomy may provide similar oncologic outcomes to RC while maintaining bladder and sexual functions. Of the two bladder-sparing options, PC has advantages over TURBT as a third of patients are understaged with TURBT and PC allows for full thickness examination of the bladder wall and concurrent lymphadenectomy resulting in more accurate staging and prognosis .

We herein report our contemporary experience with a highly select cohort of patients who received neoadjuvant chemotherapy followed by PC performed for curative intent at a single tertiary institution.

2. Patients and Methods

2.1. Study Population
2.2. Variables and Outcomes
2.3. Statistical Analysis

3. Results

Number of patients

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Moving From The Lab To The Clinic

Dr. Glickmans laboratory is now collaborating with urologic surgeon Bernard H. Bochner to explore the clinical implications of this discovery particularly, whether analyzing a patients bladder cancer cells can reliably predict his or her responsiveness to BCG therapy.

With the support of a grant from The Society of MSKCC, Dr. Redelman-Sidi is trying to develop a lab test that would analyze urine samples, which usually contain cancer cells shed from the bladder. These cells could be tested both for their tendency to take up BCG and also for the presence of BCG-activating, cancer-causing mutations.

This would allow us to screen early-stage patients routinely before starting BCG therapy to make sure its the best course of treatment, Dr. Glickman says.

Why Should I Choose Memorial Sloan Kettering For Bladder Cancer Treatment

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Memorial Sloan Ketterings team of bladder cancer experts delivers the highest quality compassionate cancer care. We take into account each individuals needs and develop a personalized treatment plan.

At MSK, we offer:

  • A multidisciplinary team of experts that is among the most experienced in the field. The team includes world-class specialists in surgery, chemotherapy, radiology, pathology, and nursing.
  • Close collaboration among these experts. Our team meets regularly to discuss each of the people we care for. We draw on our vast experience to determine the best course of treatment. For example, our surgeons and oncologists work closely together to ensure that people who need chemotherapy before surgery begin this treatment as soon as possible. Starting care right away has been shown to produce better outcomes for our patients.
  • Skilled and specialized surgeons. Our surgeons use a variety of advanced approaches to remove bladder tumors. We take every measure to preserve urinary and sexual function. For many people with early-stage bladder cancer, we can successfully treat the disease with minimally invasive procedures, including robot-assisted surgery.

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Resuming An Active Life

Three and a half years later, Burt feels completely back to normal. Although he is now largely retired emeritus from the medical staffs at Washington University and Mercy Hospital in St. Louis he continues to be active. I think Im physically in better shape now than before I had cancer, he says. He comes to MSK twice a year for scans to make sure the cancer hasnt returned.

Burts case has also contributed to scientific knowledge about plasmacytoid variant carcinoma, as Drs. Bochner and Bajorin and their MSK colleagues continue to research this disease. In 2016, they published findings on the genetics of this cancer type and identified a gene called CDH1that plays a central role in triggering the runaway invasion of tumor cells. Burts tumor was one of those analyzed in the study.

Burt wants others who are diagnosed with bladder cancer to be mindful that its now a very treatable disease. An array of therapies have emerged recently.

I think the most important thing for a patient is to be seen at a center that specializes in this cancer, he says. There has been an explosion of complex information, with genomic studies, treatment refinements, and surgical options. It all needs to be incorporated by an expert team. It takes a place like MSK to make it work in the best way possible.

Imaging Of The Urinary Tract

Various imaging tests can be used to examine the urinary tract. These may include:

  • CT scans, which obtain cross-sectional pictures of the body and can help doctorsdetermine if the cancer cells are only in the bladder or if they have spread to other areas
  • MRI, which can help doctors see if the cancer has invaded the muscle in the bladder wall and, if so, how deeply
  • PET scans, which take images that help doctors tell apart active and dormant tissue to help determine whether its normal or cancerous

These imaging tests often involve contrast dye that is injected into your hand or arm. The dye flows into your bladder to identify areas that might be cancerous.

