If you were suddenly kidnapped and blindfolded, then abandoned in a foreign land, you would want the best possible map to get safely to the border where you could figure out a homeward-bound plan. For men who are diagnosed with high-risk prostate cancer (PCa), it’s as if a hostile unknown enemy has abducted them, deprived them of the solutions that usually let them see their way out of a problem, and given them no information to plan their best way out of the situation.

High-risk PCa: a Big Unknown

PCa patients whose clinical factors include a high PSA, high Gleason grade group or PI-RADS score, and late stage are at greater risk for PCa infiltration of the lymph system, or even distant metastasis (mets). Common sense suggests that the sooner they undergo an aggressive treatment with curative intent (i.e. radical prostatectomy, high dose radiation, or a combo of surgery and adjuvant radiation), the better the chance of catching all the cancer in the prostate and immediate vicinity.

However, before implementing such invasive treatment, it’s important in high-risk cases to determine if “the horse has already left the barn” (as many patients put it). Has it or hasn’t it? This is a Big Unknown because conventional imaging (including multiparametric MRI, bone scans, and CT scans) can’t identify very small areas of PCa spread. Only “seeing” the true extent of the disease can remove the blindfold and point the way to an appropriate treatment plan.

PSMA PET scan offers better detection

A new type of imaging utilizes a molecule that is abundant on PCa cancer cells. It is called Prostate Specific Membrane Antigen (PSMA). Its function on the cell’s outer membrane is to recognize and take in substances that PCa thrives on. A PSMA PET scan is like the Trojan horse that concealed Greek soldiers into the city of Troy. It bonds a tiny radioactive isotope to something the PSMA molecules will take in and act as a PCa identifier. When the bonded isotopes are injected into the patient’s blood and circulate, PCa cells anywhere in the body will absorb the isotope into the cell. Then, they “light up” during the PET scan, revealing their presence. Thus, even very small colonies of PCa cells that would have been missed by MRI or CT are revealed. And, by the way, the isotopes themselves have less radiation exposure than a CT scan. Detecting these colonies will then impact clinical decision-making.

Recent study demonstrates PSMA PET superiority

In March, 2020 The Lancet journal published a randomized study comparing PSMA PET with conventional CT and bone scan for the detection of metastatic lesions in patients scheduled for prostatectomy or radiation therapy.^[i] The study ran from 2017-19, with 302 participants who had high-risk PCa, defined as clinical stage >T3, PSA > 20 ng/mL, or Gleason grade group 3-5. The patients were randomly assigned to either PSMA PET scans or CT plus bone scans. 295 men were available for follow-up, and of those 30% were found to have pelvic node metastasis or distant metastasis. The following chart compares the results of the two imaging approaches:

	PSMA PET	CT plus bone scan
Exposure to radiation levels	8.4 millisieverts	19.2 millisieverts
PCa sensitivity (true positive)	85%	38%
PCa specificity (true negative)	98%	91%
Detection of pelvic node mets	95%	74%
Detection of equivocal mets (could be or not)	7%	23%

Other findings include:

• Overall, PSMA PET-CT had 27% greater accuracy than that of conventional imaging
• First-line conventional imaging led to less management strategy change (15% vs 28%)
• Second-line conventional imaging also led to less management strategy change (5% vs 27%)

In a statement, lead author Professor Michael Hofman stated, “Taken together, our findings indicate that PSMA-PET/CT scans offer greater accuracy than conventional imaging and can better inform treatment decisions… We recommend that clinical guidelines should be updated to include PSMA PET/CT as part of the diagnostic pathway for men with high-risk prostate cancer.”^[ii]

EAU Guidelines

The European Association of Urology (EAU), in its prostate cancer guidelines, notes that PSMA PET improves the detectability of PCa lesions, and is an “attractive target because of its specificity for prostate tissue, even is expression of PSMA in other non-prostatic malignancies, sarcoidosis or benign bone disease, may cause incidental false-positive findings.”^[iii] In reviewing numerous previous studies on PSMA PET, the guidelines point out that regarding lymph node involvement, it has higher sensitivity compared to multiparametric MRI, abdominal contrast-enhanced CT or choline PET/CT.

As of this writing, the EAU Guidelines do not specifically include PSMA PET as a standard of care in the diagnostic pathway for high-risk prostate cancer, but their summary of available data underscores Prof. Hofman’s observation. I believe that in a very short time, PSMA PET will indeed be embraced as an essential component of gathering accurate information in order to generate the most appropriate treatment roadmap for high-risk PCa patients.

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.

[i] Hofman MS, Lawrentschuk NL, Francis RJ, Tang C et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomized, multi-centre study. Mar. 22, 2020. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30314-7/fulltext
[ii] Ingram, Ian. “PSMA PET/CT Better Detects Prostate Cancer Spread.” MedPage Today, Mar. 24, 2020.
[iii] Motter N, van den Bergh RCN, Briers E et al. EAU guidelines: prostate cancer. Uroweb. https://uroweb.org/guideline/prostate-cancer/