Risk of Prostate Cancer Reclassification Varies With Time

MedicalResearch.com Interview with:
Mufaddal Mamawala, MBBS, MPH, CPH

Biostatistician Johns Hopkins School of Medicine
Brady Urological Institute

Medical Research: What is the background for this study? What are the main findings?

Dr. Mamawala: Twenty years after prostate-specific antigen (PSA) was FDA approved for the diagnosis of prostate cancer, its use remains highly controversial. There has been an ‘over- diagnosis’ and ‘over-treatment’ of low-risk prostate cancers that would have never progressed to a more lethal form of the disease during one’s life. Active surveillance (AS) is an alternative to immediate treatment, which allows for monitoring of favorable risk patients with selective delayed intervention among those with disease progression. However  ‘misclassification’ is a cause of concern for patients in the initial years of been in AS. The initial biopsy may have missed an area of prostate with an aggressive cancer, due to under-sampling of cores or due to randomness, such that this patient could get misclassified as having a low-risk disease and by the time the follow-up biopsy shows an aggressive cancer the window of curability is lost.

However with more sampling of the prostate there is more likelihood to find an aggressive cancer. As such if the patient is compliant with their biopsies, and more prostate is sampled under the microscope, better are the chances of finding a higher risk cancer. Conversely if the patient has more biopsies that show no high-risk cancer then they are less likely to have a high-risk cancer on future biopsies. Thus we wanted to evaluate the risk of reclassification, from a low-risk disease to a high-risk disease (higher Gleason score, or increase in extent of the disease), over a period of time in compliant active surveillance patients.  The length of time under Active surveillance without reclassification has not been evaluated as a predictor of future reclassification. Biopsies are invasive procedures, and the fact that patient has to undergo this invasive procedure regularly is a deterrent from been in Active surveillance. This study would help to make informed decisions about the need for doing frequent biopsies in light with other clinical factors especially in older patients who had many non-reclassifying biopsies before.

We found that the risk of reclassification was not equally distributed across time. As a result of ‘under sampling’ of prostate at diagnostic biopsy we had highest rates of reclassification in the first two years of been in Active surveillance with more than 50% of total reclassifications happening during those two years. The ‘low-risk’ and the ‘very-low-risk’ groups, determined by the Epstein criteria, had similar rates of reclassification in the first two years. After first two years the ‘low-risk’ group were 2.4 times as likely to have a higher risk of reclassification than the ‘very-low-risk’ group. In both the groups the risk of reclassification declined over time significantly by at least 30% with each biopsy that did not show reclassification.

Medical Research: What should clinicians and patients take away from your report?

Dr. Mamawala:

  • Firstly, there is an increase risk of been misclassified in the initial years of been in Active surveillance.
  • Secondly, if one is compliant with their biopsies, after two years with each biopsy that shows no reclassification, the patient’s risk of having a higher-risk cancer on next biopsy goes down. The non-reclassified compliant patients who are in Active surveillance for over two years could be reassured that their risk of reclassification is much less than what it was at the time of diagnosis and is declining with time after each biopsy that fails to reveal reclassification. This should give them a motivation to be in Active surveillance. The longer they are in Active surveillance without reclassification, the better their chances of never getting detected with a higher-risk disease. Also for such patients appropriate decisions could be made regarding the frequency of future surveillance biopsies.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Mamawala: The risk of reclassification varies with time and is strongly related to how many biopsies, ‘litmus tests’, the patients passed. It would be worthwhile to estimate the risk of reclassification in patients who follow less stringent criteria of follow-up. The goal is to inform the patient about their question of  ‘If I enroll now what’s my risk of getting a high-risk cancer in future?’


Conditional Probability of Reclassification within an Active Surveillance Program for Prostate Cancer

Alam R, Carter HB, Landis P, Epstein JI, Mamawala M
J Urol. 2015 Jan 5. pii: S0022-5347(14)05219-7. doi: 10.1016/j.juro.2014.12.091.
[Epub ahead of print]

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