Tag: News

Prevalence and Clinical Outcomes of Advanced Prostate Cancer Patients with Inherited DNA-Repair Mutations

DNA Helix_NCICollaborative work has shown that approximately 12% of men with advanced prostate cancer have inherited, or germline, DNA-repair mutations that disrupt the normal function of the genes involved in repairing damaged DNA. Somatic alterations in DNA-repair pathways are also common in prostate cancer, particularly in late-stage disease. Somatic alterations affect only tumor cells, but are not inherited or passed on. Inherited mutations in DNA-repair genes – such as BRCA2, ATM, and CHEK2 – are associated with an increased risk of several other cancers as well as prostate cancer, including breast, ovarian, and pancreatic cancer. In particular, mutations in BRCA2, associated with 1.8% of overall prostate cancer cases, have been associated with more aggressive prostate cancer characteristics and worse outcomes, including increased risk of recurrence and poorer overall survival rates.

As a result of the increasing number of men with these types of mutations, the National Comprehensive Cancer Network (NCCN) guidelines have recently changed, now recommending genetic testing for all men with metastatic prostate cancer.

Weill Cornell Medicine

“Genetic testing for inherited mutations may provide some men with prognostic information about their prostate cancer risk,” says Dr. Scott Tagawa, Director of the Weill Cornell Medicine and NewYork-Presbyterian Genitourinary (GU) Oncology Program. “Even more importantly, genetic testing can also be used to inform screening of family members and may increasingly inform precision-medicine based approaches to manage the disease using specific molecular features such as DNA-repair genes,” says Dr. Tagawa.

How do Inherited Mutations Impact Treatment?

Clinical research studies are continually being conducted to investigate new ways to treat advanced prostate cancer patients with germline DNA-repair mutations since these patients comprise a unique subset of patients. Currently, little has been known about whether DNA-repair mutation status impacts benefit from standard therapies for the disease and this is just one area that needs to be researched in order to specifically tailor treatment options for this subset of patients.

Weill Cornell Medicine and NewYork-Presbyterian’s Drs. Himisha Beltran, Scott Tagawa and David Nanus, along with collaborators from around the globe, address this in research published today in the high impact factor journal European Urology and simultaneously presented at the American Society of Oncology (ASCO) 2018 Genitourinary (GU) Cancers Symposium by Dr. Misha Beltran. The researchers reviewed 390 medical records of patients who previously participated in a New England Journal of Medicine (NEJM) study examining men with advanced prostate cancer with known germline DNA-repair mutations and those without these mutations. The goal of the research was to determine whether germline mutations in DNA-repair genes impact the benefit of standard therapies for metastatic prostate cancer, such as docetaxel chemotherapy and androgen receptor signaling inhibitors abiraterone acetate and enzalutamide. Results showed that all patients appeared to benefit from standard therapies similarly to other metastatic prostate cancer patients, regardless of germline mutation status.

“The data suggest that metastatic prostate cancer patients with inherited mutations in DNA damage repair genes, including those with BRCA2 mutation, derive similar benefit from standard of care therapies in terms of both response rate and progression-free survival,” says Dr. Scott Tagawa. “While we continue to investigate additional agents thought to preferentially benefit those with DNA repair alterations, current evidence indicates that detection of any of these mutations should not prevent metastatic prostate cancer patients from receiving standard therapies including taxanes, abiraterone and enzalutamide, as standard of care treatment.”

Additionally, sophisticated genetic analysis and testing may be performed by genetic counselors and widely-available commercial testing is also available to physicians and patients. Dr. Panagiotis Vlachostergios, fellow and medical oncologist at Weill Cornell Medicine and NewYork-Presbyterian, presented research at ASCO Genitourinary (GU) Cancers Symposium focused on using a commercial 30-gene panel to test men with localized prostate cancer and advanced prostate cancer for the presence of inherited gene mutations. Out of the 17 men with localized disease and 35 men with metastatic prostate cancer, eight of 52 (15%) were found to have a germline alteration. A higher percentage of men with an inherited mutation had localized (23.5%) versus advanced disease (11.4%), though testing might have been biased towards those with family history of cancer or those diagnosed with high-grade cancer at earlier age.

