Watchful wait
Prostate cancer is not a death sentence
The bad news is that in any given year 200,000 American and 2,800 Israeli men are diagnosed with prostate cancer, the second-most-common malignancy in the US and third-most-prevalent type in this country. About 26,000 US men and 450 Israelis annually die of the tumor.
The good news is that the vast majority of prostate tumors are low-grade and slow-growing. “Watchful waiting” and “treatment only if necessary” generally mean that the person will die of some other cause before the tumor ever becomes lethal.
One out of 12 Israeli men will contract prostate cancer. The main factor that increases the prevalence of the disease is aging; as one grows older, the risk of contracting prostate cancer increases.
Another risk factor is family history. Men who have a father affected by the disease are at a two-fold increased risk; men who carry a defective BRCA gene from a parent, which often causes breast cancer, can also be handed down to a son and raises the risk of prostate cancer. Still, most prostate cancers occur in men without a family history of it.
Other influences are an improper (too fatty) diet, obesity, lack of physical exercise, excessive alcohol consumption and smoking may increase the risk of getting prostate cancer or of developing the high-grade, fast-growing type.
The prostate is a gland about the size of a walnut that is located just in front of the rectum between the bladder and the penis. The urethra through which urine is eliminated from the body runs through the center of the prostate, which secretes fluid that nourishes and protects sperm. During ejaculation, the prostate squeezes this fluid into the urethra, and it’s expelled with sperm as semen.
Because all these important organs are in one small space, performing biopsies or surgery that could damage nerves and blood vessels is considered tricky; mistakes can cause impotence and lack of control over urination and defecation.
Former prime minister (and now imprisoned for bribery and obstruction of justice) Ehud Olmert, who has since undergone surgery and recovered from the malignancy, is probably the most famous local case of prostate cancer. But abroad, celebrities who went public include actor Robert de Nira and the late actor Dennis Hopper, who died at the age of 73 after struggling with the malignancy for several years. THE THIRD Friends of Israel Urology Symposium held earlier this month at the Tel Aviv Hilton was attended by some 450 urologists, oncologists, uro-oncologists, uro-patholothists and uro-radiologists to discuss recent developments in the field. One of the leading prostate cancer experts to attend was Prof. Eric Klein, a urologist, surgeon and oncologist who heads the Glickman Urological and Kidney Institute at the Cleveland Clinic in Ohio. A guest of Oncotest Teva (which makes technology used to predict how the disease will proceed according to the patient’s genetic profile), Klein said in an interview with The Jerusalem Post that he has visited Israel several times to participate in medical conferences and has ties with Israeli researchers and physicians, some of whom trained at the Cleveland Clinic.
At the symposium, he lectured on Transformative Innovation in Urology – What Does the Future Hold?
Founded in 1921, the non-profit academic medical center is one of the largest hospital systems in the US, with the huge main Euclid Avenue campus, nine community hospitals in the Cleveland metropolitan area plus a hospital complex in Florida. KLEIN IS the first physician in his family. “My parents were born in the US and grew up in the Brooklyn neighborhood of East New York. My grandparents came from Poland and Austria and immigrated before the Holocaust. My father was an electrician and photographer and my mother a legal secretary,” he recalled. Asked how he became interested in urology, Klein recalled that he “had a kidney stone in college. I started reading about anatomy, and the urological system fascinated me. In fact, I have no college degree. It was very unusual. I did undergraduate training at Johns Hopkins University [at Johns Hopkins University in Baltimore] and was a cum laude graduate of the University of Pittsburgh School of Medicine. “When I did a urology rotation in medical school, I liked it, because it involved surgery and seeing patients, and I could also do research.” He completed residency training in urology at the Cleveland Clinic and a fellowship in urologic oncology at Memorial Sloan Kettering Cancer Center. He joined the staff of the Cleveland Clinic in 1989 and currently serves as a member of the department of cancer biology of the Cleveland Clinic Lerner Research Institute, the Taussig Cancer Institute and the Genitourinary Malignancies Program in the Case Comprehensive Cancer Center.
Surprisingly, unlike in Israel, a growing number of American women doctors are going into urology, even though they deal mostly with male problems. “About 35% of US urologists are women. They are regarded by patients as doctors regardless of their gender.”
His wife Susan, whom he met in medical school, is a pediatric neurologist, and they have one daughter who is studying theater at Skidmore College in New York.
