It is estimated that there are more than two million American men are estimated to be currently living with prostate cancer. In the United States, prostate cancer affects one in every six men and is the most common cancer not specific to the skin. In fact, one new case of prostate cancer occurs every three minutes, and a man dies from prostate cancer every 19 minutes.

Whether uncovering the roots of prostate cancer, considering how prostate cancer treatments affect men or discussing therapy options, Keck Medicine of USC urologists are attacking prostate cancer from all directions. We work with you and your family to develop a plan that best suits your lifestyle and needs while optimally treating your cancer. We believe your care should be as individual as you are.

At Keck Medicine of USC, we are developing image-guided targeting, fusing 3-D guidance, MRI and ultrasound to increase accuracy of prostate biopsies.  After identifying the cancer, there is a wide range of different treatment options available for prostate cancer patients. These include surgery, radiation, chemotherapy, localized treatment and active surveillance. Depending on the grade and stage of your cancer you will be a candidate for a variety of treatment options.

We offer the latest in robotic and laparoscopic surgery to treat prostate cancer. We were the first institution in California to offer the latest generation of the da Vinci surgical robot in our operating room which translates to our physicians having the longest experience using this tool. Our team of doctors has performed more than 8,500 radical prostatectomies in which the prostate gland and some surrounding tissues are removed, and we continue to have excellent outcomes.

Keck Medicine of USC urologists are leaders among a handful of programs in the country that offer robotic radical prostatectomy for minimizing nerve damage in technically challenging scenarios, which translates to providing our patients with the best chance of eradicating cancer while preserving potency and continence.

Symptoms

Most early prostate cancers do not present with any symptoms. In the prostate, many non-cancerous conditions including benign prostatatic hyperplasia (or enlargement), usually present with symptoms including:

  • Urinary hesitancy (delayed or slowed start of urinary stream)
  • Urinary dribbling, especially immediately after urinating
  • Urinary retention
  • Pain with urination
  • Pain with ejaculation
  • Lower back pain
  • Pain with bowel movement
  • Excessive urination at night

Although rare, sometimes more advanced disease can be associated with these symptoms as well:

  • Bone pain or tenderness
  •  Blood in the urine (hematuria)
  • Abdominal pain
  • Anemia or low red blood cell count
  • Unintentional weight loss
  • Lethargy

Diagnosis

Before the advent of the prostate specific antigen (PSA) which serves a screening tool for prostate cancer, the diagnosis for prostate cancer was through a rectal exam.  Sometimes, a rectal exam will show an enlarged prostate with a hard, irregular surface when patients have prostate cancer.  Depending on your age and previous PSA results, you will have to undergo a prostate biopsy to determine whether or not you have cancer.

A prostate biopsy is usually done in the urologist’s office using a rectal ultrasound probe.  Samples of the prostate are taken through the probe and sent to the pathologist for review.  If the results return positive for cancer, the tumor samples will be graded using a grading system called the Gleason Grading System.

The Gleason grading system accounts for the five distinct patterns that prostate tumor cells tend to go through as they change from normal cells to tumor cells.

The cells are scored on a scale from 1 to 5:

  • “Low-grade” tumor cells (those closest to 1) tend to look very similar to normal cells.
  • “High-grade” tumor cells (closest to 5) have mutated so much that they often barely resemble the normal cells.

The pathologist looking at the biopsy sample assigns one Gleason grade to the most similar pattern in your biopsy and a second Gleason grade to the second most similar pattern. The two grades added together determine your Gleason score (between 2 and 10).

Generally speaking, cancers with lower Gleason scores (2 – 4) tend to be less aggressive, while cancers with higher Gleason scores (7 – 10) tend to be more aggressive.

It’s also important to know if any Gleason 5 is present, and most pathologists will report this. Having any Gleason 5 in your biopsy or prostate puts you at a higher risk of recurrence.Based on your PSA and biopsy results, additional testing may be done to determine the extent of the disease before making a decision for treatment.   These tests include:

  • CT scan
  • Bone scan
  • Chest X-ray

Treatment

At USC, we believe your treatment should be a choice made between you, your family and your doctor. Once we determine the stage and severity of the prostate cancer, we can help you make the choice between surgery, radiation and active surveillance.

At USC, we offer the latest in robotic and laprascopic surgery to treat prostate cancer. We were the first institution in California to offer the latest generation of the da Vinci Surgical System in our operating room. Our team of doctors has performed more than 6,000 radical prostatectomies, and we continue to have excellent outcomes.

