68Ga-PSMA-11 PET has the potential to improve patient selection for extended pelvic lymph node dissection in intermediate to high-risk prostate cancer.

INTRODUCTION: Radical prostatectomy with extended pelvic lymph node dissection (ePLND) is a curative treatment option for patients with clinically significant localised prostate cancer. The decision to perform an ePLND can be challenging because the overall incidence of lymph node metastasis is relatively low and ePLND is not free of complications. Using current clinical nomograms to identify patients with nodal involvement, approximately 75-85% of ePLNDs performed are negative. The aim of this study was to assess the added value of 68Ga-PSMA-11 PET in predicting lymph node metastasis in men with intermediate- or high-risk prostate cancer. METHODS: 68Ga-PSMA-11 PET scans of 60 patients undergoing radical prostatectomy with ePLND were reviewed for qualitative (visual) assessment of suspicious nodes and assessment of quantitative parameters of the primary tumour in the prostate (SUVmax, total activity (PSMAtotal) and PSMA positive volume (PSMAvol)). Ability of quantitative PET parameters to predict nodal metastasis was assessed with receiver operating characteristics (ROC) analysis. A multivariable logistic regression model combining PSA, Gleason score, visual nodal status on PET and primary tumour PSMAtotal was built. Net benefit at each risk threshold was compared with five nomograms: MSKCC nomogram, Yale formula, Roach formula, Winter nomogram and Partin tables (2016). RESULTS: Overall, pathology of ePLND specimens revealed 31 pelvic metastatic lymph nodes in 12 patients. 68Ga-PSMA-11 PET visual analysis correctly detected suspicious nodes in 7 patients, yielding a sensitivity of 58% and a specificity of 98%. The area under the ROC curve for primary tumour SUVmax was 0.70, for PSMAtotal 0.76 and for PSMAvol 0.75. The optimal cut-off for nodal involvement was PSMAtotal > 49.1. The PET model including PSA, Gleason score and quantitative PET parameters had a persistently higher net benefit compared with all clinical nomograms. CONCLUSION: Our model combining PSA, Gleason score and visual lymph node analysis on 68Ga-PSMA-11 PET with PSMAtotal of the primary tumour showed a tendency to improve patient selection for ePLND over the currently used clinical nomograms. Although this result has to be validated, 68Ga-PSMA-11 PET showed the potential to reduce unnecessary surgical procedures in patients with intermediate- or high-risk prostate cancer.

Impact of 68Ga-PSMA-11 PET staging on clinical decision-making in patients with intermediate or high-risk prostate cancer.

BACKGROUND: Accurate staging is of major importance to determine the optimal treatment modality for patients with prostate cancer. Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) is a promising technique that outperformed conventional imaging in the detection of nodal and distant metastases in previous studies. However, it is still unclear whether the superior sensitivity and specificity also translate into improved patient management. The aim of this study was to assess the performance of 68Ga-PSMA-11 PET for staging of intermediate and high-risk prostate cancer and its potential impact on disease management. METHODS: In this retrospective analysis, 116 patients who underwent 68Ga-PSMA-11 PET/CT or MRI scans for staging of their intermediate or high-risk prostate cancer between April 2016 and May 2018 were included. The potential impact of 68Ga-PSMA-11 PET staging on patient management was assessed within a simulated multidisciplinary tumour board where hypothetical treatment decisions based on clinical information and conventional imaging alone was determined. This treatment decision was compared with the treatment recommendation based on clinical information and 68Ga-PSMA-11 PET imaging. RESULTS: The primary tumour was positive on 68Ga-PSMA-11 PET in 113 patients (97%). Nodal metastases were detected in 28 patients (24%) and bone metastases in 14 patients (12%). Compared with clinical staging and conventional imaging, 68Ga-PSMA-11 PET resulted in new information in 42 of 116 patients (36%). In 32 of 116 patients (27%), this information would most likely have changed the management into a different therapy modality (15 patients, 13%) or adjusted treatment details (e.g. modification of radiotherapy field or lymph node dissection template; 17 patients, 14%). CONCLUSION: Information from 68Ga-PSMA-11 PET staging has the potential to change the management in more than a fourth of the patients who underwent PET staging for their intermediate to high-risk prostate cancer. Whether these more personalized 68Ga-PSMA-11 PET-based treatment decisions will improve patient outcome needs further investigation.

Clinical impact of 68Ga-PSMA-11 PET on patient management and outcome, including all patients referred for an increase in PSA level during the first year after its clinical introduction.