Klein not only sees and treats prostate cancer patients but also conducts clinical research on localized and locally advanced malignancies. He was the national coordinator for a study sponsored by the US National Cancer Institute on the effects of selenium and vitamin E on the possible prevention of prostate cancer. Studying the randomized cases of 35,500 men from 427 US hospitals in North America and Puerto Rico, he found reduction in prostate cancer risk with either selenium or vitamin E supplements. However, Klein and colleagues concluded that dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men.
“Vitamins are biologically active agents,” Klein explained. “If you have a deficiency, it could help to take a supplement. But if you have enough, taking additional vitamins can be harmful.” He also participated in a study published 13 years ago in the European Journal of Urology on the prevention of prostate cancer with finasteride (Proscar), which is used to treat benign prostatic hyperplasia (BPH) and baldness. The team found that the drug causes a substantial (nearly 25%) risk reduction across all known risk groups. High-grade cancers were noted in 6.4% of finasteride patients compared to 5.1% of men receiving a placebo. They concluded that men should be presented [with] the benefits and risks of taking finasteride and be assisted in integrating their sexual and urinary symptoms into their decision-making process. Blanket statements for or against the use of this medication ignore patient preferences and differential risk-benefit profiles from finasteride.
A US-based trial on finasteride “came to opposite conclusions, but it was discredited, and our results and recommendations stood,” he recalled.
In his eight years as editor-in-chief of the prestigious medical journal Urology, Klein has contributed 400 papers to the scientific literature and authored or edited eight books on urological cancers. THE ASSESSMENT of prostate tumors is usually measured by the Gleason scale, named after Dr. Donald Gleason, a pathologist at the Minneapolis Veterans Affairs Hospital who developed it with colleagues around half a century ago. It has been amended and refined several times since then to better evaluate the progress of men using biopsies of prostate tissue. Cancers with a higher Gleason score are more aggressive and have a worse prognosis.
One of the main dilemmas for doctor and patients in prostate cancer results from the fact that in a minority of cases, the cells grow wildly and rapidly and can spread (metastasize) to other organs, especially the bones.
“We don’t know why some prostate cancer cells grow very slowly and some rapidly. But research is ongoing around the world to try to figure this out, “Klein noted.
Prostate cancer can be screened and detected before symptoms appear by testing the blood’s level of prostate-specific antigen (PSA), which is produced by the prostate. The larger the gland, the higher PSA levels usually are, but PSA is produced also by a healthy prostate, a benignly inflamed prostate or a malignant tumor in the gland. If the PSA count is high, the patient is often sent for a biopsy to look for cancer cells.
Although other doctors are skeptical, Klein personally recommends testing PSA for a baseline level at the age of 50 to predict a lifetime risk and then to screen every five years. If the man has a high risk at 50 due to a family history or other reasons, a PSA count should be made every two years, he said.
Another dilemma is how to treat the malignancy most efficiently when the cancer cells have metastasized and the patient doesn’t react to chemotherapy or biological treatments he is given. The symposium discussed this in detail, as well as genomic testing to assess the personal risk of aggressive cancer and treatment of high-grade tumors.
In fact, the Cleveland Clinic has joined with Israelis and become a major shareholder in Cleveland Diagnostics. The company is developing a kit to test the blood for molecular markers that can identify the PSA that specifically emanates from tumor cells and not also from healthy or inflamed prostates. It also has joined the Hebrew University of Jerusalem in developing nanotechnologies to treat cancer and is partnering with Maccabi Health Services to produce startups in e-health.
Treatment of the cancer depends on a man’s age, other medical problems, the stage and grade of the cancer, one’s own and the doctor’s feelings about the need to treat it and the side effects it could cause, and the chance that the treatment will improve the patient’s situation. The most common conventional treatments include surgery, radiation, hormone therapy and chemotherapy. Newer treatments being looked at include immunotherapy to boost the body’s immune system to help resist or destroy cancer cells; vaccines and targeted therapy drugs.
Prostate cancer is a complex disease, Klein concluded.
“But it is not a death sentence. Ninety percent of men diagnosed eight years to a decade ago are still alive. In five or 10 years, we will have ‘molecular signatures’ that will tell us who needs to be treated and who can safely be watched, and what kind of treatment and when to treat patients who need this. Improved new drugs will be available. The big dream is to develop tests that allow us to monitor circulating tumor cells inside the blood. Sensors will be able to tell doctors if the patient has a metastatic cancer that is progressing, and the techniques will probably be applied to other kinds of cancers.”