Active surveillance, also referred to as watchful waiting, is a viable option for many men with low risk prostate cancer although the concept continues to cause distress and confusion. James L. Mohler, MD, of Roswell Park Cancer Institute and chair of the NCCN Guidelines Panel for Prostate Cancer, discussed the role of active surveillance as well as other treatment options recommended in the recently updated NCCN Guidelines™ for Prostate Cancer at the NCCN 15th Annual Conference.
“Not all 65 year old’s are alike”
Dr. Mohler noted that in addition to various controversial aspects of management, other factors such as the complexity of the disease and the lack of sound data to support most recommendations only compounds the challenge of treating prostate cancer.
“There are several variables that must be considered in order to tailor prostate cancer therapy to an individual patient and the NCCN Guidelines provide a solid framework on which to base these treatment discussions and subsequent decisions,” said Dr. Mohler.
Dr. Mohler discussed various organizations’ prostate cancer screening recommendations including those recently updated by the American Cancer Society as well as the NCCN Guidelines for Early Detection of Prostate Cancer.
“The current NCCN Guidelines recommend that at age 40, high-risk men begin annual PSA and DRE. All other men at age 40 should be offered a baseline PSA and DRE and if their PSA is 1.0 ng/mL or greater, they should receive annual follow-ups. If their PSA is less than 1.0, the NCCN Guidelines recommend that these men be early detected again at age 45,” said Dr. Mohler.
Dr. Mohler stressed that although PSA testing is a useful tool, it can be unreliable when used as a stand-alone measure.
“Seventy percent of men with elevated PSA levels have negative biopsies and PSA can fluctuate up to 36 percent from day to day,” said Dr. Mohler. “I believe that the rate at which a PSA level increases, the PSA velocity or PSA doubling time, is a more accurate method of diagnosing prostate cancer.”
The use of PSA for early detection is most appropriate for men who are at increased risk for developing prostate cancer including those with a first-degree relative that had prostate cancer (a brother or father, especially when diagnosed before age 65) and African-American men according to Dr. Mohler.
Dr. Mohler noted that the screening debate exploded in early 2009 as a result of the ERSPC (European) and the PLCO (American) studies published in the New England Journal of Medicine resulting in media reports stating that PSA screening has little impact on the risk of death from the disease.
Dr. Mohler explained that these studies are important, but need to be considered in view of their flaws including the lack of participant heterogeneity as only a very small number of trial participants had a family history of prostate cancer or were African-American. Also, in the European trial, the research protocols were inconsistent within the various study centers and in the American trial, the follow-up was too short and there was high contamination within the control group.
“The majority of men who participated in the two trials were not at a high-risk of developing advanced prostate cancer, so it is not surprising that PSA screening would have little impact on their risk of death from the disease,” said Dr. Mohler.
Switching gears from early detection to treatment, Dr. Mohler detailed significant additions to the updated NCCN Guidelines for Prostate Cancer describing several related to active surveillance.
The NCCN Guidelines have established a new “very low risk” category that incorporates the strictest Epstein criteria from all definitions for clinically insignificant prostate cancer. In addition, active surveillance and only active surveillance is now the recommendation for many men diagnosed with prostate cancer. Men with low risk prostate cancer who have a life expectancy of less than 10 years and men with very low risk prostate cancer with a life expectancy of less than 20 years should be offered and recommended active surveillance.
“We remain concerned about over-diagnosis and over-treatment of prostate cancer as growing evidence suggests that over-treatment of prostate cancer commits too many men to side effects that outweigh a very small risk of prostate cancer death,” stated Dr. Mohler. “The NCCN Guidelines Panel took careful consideration, including a thorough review of evolving data, of which men should be recommended for active surveillance.”
The active surveillance program recommended is defined in the NCCN Guidelines and stresses that active surveillance involves actively monitoring the course of the disease with the expectation to intervene if the cancer progresses. Dr. Mohler emphasized that patients under active surveillance must commit to a regular schedule of follow-up, which includes a prostate exam and PSA and may include repeat prostate needle biopsies.
“Ultimately this decision must be based on careful individualized weighting of a number of factors including life expectancy, disease characteristics, general health condition, potential side effects of treatment, and patient preference,” notes Dr. Mohler. “It is an option that needs to be thoroughly discussed with the patient and all of his physicians.”
Accurate life expectancy and time to death estimates are critical to guiding informed decision making in the treatment of prostate cancer. To calculate life expectancy, Dr. Mohler referenced the Principles of Life Expectancy Estimation in the NCCN Guidelines that recommend using the Social Security Administration tables and adjusting for overall health status and then comparing this to the estimated time to death from prostate cancer.
“Not all 65 year old’s are alike,” noted Dr. Mohler. “Calculating time to death from prostate cancer needs to incorporate a patient’s Gleason score, tumor volume, and tumor aggressiveness and that estimate needs to be compared carefully to a man’s physiological age, not his chronological age.”
As far as treatment modalities, two important updates were made concerning specific radiation treatment for prostate cancer to help prevent increased exposure and unnecessary side effects from radiation treatment.
The NCCN Guidelines now require daily image guided radiation therapy (IGRT) for high dose external radiation therapy. In addition, the NCCN Guidelines clarify what physicians should do when external beam radiation fails recommending a more aggressive evaluation and recommending against salvage prostectomy, cryosurgery, or brachytherapy if the recurrence is not documented with a biopsy.
Pointing to recent headlines expressing concerns about radiation safeguards Mohler stated, “The panel thought it was important that the guidelines address the increased side effects of high dose external radiation therapy (XRT) when it is not given with rigorous quality controls,” stated Dr. Mohler.
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