From OncoLog, December 2004, Vol. 49, No. 12
Advances in Prostate Cancer Treatment
by David Galloway
A diagnosis of prostate cancer carries a vastly different meaning for a patient today than it did 15 years ago. These cancers are being detected at earlier stages, and tumor control rates are soaring.
Since the advent of the prostate-specific antigen (PSA) test in the early 1990s, many prostate cancers are being treated before they are even palpable on a physical examination. Now, more than half of the patients seen for radiation therapy have been diagnosed at this early stage, said Deborah A. Kuban, M.D., a professor in the Department of Radiation Oncology at The University of Texas M. D. Anderson Cancer Center.
PSA testing has allowed physicians to discover many cases of prostate cancer that might have gone undetected in the past. This led to what appeared to be an increased incidence of prostate cancer in the early 1990s. “It is clear that, through PSA testing and newer, more aggressive biopsy strategies, we certainly find more cancers,” said Curtis A. Pettaway, M.D., an associate professor in the Department of Urology at M. D. Anderson.
“And so the question becomes: Are we now finding some cancers that we don’t need to find? Perhaps some of the cancers we’re finding would never have caused the patient a problem,” Dr. Pettaway said.
Paul Mathew, M.D., an assistant professor in the Department of Genitourinary Medical Oncology at M. D. Anderson, cited “a very apt aphorism” by the late Willet Whitmore, Jr., M.D., of Memorial Sloan-Kettering Cancer Center in New York: “If cure is necessary, is it feasible? And if cure is feasible, is it necessary?” Dr. Mathew said that dichotomy frames the current view of localized prostate cancer. A 50-year-old patient with an aggressive type of prostate cancer is almost certain to die of his disease unless it is cured. “It’s clearly necessary,” he said, “but is it feasible? Do we have clear evidence that radical prostatectomy offers cure in a high-grade prostate cancer? Surprisingly, this is still a controversial area.” On the other hand, in an 80-year-old patient with a low-grade cancer, “If you remove his prostate, he’d be cured. But is it really necessary?” Such a patient might well live the rest of his life without experiencing significant problems related to the cancer.
To evaluate those options, a patient’s risk of treatment failure is assessed on the basis of his PSA level, tumor stage, and combined Gleason score. Patients with a PSA level less than 10, a tumor stage of T2a (a small, palpable tumor confined to the gland) or lower, and a Gleason score of 6 or less are in the low-risk category, with an 80% or greater chance of long-term control. Those with a PSA level higher than 20, a tumor stage of T3 (outside of the gland) or higher, and a Gleason score of 8 or higher are in the high-risk category with less than a 50% chance of long-term control. All those in between are in the intermediate-risk group.
For patients whose life expectancy and comorbidities suggest that they are likely to die of something other than prostate cancer, cure is not considered necessary, so a strategy of watchful waiting is typically chosen. The patient’s PSA level is checked every four to six months and, as long as the cancer remains minimal, treatment remains unnecessary.
For younger patients or for those with more aggressive cancers, though, treatment is necessary, and several options are available. “And because, in many patients, we can’t truly say that one option is better than the others, it comes down to the patient’s decision,” Dr. Kuban said.
Radiation options
Although it can be delivered in a nearly endless variety of configurations, radiation therapy comes in two basic forms: internal or external.
External-beam radiation therapy has changed dramatically over the years because of technological improvements in imaging and in the treatment devices themselves. With the rise of computed tomography, sonography, and intensity-modulated radiation therapy (which uses lead blocking devices to shape the beam and delivers the dose from several different angles), it is now possible to deliver a higher dose of radiation to the prostate while sparing the rectum and bladder, minimizing the complications that plagued patients treated for prostate cancer in the past.
