Active Surveillance May Be Safe After Prostate Tumor Upgrade

Neil Osterweil

June 26, 2015

Men with low-risk prostate cancer on active surveillance whose tumors are upgraded after a biopsy might not have to rush into surgery, according to new research.

In these men, the risk for further upgrading, should they choose to remain on surveillance for a while, is relatively low.

"What this study says is that for those who are on the fence or want some additional time to think about it, it's likely safe to wait for treatment, said Christopher J. Welty, MD, a urology fellow at the University of California, San Francisco.

"You don't have to jump onto treatment right away just because of an upgrade," he told Medscape Medical News.

The men in this study had localized low-risk prostate cancer — a Gleason score of 3 + 3 or lower and a clinical stage of T1 or T2. All had a tumor upgrade while being managed with active surveillance

The majority of the men who chose to remain on active surveillance after a tumor upgrade, rather than undergo immediate treatment, had no further progression of tumor grade.

Notably, of the men who went on to radical prostatectomy, only 6% had a further upgrade on surgical pathology, and 34% of specimens were downgraded.

The findings were published in the July issue of the Journal of Urology.

"These data suggest that immediate surgery is not always necessary when Gleason score upgrading is found in men undergoing active surveillance," writes Leonard S. Marks, MD, from the University of California, Los Angeles School of Medicine, in an accompanying editorial.

When to Treat?

The vagaries of the management of low-risk prostate cancers prompted the investigators to evaluate whether delaying treatment in men with a tumor upgrade during active surveillance could result in adverse outcomes.

They took a retrospective look at 525 men who were followed for at least 6 months after a diagnosis of lower-risk prostate cancer. All of the men had a minimum of six cores taken at prostate biopsy; 33% were positive and no single core was more than 50% positive.

Overall, 219 of the men had a tumor upgrade; 150 (68%) were upgraded to a Gleason score of 3 + 4, and 69 (32%) were upgraded to a score of 4 + 3 or greater. Median time to upgrade was 23 months.

At the time of the analysis, 26 men (17 with 3 + 4 and nine with 4 + 3) had not undergone a second biopsy or treatment. Of these 26 men, 17 were followed with prostate-specific antigen (PSA) testing and/or ultrasound, and nine did not have a follow-up visit after upgrading.

For the remaining 133 men with an initial upgrade to 3 + 4, 57 (43%) remained on active surveillance and went on to a second biopsy. After that biopsy, seven were upgraded again and 23 were downgraded.

After the second biopsy that followed the initial upgrade, 23 men remained on surveillance and went on to a third biopsy, two men were upgraded, and 14 were downgraded. Of the remaining men, 12 went on to a fourth biopsy (two upgraded, five downgraded) and a six went on to a fifth biopsy (four downgraded).

Of the remaining 60 men who had an initial upgrade to a Gleason score of 4 + 3 or greater, 11 stayed on surveillance and underwent a second biopsy, leading to three upgrades. Four men went on to a third biopsy, leading to one upgrade. Only one of the men in this group stayed on active surveillance until the fourth biopsy.

Overall, 163 of the 219 men (74%) sought treatment after an upgrade. Of these, 113 (69%) underwent radical prostatectomy, 46 (28%) underwent radiation therapy, two (1%) underwent cryotherapy, and two received androgen-deprivation therapy.

At 5 years, more patients with an initial upgrade to a Gleason score of 3 + 4 than with an initial upgrade to 4 + 3 or greater had not gone on to treatment (22% vs 10%).

As noted above, at the time of radical prostatectomy, only 6% of tumors were upgraded from the highest preoperative Gleason score, whereas 34% were downgraded.

On logistic regression analysis, the only contributor to adverse pathologic outcome at the time of radical prostatectomy was a cancer volume at initial diagnosis of at least 33% of positive cores or more than 50% of a single core (odds ratio, 3.33; P = .02).

Age at diagnosis was not significantly predictive of adverse outcomes, nor were PSA density, time to initial upgrade, time from initial upgrade to surgery, initial upgrade category, overall prostate volume at diagnosis, or Cancer of the Prostate Risk Assessment score at diagnosis.

In his editorial, Dr Marks suggests that targeted prostate biopsy performed with MRI–ultrasound fusion might help determine which patients can be safely managed with active surveillance because it allows for tracking of specific tumor sites over time and can help reduce sampling errors in follow-up biopsies.

"In the near future, targeted prostate biopsy will likely lead to the redefinition of current standards for enrollment, follow-up, and active treatment of men in active surveillance programs," he writes.

The study was supported by the US Department of Defense Prostate Cancer Research Program. One of the study investigators, Peter Carroll, MD, from the University of California, San Francisco, reports financial interests and/or other relationships with the National Institutes of Health, the Department of Defense, Myriad Genetics, AUA Update, Genomic Health, and Medivation/Astellas. Dr Marks has disclosed no relevant financial relationships.

J Urol. 2015.194:8-9, 85-90. Editorial, Abstract

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