Surgery

A radical prostatectomy involves removal of the prostate gland and the seminal vesicles. This also usually involves removal of the lymph nodes that drain the prostate. Whether done through a larger open incision or using smaller cuts and longer instruments with the robotic approach, our ultimate goal is to remove the cancer. Based on your medical history and preferences, our doctors will guide you in making the best decision if you choose surgery. As with any procedure, radical prostatectomy comes with certain risks and possible complications. Our doctors will speak with you during your consultation to make sure you understand these risks before making a decision.

Robotic Radical Prostatectomy

Robotic radical prostatectomy is a highly precise anatomic surgical procedure with excellent outcomes to optimally preserve erections and continence.

The USC Institute of Urology’s highly experienced minimally invasive urologists have now performed more than 3,000 robotic/laparoscopic radical prostatectomy surgeries, which is one of the largest experiences in the country. Our oncologic (cancer-free) and functional (potency, continence) outcomes are amongst the best anywhere.

  • Risk stratification and clinical outcomes are highly reproducible
  • Negative surgical margins are an important prognostic predictor of overall survival, biochemical and clinical recurrence. In patients with organ-confined disease, our negative margin rates exceed 95 percent. In patients with focal extra-prostatic extension (stage pT3a), our negative margin rates with degrees of nerve-preservation are 82%. These outcomes are amongst the best in the literature.
  • Local recurrence (<1 percent), clinical recurrence (<5 percent), and death from prostate cancer (0.2 percent) have been uncommon in our patients undergoing radical prostatectomy for stage T1 and T2 disease.
  • For our patients, our large experience translates into excellent cancer and quality of life outcomes. In order to minimize nerve damage, we pioneered a novel “energy-free” technique of nerve-sparing radical prostatectomy, often performed with real-time trans-rectal ultrasound monitoring. In patients with excellent erections at baseline, more than 82% regain erections good enough for intercourse at one year after surgery.
  • We offer robotic radical prostatectomy for select patients with non-metastatic high risk disease, such as Gleason > 8 disease, and patients with focal extra-prostatic extension, in the setting of a clinical trial.
  • We are amongst a handful of programs in the country who offer robotic radical prostatectomy in technically challenging scenarios, such as patients who have failed radiotherapy or seed implants, and after transurethral resection of the prostate, hormonal therapy and prior pelvic surgery such as hernia repair, aortic surgery and other abdominal surgery.

Radiation

In patients whose health makes surgery too risky, radiation therapy is often the preferred alternative. Radiation therapy to the prostate gland is either external or internal.

  • External beam radiation therapy is done in a radiation oncology center by our specially trained radiation oncologists, usually on an outpatient basis. Before treatment, a therapist will mark the part of the body that is to be treated with a special pen. The radiation is delivered to the prostate gland using a device that looks like a normal X-ray machine. The treatment itself is generally painless. Side effects may include: impotence; incontinence; appetite loss; fatigue; skin reactions, such as redness and irritation; rectal burning or injury; diarrhea; inflamed bladder; and blood in urine. External beam radiation therapy is usually done five days a week for six to eight weeks.
  • Prostate brachytherapy or internal radiation involves placing radioactive seeds inside you, directly into the prostate. Internal radiation therapy is directed to the prostate thereby reducing damage to the tissues around the prostate. Prostate brachytherapy is often used for early, slow-growing prostate cancers. It also may be combined with external beam radiation therapy for some patients with more advanced cancer. Side effects may include pain, swelling or bruising in your penis or scrotum, red-brown urine or semen, impotence, incontinence and diarrhea.

Medical Therapy

Medicines can be used to adjust the levels of testosterone, which is called hormonal manipulation. Because prostate tumors require testosterone to grow, reducing the testosterone level often works very well at preventing further growth and spread of the cancer. Hormone manipulation is mainly used to relieve symptoms in men whose cancer has spread.

Chemotherapy is often used to treat prostate cancers that are resistant to hormonal treatments. An oncologist will usually recommend a single drug or a combination of drugs.

Robotic Surgery

With any cancer treatment, the first priority is survival. Several large studies suggest there is a greater chance of long-term survival for patients undergoing surgery over other potential treatments. When surgery is required to treat prostate cancer, surgeons perform a radical prostatectomy in which the prostate gland and some surrounding tissues is removed. This operation may be done through open surgery or laparoscopically using robotics.

