Robot-assisted prostate-specific membrane antigen (PSMA)–radioguided salvage surgery has emerged as a potential treatment approach for patients with limited recurrent prostate cancer. Although its technical feasibility and safety have been demonstrated, questions remain regarding long-term oncological outcomes and the need for subsequent treatment.
A study titled “Oncological Outcomes of Robot-assisted PSMA-guided Salvage Surgery in Recurrent Prostate Cancer: Insights from the Prospective TRACE-I Trial” was published in European Urology Focus on August 29, 2026.
The study was conducted by Lotte G. Zuur, Hilda A. de Barros, Vera A. Ottens, Anne-Claire Berrens, Matthias N. van Oosterom, Maarten L. Donswijk, Jeroen J.M.A. Hendrikx, Fijs W.B. van Leeuwen, Henk G. van der Poel, and Pim J. van Leeuwen.
This post hoc analysis of the prospective TRACE-I trial evaluated PSA response, biochemical progression-free survival, distant metastasis-free survival, and therapy-free survival following robot-assisted PSMA-guided salvage surgery in patients with recurrent prostate cancer.
PSMA-Guided Salvage Surgery in Recurrent Prostate Cancer
PSMA-targeted positron emission tomography/computed tomography (PET/CT) has improved the detection of recurrent prostate cancer, particularly in patients with low prostate-specific antigen (PSA) levels.
For patients with limited recurrent disease, metastasis-directed approaches, including salvage radiotherapy and salvage lymph node dissection, are being investigated as potential strategies to postpone systemic treatment. However, conventional salvage surgery may fail to remove all metastatic lesions, contributing to persistent or recurrent PSA elevation.
PSMA-radioguided surgery (RGS) was developed to improve intraoperative identification of PSMA-expressing lesions. The TRACE-I trial previously demonstrated the feasibility and safety of robot-assisted PSMA-RGS using a technetium-99m–labeled PSMA tracer and a DROP-IN gamma probe. The current analysis focused on the longer-term oncological outcomes of patients treated using this approach.
TRACE-I Trial Design and Patient Characteristics
TRACE-I (NCT03857113) was a prospective, single-arm feasibility study conducted at the Netherlands Cancer Institute between 2020 and 2023. The oncological analysis included 30 patients with biochemical recurrence following radical prostatectomy, radiotherapy, or both, and no more than three pelvic lesions identified on PSMA-PET/CT.
Among the participants:
- 19 patients (63%) had previously undergone radical prostatectomy.
- 9 patients (30%) had received radiotherapy.
- 2 patients (7%) had undergone both treatments.
The median age was 68 years, and the median PSA level at the time of surgery was 1.02 ng/mL. Most patients (87%) had a single PSMA-PET/CT–positive lesion, while 23 patients (77%) had nodal recurrence and seven (23%) had local recurrence.
Before surgery, patients received [99mTc]Tc-PSMA-I&S, followed by single-photon emission computed tomography/CT imaging to confirm tracer uptake. Robot-assisted salvage surgery was then performed using a DROP-IN gamma probe to identify PSMA-avid lesions intraoperatively. The analysis assessed early PSA response, biochemical progression-free survival (bPFS), distant metastasis-free survival (dMFS), and therapy-free survival (TFS).
Surgical Outcomes and Early PSA Response
The DROP-IN gamma probe successfully identified 32 of the 34 PSMA-avid lesions (94%) previously detected on PSMA-PET/CT. Surgical resection was successful in 29 of 30 patients (97%). In seven patients (23%), histopathological examination identified additional lesions that had not been detected on preoperative imaging.
Postoperative complications occurred in 10 patients (33%). Most were minor, with nine classified as Clavien-Dindo grade I. One patient (3%) experienced a grade IIIb complication involving a ureteral injury requiring surgical reimplantation. No grade IV or V complications were reported. Early biochemical responses were observed in most patients.