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A Breakthrough In Bladder Cancer

Excitingly, many of these patients are similarly responsive to the same therapy that was so effective in the outlier patient, MSK clinician-scientist David Solit, who directs the Marie-Josée and Henry R. Kravis Center for Molecular Oncology , noted in a recent interview on this blog. The approach has enabled us to resurrect therapies whose development was previously halted.

In 2012, Dr. Solit and his co-workers published a groundbreaking study of a patient with advanced bladder cancer who participated in a clinical trial of a drug called everolimus and responded surprisingly well. The researchers decided to survey this patients disease in depth by sequencing the entire genome of her tumor. An examination of other patients on the trial showed that only those with TSC1 mutations in their tumors benefited from the drug.

Cancer genomics researchers Michael Berger and David Solit. Dr. Berger led the development of a tumor sequencing test that is used to guide treatment choices and identify patients who are candidates for basket trials.

Symptoms Of Bladder Cancer

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Blood in the urine is the main symptom of bladder cancer. You may also feel a need to urinate more often or experience pain when urinating. Other problems, such as urinary tract infections, can cause these symptoms. If you experience any of these symptoms, speak to your urologist or primary care provider as soon as possible.

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Bladder Cancer Doctors Surgeons And Experts

As a Memorial Sloan Kettering patient, you benefit from the experience and compassion of a team that treats nearly 400 people with bladder cancer each year. Were committed to getting you the best outcome possible. We maintain our relationship with you after you complete treatment, so you get the follow-up care you need not just to survive but to thrive.

Working as a team, our bladder cancer specialists in urology, medical oncology, urologic surgery, radiation oncology, pathology, and radiology will shape the best treatment approach for you.

Select from the list below to learn more about how our bladder cancer experts can help you.

What Are The Symptoms Of Bladder Cancer

In most cases, the first sign of bladder cancer is blood in the urine. Other symptoms may include feeling pain or burning during urination or a change in urination habits. This can include frequent urination or a need to go but being unable to pass urine. More-advanced bladder cancer may involve lower back pain on one side, feeling tired or weak, or having no appetite and losing weight. All of these symptoms may be caused by something other than bladder cancer, but its important to have them checked out.

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What Is Bladder Cancer

Bladder cancer is a disease that usually begins in the cells that line the inside of the bladder. It typically affects people older than 70 and occurs more often in men. Bladder cancer is the fifth most common form of cancer overall and the fourth most common among men.

Bladder cancer usually responds well to treatment when diagnosed early. However, people who have been successfully treated for bladder cancer should be monitored afterward. Bladder cancer can return even years later.

Inherited Germline Cancer Susceptibility Gene Variants In Individuals With Nonmuscle

Bladder Cancer Symptoms

*Corresponding Author:

Current address for T. Clinton: Division of Urology, Department of Surgery, Brigham and Women’s Hospital and Dana-Farber Cancer Center, Boston, Massachusetts current address for N. Almassi: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio and current address for L. Zhang: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.

Corresponding Author:

Clin Cancer Res 2022 XX:XXXX

Clin Cancer Res

  • Accepted Manuscript July 14 2022
  • Eugene J. Pietzak, Karissa Whiting, Preethi Srinivasan, Chaitanya Bandlamudi, Aliya Khurram, Vijai Joseph, Aleksandra Walasek, Emily Bochner, Timothy Clinton, Nima Almassi, Hong Truong, Manuel R. de Jesus Escano, Michal Wiseman, Diana Mandelker, Yelena Kemel, Liying Zhang, Michael F. Walsh, Karen A. Cadoo, Jonathan A. Coleman, Hikmat Al-Ahmadie, Jonathan E. Rosenberg, Gopakumar V. Iyer, David B. Solit, Irina Ostrovnaya, Kenneth Offit, Mark E. Robson, Zsofia K. Stadler, Michael F. Berger, Dean F. Bajorin, Maria Carlo, Bernard H. Bochner Inherited Germline Cancer Susceptibility Gene Variants in Individuals with NonMuscle-Invasive Bladder Cancer. Clin Cancer Res 2022

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    Genetic Analysis Of Bladder Tumors

    For people with advanced bladder cancer that has spread, we use a test called MSK-IMPACT. It can look for genetic mutations and other changes in a tumor. This test provides essential information that can guide treatment choices and, in some cases, identify candidates for a clinical trial. It can also spare people from treatments that are not likely to be effective. MSK-IMPACT was developed by MSK pathologists and researchers. It has been used to analyze the tumors of MSK patients with advanced cancer since January 2014. It was authorized by the Food and Drug Administration in November 2017.

