The DROP-IN gamma probe facilitates minimally invasive, robot-assisted prostate-specific membrane antigen–targeted radioguided surgery in patients with recurrent prostate cancer. This procedure holds ...promise for improving the intraoperative identification and removal of prostate cancer lesions.
It has been proven that intraoperative prostate-specific membrane antigen (PSMA)-targeted radioguidance is valuable for the detection of prostate cancer (PCa) lesions during open surgery. Rapid extension of robot-assisted, minimally invasive surgery has increased the need to make PSMA-radioguided surgery (RGS) robot-compliant.
To evaluate whether the miniaturized DROP-IN gamma probe facilitates translation of PSMA-RGS to robotic surgery in men with recurrent PCa.
This prospective feasibility study included 20 patients with up to three pelvic PCa recurrences (nodal or local) on staging PSMA positron emission tomography (PET) after previous curative-intent therapy.
Robot-assisted PSMA-RGS using the DROP-IN gamma probe was carried out 19–23 h after intravenous injection of 99mtechnetium PSMA-Investigation & Surgery (99mTc-PSMA-I&S).
The primary endpoint was the feasibility of robot-assisted PSMA-RGS. Secondary endpoints were a comparison of the radioactive status (positive or negative) of resected specimens and final histopathology results, prostate-specific antigen (PSA) response following PSMA-RGS, and complications according to the Clavien-Dindo classification.
Using the DROP-IN probe, 19/21 (90%) PSMA-avid lesions could be resected robotically. On a per-lesion basis, the sensitivity and specificity of robot-assisted PSMA-RGS was 86% and 100%, respectively. A prostate-specific antigen (PSA) reduction of >50% and a complete biochemical response (PSA <0.2 ng/ml) were seen in 12/18 (67%) and 4/18 (22%) patients, respectively. During follow-up of up to 15 mo, 4/18 patients (22%) remained free of biochemical recurrence (PSA ≤0.2 ng/ml). One patient suffered from a Clavien-Dindo grade >III complication.
The DROP-IN probe helps in realizing robot-assisted PSMA-RGS. The procedure is technically feasible for intraoperative detection of nodal or local PSMA-avid PCa recurrences.
A device called the DROP-IN probe facilitates minimally invasive, robot-assisted surgery guided by radioactive tracers in patients with recurrent prostate cancer. This procedure holds promise for improving the intraoperative identification and removal of prostate cancer lesions.
Objective
To investigate whether combination treatment of prostate‐specific membrane antigen (PSMA)‐based radioguided surgery (RGS) with short‐term androgen deprivation therapy (ADT) improves ...oncological outcomes in men with oligorecurrent prostate cancer (PCa) as compared to treatment with short‐term ADT only.
Methods
The TRACE‐II study is an investigator‐initiated, prospective, randomised controlled clinical trial. Patients (aged >18 years) with hormone‐sensitive recurrent PCa after radical prostatectomy or radiotherapy (brachytherapy or external beam radiotherapy), with involvement of ≤2 lymph nodes or local oligorecurrent disease within the pelvis as determined by PSMA positron emission tomography (PET)/computed tomography (CT) are randomly assigned in a 1:1 ratio between 6‐month ADT (Arm A) or 6‐month ADT plus RGS (Arm B). The primary objective is to determine clinical progression‐free survival (CPFS) at 24 months. After PSMA‐RGS, CPFS is defined as the time between the start of treatment and the appearance of a re‐recurrence (any N1 or M1) as suggested by PSMA‐PET/CT or symptoms related to progressive PCa, or death from any cause. The secondary objectives include metastasis‐free survival at 2, 5 and 10 years, biochemical progression‐free survival at 2 years, and patient‐reported quality of life at 2, 5 and 10 years. A total of 60 patients, 30 per arm, will be included. The trial is powered (80%) to detect at least a 30% absolute difference in CPFS between the two study arms in the period 2 years after randomisation. We expect to enrol the required participants in 3 years. The study has an expected duration of 5 years in total.
