Category: Genitourinary Cancer

Stereotactic Body Radiation for Prostate Cancer

JOSEPHINE KANG, MD, PhD

Linear Accelerator Stereotactic Body Radiation
One of the linear accelerators used to deliver stereotactic body radiation therapy (SBRT) for prostate cancer at Weill Cornell Medicine/NewYork-Presbyterian Hospital

Advances in radiation therapy have enabled physicians to deliver high doses of radiation treatment with extreme precision, shortening treatment duration and reducing exposure to normal organs. For men with localized prostate cancer that hasn’t spread outside the prostate gland, this has led to radiation treatments that can be completed within just five treatments.

Initially this approach was developed on the Cyberknife Radiosurgery Platform. Cyberknife radiosurgery doesn’t actually refer to a knife or traditional “surgery,” but rather a specific type of machine that delivers radiation. Now, this five-treatment radiation for prostate cancer can be delivered using many different types of radiation machines, and as a result has undergone a bit of a name change. We now refer to this treatment as “stereotactic body radiation” or SBRT for short.

There are multiple reasons to select SBRT as treatment for prostate cancer. First, it only requires a total of five treatments over the span of one to two weeks, in contrast to standard external beam radiotherapy, which requires nine weeks of daily treatments. Additionally, prostate cancer success rates from SBRT appear comparable to other treatment modalities based on monitoring for up to nine years post-treatment. These outcomes were recently reported at the 2016 American Society of Clinical Oncology (ASCO) Genitourinary meeting.

This retrospective study reflects the longest follow up monitoring to date and demonstrates local control of the cancer, with nine-year freedom from PSA failure (rise of 0.2 ng/ml above nadir) of 95% for low-risk patients, 89% for intermediate-risk patients, and 66% for high-risk patients (determined based on National Comprehensive Cancer Network risk criteria). In the study, toxicity from radiation was low, and the dose utilized was 7.0 – 7.25 Gy per fraction. In prostate SBRT, appropriate treatment dosing is critical as higher doses have been linked with unacceptably high rates of toxicity. At the level used in the study, patients reported some bowel and urinary side effects that lasted less than one year. Overall, this study suggests that increased radiation doses and additional hormonal therapy did not improve outcomes; however, prospective studies are ongoing.

There is now enough data regarding using SBRT for prostate cancer treatment that it is an accepted treatment regimen by the American Society of Radiation Oncology (ASTRO), and the National Comprehensive Cancer Network (NCCN) guidelines. However, these guidelines explicitly state that prostate SBRT should, when elected, be performed at a center with high-volume and expertise. The physicians at Weill Cornell Medicine and NewYork-Presbyterian are very experienced in delivering SBRT for localized prostate cancer and have published many articles on this approach and when it should be used.

We will soon be opening a randomized study looking at prostate SBRT in conjunction with rectal spacer versus endorectal balloon in an ongoing effort to refine our treatments. The rectal spacer is a gel, placed between the prostate and rectum. By displacing the rectum from the prostate, it reduces exposure of the rectal wall to radiation. The spacer degrades over a period of three months and has been shown to reduce toxicity in patients undergoing standard external beam radiation therapy. We hypothesize that there will be similar toxicity reduction after SBRT. An endorectal balloon is another way to reduce overall rectal wall dose, by pushing the posterior rectal wall away from the prostate during radiation treatment.

As data for prostate SBRT continues to mature, more individuals with low- and intermediate-risk prostate cancer will likely opt for this convenient and efficacious form of radiation over more protracted courses.

Hi-Tech Blood Biomarker Signals When a Strategic Switch in Chemotherapy Will Benefit Prostate Cancer Patients

For men with metastatic prostate cancer that grows despite hormonal therapy (also referred to as castration-resistant prostate cancer), chemotherapy has been a mainstay. The class of chemotherapy that has consistently proved to improve survival for men with advanced prostate cancer is called “taxanes.”

Taxanes target microtubules, which are structures in cells that are involved in cell division, as well as the trafficking of important proteins. In prostate cancer, one of the main ways taxane chemotherapy works to kill the cancer cells involves blocking the movement of the androgen receptor (AR) along the microtubule “tracks” towards the cell nucleus, a mechanism we discovered here at Weill Cornell Medicine.

There are two taxanes FDA-approved to treat prostate cancer, docetaxel (brand name: Taxotere) and cabazitazel (brand name: Jevtana). While the drugs are similar, men whose tumors have grown despite taking one drug often respond to the other. The challenge for oncologists has been pinpointing when exactly to switch treatments.

ScottTagawa_ASCO2016_TAXYNERGYDr. Scott Tagawa presented exciting results from a phase II clinical trial at the 2016 American Society for Clinical Oncology (ASCO) annual meeting demonstrating the power of this treatment switch, and when to make the switch.