PURPOSE: The fast-increasing use of positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) ligand for the imaging of prostate cancer (PCA) biochemical recurrence has led to a rapid change in treatment concepts. Since the superiority of 68Ga-PSMA-11 PET in detecting recurrent PCA is well established, the aim of our study was to assess its effect on management and outcome in all patients imaged during the first year after its introduction into clinical routine. METHODS: Of 327 patients imaged, 223 were referred for recurrent PCA and gave written informed consent for further analysis of their data for this retrospective consecutive cohort analysis. Twenty patients were lost to further follow-up. The rate of detection of recurrence by 68Ga-PSMA-11 PET was based on the clinical reports. Management before the availability of PET diagnostic information was assessed according to guidelines (therapy option without 68Ga-PSMA-11 PET). In the 203 patients with follow-up 6 months after 68Ga-PSMA-11 PET, the therapies effectively implemented as well as follow-up PSA levels were evaluated, with a PSA value of <0.2 ng/ml representing a complete response and a decrease in PSA value of at least 50% from baseline representing a partial response. RESULTS: 68Ga-PSMA-11 PET was positive and identified recurrence in 166 of the 223 patients (74%), with a detection rate of 50% for recurrent disease at low PSA values of <0.5 ng/ml. 68Ga-PSMA-11 PET led to a change in management in 122 of the 203 patients (60%). A substantial increase in the use of metastasis-targeted treatment and a reduction in the use of systemic treatment were observed, with 59 of the 203 patients (29%) undergoing targeted radiotherapy (RTXa) only, and 20 patients (10%) undergoing RTXa with hormonal therapy as the two most frequently selected therapy options. The proportion of patients in whom systemic therapy was selected decreased from 60% (133 of 223 patients) to 34% (70 of 203 patients) on the basis of the information provided by the 68Ga-PSMA-11 PET scan. PSMA PET-directed metastasis-targeted treatment led to a complete response after 6 months in 45% of patients. CONCLUSION: The high rate of recurrence detection by PSMA PET was confirmed and PSMA PET led to a change in management in 60% of patients. Focal therapy for PSMA-positive lesions is a promising approach with complete responses in 45% of patients.

Detection Rate and Localization of Prostate Cancer Recurrence Using 68Ga-PSMA-11 PET/MRI in Patients with Low PSA Values ≤ 0.5 ng/mL.

A first analysis of simultaneous 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/MRI showed some improvement in the detection of recurrent disease at low serum prostate specific antigen (PSA) values below 0.5 ng/mL compared with the already high detection rate of 68Ga-PSMA-11 PET/CT. We therefore focused on all patients with biochemical recurrence and PSA values no higher than 0.5 ng/mL to assess the detection rate for 68Ga-PSMA-11 PET/MRI. Methods: We retrospectively analyzed a cohort of 66 consecutive patients who underwent 68Ga-PSMA-11 PET/MRI for biochemical recurrence with a PSA value no higher than 0.5 ng/mL at our institution. Median PSA level was 0.23 ng/mL (range, 0.03-0.5 ng/mL). Detection of PSMA-positive lesions within the prostate fossa, local and distant lymph nodes, bones, or visceral organs was recorded. In addition, all scans with 68Ga-PSMA-11 PET/MRI-positive lesions were retrospectively assessed to analyze if lesions were detected inside or outside a standard salvage radiotherapy volume. Results: Overall, in 36 of 66 patients (54.5%) PSMA-positive lesions were detected; in 26 of 40 (65%) patients with a PSA level between 0.2 and 0.5 ng/mL and in 10 of 26 (38.5%) patients with a PSA level less than 0.2 ng/mL. Even at those low PSA values, only 8 of 66 (12.1%) patients had exclusive local recurrence. Lymph nodes were detected in 23 patients and bone metastases in 5 on 68Ga-PSMA-11 PET/MRI. In 26 of 66 patients (39.4%), PSMA-positive lesions were located outside a standard salvage radiotherapy volume. Conclusion: Our data confirm that 68Ga-PSMA-11 PET/MRI has a high detection rate for recurrent prostate cancer, even at low PSA levels no higher than 0.5 ng/mL. In addition, we show that 68Ga-PSMA-11 PET/MRI detected PSMA-positive lesions outside a standard salvage radiotherapy volume in 39.4% of all patients.

Radiotherapy for pelvic nodal recurrences after radical prostatectomy: patient selection in clinical practice.

AIM: There is no general consensus on the optimal treatment for prostate cancer (PC) patients with intrapelvic nodal oligorecurrences after radical prostatectomy. Besides androgen deprivation therapy (ADT) as standard of care, both elective nodal radiotherapy (ENRT) and stereotactic body radiotherapy (SBRT) as well as salvage lymph node dissection (sLND) are common treatment options. The aim of our study was to assess decision making and practice patterns for salvage radiotherapy (RT) in this setting. METHODS: Treatment recommendations from 14 Swiss radiation oncology centers were collected and converted into decision trees. An iterative process using the objective consensus methodology was applied to assess differences and consensus. RESULTS: PSMA PET/CT was recommended by 93% of the centers as restaging modality. For unfit patients defined by age, comorbidities or low performance status, androgen deprivation therapy (ADT) alone was recommended by more than 70%. For fit patients with unfavorable tumor characteristics such as short prostate-specific antigen (PSA) doubling time or initial high-risk disease, the majority of the centers (57-71%) recommended ENRT + ADT for 1-4 lesions. For fit patients with favorable tumor characteristics, there were low levels of consensus and a wide variety of recommendations. For 1-4 nodal lesions, focal SBRT was offered by 64% of the centers, most commonly as a 5-fraction course. CONCLUSIONS: As an alternative to ADT, ENRT or SBRT for pelvic nodal oligorecurrences of PC are commonly offered to selected patients, with large treatment variations between centers. The exact number of lymph nodes had a major impact on treatment selection.