Active surveillance (AS) for patients with prostate cancer include follow-up with serial prostate biopsies; however, prior research has not determined the optimal biopsy frequency during follow-up.


Assessing Biopsy Frequency

To better assess treatment goals for this patient population, Brian Denton, PhD, Christine Barnett, PhD, and colleagues investigated longitudinal AS biopsy data to determine whether the frequency of biopsy could be reduced without substantially prolonging the time to the detection of disease with a Gleason score of 7 or greater. Their results were recently published in Cancer.

“Reducing the number of biopsies a patient undergoes during active surveillance without compromising survival can improve patients’ lives by reducing the pain, anxiety, and risk of infection associated with biopsy,” says Dr. Barnett. “Infection is a growing concern for this patient population, since recent studies suggest that infection rates for patients undergoing active surveillance increase as a function of the number of biopsies that they have undergone.”

Using data from 1,375 men with low-risk prostate cancer enrolled in AS at Johns Hopkins, a hidden Markov model was developed to estimate the probability of under-sampling at diagnosis, the annual probability of grade progression, and the 10-year cumulative probability of reclassification or progression to a Gleason score of 7 or greater. The model simulated 1,024 potential AS biopsy strategies for the 10 years after diagnosis. For each of these strategies, the model predicted the mean delay in the detection of disease with a Gleason score of 7 or greater.

Patient Preference Is Key
The model estimated the 10-year cumulative probability of reclassification from a Gleason score of 6 to a Gleason score of 7 or greater to be 40.0%. The probability of under-sampling at diagnosis was 9.8%, and the annual progression probability for men with a Gleason score of 6 was 4.0%. On the basis of these estimates, a simulation of an annual biopsy strategy estimated the mean time to the detection of disease with a Gleason score of 7 or greater to be 14.1 months; however, several strategies eliminated biopsies with only small delays (<12 months) in detecting grade progression (Figure).

“Many guidelines have been advocated for optimal biopsy frequency, but none are universally agreed upon,” says Dr. Denton. “The guidelines vary greatly in terms of the frequency of biopsies, which are painful and cause anxiety for patients, sometimes causing patients to stop active surveillance altogether. We believe that the best strategy depends on the patient’s preferences regarding risk of cancer progression compared with the harm from biopsies.”

Drs. Denton and Barnett stress that although annual biopsy for low-risk men on AS is associated with the shortest time to the detection of disease with a Gleason score of 7 or greater, several alternative strategies may allow less frequent biopsies without sizable delays in detecting grade progression.

“We were surprised to see that published guidelines are very ‘efficient’ when compared with model-based optimized guidelines,” says Dr. Denton. “By efficient we mean that for a given frequency of biopsies (eg, every year, every 2 years, etc.), the mean delay in detection is very close to the minimal optimal delay. The study provides evidence that reducing the number of biopsies from annual to a lower frequency is associated with small increases in mean time to detecting progression. Based on our study results, patient preference should play an important role in determining the best course of action.”

References

Barnett, C, Auffenberg, G, Denton, B, et al. Optimizing active surveillance strategies to balance the competing goals of early detection of grade progression and minimizing harm from biopsies. Cancer. 124(4), 698-705. Available at: https://doi.org/10.1002/cncr.31101