Surgery in Motion99mTechnetium-based Prostate-specific Membrane Antigen–radioguided Surgery in Recurrent Prostate Cancer
Introduction
Prostate cancer (PC) is a global health issue and the most commonly diagnosed cancer in men worldwide [1]. Even after curative-intended primary treatment by radical prostatectomy and/or radiation therapy, a significant number of patients experience biochemical recurrence (BCR) during follow-up. Besides local relapse, PC recurrence within lymph nodes (LNs) is common in early BCR. In some of these patients, salvage LN dissection may be considered as an individual therapeutic option [2]. However, two main challenges for the successful surgical treatment of those patients exist.
First, correct assessment of the true metastatic spread is crucial. Here, the introduction of positron emission tomography (PET) agents targeting the prostate-specific membrane antigen (PSMA) has led to substantial improvements [3]. PSMA represents a cell surface protein that is highly overexpressed on most PC cells. Small-molecular 68Ga-labeled ligands targeting PSMA have successfully been introduced into the clinics for PET imaging of PC [4]. 68Ga-PSMA-ligand PET is able to visualize metastatic lesions both at low prostate-specific antigen (PSA) values and in small subcentimeter metastatic LNs [5], [6], [7], [8]. Level 2b evidence based on these superior detection rates after radical prostatectomy led to a grade A recommendation of PSMA PET/computed tomography (CT) by the European Association of Urology [9].
Second, as metastatic LNs can atypically be located and/or are morphologically unremarkable, reliable intraoperative identification and removal of metastatic LNs are still challenging. Most recently, radioactive labeling of PSMA ligands with gamma-emitting radionuclides such as 111Indium (111In-PSMA imaging and therapy [111In-PSMA-I&T]) or 99mTechnetium (99mTc-PSMA investigation and surgery [99mTc-PSMA-I&S]) was established [10], [11]. These agents can be used for preoperative single photon emission computed tomography (SPECT) imaging and, in addition, surgical guidance with conventional gamma probes [12], [13]. For routine clinical application, 111In-PSMA-I&T is suboptimal due to its high cost, considerable radiation exposure, and restricted availability of 111InCl3 [14], [15]. In contrast, 99mTc-PSMA-I&S represents a valuable alternative based on easy access to 99mTc from 99Mo/99mTc generators as routine equipment in a nuclear medicine department at a relatively low cost.
Thus, the aim of this investigation was to describe the technique as well as feasibility of 99mTc-PSMA-I&S–based radioguided surgery (99mTc-PSMA-RGS) for removal of recurrent PC lesions and report on short-term outcomes.
Section snippets
Patients
Thirty-one consecutive patients with BCR after primary radical prostatectomy who underwent 99mTc-PSMA-RGS between September 2015 and May 2016 were included in this retrospective analysis. The median PSA value at the time of 99mTc-PSMA-RGS was 1.13 ng/ml (range: 0.29–3.81 ng/ml). Detailed patient characteristics are presented in Table 1.
All patients showed either a single or ≤4 metastatic soft-tissue lesions determined by 68Ga-PSMA N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]
99mTc-PSMA-RGS and comparison of gamma probe measurements with histopathology
99mTc-PSMA-RGS was able to identify and remove all lesions detected on preoperative 68Ga-PSMA-11 PET in all patients. In total, 132 surgical specimens were removed (median specimens per patient: 4; range: 1–10). Forty-six specimens were classified as positive and 86 were considered negative.
The count rate of the background reference ranged between 0 and 4 counts/s. For positive specimens, the median count rate during ex vivo gamma probe measurements was 21.5 (range: 4–246) counts/s, while
Discussion
The introduction of PSMA-targeting PET imaging has led to substantially improved visualization of small tumor deposits in patients with biochemically recurrent PC [7], [8], [17]. In parallel, salvage surgery has gained increasing interest in patients with locoregional oligometastatic disease to positively influence disease progression and delay the need for further systemic treatment [18], [19], [20]. However, no consensus about the extent of LN dissection and the templates that need to be
Conclusions
We demonstrate the feasibility of 99mTc-PSMA-RGS to guide intraoperative identification and surgical removal of metastatic LN in PC patients scheduled for salvage surgery. The surgical technique complemented by ex vivo gamma probe measurement with immediate feedback about successful removal of tumor deposits is highly useful to identify and excise small or atypically localized lesions, as seen on preoperative PSMA PET. However, caution is advised as both the procedure of 99mTc-PSMA-RGS and PSMA
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These authors shared first authorship.