Though National Cancer Institute (NCI) statistics reveal that prostate cancer is the most frequently diagnosed cancer in the United States, we know less about its causes and risks than we do about almost every other major cancer. And the knowledge gap is substantial.
While prostate cancer survival rates have increased in recent years for cancer diagnosed at a localized or regional stage, the NCI reports no movement at all in survival rates among those men with distant-stage prostate cancer. CLP asked three nationally known physicians who are on the front lines in the treatment of prostate cancer for their views on some of the latest treatment and diagnostic techniques.
Louis Potters, MD, FACR
Louis Potters, MD, FACR, serves as medical director of the New York Prostate Institute (NYPI) in Oceanside, NY. The NYPI specializes in treatment of prostate cancer using seed-implantation and external-radiation therapies.
Potters says the recent decline in prostate mortality experienced by American men is continuing. But the exact reasons remain unclear. Some credit early prostate screenings and intervention; others believe the biology of prostate cancer disease is in the midst of changing.
“If one examines the ‘year of treatment’ as an independent factor to predict outcome, regardless of the treatment technique, it is clear that patients diagnosed recently do better than those 10 years ago, everything being equal,” Potters says. “Again, some say this is a result of early detection, while others suggest something inherent in the disease biology. Either way, a lower disease-specific mortality is good news for men diagnosed with this disease.”
The prostate specific antigen (PSA) blood test remains the bellwether marker for prostate-cancer detection and follow-up treatment. While a number of interesting new serum markers are in the development stage, the PSA remains the most statistically durable. Potters says it is clear that no single PSA value on its own is of as much value as a series of PSA values, whether for disease detection or treatment follow-up. The change in PSA is now accepted as being more important than the static value.
“Patients with rapid elevations in the PSA value, called PSA velocity, are more likely to be diagnosed with this disease than those men with a static, non-changing PSA value, even if above normal,” Potters says. “The trends are toward establishing age-related PSA velocity characteristics that will better direct patients for prostate biopsies or additional follow-up.”
Described by some as the biggest advance in prostate cancer treatment in decades, intensity modulated radiation therapy (IMRT) is a painless, nonsurgical procedure that uses highly conformal beams from external sources to deliver radiation to a targeted cancer while reducing collateral damage to normal surrounding tissue. The IMRT approach works particularly well for prostate cancer where the proximity to the rectum has limited external-beam dose. However, the data is still early regarding the effectiveness of IMRT compared with other prostate cancer treatments.
“Now with IMRT, the radiation dose delivered to the prostate can be increased by about 10% to 12% without added toxicity,” Potters says. “Early nonrandomized data appear to indicate that the higher doses of radiation are associated with higher biochemical freedom from recurrence rates. Therefore, IMRT has become the new standard for delivering external-beam radiation for prostate cancer.”
IMRT is very expensive treatment and has not been compared directly with surgery or brachytherapy, Potters says. “If one accepts the notion of ‘dose response,’ then treatment with brachytherapy still offers higher prostate doses of radiation and can be delivered at one third the cost of IMRT delivery,” he says.
Asked about which radiation regimen he prefers, Potters admits his bias and says he prefers to treat low- and intermediate-risk prostate cancer with brachytherapy. This minimally invasive procedure uses hollow needles to implant radioactive seeds roughly the size of a grain of rice into cancer tissue. The procedure is only performed once.
“There are a variety of sources—I-125, Pd-103, or Cs-131—that can be used, and the implant is tolerated well,” he says. “Unlike IMRT and surgery, the patient may return to 100% normal activity within 24 hours, and the likelihood of sexual dysfunction is less than with IMRT or surgery.”
The brachytherapy seeding technique now has results dating back 15 years – which represents the entire ‘PSA era’ – and those outcomes are as good as surgery. “Whether IMRT is as good as brachytherapy is years away from being known,” Potters says.
Stereotactic radiosurgery (SRS) is used to treat cancers in the brain as well as other abnormalities throughout the body. “While the term ‘radiosurgery’ is recognized for brain and spine treatment, body stereotactic radiation therapy is becoming available and can be used to treat prostate cancer,” Potters says. “The concept is to add confidence to the conformality and pinpointing of the beam, even relative to IMRT. Therefore, high-fraction radiation can be delivered, as compared to low dose per fraction of IMRT or 3D or conventional radiation delivery.”
With the SRS approach, an entire prostate treatment may be completed in three to five treatments as compared to 44 daily treatments with IMRT. “Clearly there is potential, and ongoing studies are just getting started with this technique,” he says.
Potters says the concept of dose response is universal to radiation therapy. Likewise, the concept of hypofractionation with stereotactic radiation delivery is universal for multiple disease sites. “One driving force for using these delivery methods for prostate cancer is the high prevalence of this disease and the ease of accruing patients onto studies. But these techniques are not limited to prostate cancer,” he says.
J. Brantley Thrasher, MD, FACS
A professor and chairman of the Urology Department at the University of Kansas Medical Center in Kansas City, J. Brantley Thrasher, MD, FACS, has been involved in both basic science and clinical research in the development of improved diagnostics techniques and treatments for cancers of the prostate, bladder, and kidneys. He is a prolific author and frequent lecturer on behalf of the American Urological Association and other groups.