At the first PSA assessment, performed 2–12 weeks after surgery, 28 of 30 patients (93%) experienced a PSA decline. Overall, 20 patients (66% of the study cohort) reached a PSA level below 0.2 ng/mL after radical prostatectomy or a PSA nadir following radiotherapy, according to the study’s response assessment. These findings demonstrated that robot-assisted PSMA-RGS was associated with early biochemical responses in patients with limited recurrent prostate cancer.
Long-Term Oncological Outcomes
Despite the high rate of early PSA decline, biochemical progression remained common during follow-up. At a median follow-up of 39 months, 25 of 30 patients (83%) had experienced biochemical progression. The estimated median time to biochemical progression was 7.5 months.
The Kaplan-Meier estimates showed:
- 12-month bPFS: 40% (95% CI, 26–62%).
- 24-month bPFS: 30% (95% CI, 17–52%).
- 24-month dMFS: 62% (95% CI, 46–82%).
- 24-month TFS: 58% (95% CI, 43–80%).
Although only 30% of patients remained free from biochemical progression at two years, the 58% therapy-free survival rate indicated that a proportion of patients had not required additional treatment during this period.
Overall, 16 patients (53%) received subsequent salvage therapy, including androgen deprivation therapy, radiotherapy combined with systemic treatment, or additional salvage lymph node dissection. These outcomes suggest that PSMA-guided salvage surgery may provide a treatment-free interval in selected patients, although the study’s noncomparative design does not establish whether surgery prolongs this interval relative to other management approaches.
Recurrence Patterns and Patient Selection
The analysis also examined the anatomical distribution of recurrent disease after surgery. Among the 25 patients who developed biochemical progression, follow-up PSMA-PET/CT detected visible recurrence in 23.
Pelvic nodal recurrence was reported in 11 patients (37% of the overall cohort), with one additional patient (3%) experiencing combined local and pelvic nodal recurrence. Extrapelvic nodal recurrence was reported in six patients (20%), while bone involvement, either alone or combined with extrapelvic nodal recurrence, was identified in five patients (17%). These findings indicate that both locoregional and distant recurrence remain important challenges following PSMA-guided salvage surgery.
The investigators also explored clinical factors associated with biochemical progression. In univariable Cox regression analysis, a longer interval between previous treatment and PSMA-RGS was associated with an increased risk of biochemical progression (HR 1.13; 95% CI, 1.03–1.23; p = 0.007).
However, the investigators emphasized that this finding was exploratory and should be interpreted cautiously because of the limited sample size. The detection of additional metastatic lesions on postoperative histopathology also highlighted the limitations of preoperative PSMA-PET/CT in identifying all sites of disease.
Together, these observations underscore the importance of careful patient selection and the need to better understand which patients are most likely to achieve sustained disease control after salvage surgery.
Future Directions for PSMA-Guided Surgery
The TRACE-I findings provide prospective-cohort data on the oncological outcomes of robot-assisted PSMA-RGS, extending beyond the previously reported technical feasibility and safety results. Nevertheless, the analysis has several limitations. Oncological outcomes were assessed retrospectively within a small, single-center cohort, and there was no control group. Differences in previous treatment and surgical approaches also complicate interpretation. As a result, the findings cannot establish a definitive oncological benefit of PSMA-RGS compared with alternative treatment strategies.
Further prospective research is needed to determine whether combining PSMA-guided surgery with radiotherapy or systemic treatment can improve longer-term disease control. The randomized TRACE-II trial (NCT05555017) is evaluating the oncological benefit of combining PSMA-guided salvage surgery with short-term androgen deprivation therapy.
Conclusion
The post hoc analysis of the prospective TRACE-I trial demonstrated that robot-assisted PSMA-guided salvage surgery was associated with early PSA declines in most patients with limited recurrent prostate cancer. However, biochemical progression remained frequent, with a two-year bPFS rate of 30%. At the same time, two-year therapy-free survival reached 58%, indicating that some patients remained without additional treatment following surgery.
The full article is available in European Urology Focus.
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