68Ga-PSMA Positron Emission Tomography/Computed Tomography Provides Accurate Staging of Lymph Node Regions Prior to Lymph Node Dissection in Patients with Prostate Cancer

Herlemann, Annika; Wenter, Vera; Kretschmer, Alexander; Thierfelder, Kolja M.; Bartenstein, Peter; Faber, Claudius; Gildehaus, Franz-Josef; Stief, Christian G.; Gratzke, Christian; Fendler, Wolfgang P.

doi:10.1016/j.eururo.2015.12.051

Cited by 258 publications

(197 citation statements)

References 21 publications

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“…Nine patients with LNs found positive by histopathology but negative by 68 Ga-PSMA-11 PET harbored only micrometastases in single LNs (mean size of negative LNs, 3 mm). Impaired detection of LN metastases smaller than 5 mm was anticipated and was also reported by other groups with similar results for the overall performance of 68 Ga-PSMA-11 PET for node staging (81,94,95).…”

Section: Primary Stagingsupporting

confidence: 65%

Prostate-Specific Membrane Antigen Ligands for Imaging and Therapy

et al. 2017

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The prostate-specific membrane antigen (PSMA) is highly expressed on most prostate cancer (PC) cells. Therefore, the targeting of PSMA has become increasingly important over the last decade. Glu-ureabased PSMA ligands used for both imaging and radioligand therapy are the mainstays of the current success. For PET imaging, both 68 Gaand 18 F-labeled agents have been successfully translated to clinical applications. Mainly retrospective cohort studies have shown a high value in the setting of biochemical recurrence, with high detection rates even in the presence of low prostate-specific antigen levels. Preliminary data indicated that radioguided surgery with PSMA ligands may help to further improve patient outcomes because it facilitates the removal of small tumor deposits that are otherwise difficult to detect. For primary PC, PSMA ligand PET imaging has been shown to be superior to cross-sectional imaging for the detection of metastatic lymph nodes. In addition, it promises to also provide intraprostatic tumor localization, especially when used in combination with multiparametric MRI. Increasing numbers of studies have reported considerable changes in management resulting from PSMA ligand PET imaging for both biochemical recurrence and primary disease. The use of 177 Lu-PSMA-based radioligand therapy has demonstrated a reasonable response, mainly as defined by a prostate-specific antigen response of more than 50%, comparable to other recently introduced agents. Especially given the high level of safety of 177 Lu-PSMA radioligand therapy, with only minimal grade 3 and 4 toxicities reported so far, it has the potential to expand options for metastatic castrationresistant PC. This review is intended to provide a comprehensive overview of the current literature on low-molecular-weight PSMA ligands for both PET imaging and therapeutic approaches, with a focus on agents that have been clinically adopted.

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Section: Primary Stagingsupporting

confidence: 65%

Prostate-Specific Membrane Antigen Ligands for Imaging and Therapy

et al. 2017

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“…Several first studies have demonstrated the high clinical value of 68 Ga-PSMA HBED-CC PET/CT in patients with recurrent PC after primary treatment (17,18,25,26). Besides reporting first on the superior performance of 68 Ga-PSMA HBED-CC PET/CT mainly in recurrent PC, Afshar-Oromieh et al also demonstrated a high specificity of 68 Ga-PSMA HBED-CC PET in a subgroup of patients with histologic verification (17).…”

Section: Discussionmentioning

confidence: 96%

“…Besides reporting first on the superior performance of 68 Ga-PSMA HBED-CC PET/CT mainly in recurrent PC, Afshar-Oromieh et al also demonstrated a high specificity of 68 Ga-PSMA HBED-CC PET in a subgroup of patients with histologic verification (17). In addition, so far only 2 further studies reported on the use of 68 Ga-PSMA HBED-CC PET for LN restaging with histologic evaluation of all patients (25,26). However, both studies encompass not only patients scheduled for restaging after biochemical failure but also patients undergoing primary radical prostatectomy including lymphadenectomy.…”