Conclusions
Combining RGS with short‐term ADT might be oncologically beneficial for patients with oligorecurrent PCa. In this first randomised controlled trial, we are investigating the potential oncological benefits of this combined treatment, while also focusing on maintaining quality of life.
Targeted real-time imaging during robot-assisted radical prostatectomy provides information on the localisation and extent of prostate cancer. We assessed the safety and feasibility of the ...prostate-specific membrane antigen (PSMA)-targeted fluorescent tracer OTL78 in patients with prostate cancer.
In this single-arm, phase 2a, feasibility trial with an adaptive design was carried out in The Netherlands Cancer Institute, Netherlands. Male patients aged 18 years or older, with PSMA PET-avid prostate cancer with an International Society of Urological Pathology (ISUP) grade group of 2 or more, who were scheduled to undergo robot-assisted radical prostatectomy with or without extended pelvic lymph node dissection were eligible. All patients had a robot-assisted radical prostatectomy using OTL78. Based on timing and dose, patients received a single intravenous infusion of OTL78 (0·06 mg/kg 1–2 h before surgery dose cohort 1, 0·03 mg/kg 1–2 h before surgery dose cohort 2, or 0·03 mg/kg 24 h before surgery dose cohort 3). The primary outcomes, assessed in all enrolled patients, were safety and pharmacokinetics of OTL78. This study is completed and is registered in the European Trial Database, 2019-002393-31, and the International Clinical Trials Registry Platform, NL8552, and is completed.
Between June 29, 2020, and April 1, 2021, 19 patients were screened for eligibility, 18 of whom were enrolled. The median age was 69 years (IQR 64–70) and median prostate-specific antigen concentration was 15 ng/mL (IQR 9·3–22·0). In 16 (89%) of 18 patients, robot-assisted radical prostatectomy was accompanied by an extended pelvic lymph node dissection. Three serious adverse events occurred in one (6%) patient: an infected lymphocele, a urosepsis, and an intraperitoneal haemorrhage. These adverse events were considered unrelated to the administration of OTL78 or intraoperative fluorescence imaging. No patient died, required a dose reduction, or required discontinuation due to drug-related toxicity. The dose-normalised maximum serum concentration (Cmax/dose) in patients was 84·1 ng/mL/mg for the 0·03 mg/kg dose and 79·6 ng/mL/mg for the 0·06 mg/kg dose, the half-life was 5·1 h for the 0·03 mg/kg dose and 4·7 h for the 0·06 mg/kg dose, the volume of distribution was 22·9 L for the 0·03 mg/kg dose and 19·5 L for the 0·06 mg/kg dose, and the clearance was 3·1 L/h for the 0·03 mg/kg dose and 3·0 L/h for the 0·06 mg/kg dose.
This first-in-patient study showed that OTL78 was well tolerated and had the potential to improve prostate cancer detection. Optimal dosing was 0·03 mg/kg, 24 h preoperatively. PSMA-directed fluorescence imaging allowed real-time identification of visually occult prostate cancer and might help to achieve complete oncological resections.
On Target Laboratories.
Prostate-specific membrane antigen (PSMA) PET is used to select patients with recurrent prostate cancer for metastasis-directed therapy. A surgical approach can be achieved through radioguided ...surgery (RGS), using a Drop-In γ-probe that traces lesions that accumulate the radioactive signal. With the aim of guiding patient selection for salvage surgery, we studied the correlation between the SUV
of lesions on preoperative PSMA PET/CT and their intraoperative counts/s measured using the Drop-In γ-probe.
