The Genitourinary (GU) Oncology Program at Weill Cornell Medicine is dedicated to providing cutting-edge care for every stage and type of prostate, kidney, bladder and testicular cancer. Read the blog to find articles on prostate cancer.
Radiotherapy is a core element of prostate cancer treatment, yielding cures in men with localized disease. The goal of prostate cancer radiotherapy is to deliver high doses of radiation to the prostate gland while avoiding the surrounding bladder and rectum, thus preventing unwanted urinary and gastrointestinal side effects and preserving patient quality of life.
Radiotherapy guided by magnetic resonance imaging (MRI) allows clinicians to visualize a tumor as well as its neighboring organs in order to most accurately deliver treatment to the target region.
Weill Cornell Medicine and NewYork-Presbyterian Hospital (WCM/NYP) are proud to be the first – and only – medical institution in the northeast to offer patients the most premier MRI-guided radiotherapy technology available: the MRIdian Linear Accelerator, by ViewRay. The MRIdian Linac’s unique ability to track a patient’s tumor in real time during treatment makes it by far the most advanced modality of delivering radiation.
Real-time visualization is significant due to the constant flux of internal human anatomy, including changes in respiration, digestion and bladder fill that can influence the position of the prostate within the body. Even a minor shift of the tumor target during treatment can have major implications related to potential side effects of radiation. If the bladder or rectum displace the prostate during treatment, the MRIdian Linac machine will cease delivery of radiation and not resume until the prostate moves back in bounds of the target region. Whereas other modalities track small fiducial markers implanted in the prostate, this machine allows clinicians to see and track the tumor itself.
In addition, WCM/NYP is the only center in the area to offer combined use of MRI-guided radiotherapy with the rectal SpaceOAR, a hydrogel barrier that is temporarily placed between the prostate and rectum to shield the rectum from radiation and further reduce potential side effects.
Watch the video below to learn more about this state-of-the-art technology from WCM/NYP radiation oncologist Dr. Himanshu Nagar.
Premier MRI-Guided Radiotherapy Technology Enables Real-Time Tumor Tracking - YouTube
Our team is at the forefront of utilizing prostate-specific membrane antigen (PSMA)-targeted therapies in the treatment of prostate cancer.
PSMA is a protein on the surface of prostate cancer cells that enables a targeted approach to locate and image or treat these cells wherever they are in the body, even those that have escaped (metastasized) to other organs. We are able to target PSMA using different types of drugs, including small molecules and antibodies.
From delivering exceptional care in the clinic, to presenting at scientific conferences and publishing research in high-impact medical journals, our Genitourinary (GU) Oncology Program had an exceptionally busy 2018. We continue to work diligently to develop new and more effective therapies to treat advanced prostate, bladder and kidney cancers, while educating the community about cutting-edge advancements in the field.
As we look back on 2018, we wish to share a brief update of our research and accomplishments. Here’s what our team has been up to over the past year.
New Faces Most recently, we were proud to welcome Dr. Cora Sternberg, a global thought-leader in the GU oncology space, to our team. Dr. Sternberg will facilitate the continued growth and development of clinical and translational research programs in GU malignancies, as well as serve as Clinical Director of the Englander Institute for Precision Medicine (EIPM) to develop strategies to incorporate genomic sequencing and precision medicine within our Program and across Weill Cornell Medicine and NewYork-Presbyterian.
New Events More than 200 prostate cancer patients and loved ones attended our inaugural New York City Prostate Cancer Summit, a multi-institutional collaboration between Weill Cornell Medicine, NewYork-Presbyterian Hospital, Columbia University Irving Medical Center and Memorial Sloan Kettering Cancer Center. This educational and advocacy event featured presentations and panel discussions from local medical experts and national advocacy leaders, with topics including nutrition, screening, coping and anxiety, immunotherapy and much more. Our second annual Summit is slated for September 2019 during Prostate Cancer Awareness Month. Stay tuned for details.
New Research Developments
• Based upon our prior work with fractionated dosing of our radiolabeled antibody 177Lu-J591, we performed the world’s first phase 1 dose-escalation trial of 177Lu-PSMA-617 without finding any dose-limiting toxicity (no major side effects despite higher and higher doses), presenting the initial results at the European Society for Medical Oncology (ESMO) 2018 Congress. The phase II portion of the trial is ongoing. We are also leading the first trial combining two different targeting agents (J591 and PSMA-617) designed to deliver more radiation to tumors and less to other organs.
• Alpha particles are several thousand-fold more potent than beta-emitters such as 177 Lu. We are completing the phase 1 dose-escalation portion of the world’s first-ever clinical trial utilizing a powerful alpha particle (225Ac) directed almost exclusively at prostate cancer cells by linking it with our J591 antibody, which avoids salivary glands.
• As prostate-specific membrane antigen (PSMA) targeting enters “prime time,” the United States Department of Defense (DOD) has recognized our significant contributions to this evolving field with a grant that will allow us to research optimal patient selection for PSMA-targeted radionuclide therapy and assess the treatment’s immune effects.