    Mutations Open The Door

    An important insight into what makes the entry of BCG into cells possible arose from a collaboration between the Glickman lab and Memorial Sloan Kettering cell biologist Xuejun Jiang. In June 2012, this team reported in the Journal of Biological Chemistry that cancer cells with mutations in the gene PTEN are highly susceptible to mycobacterial infection. The PTEN protein normally acts as a tumor suppressor impaired PTEN function appears to increase a cells vulnerability to becoming cancerous and also to mycobacterial infection.

    To investigate whether this correlation holds true in bladder cancer cells, Drs. Redelman-Sidi, Glickman, and colleagues treated six distinct cell lines groups of genetically identical cells developed from a single cell with BCG and measured the degree to which the BCG bacterium was taken up by the cells.

    They discovered that the cell lines that most readily took up BCG contained one of several cancer-causing mutations, including mutations in PTEN, known to be involved in the onset of bladder cancer. The cell lines resistant to BCG did not have these particular mutations, but they could be converted to BCG-receptive cells if the mutations were induced. Moreover, these converted cells readily took up BCG via a pathway different from the one BCG usually employs to enter immune cells.

    These mutations activate a mechanism in the bladder cancer cells that allows BCG to enter and destroy them, Dr. Glickman says.

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    Transurethral Resection And Bladder Preservation

    Transurethral resection is the most common type of surgery for bladder cancer. It is used to treat early-stage bladder cancer that has not grown into the muscle. The surgeon inserts a cystoscope through the urethra and into the bladder to remove any tumors. The tumors are then sent to a lab to be examined by a pathologist. The pathologist can help determine whether additional treatment may be needed. After the procedure, you can usually return home the same day or the next day.

    TUR alone may be able to eliminate bladder cancer that has not grown into the muscle. However, we may recommend additional treatments to lower the risk of the cancer returning. These may include bacillus Calmette-Guérin therapy or intravesical chemotherapy.

    Cystectomy Neobladder And Urinary Diversion

    Diagnosing and Treating Bladder Cancer

    A cystectomy is surgery to remove the bladder. This procedure is used to treat bladder cancer that has grown into the muscle. A partial cystectomy removes only a portion of the bladder. A radical cystectomy removes the entire bladder as well as nearby lymph nodes and organs that may contain cancer.

    During a partial or radical cystectomy, the surgeon may be able to create a new bladder, called a neobladder. It is built from part of the small intestine. If a neobladder is not possible, the surgeon may divert urine through part of the small intestine to an opening on the outside of the abdomen. This is called a stoma.

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    Preoperative Irradiation And Cystectomy For Bladder Cancer

    Corresponding Author

    Dr. Joseph A. Smith Jr. MD

    Urologic Service, Department of Surgery, and the Department of Radiation Therapy, Memorial Sloan-Kettering Cancer Center, New York, New York

    Mostafa Batata MD

    Urologic Service, Department of Surgery, and the Department of Radiation Therapy, Memorial Sloan-Kettering Cancer Center, New York, New York

    Harry Grabstald MD

    Urologic Service, Department of Surgery, and the Department of Radiation Therapy, Memorial Sloan-Kettering Cancer Center, New York, New York

    Pramod C. Sogani MD

    Urologic Service, Department of Surgery, and the Department of Radiation Therapy, Memorial Sloan-Kettering Cancer Center, New York, New York

    Harry Herr MD

    Urologic Service, Department of Surgery, and the Department of Radiation Therapy, Memorial Sloan-Kettering Cancer Center, New York, New York

    Willet F. Whitmore Jr. MD

    Urologic Service, Department of Surgery, and the Department of Radiation Therapy, Memorial Sloan-Kettering Cancer Center, New York, New York

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