A secondary analysis based on the prospective, single-arm, and single-center feasibility study was conducted (NCT03857113). Patients (
= 29) with biochemical recurrence after previous curative-intent therapy and a maximum of 3 suggestive lesions within the pelvis on preoperative PSMA PET/CT were included. Patients treated with androgen deprivation therapy within 6 mo before surgery were excluded. All patients received an intravenous injection of
Tc-PSMA-I&S 1 d before surgery. Radioguidance was achieved using a Drop-In γ-probe. Correlation was determined using the Spearman rank correlation coefficient (ρs). Subgroup analysis was based on the median SUV
In total, 33 lesions were visible on the PSMA PET/CT images, with a median overall SUV
of 6.2 (interquartile range IQR, 4.2-9.7). RGS facilitated removal of 31 lesions. The median Drop-In counts/s were 134 (IQR, 81-220) in vivo and 109 (IQR, 72-219) ex vivo. The intensity of the values correlated with SUV
(ρs = 0.728 and 0.763, respectively;
< 0.001). Subgroup analysis based on median SUV
in the group with an SUV
of less than 6 showed no statistically significant correlation with the numeric signal in vivo (ρs = 0.382;
= 0.221) or the signal-to-background-ratio (ρs = 0.245;
= 0.442), whereas the group with an SUV
of 6 or more showed respective statistically significant positive correlations (ρs = 0.774
< 0.001 and ρs = 0.647
= 0.007).
Our findings indicate that there is a direct relation between SUV
on PSMA PET/CT and the readout recorded by the surgical Drop-In probe, thereby indicating that SUV
can be used to select patients for PSMA RGS. For more definitive subgroup definitions for treatment recommendations, further studies are necessary to validate the present findings.
Prostate-specific membrane antigen (PSMA) PET is used to select patients with recurrent prostate cancer for metastasis-directed therapy. A surgical approach can be achieved through radioguided ...surgery (RGS), using a Drop-In γ-probe that traces lesions that accumulate the radioactive signal. With the aim of guiding patient selection for salvage surgery, we studied the correlation between the SUVmax of lesions on preoperative PSMA PET/CT and their intraoperative counts/s measured using the Drop-In γ-probe. Methods: A secondary analysis based on the prospective, single-arm, and single-center feasibility study was conducted (NCT03857113). Patients (n = 29) with biochemical recurrence after previous curative-intent therapy and a maximum of 3 suggestive lesions within the pelvis on preoperative PSMA PET/CT were included. Patients treated with androgen deprivation therapy within 6 mo before surgery were excluded. All patients received an intravenous injection of 99mTc-PSMA-I&S 1 d before surgery. Radioguidance was achieved using a Drop-In γ-probe. Correlation was determined using the Spearman rank correlation coefficient (ρs). Subgroup analysis was based on the median SUVmax. Results: In total, 33 lesions were visible on the PSMA PET/CT images, with a median overall SUVmax of 6.2 (interquartile range IQR, 4.2–9.7). RGS facilitated removal of 31 lesions. The median Drop-In counts/s were 134 (IQR, 81–220) in vivo and 109 (IQR, 72–219) ex vivo. The intensity of the values correlated with SUVmax (ρs = 0.728 and 0.763, respectively; P < 0.001). Subgroup analysis based on median SUVmax in the group with an SUVmax of less than 6 showed no statistically significant correlation with the numeric signal in vivo (ρs = 0.382; P = 0.221) or the signal-to-background-ratio (ρs = 0.245; P = 0.442), whereas the group with an SUVmax of 6 or more showed respective statistically significant positive correlations (ρs = 0.774 P < 0.001 and ρs = 0.647 P = 0.007). Conclusion: Our findings indicate that there is a direct relation between SUVmax on PSMA PET/CT and the readout recorded by the surgical Drop-In probe, thereby indicating that SUVmax can be used to select patients for PSMA RGS. For more definitive subgroup definitions for treatment recommendations, further studies are necessary to validate the present findings.
