Quest Winter09 : Page 1

Quest t “Watchful Waiting” Is Really “Wishful Waiting” for Many Patients by William J tchful “Watchful Waiting” Is Really “Wishful Waiting” for Many Patients by William J. Catalona, MD O ne option now offered to men who are diagnosed with seemingly less aggressive prostate cancer is active surveillance or “watchful waiting.” The idea is that some patients won’t need treatment; their cancer will not progress and they can avoid surgery or other invasive treatment. The theory goes that if the cancer does progress, they can be treated at that time. It’s easy to see why the option is attractive. What man would want to have a radical prostatectomy or other invasive treatment if a “wait and see” approach would work. Unfortunately, in many cases, it doesn’t. The more appropriate name for “watchful waiting” is “wishful waiting.” We need to ask: Is cure necessary when possible? In my opinion, the answer, in most cases, is an unequivocal yes. Disadvantages of Active Surveillance At the time of diagnosis, no physi- cian can tell a patient how his prostate cancer will progress unless it has the characteristic features of aggressive cancers: Gleason grade 7 or higher, extensive involvement of biopsy cores with cancer, or rapidly rising PSA. One sure thing is that the patient Cheetahs are built for hanging out on a limb. For humans, it's an uncomfortable if not to say impossible situation. has cancer in the prostate. Another is that what appear to be less aggressive and low volume tumors can change to aggressive and fast growing tumors in the midst of “watchful waiting.” In those cases, the opportunity is missed to remove the cancer when cure was possible. The main disadvantages of active surveillance are: T It can delay prompt treatment of life-threatening tumors. It requires repeated biopsies that often make subsequent nerve-sparing surgery more difficult. It causes many patients anxiety about living with untreated cancer, thus diminishing their quality of life. (Continued on page 9.) he URF appreciates and needs your support for its lifesaving mission to support research and patient education in prostate cancer. Please consider an end of the year donation. © photo by Connie Lippowitsch

"Watchful Waiting" Is Really "Wishful Waiting" for Many Patients

William J. Catalona, MD

One option now offered to men who are diagnosed with seemingly less aggressive prostate cancer is active surveillance or “watchful waiting.” The idea is that some patients won’t need treatment; their cancer will not progress and they can avoid surgery or other invasive treatment. The theory goes that if the cancer does progress, they can be treated at that time.<br /> <br /> It’s easy to see why the option is attractive. What man would want to have a radical prostatectomy or other invasive treatment if a “wait and see” approach would work.<br /> <br /> Unfortunately, in many cases, it doesn’t. The more appropriate name for “watchful waiting” is “wishful waiting.” We need to ask: Is cure necessary when possible?<br /> <br /> In my opinion, the answer, in most cases, is an unequivocal yes.<br /> <br /> Disadvantages of Active Surveillance<br /> <br /> At the time of diagnosis, no physician can tell a patient how his prostate cancer will progress unless it has the characteristic features of aggressive cancers: Gleason grade 7 or higher, extensive involvement of biopsy cores with cancer, or rapidly rising PSA.<br /> <br /> One sure thing is that the patient has cancer in the prostate. Another is that what appear to be less aggressive and low volume tumors can change to aggressive and fast growing tumors in the midst of “watchful waiting.” In those cases, the opportunity is missed to remove the cancer when cure was possible.<br /> <br /> The main disadvantages of active surveillance are: It can delay prompt treatment of life-threatening tumors.<br /> <br /> It requires repeated biopsies that often make subsequent nerve-sparing surgery more difficult.<br /> <br /> It causes many patients anxiety about living with untreated cancer, thus diminishing their quality of life.<br /> <br /> No Validated Criteria<br /> <br /> Validated criteria for selecting patients to participate in active surveillance don’t exist. In addition, no validated triggers for switching from surveillance to active treatment exist.<br /> <br /> Perhaps, with more refined tests and more genetic information, validated criteria will be established. But for now, the present “wait and see” just isn’t good enough.<br /> <br /> Our study, and others, show that some patients who would seemingly qualify for surveillance from their biopsy and other diagnostic information – but decided to be treated with prostatectomy – had aggressive tumor features in their prostatectomy specimens. If they had postponed treatment, the cancer would most likely have been advanced and cure would not have been possible.<br /> <br /> Treatments After Active Monitoring<br /> <br /> In a Toronto study (Klotz L, Urol. Oncol,<br /> <br /> 2006) , 200 patients in active monitoring were followed for up to 10 years. About 60% remained on active monitoring, but of patients who underwent radical prostatectomy because their cancer had progressed; 58% had tumor extension beyond the prostate and 8% had lymph node metastases.<br /> <br /> In a Johns Hopkins study of 48 patients who had a radical prostatectomy after failing active surveillance, 35% had extraprostatic extension (EPE) of their cancer, the spreading of prostate cancer outside of the prostate; 15% had positive margins, cancer cells at the edge of tissue that’s been removed; and 6% had seminal vesicle/lymph node involvement.<br /> <br /> Cancer Cells Divide Exponentially<br /> <br /> Cancer cells increase in number exponentially with each cell division: from 1 to 2 to 4 to 8 to 16 to 32 to 64 and so on to a rapidly increasing large number. While we know each subsequent cell division results in a doubling of cancer cells; we don’t know the number of cancer cells multiplying – and the rate of that doubling – between each PSA or biopsy during the “watching.”<br /> <br /> Some Patients Slip Through the Cracks<br /> <br /> With both active surveillance and focal therapy (the lumpectomy of prostate cancer), potentially life-saving treatment may be delayed in some patients with initially understaged disease, meaning the initial biopsy did not reflect true involvement and aggressiveness of the cancer.<br /> <br /> Some of these patients will slip between the cracks and unnecessarily suffer and die from prostate cancer.<br /> <br /> Not Proven<br /> <br /> In healthy men with potentially curable prostate cancer and a long life expectancy, active surveillance and focal therapy should be considered investigational.<br /> <br /> More clinical research is needed to evaluate the tradeoffs before they can be considered legitimate treatment options.<br /> <br />

Detecting The Undetectable

New Technology Could Define New PSA “Zero”<br /> <br /> Ateam of Northwestern University researchers, using an extremely sensitive tool based on nanotechnology, has detected previously undetectable levels of prostate-specific antigen (PSA) in patients who have undergone radical prostatectomy.<br /> <br /> “Now, we are testing the findings further with serum samples from my patients,” Dr. Catalona said. “The test is not available for use and will not be available until is it approved by the FDA, which will require more time, but it looks promising.” This ability to easily and quickly detect very low levels of PSA may enable doctors to diagnose men with prostate cancer recurrence years earlier than is currently possible.<br /> <br /> “We have defined a new zero for PSA,” said Chad A. Mirkin, George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences.<br /> <br /> “This level of sensitivity in detecting low concentrations of PSA will take the blinders off the medical community, especially when it comes to tracking residual disease.” “This new PSA test may alter the management of patients who have been treated with surgery for prostate cancer,” Dr. Catalona said.<br /> <br /> Studies have shown that postoperative radiation therapy given early to patients with adverse pathology, called adjuvant radiation, reduces the recurrence rate and improves survival, “Because the ‘nano-PSA assay’ is more sensitive than the current commercially available PSA tests, it may allow physicians to target adjuvant radiation for patients destined to have a life-threatening tumor recurrence,” Dr. Catalona said.<br /> <br /> Also, this new test could track PSA levels early to evaluate the effectiveness of treatments for recurrent cancer such as radiation, hormone and chemotherapies.<br /> <br /> QUEST will keep readers informed about the progress of this research.<br /> <br />

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