Radio-guided surgery in the treatment of recurrent, initially localized prostate cancer

The re-treatment of patients with recurrent prostate cancer after initial, first-line treatment for what was initially diagnosed as localized disease can be complicated. Success (i.e., effective re-treatment with curative intent) in the re-treatment of such patients is often dependent on the ability to identify exactly where recurrence has occurred.

One of the uses of some of the newer forms of radio-ligand, such as 68Ga-PSMA, is that the use of these radio-ligands in combination with a PET scan is often able to identify areas of soft tissue or individual lymph nodes in which cancer has recurred (or from which the cancer was not completely removed in the first place) with the level of accuracy that is needed to implement radio-guided re-treatment. With the ability to identify such small foci of cancer with accuracy comes the potential to treat those areas of cancer recurrence with a high degree of specificity and accuracy (as opposed to using the older and more traditional methods of radiation of the entire prostate bed or of the entire pelvic area, with or without concomittant androgen deprivation therapy, as appropriate).

A new paper by Horn et al. in the German journal Der Urologie, provides us with data on the surgical re-treatment of their initial cohort of 63 patients, all re-treated surgically after the use of 68Ga-PSMA PET scanning to identify the exact location of disease recurrence after first-line treatment.

Horn et al. report the following:

  • All 63 patients first underwent a 68Ga-PSMA PET scan.
  • All 63 patients were then re-treated for their re-current prostate cancer using radio-guided surgery based on the results of the 68Ga-PSMA PET scans of the individual patients.
  • Clavien–Dindo grade III complications occurred in 6 of 63 patients (9.5 percent).
  • The 63 patients provided a total of 277 surgically removed tissue specimens that had appeared suspicious for cancer recurrence.
  • These 277 specimens provided the following data regarding the predictive accuracy of the 68Ga-PSMA PET scans and the removal of the correct tissue:
    • Sensitivity, 86.2 percent
    • Specificity, 96.4 percent
    • Positive predictive value, 94.0 percent
    • Negative predictive value, 91.5 percent
  • Oncological follow-up data was available for 59/63 patients (92 percent).
    • PSA levels dropped to < 0.2 ng/ml in 38/59 patients (64 percent)
    • Of these 38 patients, 17 (45 percent) were free of biochemical recurrence after a median follow-up of 12.3 months (range, 6.7 to 31.9 months).

The authors state in conclusion that PSMA radio-guided surgery (PSMA-RGS)

proved to be of high value in patients with localised prostate cancer recurrence for exact localisation and resection of oftentimes small metastatic tissue using intraoperative and ex vivo gamma-probe measurements. Furthermore, PSMA-RGS has the potential to positively influence oncological outcomes. However, patient identification on the basis of 68Ga-PSMA PET imaging and clinical parameters is crucial to obtain satisfactory results.

We should of course note that this type of radio-imaging technique can be used to deliver a variety of types of therapeutic intervention, and not just surgical intervention. The more obvious possibilities include stereotactic body radiation therapy, high-intensity focused ultrasound (HIFU), and cryotherapy.

What is important about this paper is not simply that it shows how radio-guided surgery can be used as a method to offer highly focused re-treatment to patients with small areas of recurrence after their first-line treatment. Rather, it shows us clearly the value of radio-ligands like 68Ga-PSMA in combination with PET scanning as a method by which we can identify areas of recurrence with high degrees of accuracy and then treat those areas of recurrence with curative intent with a relatively high degree of effectiveness — potentially using any one of a number of differing techniques that may be deemed more or less suitable for individual patients.

However, we need to also recognize that “we have a ways to go”. In this particular cohort, 21/59 patients (36 percent) treated in this way did not see their PSA level drop down to < 0.2 ng/ml post-treatment. This implies either a failure of the 68Ga-PSMA PET scans to accurately identify cancerous tissue that needed to be removed or a failure of the surgical technique to completely remove tissue that needed to be removed despite its identification. And of course experience in the use of thsi technique may also be highly relevant to the quality of performance.

3 Responses

  1. I know some surgeons like to have an mpMRI for a similar purpose. There is a technique that was developed in Belgium that used an indium or gadolinium PSMA indicator intraoperatively (using a real-time gamma ray camera) to find cancerous lymph nodes for salvage ePLND. I thought that could be used during a prostatectomy to tell the surgeon where to cut wide, and importantly, where he doesn’t have to. I wonder how this technique compares to taking frozen sections with a pathologist standing by. An advantage may be avoiding slicing into the tumor.

  2. Among patients in my acquaintance with recurrent prostate cancer, it has been commonplace to get a [11C]acetate PET scan to find the site of recurrence, and then hit it with radiation if possible. (The newer 68Ga scans seem likely to replace 11C in this setting, given the inconvenience of working with 11C.) Limitations of this approach are (1) the lesion(s) found must be visible on CRT or MRI in order to be targeted by radiation, and (2) there is usually no histological verification that the targeted sites were indeed cancerous.

    PSMA-RGS overcomes both these limitations.

    I have to wonder about the reported negative predictive value of 91.5%. I take this to mean that the surgeon cut out a few nodes/specimens that did not give a radio signal, and 8.5% of them turned out to be cancerous. I have to wonder how many more such sites there were that the surgeon did not cut out that were also cancerous. In other words, the true “specificity” of this procedure could be lower than the reported value.

    I also wonder whether there isn’t some concern about radiation exposure for the surgeon and others in view of the intimate contact with radioactive tissue.

  3. Dear Tom:

    I am quite sure that the surgeons and their nuclear medicine colleagues worked out beforehand how to ensure that surgical exposure to ionizing radiation was well within the necessary safety limits. All hospitals have radiological safety committees that are responsible for overseeing such matters and ensuring that appropriate protocols are in place to manage such risk.

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