A fictitious man named Craig was diagnosed with prostate cancer at age 64. His conventional 12-core TRUS biopsy showed he had Grade Group 2 (Gleason 3 + 4) only on the right side of his gland. Since he and his wife of 38 years, Sheila, had a good sex life, erectile function was important to Craig. He did not, however, like the idea of a partial gland treatment possibly leaving cancer growing. After having a bone scan and full-body CT scan—both of which did not show any prostate cancer spread–he chose to have a nerve-sparing robotic prostatectomy. Then came bad news.

First, his disease had been under-diagnosed. After surgery, his prostate was found to have one spot of Grade Group 4 (Gleason 4 + 4) missed by the biopsy. Worse, because his surgeon had also removed lymph nodes close to the gland, two of them were also positive for prostate cancer. Craig was stunned. His urologist recommended 6 months of hormone therapy followed by radiation.

If you know anything about hormone therapy—also called chemical castration—you know that it zaps a man’s sex drive. But Craig accepted the recommendation, took the injections and the radiation. His PSA dropped below zero. He was happy about that, and waited for his libido to return. About a year later, he woke up one morning with an erection. His PSA was stable at less than zero, and his manhood was saved! For their 40th anniversary, Craig and Sheila drank champagne and made sweet love.

Then comes the really bad news. Eighteen months after Craig and Sheila picked up their sex life where they left off, Craig’s PSA test registered 1.8. A re-test at three months revealed 2.0. The couple were devastated, but his urologist assured them that that two newly available PET scans that can detect even very small areas of prostate cancer spread, and with new immunotherapies, there was every reason to hope for many years of good health. Wanting the greatest odds of success, Craig asked, “Which scan is the best?”

Axumin vs. Gallium-68 – what does research show?

The two scans mentioned by Craig’s urologist are ¹⁸F-fluciclovine PET/CT (Axumin®) and Ga 68 PSMA-11 (Gallium 68 PSMA-11). Both of them use radioactive tracer element, or radiotracer, linked to a molecule that is attractive to prostate cancer cells. When the cancer cells “take up” the attractive molecule with its radioactive cargo, the radiation from element is concentrated in the cluster of cells (tumor). The radiation “lights up” on the scanner, revealing the tumor location. Both scans involve an intravenous injection of the radiotracer/molecule to travel through blood circulation to the tumor.

Each type of scan relies on a different radiotracer linked to a different molecule:

• Axumin uses the radiotracer ¹⁸Fluorine bound to an amino acid. Prostate cancer cells absorb amino acids much faster than normal cells do, so the radiotracer quickly concentrates in the tumor cells before healthy tissues can take it up.
• Gallium 68 PSMA-11 is a drug formulated with the radiotracer ⁶⁸Gallium to bind with a surface protein on prostate cancer cells called prostate specific membrane antigen (PSMA). This is different than the PSA found in the blood test. PSMA is a type of receptor or magnet that is abundant on the outer membrane of prostate cancer cells. It forms a chemical bond with the drug, causing the radioactive emission to concentrate on the tumor cells.

Both types of scans have had clinical success in spotlighting even very small, newly forming tumors that have spread beyond the prostate gland in areas such as the prostate bed, the pelvic lymph nodes, bones, and other organs in the body. Once locations are identified, there are many targeted therapies currently used and in development to manage these metastatic prostate cancer tumors.

The question remains, is one type of scan better than the other? Considerable research is being done to find an answer, since they are both good. For example, a 2017 paper by Calais, et al. reports a head-to-head study of 10 patients with suspected recurrent prostate cancer but very low PSA (< 1.1 ng/mL) who had had a Axumin scan followed within a few months by Gallium 68 PSMA-11. The results showed that Gallium 68 PSMA-11 improved detection over the Axumin scan as follows:

• Axumin missed prostate cancer in 5 patients that Gallium 68 PSMA-11 picked up
• In 2 patients that had positive results with both Axumin and Gallium 68 PSMA-11, Axumin missed additional lymph node metastasis that Gallium 68 PSMA-11 detected
• In the remaining 3 patients, both types of scans were negative for metastasis.^[i]

However, this study involved a small number of patients, and only after they had undergone Gallium 68 PSMA-11 scans were they found to have had previous Axumin scans, thus being a retrospective study.

A more recent, prospective (advance design) comparison study came from members of the same team. It involved 50 post-prostatectomy patients with PSA < 2.0 ng/mL who had both scans < 15 days apart. This study confirmed the superiority of Gallium 68 PSMA-11 as follows:

• Axumin detection rates were significantly lower than with Gallium 68 PSMA-11
• In the pelvic node region, Axumin detected 4 positive nodes vs. 15 with Gallium 68 PSMA-11
• In regions beyond the pelvic area, Axumin found no positive lesions vs. 8 with Gallium 68 PSMA-11

The authors concluded, “With higher detection rates, PSMA should be the PET tracer of choice when PET-CT imaging is considered for subsequent treatment management decisions in patients with prostate cancer and biochemical recurrence after radical prostatectomy and low PSA concentrations…”^[ii]

As with all scientific research, results can vary from one study to another. Another prospective comparison using 58 patients who were scanned with both methods an average of 9 days apart found similar results to the above 2 studies:

✓ Overall detection rates were 79.3% for Axumin vs. 82.8% for Gallium 68 PSMA-11

✓In the pelvic node region, Axumin had a 46.4% detection rate vs. 50% for Gallium 68 PSMA-11

✓ In bone metastasis, Axumin’s detection rate was 25.9% vs. 36.2% for Gallium 68 PSMA-11

However, Axumin performed better at detecting potentially curable localized lesions near the bladder, at a rate of 37.9% vs. 27.6% for Gallium 68 PSMA-11.^[iii] Overall, the authors concluded that Axumin’s performance was nearly as good as that of Gallium 68 PSMA-11.

Which method is best?

To return to Craig’s situation, his direct question to the urologist is warranted. Both scanning methods are game-changers for early detection of biochemical recurrence, because they facilitate treatment plans with the greatest chances for success. However, if his doctor has been following the research, he would be likely to prescribe Gallium 68 PSMA-11 rather than Axumin.

As of this writing, the use of Gallium 68 PSMA-11 appears to offer more accuracy than Axumin, with the possible exception of localized recurrence near the bladder. The timing is right for Craig. As of Dec. 1, 2020, Gallium 68 PSMA-11 is FD-approved for PET imaging of post-treatment prostate cancer patients whose PSA is rising (biochemical recurrence). It is also approved for untreated patients who are suspected of having advanced or metastatic prostate cancer at the time of diagnosis.

With luck, Craig’s scan will pinpoint one or two lesions that can be well managed by a urological oncologist, possible with curative effect. We join patients like our fictitious Craig whose advanced or recurrent prostate cancer can now be detected very early, thanks to Gallium 68 PSMA-11.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Calais J, Fendler WP, Herrmann K, Eiber M, Ceci F. Comparison of 68 Ga-PSMA-11 and 18 F-Fluciclovine PET/CT in a Case Series of 10 Patients with Prostate Cancer Recurrence. J Nucl Med. 2018 May;59(5):789-794.
[ii] Calais J, Ceci F, Eiber M, Hope TA et al. 18 F-fluciclovine PET-CT and 68 Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial. Lancet Oncol. 2019 Sep;20(9):1286-1294.
[iii] Pernthaler B, Kulnik R, Gstettner C, Salamon S et al. A Prospective Head-to-Head Comparison of 18F-Fluciclovine With 68Ga-PSMA-11 in Biochemical Recurrence of Prostate Cancer in PET/CT. Clin Nucl Med. 2019 Oct;44(10):e566-e573.