Thrasher credits a combination of factors for the decreasing number of deaths attributable to prostate cancer. The PSA screening test, developed in the early 1980s, is now in wider use than ever before. That is leading to greater awareness among aging males and earlier detection. He also credits effective application of hormonal therapy. The PSA blood test continues as the most widely used prostate cancer marker today.
“While PSA is not perfect as a diagnostic, it’s fantastic as a surveillance marker,” Thrasher says. “Will there be better markers developed in the future? Probably yes.”
While much research and many laboratory efforts have been focused on the front end of prostate disease—developing markers capable of distinguishing slow-growing cancers from the more aggressive cancers—Thrasher and the teams at his two laboratories are concentrating on the back end. They’re searching for treatments that can prevent the return or growth of tumors during the late stages of prostate cancer.
As for his treatment preferences, Thrasher says nothing has emerged as a certain “better than” regimen. “Compared to the old four-field box technique for radiation delivery, today’s approaches use computer-simulated software to more accurately direct the radiation and lower the potential side effects,” Thrasher says.
According to Thrasher, focal therapy for prostate cancer is “not there yet” and may be a long time coming simply because of the inability to pinpoint tumor location in and around the prostate gland. “We have a difficult time determining the exact location of prostate tumors and are still having to treat the entire prostate,” he says.
Prostate cancer shares several characteristics with breast cancer. Both are adenocarcinomas, both are hormonally sensitive, and radiation treatment regimens for both are similar. “But in breast cancer, we have the tools to precisely target the cancer—that’s not good enough yet in prostate cancer,” Thrasher says. “For example, lung and liver cancer can be focally treated; not true with prostate cancer.”
One in six American men will be affected by prostate cancer during his lifetime, and 30,000 die from it each year. “We don’t know what causes prostate cancer, but we have found familial links in the cancer and we continue to research dietary and race connections to prostate cancer,” Thrasher says.
Several studies show prostate cancer is less common in populations that consume a low-fat, high-fiber, high-soy diet. Little evidence has surfaced that switching to a healthier diet after years of eating high-fat foods can lead to a healthier, cancer-free prostate, but research is moving forward. Lower incidence of prostate cancer has been documented among men who eat lots of tomato-based foods, especially tomato sauce cooked with a little olive oil.
Henry Z. Montes, MD
Now in his sixth year as radiation oncologist at Radiation Centers of Ventura County in California, Henry Z. Montes, MD, provides advanced treatment for patients with cancers of the prostate, breast, and skin. He previously served as Radiation Oncology Associate Medical Director at the Palm Springs Desert Hospital Comprehensive Cancer Center.
He says that now there is a range of radiation-delivery techniques from which he can choose, as well as emerging approaches to consider for biologically killing cancers. His choice involves determining the state of the cancer involved and whether it is confined to the gland, the tissue surrounding the gland, or has spread elsewhere. Among the imaging tools he uses for treating prostate cancer are magnetic resonance imaging, computed tomography, ultrasound, and prostascint scans.
”For low-risk patients, where cancer appears to be limited to the gland, the treatment choice is most often dictated by the side effects profile,” Montes says. “For those with greater than 10% risk of prostate cancer outside of the gland, we worry that the very focal, localized radiation methods may be not be sufficient and may need to use supplemental methods of radiation to cover the surrounding risk area. Also, for high-risk patients (elevated Gleason Score, high PSA), we would consider the addition of hormonal therapy.”
Montes forecasts increasing reliance on image guided radiation therapy (IGRT), an image-tracking technique that makes use of internal markers to track the tissue at risk in real time. This dramatically reduces the need for large target margins, which have traditionally been used to compensate for errors in localization. As a result, the amount of healthy tissue exposed to radiation can be reduced, minimizing the incidence of side effects and allowing for increasing doses of radiation to the tissue at risk (prostate).
Also drawing interest are techniques involving hyperthermia (heating the tissue) and cryotherapy (freezing the tissue), he says. “These are both evolving now and they make sense, but the technology is not mature enough. Can we localize the heating or optimize the freezing to effectively combat the cancer? There isn’t enough data in yet to answer that conclusively, but the potential is there,” Montes says.
Tissue ablation using cryogenic techniques has been studied as an alternative to surgery for many years. Early techniques dating to the 1960s used liquid nitrogen as the cryogen. But lack of control over freezing-thawing characteristics and significant complications and adverse side effects doomed first-generation equipment.
The PSA blood test continues as the preferred marker, Montes says. For younger men, readings from 0 to 4 are the standard. Elevated PSAs are common in men 50 and older, and most often signal growth of the prostate gland rather than the presence of cancer, he says.
Several new prostate-cancer markers, now under investigation, will probably replace the PSA blood test down the pike. “What I’ve seen indicates they’re more sensitive markers,” Montes says.
Nicholas Borgert is a contributing writer for Clinical Lab Products.