The introduction of the tethered DROP‐IN gamma probe has enabled targeted robot‐assisted radioguided prostate cancer (PCa) resection of pelvic sentinel lymph nodes (SLNs) and prostate‐specific ...membrane antigen (PSMA)‐positive lesions. While both procedures use 99mTc‐isotopes, the two vary in signal and background intensity. To understand how the different levels of image guidance impact surgical decision‐making, computer‐vision algorithms are used to extract the DROP‐IN probe kinematic form clinical videos. 44 PCa patients undergo SLN (25) and PSMA‐targeted (19) resections. PSMA‐PET/CT and SPECT/CT create preoperative roadmaps, and intraoperative probe signal intensities are recorded. Using neural network‐based software, probe trajectories are extracted from videos to extract multiparametric kinematics and generate decision‐making and dexterity scores. PSMA‐targeted resections yield significantly lower nodal signal intensities in preoperative SPECT‐CT scans (three‐fold; p = 0.01), intraoperative probe readouts (eight‐fold; p < 0.001), and signal‐to‐background ratios (SBR; two‐fold; p < 0.001). Kinematics assessment reveal that the challenges encounter during PSMA‐targeted procedures converted to longer target identification times and increase in probe pick‐ups (both five‐fold; p < 0.001). This results in a fourfold reduction in the decision‐making score (p < 0.001). Reduced signal intensities and intraoperative SBR values negatively affect the impact that image‐guided surgery strategies have on the surgical decision‐making process.
The tethered DROP‐IN gamma ray detector provides surgical robots with the sensory guidance needed to identify lymph node metastases. Metastases can be targeted via lymph node or prostate membrane antigen‐specific radiopharmaceuticals. By realizing automated instrument tracking, how the choice of radiopharmaceutical impacts the DROP‐IN use and the surgical decision‐making process is studied.
To investigate whether combination treatment of prostate-specific membrane antigen (PSMA)-based radioguided surgery (RGS) with short-term androgen deprivation therapy (ADT) improves oncological ...outcomes in men with oligorecurrent prostate cancer (PCa) as compared to treatment with short-term ADT only.
The TRACE-II study is an investigator-initiated, prospective, randomised controlled clinical trial. Patients (aged >18 years) with hormone-sensitive recurrent PCa after radical prostatectomy or radiotherapy (brachytherapy or external beam radiotherapy), with involvement of ≤2 lymph nodes or local oligorecurrent disease within the pelvis as determined by PSMA positron emission tomography (PET)/computed tomography (CT) are randomly assigned in a 1:1 ratio between 6-month ADT (Arm A) or 6-month ADT plus RGS (Arm B). The primary objective is to determine clinical progression-free survival (CPFS) at 24 months. After PSMA-RGS, CPFS is defined as the time between the start of treatment and the appearance of a re-recurrence (any N1 or M1) as suggested by PSMA-PET/CT or symptoms related to progressive PCa, or death from any cause. The secondary objectives include metastasis-free survival at 2, 5 and 10 years, biochemical progression-free survival at 2 years, and patient-reported quality of life at 2, 5 and 10 years. A total of 60 patients, 30 per arm, will be included. The trial is powered (80%) to detect at least a 30% absolute difference in CPFS between the two study arms in the period 2 years after randomisation. We expect to enrol the required participants in 3 years. The study has an expected duration of 5 years in total.
Combining RGS with short-term ADT might be oncologically beneficial for patients with oligorecurrent PCa. In this first randomised controlled trial, we are investigating the potential oncological benefits of this combined treatment, while also focusing on maintaining quality of life.
Our objective was to assess the diagnostic value of the sentinel node (SN) procedure for lymph node staging in primary intermediate- and high-risk prostate cancer patients with node-negative results ...on prostate-specific membrane antigen PET/CT (miN0).
From 2016 to 2022, 154 patients with primary, miN0 PCa were retrospectively included. All patients had a Briganti nomogram-assessed nodal risk of more than 5% and underwent a robot-assisted SN procedure for nodal staging. The prevalence of nodal metastases at histopathology and the occurrence of surgical complications according to the Clavien-Dindo classification were evaluated.
The SN procedure yielded 84 (14%) tumor-positive lymph nodes with a median metastasis size of 3 mm (interquartile range, 1-4 mm). In total, 55 patients (36%) were reclassified as pN1. A complication of Clavien-Dindo grade 3 or higher occured in 1 patient (0.6%).
The SN procedure classified 36% of patients with miN0 prostate cancer with an elevated risk of nodal metastases as pN1.
