Gallium-68 PSMA PET scanning “is a game changer” in prostate cancer

The “game changer” statement above comes from an independent review of the potential value of gallium-86-labeled prostate-specific molecular antigen (68Ga PSMA) PET scanning in the evaluation of selected men with prostate cancer. The review was written very specifically with regard to the potential future use of 68Ga PSMA PET scanning in the UK’s National Health System.

The review by Afaq and Bomanji in the British Medical Bulletin addresses, with great specificity, what will be needed to assure wide availability of 68Ga PSMA PET scanning in the UK and which types of patient will benefit. The entire, relevant paragraph from the abstract of the review reads as follows:

68Ga-PSMA PET is a game changer and superior to choline PET and other established tracers which have been used in prostate cancer evaluation. Detection of recurrence at the prostate bed remains challenging due to bladder and urethral tracer accumulation. The main strength of PSMA PET/CT is its ability to identify small (< 8 mm) pathological lymph nodes, upstaging nodal status in up to two-thirds of cases. Additionally, PSMA PET/CT, detects bone and bone marrow metastases missed by conventional bone and CT imaging. Thus, PSMA PET/CT has major impact on patient management, with studies reporting overall changes in 39–76% of cases.

However, it then goes on to discuss the cost/value issues that will need to be addressed in order to make the decision about whether the investment in new PET scanning centers required to make such procedures widely available in the UK can be justified.

This is a question that won’t just challenge systems like the nation-wide National Health Service in the UK. It will also challenge a whole other spectrum of health service providers in the US, and most particularly those like the Veterans Administration, Kaiser Permanente, TriCare, and others in which the provision of medical services is actually the responsibility (financial and logistical) of the payer for those services.

Some European countries, and Australia, have already started to address this issue in practical terms since they have longer experience with the potential of 68Ga PSMA PET scanning. Hopefully we in the US will be able to take advantage of their experience in making our own decision about investing in this technology over the next few years.

4 Responses

  1. 68Ga also for neuroendocrine differentiation in prostate cancer?


    Sitemaster and Allen: Just this morning I saw another report about gallium-68 in a different role, different mode, and in pancreatic cancer patients that yet may be highly relevant to prostate cancer patients.

    The researchers were investigating how neuroendocrine tumors (NETs) could be detected using gallium-68 DOTA peptides broadcasting to an MRI machine with PET/CT also playing a role; I was unclear about the use of MRI and PET/CT in the study, though both were mentioned.

    The relevance to prostate cancer is that there has been a substantial increase in neuroendocrine cell differentiation that apparently results from profound androgen deprivation, as is being noticed in patients on Zytiga and Xtandi. (This differentiation is apparently pretty well known, but new to me until 2 years ago. Here’s a link to just one recent paper about it. I caught that in searching PubMed for “prostate cancer AND neuroendocrine differentiation”, which turned up 746 hits; many had both neuroendocrine and prostate cancer in the titles of the latest 20 papers listed. Dr. Charles “Snuffy” Myers has addressed this issue and has mentioned his belief that estrogen can prevent or even reverse this conversion of regular prostate cancer cells to NET cells.)

    It was a small study, looking for and finding a very substantial difference in the tumor-to-background [signal] ratio (TBR); the results were impressive. See this commentary on the CancerNetwork web site or click here for the original abstract.

    Here’s a key paragraph:

    ‘“A unique and important feature of NETs is that they express somatostatin receptors, which can be targeted with radiolabeled peptides for imaging and treatment,” wrote study authors led by Mustapha El Lakis, MD, of the National Cancer Institute in Bethesda, Maryland. “Positron emission tomography with computed tomography using somatostatin analogues labeled with positron-emitting 68Ga dota peptides has been shown to be more accurate than other agents for detecting many types of NETs.”‘

  2. I wholly agree that Ga PSMA PET/CT scans can detect sites of recurrence for most patients with PSA recurrence. But we have to be fair. Ga PSMA change the game but we hardly know whether the change of the game adds for the patients. Paradoxically we only know that patients with a negative Ga PSMA benefit from salvage radiotherapy for the prostate bed (compared with no treatment). For patients with cancerous sites in lymph nodes at recurrence, we know from 12 studies that targeted treatment with salvage lymph node dissection or regional radiotherapy leads to a new progress in about 18 months. So traditional treatments with a curative intention did not lead to a cure of these patients. It may be extrapolated that new studies will show the same lack of cure. One option, of course, would be to add systemic PSMA-based radioligand therapy for such patients, but to my knowledge only one trial has tested that idea although Lu PSMA radioligand therapy is known to be effective with only moderate side effects.

  3. Dear Finn:

    I don’t think that anyone is suggesting, as yet, that we know how to best treat all men whose disease recurrence(s) can be relatively accurately identified and located using new scans like the 68Ga PSMA PRT/CT scans. We don’t even know which of the differing 68Ga PSMA molecules may offer the most accurate PET/CT outcomes in terms of location of the recurrence(s) — yet.

    The “game changing” issue is simply that this form of scan transforms the opportunities over time. Once we are confident that we can locate small areas of recurrence with a high level of accuracy, there are all sorts of possible ways that we may be able to treat such recurrences with highly targetable forms of therapy. Some such treatments may be implemented with curative impact in some patients. In other patients it may be possible to extend progression-free survival by a significant period of time (but not actually “cure” them). This offers us a whole range of new research opportunities — and this is not just an academic issue.

  4. Dear Finn:

    You wrote that:

    “For patients with cancerous sites in lymph nodes at recurrence, we know from 12 studies that targeted treatment with salvage lymph node dissection or regional radiotherapy leads to a new progress in about 18 months.”

    If I understand this statement — salvage pelvic lymph node radiation does not work.

    Can you list the 12 studies?

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