Both the results published in European Urology and research presented at the 2018 ASCO GU Cancer Symposium underscore the importance of genetic testing to determine what, if any, mutations may be present in prostate cancer in order to determine the best possible treatment options. While the published data supports the use of standard therapies in those with metastatic prostate cancer who have germline DNA-repair mutations, not all patients respond to these types of treatment, demonstrating the need for alternate treatment options for this patient population. Weill Cornell Medicine and NewYork-Presbyterian are in the process of opening several clinical trials to include men with prostate cancer in need of different lines of therapy. Clinical trials testing PARP inhibitors, a drug target for cancer therapy that appears to be more effective in prostate cancer patients with DNA-repair mutations, are ongoing and may offer additional therapy options for this group of patients in the near future.

Benefits of Surgery in Older Adults with Metastatic Urothelial Carcinoma Evaluated Using Largest Dataset of its Kind

Bladder_FBUrothelial carcinoma is the most common type of bladder cancer, also affecting other parts of the urinary system. It is an aggressive disease and its treatment remains challenging for clinicians. Currently, each year there are nearly 80,000 new cases of urothelial cancer and approximately 16,000 deaths from the disease, according to the American Cancer Society. Unfortunately, there are limited therapeutic options for those with advanced urothelial carcinoma especially after the disease spreads to other distant organs (metastasis). Even with platinum-based chemotherapy and the introduction of immunotherapy, median overall survival is poor, and a five-year survival is only 15%.

The idea of metastasectomy (surgical removal of metastatic tumors) has been proven to be an established option in the treatment of patients with other solid tumors, however, little is known regarding the benefit and safety of this type of surgery for urothelial carcinoma patients because previous studies were mostly from single institutions and limited by small sample size.

Drs. Bishoy Faltas, Scott Tagawa, Jim Hu, along with others at Weill Cornell Medicine and NewYork-Presbyterian Hospital, partnered with the Center for Health Policy and Outcomes and Memorial Sloan Kettering Cancer Center to address this very question and their research has now been published in Urologic Oncology: Seminars and Original Investigations. Their goal was to examine the use and outcomes of surgery in older patients with urothelial carcinoma in a large population-based dataset. To do this, clinicians conducted a SEER-Medicare study. SEER is a database run by the National Institutes of Health (NIH) that collects large population-based data that provide detailed information about Medicare beneficiaries with cancer. The research was analyzed based on the billing codes the physician’s offices used when submitting insurance claims.

Using this data, clinicians found 70,648 urothelial carcinoma patients and from those, they identified 497 patients who had at least one surgery to remove a metastatic lesion during a median follow-up of 40 months. The median overall survival after the first surgery was 19 months. In this selected patient population, over a third of patients were alive at three years. The median length of stay after surgery was seven days with 10% of patients having at least one complication within 30 days of discharge.

Close-up of gloved hands passing the surgical scissors“It would be very difficult to conduct a randomized clinical trial testing surgery versus no surgery in those with urothelial carcinoma, so reviewing a large dataset retroactively is the next best thing,” says Dr. Bishoy Faltas, Assistant Professor and medical oncologist at Weill Cornell Medicine’s Genitourinary Oncology Program. “Our study shows that in well-selected patients with urothelial carcinoma with a reasonable life expectancy, resection of metastatic lesions is safe and associated with long-term survival and potential cures,” says Dr. Faltas.

What are Other Benefits of Surgery?

Aside from the fact that surgery can prolong life for those with urothelial carcinoma, there are other benefits as well. One of the benefits is enabling the testing of tissue that is removed. Studying this tissue allows clinicians to continue performing precision medicine and treating the individual, not the disease. As described in a previous research study conducted by Dr. Bishoy Faltas titled, “Clonal Evolution of Chemotherapy-Resistant Urothelial Carcinoma” published in Nature Genetics, it has been proven that tumors change and undergo clonal evolution over time especially in metastases after chemotherapy.