• Thanks to developing technology utilizing circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), we are able to draw information about a patient’s tumor via a simple blood test. In our findings published by the American Association for Cancer Research (AACR) Clinical Cancer Research journal, we analyzed the relationship between chemotherapy treatment and expression of androgen receptor (AR) variants in CTCs of men with metastatic prostate cancer.
• We led a phase II clinical trial through the Prostate Cancer Clinical Trials Consortium (PCCTC) and discovered that an aggressive subset of disease called neuroendocrine prostate cancer (NEPC) is driven by a gene with an associated target known as aurora kinase. Further investigation into targeting of the gene may help us to refine therapy for this difficult-to-treat patient population. Our findings were published as a cover story in Clinical Cancer Research.
• Working with collaborators and funded by the Prostate Cancer Foundation (PCF), we have developed unique genomics sequencing methodology called PCF SELECT that allows us to identify actionable mutations in men with advanced prostate cancer.
• The number of United States Food and Drug Administration (FDA)-approved drugs for patients with advanced kidney cancer continues to grow. Dr. Ana Molina leads our team in offering clinical trials focused on novel targeted agents, combination treatments, and risk-directed therapies for various subtypes of kidney cancer.
• Working together with the Englander Institute for Precision Medicine, we are evaluating genetic signatures from patient tumor specimens and developing organoids that can be used to test novel pathways and tailor treatment to each individual patient.
• Laboratory studies of our in vivo kidney cancer models have resulted in discoveries regarding the metabolism of the disease. Understanding the role of the mitochondria (a cell’s power generator) in kidney cancer is leading us to novel therapeutic approaches to block tumors from growing and spreading.
• Five immune therapies are now FDA-approved for people with advanced bladder cancer. We continue research to improve upon these agents by combining them with targeted therapeutics with the potential to replace chemotherapy. Collaboration with EIPM will help us to identify tumors most likely to benefit from these treatments.
• Dr. Bishoy Faltas and his lab team are focused on understanding the role of a specific family of proteins that cause mutations (genetic errors) that may be the underlying cause of bladder cancer. This research will enable us to develop new treatments to target the newly-identified genes that drive the disease.
• Based upon Dr. Faltas’ prior high-impact Nature Genetics publication that identified the genetic mechanisms by which bladder cancers become resistant to chemotherapy and new drug targets, we are launching an innovative new clinical trial utilizing a targeted drug that inhibits bladder cancer growth, the first time this type of drug is being tested in bladder cancer.
• We are conducting clinical trials of two antibody-drug conjugates (sacituzumab govitecan and enfortumab vedotin) designed to deliver potent chemotherapy-like toxins preferentially to cancer cells. This type of therapy is anticipated to become one of the standard approaches to bladder cancer treatment.
• Using samples of patient tumors (drawn via needle biopsy), we can create small 3-D tumor representations known as organoids that mimic the way that cancer cells grow within the body and respond to treatment. Our team has worked to develop this exciting new form of precision medicine, which is especially significant for rare cancers with a lack of preclinical models available for study.
We are moving closer to our ultimate goal of curing genitourinary cancers and look forward to continued progress in the years ahead.
Prostate cancer is estimated to claim the lives of almost 30,000 men this year. That’s 30,000 husbands, fathers, brothers and friends.
One of our best defenses against this disease is education and awareness, granting men and their families the knowledge and power to take the appropriate steps toward optimal health and longevity.
To support this goal, some of New York City’s most prestigious prostate cancer treatment centers are joining forces to host a symposium on Saturday, September 22, 2018. This inaugural NYC Prostate Cancer Summit: An Advocacy, Awareness and Educational Event to Empower Patients and Loved Ones will be led by experts from Weill Cornell Medicine, NewYork-Presbyterian Hospital, Columbia University Medical Center, and Memorial Sloan Kettering Cancer Center.
Here’s a sneak peek at some of the hot topics and expert speakers slated for this premier event.
Updates in Prostate Cancer: From Screening to Diagnosis and Treatment Screening, Active Surveillance and Prostate Cancer Biomarkers
Douglas Scherr, MD, Weill Cornell Medicine
Elias Hyams, MD, Columbia University Medical Center
Mark Stein, MD, Columbia University Medical Center
Imaging, Immunotherapy and Other New Targeted Therapies
Scott Tagawa, MD, MS, Weill Cornell Medicine
Joseph R. Osborne, MD, PhD, Weill Cornell Medicine
Susan Slovin, MD, PhD, Memorial Sloan Kettering
Charles Drake, MD, PhD, Columbia University Medical Center
Nutrition and Diet Louis Aronne, MD, Weill Cornell Medicine
Coping, Anxiety and Survivorship Andy Roth, MD, Memorial Sloan Kettering
Prostate Cancer Advocacy Panel ZERO: The End of Prostate Cancer – Colony Brown, Vice President of Marketing & Communications
Us TOO International – Chuck Strand, Chief Executive Officer
American Cancer Society Cancer Action Network – Michael Devoli, Director, New York Metro Government Relations
In addition to having exclusive access to these discussions, patients and loved ones will also be able to connect with fellow attendees and obtain resources related to prostate cancer treatment options and quality of life.
