Introduction: Eila Skinner, MD
Chair of the Department of Urology
Stanford University Medical Center
September 6, 2014
Sheraton Hotel, Palo Alto
Prostate cancer tends to be relatively slow-growing, which means that it typically takes a number of years to become large enough to be detected and even longer to spread beyond the prostate. It’s still extremely serious and the second most-common cause of cancer deaths in U.S. men (lung cancer is first). And because the prostate is close to several vital organs, prostate cancer and its treatment can disrupt normal urinary, bowel, and sexual function.
Prostate cancer affects one in six American men, and studies have shown that most men over the age of 70 have some form of the disease. As research and innovations in technology and treatments enable earlier detection and more effective care, more people are surviving cancer and living longer after a diagnosis. But how it is treated and when it is treated remains debated among prostate specialists.
The Stanford Cancer Center, with support from the Canary Foundation and the Early Detection Research Network, recognized September as National Prostate Health Month by bringing together several specialists to discuss the latest screening and treatment advances in prostate cancer.
Active Surveillance for Prostate Cancer
James Brooks, MD
Professor of Urology
Though the accuracy of prostate specific antigen (PSA) tests has been brought into question, PSA remains a powerful detection tool and mortality rates have dropped significantly since PSA screening was introduced. Much of the current controversy falls under how to approach early-stage prostate cancer and who would most benefit from treatment.
While the number of men with prostate cancer has risen, most die of other causes. About one third of men in their 40s show some sign of prostate cancer, and the percentage increases with age. But elevated PSA levels are not necessarily a sign of cancer, and many men with indolent or latent cancer never develop symptoms. The challenge lies in determining who will require treatment and who will not benefit, avoiding unnecessary biopsies or unwanted side effects from treatment.
“There’s a new paradigm for who will need treatment and who can be watched,” Dr. Brooks said. “Not all cancers warrant aggressive treatment. The benefits of treatment do not always outweigh the risks.”
In the past, many clinicians took an approach called “watchful waiting” that tracked changes in a man’s symptoms and introduced treatment after cancer developed. Today, many have adopted an approach of active surveillance, which involves recurring tests and monitoring of progression before introducing therapeutic intervention. The national Prostate Active Surveillance Study (PASS) collected samples from 1,100 men to test for biomarkers associated with aggressive prostate cancer. One-third of the participants have gone on to receive treatment.
New insights into the genetic makeup of cancer and improved technologies are leading to more focused diagnosis and treatment. Trials using targeted microbubbles, which use contrast agents to deliver drugs and genes that are then activated by ultrasound, have shown to home in on prostate cancer cells. An image-guided biopsy system combines a type of magnetic resonance imaging (MRI) with ultrasound pinpoints tumors for precisely targeted procedures.
Surgical Management of Prostate Cancer
Benjamin Chung, MD
Assistant Professor of Urology
New technologies are allowing surgeons to use minimally invasive approaches using robotics to treat prostate cancer. Robotic-assisted laparoscopic prostatectomy (RALP) systems, like DaVinci, use the smallest possible incisions, making surgery less painful with shorter recovery time and decreased blood loss for patients. Cancer outcomes, complications, and safety appear to be comparable to results from open surgery, but surgeon experience with RALP is important for achieving good outcomes.
Because the prostate is small and difficult to reach, robotics offers several advantages for surgeons as well. Robotic surgical systems help to reduce or eliminate any slight hand tremors, provide greatly increased magnification in 3-D, and offer more flexibility and maneuverability than traditional laparoscopic instrumentation. In a RALP procedure, the surgeon sits at a console in the operating room and uses hand controls to directly guide all the movements of the robotic system accurately and precisely.
Dr. Chung stated that all interventions for prostate cancer can lead to side effects, such as urinary incontinence and erectile dysfunction. The possibility of complete urinary incontinence is very unlikely after RALP. The intense magnification of robotic surgery systems provides more detail during vesicourethral anastomosis, the process of suturing a new connection between the bladder and the urethra, and can help identify the intricate network of nerves needed to preserve erectile function after surgery.
Radiation Oncology for Prostate Cancer
Mark Buyyounouski, MD
Associate professor of Radiation Oncology
Improved biological insights and advances in technology have made a great impact on radiation therapy. New tools use lower doses of radiation that can be applied with pinpoint accuracy, targeting the tumor and sparing nearby health tissue. Stanford has been a long-time pioneer in developing and refining the field.
When planning treatment, specialists stage patients by risk and how far the cancer how progressed based on PSA levels. But they also look at the progression of the disease and other factors to individualize care and recommendations. They will look at the biopsy, patterns in the PSA levels, and other secondary factors before deciding on the best approach.
Patients are treated with Volumetric Modulated Arc Therapy (VMAT), a system that focuses radiation in way that minimizes exposure to surrounding healthy tissues, resulting in fewer side effects, and cuts treatment time by delivering a higher and more targeted dose to the cancer site. CT scans or MRIs are used to create maps of the target area, and markers are then embedded for image-guided therapy.
A technique called fractionated radiotherapy uses small doses of radiation over time, which allows normal cells time to recover. Stanford commonly uses hypo-fractionation, which uses higher doses of radiation per day that may shorten overall treatment time without compromising toxicity.
Brachytherapy involves placing devices containing radiation in the prostate gland close to the cancer cells, which kills the cancer cells while causing less damage to healthy tissue nearby. Brachytherapy is commonly combined with VMAT.
Temporary prostate brachytherapy involves placing hollow needles in the prostate where a radioactive source can deliver treatment for several minutes before the needles are removed. Permanent prostate brachytherapy involves placing radioactive seeds in the prostate, where they slowly release radiation. The temporary approach provides short-term exposure in a same-day procedure; this strategy tends to show better PSA control and survival because of its higher doses of radiation.
These therapies may be used in conjunction with androgen deprivation therapy (ADT), which suppresses the hormones that encourage prostate cancer cells to grow. Studies are being planned to assess the outcomes of using brachytherapy alone to determine whether it can reduce treatment.
“When it comes to radiation therapy, more is better. The higher the dose, the better the outcome,” Dr. Buyyounouski said. “The goal is to target the tumor while sparing the adjacent tissue.”
Drug Treatments for Prostate Cancer
Sandy Srinivas, MD
Associate Professor of Medical Oncology
Lowering testosterone levels has been used to treat prostate cancer since the 1940s, but new therapies are being introduced and refined for patients who do not respond to standard treatment. Since 2010, six new drugs have been approved by the FDA. Chemotherapy is primarily used if the cancer has spread outside the prostate, often to the bones. These drugs are designed to prolong life, not simply lower PSA levels.
The most commonly used chemotherapy drug is docetaxel, which interferes with cell division. Because cancer cells divide faster than normal cells, they are more likely than normal cells to be affected by this drug.
Immunotherapy uses a patient’s own cells to stimulate the immune system’s T cells to respond against the cancer. Androgen targeting agents cause testosterone levels to drop, which consequently drops PSA levels as well. Bone targeting drugs (radium 223) treat metastatic cancers in bone by mimicking calcium in areas affected by increased cell activity.
Traditionally chemohormones are used when other treatments have failed. However, studies have shown that drugs approved for late-stage disease help to suppress tumor development when used early on. In one trial, men who received chemotherapy in conjunction with hormone therapy lived 13 months longer than those who received only hormone therapy.
“Used early on, and in new combinations, these drugs show dramatic results. The higher the risk, the greater the benefit,” said Dr. Srinivas. “The goal is identify more new targets so we can develop more new drugs.”
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