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Prostate Cancer: A Tale of Two Therapiesby John LeBas Prostate cancer is a tricky foe. On the plus side, long-term overall survival is very high when the disease is found and treated before metastasis. But on the negative side, treatment may result in such side effects as decreased sexual, bladder, and bowel functions. Fortunately, new options have emerged at each extreme of the treatment spectrum: robot-assisted radical prostatectomy, which may cure the disease while avoiding side effects, and active surveillance, which keeps patients off treatment unless regular testing detects disease progression. Physicians at The University of Texas M. D. Anderson Cancer Center say such treatment options are allowing them to eradicate or control prostate cancer in more men with less reduction in their quality of life. Robotic surgery: Precision is key In M. D. Anderson’s robotic surgery suite, a patient lies belly-up on the operating table. A 1,500-pound robotic machine hulks overhead, its four metallic arms inserted into the man’s abdomen. Yet for all its bulk, this surgeon-controlled device is performing the most delicate of tasks—removal of a cancerous prostate, a procedure in which a successful outcome is determined in millimeters. At the helm is Dr. John W. Davis, an assistant professor in M. D. Anderson’s Department of Urology. From a nearby console that looks like an arcade racing game, he controls the robot’s movements using toggles and pedals while watching a 3-D video feed from a camera inside the patient. His other tools are essentially the same as any other surgeon’s—gripping, snipping, and cauterizing instruments. But the advantage is that they, too, are attached to the robot’s laparoscopic arms, which allow Dr. Davis to access and remove the diseased prostate with minimal tissue disturbance and a high degree of precision. “The point,” he says, “is that this is minimally invasive.” Impotence and urinary incontinence have long been among the possible complications resulting from radical prostatectomy. But in robot-assisted surgery, which is essentially next-generation laparoscopic surgery, the surgeon has the opportunity to reduce such complications. The reasons for this become clear as the procedure plays out on one of the video monitors in the surgical suite. The laparoscopic arms, which taper down to less than a half an inch in diameter, are inserted through a row of four evenly spaced incisions across the patient’s abdomen. As is true in other laparoscopic surgeries, this reduces the amount of muscle and other tissue that must be cut, reducing the time needed to heal. Most patients who undergo a robot-assisted prostatectomy are walking within a day. Once the arms are inside the patient, Dr. Davis can see most of the pelvic cavity and position the tools as needed. He separates connective tissue to move the arms past the bladder; the robotic device allows him to make precise cuts and avoid damaging nerves that control erectile function. Bleeders are quickly sealed with the cauterizing tool, if appropriate. However, near the nerve bundles that control erectile function, bleeders are carefully clipped or oversewn to avoid thermal damage. “Having a magnified, 3-D view and reduced bleeding is a tremendous advantage. The biggest challenge of open surgery is the smaller field of view,” says Dr. Davis, who has performed more than 400 robot-assisted radical prostatectomies. Then, the diseased prostate is revealed as he snips through the bladder. He carefully slices the prostate free—and precision here is key, since clear surgical margins are desired but there is little tissue to spare. “The prostate is surrounded by so much, such as nerves, the rectum, and urinary control muscles,” Dr. Davis says. “Treating prostate cancer with surgery is a different game than surgery for colon cancer, for example. We don’t have 5 extra centimeters to work with—the margins are measured in millimeters.” Once resected, the prostate is dropped into a small plastic bag and extracted through one of the laparoscopic tubes.