Section: Discussionmentioning

confidence: 99%

Value of ⁶⁸Ga-PSMA HBED-CC PET for the Assessment of Lymph Node Metastases in Prostate Cancer Patients with Biochemical Recurrence: Comparison with Histopathology After Salvage Lymphadenectomy

et al. 2016

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The purpose of this study was to evaluate the accuracy of Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga(HBED-CC)] PET compared with morphologic imaging for the assessment of lymph node metastases (LNM) in patients with recurrent prostate cancer. Methods: Forty-eight patients (median age, 71 y; interquartile range, 66-74 y) with biochemical recurrence (median prostate-specific antigen level, 1.31 ng/mL; interquartile range, 0.75-2.55 ng/mL) who underwent 68 Ga-prostate-specific membrane antigen (PSMA) HBED-CC PET/CT or PET/MR and salvage lymphadenectomy were retrospectively included. Institutional review board approval and written informed consent were obtained from all patients for the purpose of anonymized evaluation and publication of their data. Standardized predefined lymph node (LN) template fields (n 5 10) were evaluated in 68 Ga-PSMA HBED-CC PET and morphologic imaging for the presence of LNM using a 5-point-scale. Additionally, SUV mean/max and size of suspicious lesions were determined. Specificity of 68 Ga-PSMA HBED-CC PET imaging for PET-positive LNs was defined by comparison to histopathology. The diagnostic accuracy of 68 Ga-PSMA HBED-CC PET compared with morphologic imaging alone was assessed, and areas under the receiver-operating-characteristic curves are presented. Results: LNM were found histologically in 68 of 179 resected anatomic LN fields (38.0%). The specificity of 68 Ga-PSMA HBED-CC PET and morphologic imaging was 97.3% and 99.1%, respectively. However, 68 Ga-PSMA HBED-CC PET detected LNM in 53 of 68 histopathologically proven metastatic LN fields (77.9%) whereas morphologic imaging was positive in only 18 of 67 (26.9%). 68 Ga-PSMA HBED-CC PET imaging performed significantly superior to morphologic imaging for detection of LNM (difference in the areas under the receiver-operating-characteristic curves, 0.139; 95% confidence interval, 0.063-0.214; P , 0.001). In 68 Ga-PSMA HBED-CC PET, the mean size of PET-positive LN measured by CT or MRI was 8.3 ± 4.3 mm (range, 4-25 mm), and LNs, which were suspicious only in CT or MRI, presented with a mean size of 13.0 ± 4.9 mm (range, 8-25 mm). Conclusion: 68 Ga-PSMA HBED-CC PET imaging is a promising method for early detection of LNM in patients with biochemical recurrent prostate cancer. It is more accurate than morphologic imaging and thus might represent a valuable tool for guiding salvage lymphadenectomy.

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“…The excellent specificity of PSMA ligands, especially for lymph node metastases, was demonstrated in several studies (21,39,46,(83)(84)(85). Therefore, any focal uptake of the PSMA ligand higher than the surrounding background uptake in morphologically visible lesions and not associated with physiologic uptake should be considered suggestive.…”

Section: Pathologic Psma Uptake Related To Pc and Metastasesmentioning

confidence: 99%

“…In detecting sites of nodal or bone involvement in preoperative patients, cross-sectional imaging has shown a limited pooled sensitivity and specificity of 42% and 82%, respectively, for CT and 39% and 82%, respectively, for MRI (3), as up to 80% of lymph node metastases in PC are harbored in normal-sized lymph nodes (2). Several studies showed a clear superiority of PSMA ligand PET/CT over standard-of-care imaging (CT, MRI, or bone scanning) (21,(46)(47)(48)(49). For example, in a retrospective analysis of 130 patients with primary intermediate-to high-risk PC using templatebased pelvic histopathology as a reference, 68 Ga-PSMA-11 PET performed significantly better than morphologic imaging for N staging both on a patient and a template basis (P 5 0.002 and , 0.001, respectively).…”

Section: Primary Stagingmentioning

confidence: 99%