In prostate cancer surgery, the delicate nerves that are attached to blood vessels must be separated from the prostate before its removal. The robotic surgery team at Keck Medicine of USC remains at the forefront of robotic radical prostatectomy by using an athermal technique of nerve sparing which creates positive outcomes for patients. Our surgeons pioneered the use of intraoperative real-time trans-rectal ultrasound guidance to enhance the precision of nerve-sparing and oncologic efficacy.

In terms of cancer control, in several large published studies, robotic prostatectomy has shown better rates of positive surgical margins than large studies of other forms of surgery.

Urinary continence and sexual function after treatment are also of concern for prostate cancer patients. Studies show patients who undergo a robotic prostatectomy may experience a faster return of urinary continence following surgery and lower rates of urinary pain than radiation (brachytherapy) patients. Several studies also show patients who are potent prior to surgery recover their sexual function (defined as an erection for intercourse) within a year following robotic surgery.

In addition to the already published research projects, our team continues to move the field forward. We are currently at the forefront of developing novel, cutting-edge robotic and image-guided prostate biopsy and focal therapy treatments. Also, we are helping develop a new treatment concept for prostate cancer: “male lumpectomy.” These newer treatments will allow us to provide cancer control, without any compromise of erections or urinary continence. Our near-term goal: advance prostate cancer surgery to a new level, wherein excellent cancer outcomes are provided while maintaining quality of life in terms of erections and continence.

Research and Clinical Trials

Basic Science Projects
•    How Genetic Predisposition Affects Prostate Cancer Risk
This project seeks to unravel fundamental mechanisms of prostate cancer risk, one of the most widespread cancers in the United States and the world. Additionally, men from African ancestry have nearly twice the risk for prostate cancer development than men from other racial-ethnic groups and genetic factors probably significantly contribute to this increase. Recently, genetic variation in protein non-coding regions associated with prostate cancers has been shown by us to be involved in the regulation of other distant genes. In this project, we will expose exactly how (mechanism) this is brought about, to reveal molecular targets for prophylactic measures in men at high risk.

•    Androgen Receptor and Advanced Prostate Cancer
Too many prostate-cancer treatments, especially those relying on the suppression of the male sex hormone androgen, eventually fail to slow the advance of the disease. One explanation for this is the absence of any systematic knowledge on the role and function of the androgen receptor in the course of prostate cancer development. Recent findings from us and others indicate that the androgen receptor is the key master regulator that determines disease progression to androgen independence and ultimately contributes to death from prostate cancer.

•    A Novel Transcription Factor, Runx2 and Prostate Cancer Progression
Building on our recent findings of strong physical and functional interactions between the androgen receptor and Runx2, two transcription factors with pivotal roles in prostate cancer, we are now investigating how this interaction affects expression of genes that may drive advanced disease and why the outcome of the interaction varies between different genes. This will provide novel insight into molecular mechanisms of prostate cancer progression, opening new research avenues towards improved prognosis, prevention and therapeutic approaches to metastatic disease.

•    The Search of Familial Prostate Cancer Causing Genes
Prostate cancer is known to cluster in families. Several lines of evidence suggest that much of this clustering is due to inherited susceptibility. Our laboratory has focused on finding the genes that predispose these families to a high incidence of prostate cancer. The National Institutes of Health (NIH) has supported our laboratory for 16 years of this research. We are also one of the founding members of an international collaborative network with other prostate cancer research scientists from around the world, called the International Consortium on Prostate Cancer Genetics (ICPCG) that was established in 1996. Using the approach of genome-wide DNA marker scan followed by a powerful statistical analysis, we identified two chromosomal regions of 0.4 percent of the genome that may harbor the prostate causing genes. We are taking a combination approach of candidate-gene analysis and genomic sequencing to discover the prostate cancer-causing gene among the genes that reside in this 0.4 percent of the human genome. The ICPCG has been a very successful consortium that identified five DNA regions of interest, including one of the regions discovered by our troup, for prostate cancer. By working together with our colleagues around the world, we will ultimately identify prostate cancer-causing genes in these regions and eventually pave the way for therapeutic steps forward.

