One of the hardest things to be able to do, currently, in a man with progressive prostate cancer after first- or second-line therapy, is to determine his risk for lymph node-positive prostate cancer or LNPPC (i.e., one of the earliest and more common components of metastatic prostate cancer).
In men who have negative bone scans and negative CT scans, this can most accurately be done by carrying out a lymph node biopsy, but it would be a great deal easier if the need for such biopsies could eliminated entirely or if it could be limited to men who clearly and reasonably accurately showed signs of LNPCC on some form of imaging test. There is no imaging test today that has been shown to do this with really high accuracy, although a variety of imaging tests (using [18F]fluoroethylcholine-based PET/CT scans, [11C]choline-based PET scans, Feraheme-based MRIs, and other imaging methods) are able to identify this type of miocrometastasis in some men with early forms of disseminated disease.
The problem is well illustrated by the recent approval of the Mayo Clinic’s Choline-11 for Injection — which came with a clear instruction that confirmation of results of [11C]choline-based PET scans must always be carried out through the use of lymph node biopsy (because of the risk for false positive results) and from a recent article by Tilki et al. (which illustrates a similar risk for false positive results in the use of [18F]fluoroethylcholine-based PET/CT scans).
Tilki et al. set out to assess the accuracy of [18F]fluoroethylcholine-based PET/CT scans in detection of LNPPC in men with rising PSA levels after first-line radical prostatectomy. To do this they compiled data from 56 patients between June 2005 and November 2011. All 56 patients were given an [18F]fluoroethylcholine-based PET/CT scan, demonstrated a positive result on the basis of that scan, and then underwent a bilateral pelvic and/or retroperitoneal lymphadenectomy.
Here is a summary of their results:
- The patients’ average (median) PSA value at the time of scan analysis was 6.0 ng/ml.
- In 48/56 patients (85.7 percent) histologic examination confirmed the presence of LNPPC.
- The average (mean) number of lymph nodes removed per patient was 21.0 ± 18.3.
- Elements of the overall accuracy of [18F]fluoroethylcholine-based PET/CT scanning were:
- Sensitivity, 39.7 percent
- Specificity, 95.8 percent
- Positive predictive value (PPV), 75.7 percent
- Negative predictive value (NPV) 83.0 percent
- Elements of a site-based analysis of accuracy showed:
- Sensitivity, 68.4 percent
- Specificity, 73.3 percent
- PPV, 81.3 percent
- NPV, 57.9 percent
Since men at their clinic who had negative results after [18F]fluoroethylcholine-based PET/CT scanning did not receive lymphadenectomies, we have no information about the sensitivity, specificity, and NPV of negative results of such scans.
Tilki et al. conclude that while positive results of [18F]fluoroethylcholine-based PET/CT scanning could correctly predict the presence of LNPPC in about 85 percent of their patients with biochemical progression after radical prostatectomy, the test missed a significant percentage of men with metastatic lymph nodes and was not sufficiently accurate for the precise assessment of nodal recurrence. Since we also don’t know what percentage of their patients might really have had LNPPC but negative results on [18F]fluoroethylcholine-based PET/CT scanning, we have no idea of the size of that possible problem.
Ideally, we need an imaging methodology that can either identify micrometastases with high, overall and site-specific sensitivity and a high specificity (e.g., both > 90 percent, which would also imply a high PPV and a low NPV) or with a high sensitivity (> 80 percent) and a very high level of specificity (> 95 percent) that can be carried out at low cost and be confirmed by lymph node biopsy or lymphadenectomy.