ORLANDO -- Almost a third of men on active surveillance for prostate cancer had an upgrade in Gleason pathology grade during follow-up, biopsy results for almost 600 patients showed.
During median follow-up of 6.4 years, 31.3% of the localized cancers were upgraded. The proportion of men with upgraded tumors increased over time, D. Andrew Loblaw, MD, reported here at the Genitourinary Cancers Symposium. "This increase over time was not statistically significant, but it allows for some hypothesis generation."
Clinical stage at diagnosis, PSA velocity, number of involved biopsy cores, and the interval to follow-up biopsy predicted an increased likelihood of Gleason upgrading, according to Loblaw, who practices at Sunnybrook Health Sciences Center in Toronto.
Intermediate-risk tumors had an upgrade probability more than double that of low-risk tumors -- 1.9% per year compared with 0.75%, although the difference did not achieve statistical significance.
"Gleason upgrading increases with time from diagnostic biopsies and might be higher in patients with initial Gleason 7 disease as opposed to Gleason 6," Loblaw said.
Men with localized prostate cancer have a 10-year disease-specific survival exceeding 97%, making active surveillance a reasonable option for many patients. Considerable research has focused on factors that can identify men who have an increased risk of progression, but pathologic upgrading has received little attention, said Loblaw.
In the largest published study to date, investigators at the University of California San Francisco found that a third of 377 patients in surveillance had pathologic upgrading of their tumors during 4 years of follow-up (J Clin Oncol 2011; 9: 2185-2190).
However, studies have produced little information about factors associated with upgrading, said Loblaw. In an effort to gain some insight into those factors, he and his colleagues analyzed a prospective database of patients entered into active surveillance at Sunnybrook Health Sciences Center
Eligibility for active surveillance required a biopsy Gleason score =6 and a PSA level =10 ng/mL. For patients older than 70, the criteria consisted of a Gleason score =3+4 and a PSA level =15 ng/mL.
Patients had repeat PSA testing every 3 months for 2 years and then every 6 months thereafter. Scheduled follow-up biopsies occurred after 1 year and then every 3 years until age 80.
Patients and physicians considered active treatment in the event of a PSA doubling time <3 years, histologic upgrading, and clinical progression, as well as patient preference.
As of August 2012, the database included 862 patients, including 592 who had at least one repeat biopsy. The subgroup of re-biopsied patients had a median age of 68 and a median baseline PSA of 5.5 ng/mL.
Loblaw reported that 83% of the patients had T1 disease and 17% had T2. Additionally, 20.2% of patients had intermediate-risk disease, 0.3% had high-risk prostate cancer, and 79.4% had low-risk cancer.
Multivariate analysis of baseline and dynamic factors associated with upgrading identified clinical stage at diagnosis (OR 2.301, P=0.0028), percentage of involved prostate biopsy cores at diagnosis (OR 1.768, P=0.0007), PSA velocity >2 (3.274, P<0.0001), and interval to re biopsy (OR 1.437, P=0.0102).
Subsequently, 114 (62%) of men whose tumors were upgraded chose to undergo treatment. The investigators found that a higher proportion of treated patients had a Gleason score of 8 (22% versus 2.9% of untreated patients), and treated patients had a significantly higher PSA velocity (1.2 versus 0.42 ng/mL/y, P=0.01).
The likelihood of upgrading increased over time, including 18.4% of patients followed for up to a year to 36% of patients followed for 7 to 8 years, 36% of patients followed for 8 to 9 years, and 26% of patients followed for more than 9 years.
In the discussion that followed the presentation, a panel of prostate cancer specialists and the audience engaged in a prolonged discussion about the future of surveillance for localized prostate cancer. Eric Klein, MD, of the Cleveland Clinic, suggested the time has come to reconsider the focus of surveillance.
"We have all patted ourselves on the back that we can identify patients who aren't going to die of their prostate cancer, with appropriate surveillance criteria," said Klein. "Shouldn't we raise the bar now?
"Given the cost and morbidity of metastatic disease [should we be asking] how much longer patients with metastatic disease are living? Should we say the goal of therapy or surveillance ought to be to avoid metastatic disease, rather than simply avoid death?"
The Genitourinary Cancers Symposium is co-sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.
Loblaw and co-investigators had no relevant disclosures.
Primary source: Genitourinary Cancers Symposium
Source reference:
Jain S, et al "Gleason upgrading with time in a large, active surveillance cohort with long-term follow-up" GuCS 2013; Abstract 1.
Charles Bankhead
Staff Writer
Working from Houston, home to one of the world's largest medical complexes, Charles Bankhead has more than 20 years of experience as a medical writer and editor. His career began as a science and medical writer at an academic medical center. He later spent almost a decade as a writer and editor for Medical World News, one of the leading medical trade magazines of its era. His byline has appeared in medical publications that have included Cardio, Cosmetic Surgery Times, Dermatology Times, Diagnostic Imaging, Family Practice, Journal of the National Cancer Institute, Medscape, Oncology News International, Oncology Times, Ophthalmology Times, Patient Care, Renal and Urology News, The Medical Post, Urology Times, and the International Medical News Group newspapers. He has a BA in journalism and MA in mass communications, both from Texas Tech University.
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