•    Conduct a Clinical Trial With a New, Non-Toxic and Very Promising Anti-Cancer Drug
Many men with prostate cancer cannot be treated with surgery or radiation. For these patients, the search for safe and effective treatments is of the utmost importance. The initial treatment will be a form of hormone therapy, and while this is usually effective, the response is of limited duration. At that point, options are extremely limited. Clearly, we can do better. Researchers are diligently looking for more active agents in the battle against advanced prostate cancer, but as of now, there is only one FDA-approved chemotherapy agent available. The difficulty is finding a way to target the cancer without damaging other parts of the body. Working with Nobel Prize winner, Andrew Schally, MD, we discovered a unique protein on the surface of prostate cancer cells. Using this protein as a gateway into the cancer cell, we can deliver chemotherapy exactly where it is needed, sparing the rest of the body. This project received significant funding from the NIH. We are planning to start this exciting new drug treatment in September of this year as part of a clinical trial and hope it will revolutionize the treatment of advanced prostate cancer. This trial will also use several new techniques to ensure the treatment is working. We will measure actual cancer cells in the blood with a simple blood test, giving patients quick progress reports on their treatment. With innovative drugs that work in different ways and using the latest in cancer monitoring, we hope this study will start a new chapter in the treatment of prostate cancer.

•    Design and Test a New Class of Anti-Cancer Drugs
This project is designed to develop a class of agents (called MAPs) that have been shown to block aggressive behavior of prostate cancer cells, thereby exerting anti-metastatic activities. We plan to develop MAPs that can be easily used as both diagnostic imaging agents as well as therapeutic agents in men with prostate cancer. The proposed agents will be radiolabeled to enable imaging with positron emission tomography (PET) that provides noninvasive, highly sensitive and quantitative assessment of the tumor. The same unlabeled agents can provide therapy to the targeted tumor. This investigation will have an important impact on the care of men with advanced prostate cancer through development of useful dual functional agents that can serve both as an accurate diagnostic imaging probe as well as an effective therapeutic agent against advanced prostate cancer. On broader terms, our approach may have an important role as an imaging tracer to study the extent of this disease and response to treatment in other cancers.

•    Understand the Regulation of Testosterone (Male Hormone) Production in Prostate Cancer Cells
Recently, it has been shown that prostate cancer cells can produce testosterone from cholesterol similar to testicular cells. This process may make prostate cancer cells resistant to hormonal therapy. Very recently, we discovered a unique molecular pathway which regulates testosterone production in prostate cancer cells. Presently, we are conducting experiments to better understand this pathway, which, if shut down, could result in inhibition of prostate cancer cell growth in patients who fail current hormonal treatments. We are also in the process of developing new anti-cancer drugs to inhibit this molecular pathway in castration-resistant prostate cancer.

•    Identify Patients Who Are At High Risk of Prostate Cancer Recurrence After Surgery or Radiation Therapy Using a Genetic Fingerprint 
The cancer recurrence among patients diagnosed with localized tumors (limited to the prostate) can be as high as 30 percent. The clinical indicators currently available to physicians cannot accurately identify which patients will remain cancer-free after removal of the localized tumor, and which patients might have a recurrence within the next ten years. This often results in over-treatment of many ‘low-risk’ patients who would have remained indolent, and under-treatment of ‘high-risk’ patients who would benefit from earlier institution of more aggressive therapy. Therefore, it is of critical importance to more accurately determine which patients have better prognosis than others, as this may have implications for the choice of treatment and the timing of available therapies. There is evidence that subsets of patients diagnosed with localized prostate cancer already contain specific alterations in their cancer cells that will predispose them to the recurrence of more aggressive disease. The analyses of gene expression patterns in the entire genome of prostate cancer cells offer the possibility to identifying these alterations, which is a necessary first step towards reliably identify patients at high-risk of worse clinical outcomes. We plan to conduct a rigorous large-scale gene expression profiling study that characterizes prostate cancer localized tumors from a population cohort of 1,200 patients for whom long-term clinical follow-up data are available. At the conclusion of our study, we will have identified novel biomarkers of localized prostate cancer clinical outcomes. Overall, the development and clinical application of novel prognostic biomarkers would reduce the morbidity associated with over-treatment of indolent patients, and allow the identification of those patients diagnosed with localized prostate cancer who might benefit the most from more aggressive treatments.

•    Role of EphB4 and EphrinB2 in Tumor Development and Progression and Development of Novel Therapy for Prostate Cancer 
We have discovered that prostate cancer cells have a pair of unique proteins on their cell surface which are lacking in the normal prostate gland. Second, when we target these proteins with very specific antibodies, the tumor cells die. We are thus conducting detailed studies as to how these proteins are turned on in prostate cancer. Next, we wish to determine if the absolute amounts of these proteins predict for stage, grade and survival. Most importantly, we plan to conduct human trials with the antibodies to EphrinB4-EphrinB2.