Radiation can also be delivered internally through the use of radioisotopic implants. “It’s all done through a needle through the perineum, using a grid and using ultrasound ahead of time to map out where we’re going to put the needles and where we’re going to put the seeds,” Dr. Kuban said. The radioactive metallic seeds are smaller than grains of rice, and 80 to 100 of them are typically implanted into a prostate gland. The big advantage from the patient’s perspective is that it is a one-time procedure, as opposed to 42 treatments over eight and a half weeks for external-beam therapy.
“Early-stage prostate cancer can typically be treated very well with radiation alone and with a high success rate,” Dr. Kuban said.
Surgical options
Surgery comes in even more forms, but all share one goal: removal or destruction of the entire prostate gland.
The standard in radical prostatectomy is the open retropubic approach. In this type of surgery, a small midline incision is made below the navel down to the pubic bone, which allows access to the bladder and prostate. Another method is the perineal approach, entering between the scrotum and the anus. Unfortunately, the perineal approach does not allow lymph node sampling. But in patients with low-risk disease this is acceptable.
Laparoscopic surgery is increasingly being used for radical prostatectomy. “With laparoscopy, you can sample the lymph nodes and remove the prostate as completely as you would with an open incision, using five smaller incisions,” Dr. Pettaway said. “Laparoscopic prostatectomy is a challenging procedure and requires specialized training.”
Early data seem to show that there is less blood loss with this procedure than with conventional surgery. It also appears that the laparoscopic procedure allows a quicker recovery. “My feeling in talking to patients is that the ones who undergo laparoscopic prostatectomy may be getting back to normal activity a little bit quicker, maybe a week or two sooner than with the open approach,” Dr. Pettaway said.
Cryosurgery is making a resurgence due to technological advances. Previously, it was impossible to be certain the entire prostate gland was being frozen without also destroying surrounding structures. As in the external-beam radiation therapy, the advent of sonography has allowed for much more precise monitoring of the procedure. In addition, the development of a urethral warmer and temperature probe monitors placed near the rectum and external sphincter have helped decrease complications.
The next step into the future of prostate surgery is robotic surgery. “The surgeon actually performs the surgery by sitting at a remote console,” Dr. Pettaway said. “The robot is at the bedside with a human assistant.” Ports are placed just as in laparoscopic surgery, and the robot’s hands manipulate the instruments in response to movements made by the surgeon at the remote console. The biggest benefit is that the surgeon is looking at a three-dimensional image rather than trying to interpret a two-dimensional image, as in laparoscopy. “Most urologists who have tried robotic surgery say they really like it,” Dr. Pettaway said.
Nerve grafts, gene therapy, and other advances
One of the biggest concerns among patients being treated for prostate cancer is maintaining sexual function. Radical prostatectomy can include the severing of one or both cavernous nerves in order to obtain negative surgical margins. This can dramatically diminish erectile function. To address this issue, surgeons recently have begun taking the sural nerve from the leg and grafting it between the two cut ends of the cavernous nerve. Early studies in humans showed that about half the men who had the sural nerve graft were able to have erections, as opposed to about 5% of those who had a bilateral non-nerve-sparing procedure. Researchers are currently trying to determine whether sural nerve grafting would also be beneficial for men who have had only one cavernous nerve severed.
Other researchers are working with radiosensitizers and radioprotectors, drugs that make the tumor more sensitive and the healthy tissues less sensitive to the effects of irradiation. Gene therapy is also the focus of current study in the hope that researchers will find a genetic “off switch” for tumor growth.
With all these advances, when treatment of early-stage prostate cancer is required, it is now quite feasible. But the next step goes beyond treatment.
“We’ve moved all the way from treating prostate cancers at a relatively advanced stage to finding and treating them at a very early stage in many instances,” Dr. Kuban said. “But now we want to back up even further and look at preventing them altogether.” For example, M. D. Anderson is leading a large, multicenter trial to investigate whether vitamin E and selenium may be effective in preventing prostate cancer.
And no matter how technologically advanced the treatment, prevention is always a preferable option. “That would actually be the best that we could offer the patient,” Dr. Kuban said.
For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789.
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