IN-DEPTH REVIEW OF RESEARCH

Study background:

While multiple imaging tests (e.g., X-rays, MRI, CT or bone scans) are FDA-approved as diagnostics to view the spread of prostate cancer, they are limited. Some imaging tests for prostate cancer have been observed to miss the spread of the disease, while other techniques have detected abnormalities that are unrelated, resulting in “false positives.”  

In the OSPREY and CONDOR clinical trials, researchers looked at ¹⁸FDCFPyL PSMA PET/CT as a possible imaging diagnostic to better detect prostate cancer and its spread to nearby organs compared with standard imaging.

¹⁸FDCFPyL PSMA uses positron emission tomography/computed tomography (PET/CT) imaging, which uses a radioactive drug to detect levels of prostate-specific membrane antigen (PSMA). The PSMA protein is normally found at a low level in normal prostate cells, but it is significantly increased in prostate cancer cells. PSMA can be detected in other organs as prostate cancer spreads.   

If ¹⁸FDCFPyL PSMA is confirmed by future studies to better detect the spread of prostate cancer to other organs, it could be a useful diagnostic for accurately staging the disease at initial diagnosis and relapse in men who were previously treated for the disease.  

Researchers of the studies wanted to know:

If ¹⁸FDCFPyL PSMA can locate the spread of prostate cancer in newly diagnosed men and in men whose cancer returned after treatment.

Study design and findings:

OSPREY

OSPREY was a phase 2 and 3 clinical trial that was held at 10 sites throughout the U.S. and Canada. The primary goal of the study was to test whether ¹⁸FDCFPyL PSMA PET/CT could detect spread of cancer to pelvic lymph nodes (organs near the prostate gland).

The study included 268 men, ranging from ages 46 to 84, with newly diagnosed high risk prostate cancer. Of these, 252 men were candidates for radical prostatectomy (complete removal of the prostate). Prior to the study, all participants had standard imaging to detect metastasis (spread) of cancer.

During the study, participants were given ¹⁸FDCFPyL PSMA by injection. Two hours prior to PET/CT scans, patients were injected with radioactive ¹⁸FDCFPyL PSMA that specifically targets PSMA throughout the body. (Data from PET/CT scans were tabulated by three PET/CT readers who were blinded to all participant clinical information.)

Among all 268 participants:

• ¹⁸FDCFPyL PSMA PET/CT detected prostate cancer metastasis to nearby lymph nodes in 27% of men (72 of 268 participants), compared with standard imaging which detected spreading in about 4% of men.
• Of the 72 men with metastatic cancer, 39 had cancers that spread only to nearby lymph nodes, while the other 33 men had cancers that metastasized to distant lymph nodes and other organs.

Among the 252 men in the study who had surgery to remove their prostate gland and nearby lymph nodes that could be looked at to confirm if the cancer had spread or not.

• standard imaging showed 244 of 252 (almost 97%) had no cancer spread.
• ¹⁸FDCFPyL PSMA detected prostate cancer in a total of 56 out of 252 (22%) patients. This changed the staging of their disease.

Most common side effects related to ¹⁸FDCFPyL PSMA included:

• distorted sense of taste (dysgeusia)
• headache

Strength of study

• This study included a large sample size, which is needed to determine if the technology works in multiple patients and to observe if side effects are associated with its use.

Limitations of study

(Findings of this trial were presented at a meeting. Due to time constraints, presenters were not able to present all aspects of the study. Limitations listed below may be addressed in detail in a follow-up manuscript.)

• The study did not include a placebo (control) group to control for false positives.
• Researchers did not mention how much time elapsed between standard imaging and imaging with ¹⁸FDCFPyL PSMA. It is possible that the cancer may have been limited to the prostate during standard imaging if much time had passed between the two procedures.
• The trial did not distinguish between people with or without an inherited mutation. Some medical treatment/procedures have been known to work better in people with specific mutations.
• The study did not mention race/ethnicity among patients. Some races/ethnicities are more responsive to certain medical procedures than others.

CONDOR

CONDOR was a phase 3 multicenter clinical trial performed at 14 sites throughout the U.S. and Canada. The study’s primary endpoint was whether ¹⁸FDCFPyL PSMA has the capability to detect the return of prostate cancer in men who were previously treatmented for the disease.

The study consisted of 208 participants between ages 43 to 91 who were treated with androgen deprivation therapy (testosterone deficient) and received treatment for a previous diagnosis for prostate cancer by prostatectomy only, radiation therapy only, combined prostatectomy and radiation therapy, or other systematic therapy.

Blood tests were given to the men during posttreatment follow-ups. Increases in prostate-specific antigen (PSA) levels that were greater than two nanograms/milliliters suggested possible return of cancer. At the start of the study, patients underwent standard imaging and completed questionnaires about their plans to treat relapse.

During the trial, participants underwent imaging with ¹⁸FDCFPyL PSMA PET/CT. They were injected with nine millicuries of the radioactive drug ¹⁸FDCFPyL PSMA one to two hours prior to having PET/CT scans.

The results showed that ¹⁸FDCFPyL PSMA PET/CT was able to detect cancer relapse in about 62 percent of participants, whereas standard imaging methods did not detect any return of cancer among participants. Results of ¹⁸FDCFPyL PSMA scans led 64 percent of participants to change their plans to treat relapse.

The most common side effects related to ¹⁸FDCFPyL PSMA PET/CT included:

• fatigue
• headache

Strengths of study

• The study included a large sample size, which is needed to determine if the technology works in multiple patients and to observe if side effects are associated with its use.
• The study included only men whose blood analysis suggested relapse of prostate cancer.

Limitations of study

(Findings of this trial were presented at a meeting. Due to time constraints, presenters were not able to present all aspects of the study. Limitations listed below may be addressed in detail in a follow up manuscript.)

• The study did not include a placebo (control) group to control for false positives.
• No information was given about which standard imaging procedures were used in the study. This is critical to make a fair comparison between ¹⁸FDCFPyL PSMA PET/CT imaging and a specific standard imaging technology.
• The trial did not distinguish between people with or without inherited mutations. Some medical treatment/procedures have been known to work better in people with specific mutations.
• The study did not mention race/ethnicity among patients. Some medical procedures may work better or worse for people of different races and ethnicities. 

Context:

Detecting the spread of prostate cancer to other organs is necessary to accurately stage and determine the severity of the disease. More accurate staging can help men make better decisions on treatment options for prostate cancer. Based on the studies’ findings, ¹⁸FDCFPyL PSMA PET/CT detected almost eight times more metastases among OSPREY participants and 62 times more cancer among CONDOR participants when compared with standard imaging. These data suggest that newer diagnostics are needed to improve the standard processes for staging and detecting the spread of prostate cancer.

Conclusions:

OSPREY and CONDOR clinical trials looked at the capability of ¹⁸FDCFPyL PSMA PET/CT to detect prostate cancer in newly diagnosed men and in castrated men who relapsed after prostate cancer treatment. If confirmed in future studies, imaging techniques that detect the increase and spread of PSMA using PET/CT scans could be better methods to determine metastasis and staging of prostate cancer compared with standard imaging.

Posted 10/16/20