This research came to be because we thought that we might be able to increase the number of men who respond to taxane chemotherapy with an early assessment and by changing the drug for those who have a sub-optimal response. Simply put, those with no response or only an initial minor response had their drug changed at a much earlier time point then standard practice. This resulted in a higher response rate for the patients in the study.

Top Boxes_Taxynergy
In the photos from a sub optimally responding patient, almost all of the androgen receptor (AR, labeled in green) is in the nucleus (indicated by the arrow which is overlayed in blue on the right), meaning that the taxane chemotherapy treatment was unable to block AR from moving to the nucleus and thus unable to kill the prostate cancer cells.

In addition, it’s very exciting that we can examine cancer cells from a simple blood test, a process also referred to as collecting circulating tumor cells or CTCs. This allows us to assess the ability of a drug to target the pathway in real time and to tell us whether there is a positive tumor response or resistance.

These circulating tumor cells provide an opportunity for real-time molecular analysis of taxane chemotherapy and at Weill Cornell Medicine we’ve pioneered a way to examine the AR pathway with a simple blood test.

To do this we use an extremely specialized technology that captures the very small fragments or rare circulating tumor cells on a “chip.” From this chip we are able to determine which cells are responding to treatment.

Bottom Boxes_Taxynergy
In real time, we can see taxane chemotherapy kept the (green) AR out of the (blue) nucleus area in cells from a responding patient. 

In cancer care, we are always trying to maximize treatment response rates by targeting the right cells at the right time. This promising precision medicine approach offers us one more tool to better personalize treatment and improve outcomes.

 

ASCO 2016: Updates in Advanced Prostate Cancer and Precision Medicine

Advances in therapeutics have led to improvements in both survival and quality of life for patients with cancer, including men with advanced prostate cancer. Simultaneously, a number of cutting-edge scientific advances have been made in the underlying biology of advanced prostate cancer. There is great potential and power in integrating these new therapeutics and biomarkers, which is often referred to precision medicine. While great advances have already been made in this area, many remain highly sophisticated and restricted to selected centers, such as Weill Cornell Medicine and NewYork-Presbyterian Hospital, while others still need validation in a larger number of patients. Ultimately, the goal is to be able to bring these technologies and treatments to cancer patients all around the country and the world.

MishaBeltran_ASCO16
Dr. Misha Beltran speaks to a full house at the ASCO 2016 Annual Meeting in Chicago.

At the 2016 ASCO meeting, Dr. Himisha Beltran was the chair of a session entitled “Precision Medicine in Advanced Prostate Cancer: Understanding Genomics, Androgen Receptor Splice Variants, and Imaging Biomarkers.” This session intended to demystify some of the language and updates surrounding precision medicine.

Dr. Beltran spoke about important recent advances in tumor and patient genomics, such as the specific genetic alterations that we now know drive different types of tumors and play a role in the development of aggressive forms of the disease. The Cancer Genome Atlas (TCGA), a government-led initiative through the National Cancer Institute (NCI) has generated multi-dimensional maps for key genomic changes in 33 different types of cancer. It also provides a collaborative platform for physicians and researchers to search, download, and analyze data. Through the TCGA there have been critical discoveries regarding untreated primary prostate tumors with molecular classification of different subtypes that go beyond Gleason scores (the common way pathologists “grade” the aggressiveness of tumors).

Additionally, the first publication of the Stand Up to Cancer Prostate Cancer Dream Team demonstrated the genomic landscape of metastatic biopsies in the castration-resistant setting, which have differences compared to primary prostate tumors and fall into groups which may be targetable by certain therapies. Dr. Mark Rubin is the Weill Cornell Primary Investigator for the Stand Up to Cancer Dream Team. In addition, as follow up to Dr. Beltran’s initial 2011 publication, she detailed the results of Weill Cornell’s collaborative efforts leading to key discoveries in neuroendocrine and castration-resistant prostate cancer using tumor tissue as well as circulating tumor cell analysis.

Collaborator Dr. Gerhardt Attard presented data on utilizing DNA obtained from blood only, an emerging method of accessing the tumor’s genomic information in a non-invasive manner, which may decrease the need for a biopsy and allow for multiple samples to be assessed over time. One clinically relevant portion of his work, being done in collaboration with Drs. Beltran and Francesca DeMichelis, is ongoing through a Prostate Cancer Foundation – Movember Challenge Award grant. Together, we are leveraging our published genomic data on neuroendocrine and treatment-resistant prostate cancer with the circulating tumor DNA from blood technology to assess patients’ cancer status before, during, and after treatment.

In addition to improvements in tumor and blood-based biomarkers, imaging biomarkers are also being investigated. Dr. Michael Morris described standardizing the use of traditional scans to assess prostate cancer progression. In addition, there are a number of molecular imaging modalities that may demonstrate increased sensitivity in the detection of tumors as well as give insight into the biology of individual tumors, highlighted by prostate specific membrane imaging including the New York-based collaboration between Memorial Sloane Kettering Cancer Center and Weill Cornell Medicine investigators.