THE "NEW" PROSTATE CANCER INFOLINK

A report in the Journal of Nuclear Medicine suggests that gallium-68 PSMA (⁶⁸Ga-PSMA or [⁶⁸Ga]PSMA) is better than an older radionuclide in detecting recurrent lesions in men with progressive prostate cancer after first-line therapy with surgery or radiation therapy.

There are several different radionuclides that have been developed, tested, and used clinically in attempts to find a molecule that can identify, visually, through PET/CT scanning, the precise location of very small areas of cancer recurrence after first-line or second-line (initial “salvage”) treatment for localized or locally advanced prostate cancer. The most widely known of these is probably [¹¹C]choline, but there are a number of other such agents, one of which is [¹⁸F]fluoromethylcholine ([¹⁸F]FMC). The problem with almost all of the currently available radionuclides that have been tested to date is that they are not very sensitive when the patient’s PSA level is low … and it is when the patient’s PSA level is low (i.e., well below 1 ng/ml) that one would most like to be able to identify the location of the recurrence and an appropriate way to treat it.

Morigi et al. have now reported results from a small, Phase II clinical trial — in just 38 patients — designed to explore whether one of the newest radionuclides suitable for this purpose, [⁶⁸Ga]PSMA, was as good or better than [¹⁸F]FMC for locating early recurrence of prostate cancer. Some comments on the study, based on a media release from the Journal of Nuclear Medicine, also appear on the ScienceDaily web site.

Between January and April this year, the authors carried out a series of tests on a consecutive sample of men at their clinic, all of whom had a rising PSA level after first-line treatment and were eligible for targeted treatment. Men who were receiving any type of systemic therapy (such as androgen deprivation) were not eligible for inclusion in the study. Imaging tests using [⁶⁸Ga]PSMA, [¹⁸F]FMC PET/CT, and a standard diagnostic CT scan were performed sequentially on all these patients.

Here are the basic study findings from among the 38 patients enrolled:

• 34/38 patients (89 percent) had had radical prostatectomy as primary treatment.
• 4/38 patients (11 percent) had had primary radiation treatment.
• 12 patients who had had a primary radical prostatectomy had also had salvage radiation therapy.
• The patients’ average (mean) PSA level was 1.74 ± 2.54 ng/ml.
• Scan results using [⁶⁸Ga]PSMA and [¹⁸F]FMC were all negative in 12/38 patients (32 percent).
• Positive scan results were obtained in the other 26 patients (68 percent).
  • 14/26 patients (54 percent) had a positive scan result with with [⁶⁸Ga]PSMA alone.
  • 11/26 patients (42 percent) had positive scan results with [⁶⁸Ga]PSMA and with [¹⁸F]FMC.
  • 1/26 patients (4 percent) had a positive scan result with [¹⁸F]FMC alone.
• With respect to the patients’ PSA levels, detection rates were
  • 50 percent using [⁶⁸Ga]PSMA when PSA was < 0.5 ng/ml
  • 69 percent using [⁶⁸Ga]PSMA when PSA was 0.5 to 2.0 ng/ml
  • 86 percent using [⁶⁸Ga]PSMA when PSA was > 2.0 ng/ml
  • 12.5 percent using [¹⁸F]FMC when PSA was < 0.5 ng/ml
  • 31 percent using [¹⁸F]FMC when PSA was 0.5 to 2.0 ng/ml
  • 57 percent using [¹⁸F]FMC when PSA was > 2.0 ng/ml
• [⁶⁸Ga]PSMA detected more lesions than [¹⁸F]FMC (59 vs. 29, P < 0.001).
• The findings on imaging significantly affected how patients were treated.
  • There was management impact on 24/38 patients (63 percent) in total
  • In 13/24 patients (54 percent) that management impact was due to [⁶⁸Ga]PSMA imaging alone.
• Histopathologic follow-up data were available for just 10/38 patients (26 percent).
  • 9/9 lesions (100 percent) identified as positive with [⁶⁸Ga]PSMA imaging were “true positives” for prostate cancer.
  • 1/1 lesion (100 percent) identified as positive with [¹⁸F]FMC but negative [⁶⁸Ga]PSMA imaging was  a “true negative” for prostate cancer.

Morigi et al. conclude, accurately, that

In patients with biochemical failure and a low PSA level, ⁶⁸Ga-PSMA demonstrated a significantly higher detection rate than ¹⁸F-fluoromethylcholine and a high overall impact on management.

But what this study really seems to be telling us is that, like [¹¹C]choline, [⁶⁸Ga]PSMA is only reliably accurate in men whose PSA level is > 2 ng/ml, and what we need are imaging agents that can reliably detect recurrent prostate cancer at PSA levels that are more like 0.2 ng/ml or lower.

On the other hand, [⁶⁸Ga]PSMA is a lot more stable than [¹¹C]choline, which means that at least it could be used at many different nuclear medicine centers, as opposed to having to be made, one dose at a time, to treat specific patients at specific clinics that have the manufacturing capability.

Filed under: Drugs in development, Living with Prostate Cancer, Management | Tagged: detect, gallium-68, locate, PSMA, radionuclide, recurrent |