Minimal residual disease and the management of prostate cancer

The concept of “minimal residual disease” or MRD and how it affects risk for cancer-specific mortality is a subject of growing importance in the management of many cancers. But it is relatively new to the world of prostate cancer.

When it comes to prostate cancer, the concept of “minimal residual disease” is usually applied to the ability to identify very small numbers of prostate cancer cells in the blood stream or in the bone marrow after intensive treatment of men with unfavorable intermediate-risk or high-risk prostate cancer.

Murray et al. (from a team working in Chile) have recently reported prospective data based on a group of 321 patients who they followed for 10 years after initial therapy by radical prostatectomy. Here is what the authors did:

For each of this series of 321 patients, they tracked the patients’

  • Biochemical failure-free survival (based on serial PSA levels over time)
  • Time to biochemical failure
  • The presence of circulating prostate cancer tumor cells (CPCs) in their blood
  • The presence of micro-metastases (mMs) in their bone marrow

In the case of the last two evaluations, all patients provided a blood sample and a bone marrow sample only once — at 1 month after their radical prostatectomy.

Murry et al. classified the 321 patients into four groups:

  • Patients who were CPC-negative and mM-negative (Group A, n = 140)
  • Patients who were CPC-negative but mM-positive (Group B, n = 39)
  • Patients who were CPC-positive but mM-negative (Group C, n = 54)
  • Patiensts who were CPC-positive and mM-positive too (Group D, n = 88)

They then compared the outcomes of these patients at 10 years using standard Kaplan-Meier survival graphs and the so-called “restricted mean survival time” (RMST) for each group of patients.

Here is what they found at 10 years of follow-up:

  • For patients in Group A
    • Median survival was 92.7 percent (range, 86.3 to 96.2 percent)
    • RMST was 9.47 years (range, 9.24 to 9.69 years)
  • For patients in Group B
    • Median survival was 55.8 percent (range, 32.7 to 70.92 percent)
    • RMST was 9.23 years (range, 8.87 to 9.58 years)
  • For patients in Group C
    • Median survival was 6.4 percent (range, 1.2 to 18.2 percent)
    • RMST was 4.62 years (range, 4.46 to 4.77 years)
  • For patients in Group D
    • Median survival was 5.0 percent (range, 1.6 to 11.1 percent)
    • RMST was 3.57 years (range, 3.52 to 3.63 years)

Murray et al. conclude that:

CPC positive men have more aggressive disease, with increased early failure; men who are only positive for mM are at greater risk of late failure. These two forms of MRD represent different clinical entities with respect to biochemical failure and could be used to guide clinical treatment decisions.

This study offers us potential insights into a set of ways to predict which higher-risk  patients are in greatest need of early treatment to minimize risk for prostate cancer-specific death after initial therapy with curative intent. In particular, by combining testing for CPCs and mMs with tumor genotyping after radical prostatectomy in men with high-risk and unfavorable intermediate-risk prostate cancer, we may be able to have a superior method for prognosis of long-term outcomes of such patients soon after first-line surgery.

The use of these techniques after other forms of first-line therapy may be more complicated since in most cases it takes time for patients to stabilize their PSA levels after treatment. However, we expect to hear more about the application of this type of prognostic testing in the future.

3 Responses

  1. I compliment the authors for this fabulous study indicating the role of micrometastases for long-term survival, and for pointing out two relevant staging procedures for quantifying micrometastases — a phenomenon often talked about in treatment decisions but never previously quantified.

  2. So is it likely to become standard practice to take these samples after RP?


  3. Bob:

    I suspect that that will take a little time and at least one other data set that can confirm these findings.

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