But the surgery isn’t over yet. Dr. Davis must also remove lymph nodes so they can be examined for signs the cancer has spread. The robot allows him to strip these tiny sacks away from the large pelvic blood vessels and nerves that go to the legs. Lastly, to prevent urinary incontinence, he reconstructs the bladder-urethra connection—severed during the prostate removal—using a needle and suture passed down through a laparoscopic arm. In this two-layer reconstruction, a few stitches are placed to connect the urethra and bladder, which will drain through an artificial catheter until normal urinary function can resume. A single supportive stitch placed at the pelvic wall will hold the bladder in proper position and enhance muscular control. Suturing must be precise to avoid damage to the urinary control muscles. With that, the laparoscopic arms are removed, the robot is wheeled away, and the patient’s incisions are sutured—leaving relatively little outside evidence of major surgery. Deciding how—and when—to treat Radical prostatectomy is frequently recommended for the treatment of localized prostate cancer because it can usually eradicate the disease. The younger a man is when prostate cancer is diagnosed, the more likely he is to be referred for a radical prostatectomy. The median age of men who undergo prostate surgery is about 62 years, with a range of about 40 to 70 years. Depending on the patient’s age and health status, other options for treating prostate cancer may include forms of radiation therapy, such as proton therapy and brachytherapy—all of which carry their own set of side effects. Prostate cancer often progresses slowly, and since the introduction of prostate-specific antigen (PSA) testing about 20 years ago, early detection has risen sharply. Accordingly, questions have arisen about whether a prostatectomy should be performed in men who may be more likely to die of other causes. “Because of widely available PSA screening, a lot of men are diagnosed with low-grade, very small prostate cancers, but there is no evidence that earlier detection of this type of disease means longer survival,” said Dr. Jeri Kim, an associate professor in Genitourinary Medical Oncology. “Because of the sensitivity of the PSA test, clinically insignificant tumors sometimes are diagnosed and patients may, as a consequence, be overtreated with radiation or surgery. If we can avoid unnecessary treatment and its side effects in these men, that would be a major quality-of-life advancement.” Dr. Kim is principal investigator of a trial that is testing “active surveillance” for prostate cancer to help clinicians determine which men belong in that category. Active surveillance takes the older concept of “watchful waiting” a step further. Rather than waiting for clinical signs of metastatic disease—when it is too late to eradicate prostate cancer—the researchers are using a regular testing regimen that closely and frequently monitors patients for disease progression. No treatment is started unless certain progression triggers are observed. A major goal of the study is to reliably identify patients who can forgo treatment, preventing unnecessary interventions and, thus, unnecessary complications, Dr. Kim said. But the investigators also hope their study of patients’ tissue and blood specimens will yield molecular markers for prostate cancer. In the end, they also want an improved risk model to emerge, one that better predicts how and why tumors progress.
“Right now, treatment recommendations are based largely on PSA levels and Gleason scores,” Dr. Kim said. A Gleason score is a disease assessment based on microscopic evaluation of cancerous prostate tissue. “That has served us well, but not all patients with the same cancer profile have the same progression rate. By incorporating molecular markers and redefining low-risk patients, we can develop risk-adaptive management for early prostate cancer.” The trial, which opened in February 2006, aims to accrue 650 patients. It has three study arms: patients with low-risk disease; those with localized disease who have chosen not to receive treatment; and those who have co-morbidities and thus are not candidates for surgery or radiation therapy. New participants are still being accepted. In the study, a PSA test and physical exam are conducted every 6 months, and transrectal ultrasonography is performed annually. A core biopsy is performed upon entry to the study and again after 1 year; the frequency of later biopsies may vary depending on the outcome of the initial set of biopsies. The patients are surveyed twice a year about their quality of life and dietary habits. Additionally, a support group led by staff psychologists meets monthly to help patients deal with the anxiety that often results from not actively engaging in treatment and to provide information about prostate cancer. Any of the following would trigger a recommendation to begin treatment: indication of cancer on repeat biopsy, upgrade of the patient’s Gleason score, an increase in tumor size, and a 30% increase in PSA level from the baseline level. The investigators have found that most patients do not meet the disease progression benchmarks during the first year of active surveillance. Looking ahead No long-term clinical data have been published on how robot-assisted surgery and active surveillance are improving patients’ quality of life, but the fact is that fewer damaging and unnecessary treatments are being done, Dr. Davis said. M. D. Anderson recently invested in a second surgical robot, one that will offer even better range of motion and will double the institution’s capacity for ever-more-popular robotic procedures. And the techniques are being refined, through such methods as a protocol designed by Dr. Davis that separates organ and lymph node dissection between two surgeons to see if this improves cancer control. Meanwhile, research into alternative methods of treating prostate cancer continues. For example, an upcoming cryotherapy protocol for patients with early prostate cancer will attempt to control the disease by freezing part of the prostate. “Compared to 10 or 20 years ago, we can offer prostate cancer patients a greater chance at recovery while minimizing quality-of-life complications,” Dr. Davis said, “and we will have even better therapy options in the future.”For more information, call Dr. Davis at 713-792-3250, Dr. Kim at 713-792-2830, or M. D. Anderson’s patient referral line at 1-877-632-6789. Other articles in OncoLog, January 2008 issue:
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