“Understanding the evolution of urothelial carcinoma is a central biological question and one that we can only truly begin to understand by testing tissue samples from patients at various periods throughout their treatment,” says Dr. Faltas.

Another potential benefit of surgery is the cost implication. With drug prices continuing to rise, depending on insurance carriers, there is the potential that surgery may be less costly than some of the long-term medications associated with treatment for urothelial cancer. Cost implications of course vary for each patient; however, it is one of the factors along with many others that should be addressed and discussed with healthcare teams.

“There is a lot more work to be done to help treat patients with urothelial cancer, however with the dataset we’ve compiled through our latest study, we’re able to glean the potential benefits of metastasectomy in older adults with urothelial cancer, which could lead to prolonged life and potential cures.”

Movember 2017 is Here!

For nearly 10 years, we have been proud to participate in a month-long campaign to raise awareness and funds for men’s health each November, also known as Movember.

The campaign dates back to 2003 when two friends in Australia tried to bring back the moustache trend by growing out moustaches (or “mo’s” as they are commonly called in Australia) during the month of November. The following year, after realizing that this facial hair served as a conversation-starter, they decided to channel that energy to raise money for prostate cancer research.

Awareness (and mustaches) have grown over the years, and in 2007, Movember officially launched a global campaign to change the face of men’s health – literally and figuratively through increased awareness and funds. Another way people can get involved is by “moving” and setting a walking, running, biking or swimming goal and working to achieve it every day throughout Movember. Today, over 5 million people from more than 20 countries have collectively raised over $700 million dollars. The Movember Foundation uses this money to fund research around the world to reduce the number of men dying from prostate and testicular cancer, as well as mental health issues. Movember is committed to funding research that will reduce the number of deaths from prostate and testicular cancer by 50% by 2030.

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From L to R: Dr. Scott Tagawa, last year’s Movember Captain, Dr. Daniel Margolis, this year’s Movember captain

We’ve been proud Movember partners for nearly 10 years now and have benefitted from many Movember research grants to further our cancer research, most recently being named one of six teams to receive a 2017 Challenge Award from the Prostate Cancer Foundation (PCF) and the Movember Foundation to investigate new, cutting-edge treatments for metastatic prostate cancer.

This 2017 Movember-PCF Challenge Grant has funded our latest research developing new treatments for treatment-resistant advanced prostate cancer. More details on the grant and research it supports can be found here.
In past years, Movember-funded grants have supported our research in the following areas:

  • Blood tests that assess the tumor’s circulating DNA to predict reasons for treatment resistance.
  • Circulating tumor cell (CTC) tests to predict which patients are more or less likely to respond to hormonal therapy or chemotherapy.
  • Assessing the genome of initial tumors in the prostate compared to advanced, treatment resistant tumors.
  • Evaluating inflammation in adipose (fat) tissue around the prostate, which is associated with tumor growth.

Throughout the month of November, staff and physicians at Weill Cornell Medicine and NewYork-Presbyterian will be growing mustaches, exercising and raising funds for the Movember Foundation in support of our shared mission to cure cancer.

Get Involved!

  • Join our team by visiting https://moteam.co/wild-weill-cornell-mos
  • Grow a moustache and commit to going razor-free. It’s a great conversation starter to encourage friends and family members to donate to Movember.
  • Spin for a cure! Kill two birds with one stone. Get your workout in and support the Wild Weill Cornell Mos. Attend our cycling events on November 16th and 18th, with proceeds benefiting our team’s Movember fundraising goal.
  • Shave the date and celebrate the end of Movember by attending a happy hour. Stay tuned for final details including date and location.

Last year, we raised $13,000. We want to top that this year by raising $20K or more. Help us get there and remember that every dollar counts in the quest to cure cancer!