The Summit will run from 8AM – 1PM at the New York Academy of Medicine (on 5th Avenue and 103rd Street). It is completely free and open to all those impacted by prostate cancer. Breakfast and lunch will be provided.
Prostate-specific membrane antigen (PSMA) is a molecular marker present on the surface of virtually all prostate cancer cells. It can be targeted by different molecular agents that bind to PSMA. This enables a targeted approach to find and image or treat prostate cancer cells wherever they are in the body, including the cells that have escaped (metastasized) to other organs.
The most commonly used agents to target PSMA fall into two categories: small molecules (also known as peptides, ligands, or inhibitors) or antibodies (also termed monoclonal antibodies).
Small molecule- and antibody-based molecules that bind to PSMA have different physical characteristics and these have implications on the way the molecules circulate through the body.
For example, peptides and other small molecules that target PSMA are much smaller than antibodies – approximately 100-fold smaller. As a result of their small size, peptides are able to quickly travel through blood vessels and disperse throughout all body tissues – both normal and tumor – and they are also rapidly excreted by the kidney into the urine and bladder.
Conversely, the larger antibodies tend to stay within the circulating blood and flow more selectively through the larger, abnormal blood vessels within tumors than the vessels in normal tissues. Their large size also prevents them from being excreted by the kidneys. Because of these properties, peptides can penetrate tumors, as well as normal tissues, rapidly and then disappear from the body quickly, in minutes to hours; antibodies take longer to travel and enter the tumor, but this is compensated for by the longer amount of time they spend in the body (days to weeks) and their decreased likelihood to penetrate into normal tissues.
What is PSMA? - YouTube
From a diagnostic imaging perspective, small molecules are typically better, as the rapid excretion of the radiolabeled peptide quickly minimizes the radioactive background “noise” seen on a scan. Additionally, using small molecules means that patients can be injected with imaging agents and then undergo scans quickly thereafter (on the same day within 1-3 hours). Physicians can see good contrast of the cancerous cells compared to other parts of the body with this method. In comparison, patients must return approximately 3-8 days after infusion with a monoclonal antibody for scans. Some of the benefit of using small molecules is offset by the fact that they are excreted via the urine and accumulate in the urinary bladder. This may lead to an intense signal in the urinary bladder area of the scan, adjacent to the prostate gland and lymph nodes in the pelvis, thereby possibly obscuring these potential sites of tumor. On the other hand, some antibodies are taken up by the liver, obscuring visualization of that organ. Antibody fragments such as so-called “mini-bodies” (derived from the whole antibody), are half the size of a normal antibody, but still large enough so as not to be excreted in the urine, and as such, they may provide improved imaging of the prostate and the pelvic area. This is currently under investigation at Weill Cornell Medicine and NewYork-Presbyterian Hospital.
The nuances of these molecular targeting agents aside, it is clear that both peptide-, antibody or mini-body-based agents provide significantly improved targeted molecular imaging of prostate cancer compared with conventional modalities such as bone, CT, and MR scans and also have some advantages over glucose (FDG), sodium fluoride (bone), choline, or fluciclovine (FACBC) PET scans.
From a therapeutic perspective, there are theoretical advantages to the faster tumor penetration of the smaller molecule targeting agents, but this may be offset by their quick disappearance and their ability to impact normal tissue. The longer time antibodies spend circulating in the body theoretically provides for a greater amount of the treatment agent to get internalized into the cancer cells, allowing greater uptake of the payload agent (such as a radionuclide) that is being delivered to kill the cancer cells. Additionally, some antibodies may also be engineered to generate an immune response.
Does uptake in different body areas lead to side effects?
The different characteristics of small molecules and antibodies confer advantages and disadvantages when targeting PSMA on cancer cells within the body. Because of their small size, small molecules/peptides can penetrate through the depths of the tumor very quickly, but they also readily target normal tissues that express low levels of PSMA such as the salivary glands, small intestine, and kidneys. When using as a therapeutic delivery vehicle, this might lead to dry mouth, nausea, or delayed kidney damage. Luckily, no significant kidney damage has been seen in humans to date, but the number of patients treated on prospective clinical trials remains small and follow up is short. An antibody, on the other hand, does not target salivary glands or kidneys because its larger size leads to relatively restricted access to those normal sites. However, it circulates in the body for a longer period of time including high flow through the bone marrow. Antibodies tagged with radioactive particles may therefore contribute to non-specific side effects such as temporary decreased blood counts. This is a common (expected) toxicity related to the dose and schedule of the radiolabeled antibody.
Currently, it is not known whether peptide-based or antibody-based targeted PSMA prostate cancer treatments provide better results, but both approaches offer therapeutic benefit to patients. At Weill Cornell Medicine and NewYork-Presbyterian Hospital – where we have almost two decades of experience pioneering prostate cancer imaging and treatment with PSMA-targeted agents – we are the only center in the world currently able to offer both types of imaging and treatment modalities and plan to combine both within individual patients. We hypothesize that will be able to use the favorable properties of each targeting agent at slightly lower than maximal doses to deliver a higher amount of therapeutic payload to tumor with less to normal organs, further improving the tumor kill : side effect ratio and have initiated a clinical trial testing this approach.