Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer (WARMTH Act): a multicentre, retrospective study.

BACKGROUND: Actinium-225 (225Ac) prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC). We aimed to report the safety and antitumour activity of 225Ac-PSMA RLT of mCRPC in a large cohort of patients treated at multiple centres across the world. METHODS: This retrospective study included patients treated at seven centres in Australia, India, Germany, and South Africa. We pooled data of consecutive patients of any age and Eastern Cooperative Oncology Group performance status with histopathologically confirmed adenocarcinoma of the prostate who were treated with one or more cycles of 8 MBq 225Ac-PSMA RLT administered intravenously for mCRPC. Previous lines of mCRPC treatment included taxane-based chemotherapy, androgen-receptor-axis inhibitors, lutetium-177 (177Lu) PSMA RLT, and radium-223 dichloride. The primary outcomes were overall survival and progression-free survival. FINDINGS: Between Jan 1, 2016, and May 31, 2023, 488 men with mCRPC received 1174 cycles of 225Ac-PSMA RLT (median two cycles, IQR 2-4). The mean age of the patients was 68·1 years (SD 8·8), and the median baseline prostate-specific antigen was 169·5 ng/mL (IQR 34·6-519·8). Previous lines of treatment were docetaxel in 324 (66%) patients, cabazitaxel in 103 (21%) patients, abiraterone in 191 (39%) patients, enzalutamide in 188 (39%) patients, 177Lu-PSMA RLT in 154 (32%) patients, and radium-223 dichloride in 18 (4%) patients. The median follow-up duration was 9·0 months (IQR 5·0-17·5). The median overall survival was 15·5 months (95% CI 13·4-18·3) and median progression-free survival was 7·9 months (6·8-8·9). In 347 (71%) of 488 patients, information regarding treatment-induced xerostomia was available, and 236 (68%) of the 347 patients reported xerostomia after the first cycle of 225Ac-PSMA RLT. All patients who received more than seven cycles of 225Ac-PSMA RLT reported xerostomia. Grade 3 or higher anaemia occurred in 64 (13%) of 488 patients, leukopenia in 19 (4%), thrombocytopenia in 32 (7%), and renal toxicity in 22 (5%). No serious adverse events or treatment-related deaths were recorded. INTERPRETATION: 225Ac-PSMA RLT shows a substantial antitumour effect in mCRPC and represents a viable therapy option in patients treated with previous lines of approved agents. Xerostomia is a common side-effect. Severe bone marrow and renal toxicity are less common adverse events. FUNDING: None.

Cervical versus endometrial injection for sentinel lymph node detection in endometrial cancer: a randomized clinical trial.

OBJECTIVE: To evaluate the relationship between pelvic/para-aortic sentinel lymph node status and two different injection sites of 99m-technetium (99mTc)-labeled phytate in patients with endometrial cancer. METHODS: This was a randomized controlled trial involving 81 patients with endometrial cancer. In the cervical group (n=40), injections of 99mTc were performed at the 3 and 9 o'clock positions of the uterine cervix. In the endometrial group (n=41), 99mTc was injected into the fundal endometrium using a transcervical catheter. Sentinel lymph nodes were detected through pre-operative lymphoscintigraphy and intra-operatively using a handheld gamma probe. All patients underwent complete pelvic and para-aortic lymphadenectomy procedures. Pathologic ultra-staging was performed with immunostaining for cytokeratin in sentinel lymph nodes after routine hematoxylin and eosin histological examinations. The primary endpoint was the estimation of detection rates, sensitivity, false-negative rates, negative predictive value, and analysis of the distribution of pelvic and para-aortic sentinel lymph nodes. RESULTS: The rate of detection of at least one sentinel lymph node, sensitivity, and the negative predictive value was 80%, 66.6%, 96.6% for the cervical group and 85%, 66.6%, 96.9% for the endometrial group, respectively. False-negative sentinel lymph nodes were detected in one patient from each group . There was no significant difference between the groups in terms of total sentinel lymph node count, sentinel pelvic lymph node count, and pelvic bilaterality, but the para-aortic sentinel lymph node count was significantly higher in the endometrial group (p<0.001). Ultra-staging examination of the pelvic sentinel lymph nodes revealed isolated tumor cells in one patient from each group. CONCLUSION: Transcervical endometrial tracer injection in endometrial cancer revealed similar pelvic but significantly higher para-aortic sentinel lymph node detection.

Safety and Efficacy of Extended Therapy with [177Lu]Lu-PSMA: A German Multicenter Study.

Prospective results have demonstrated favorable safety and efficacy of [177Lu]Lu-PSMA radiopharmaceutical therapy for up to 6 cycles in men with metastatic castration-resistant prostate cancer. However, no systematic data are available outlining the feasibility of extended therapy beyond 6 cycles. We aim to evaluate the safety and efficacy of extended [177Lu]Lu-PSMA radiopharmaceutical therapy in patients who have received more than 6 cycles. Methods: In total, 111 patients were included in this multicenter retrospective analysis. Based on individual decisions, patients underwent uninterrupted continuation of therapy (continuous treatment) or reexposure after a therapy break (rechallenge treatment) between 2014 and 2023. Overall survival, 50% prostate-specific antigen (PSA) decline (measured 8-12 wk after treatment initiation or rechallenge), PSMA PET response, and grades per Common Terminology Criteria for Adverse Events were assessed. χ2 tests, multivariable Cox regression analysis, and log-rank tests were applied for statistical analyses. Results: Patients received extended treatment with [177Lu]Lu-PSMA, either as a continuous treatment (43/111, 38.7%) or as a rechallenge (68/111, 61.3%) treatment, with median cumulative doses of 57.4 or 60.8 GBq, respectively. Overall survival from the initiation of [177Lu]Lu-PSMA was 31.3, 23.2, and 40.2 mo for the entire cohort, the continuous treatment group, and the rechallenge treatment group, respectively. The initial 50% PSA decline was significantly higher in the retreated group than in the continuous group (57/63 [90.4%] vs. 26/42 [61.9%]; P = 0.006). A 50% PSA decline was observed in 23 of 62 patients (37.1%) after the first rechallenge. The rate of grades 3-4 toxicity was comparable between continuous and rechallenge treatments (anemia, 7/43 [16.3%] vs. 13/68 [19.1%)], P = 0.6; leukocytopenia, 1/43 [2.3%] vs. 2/67 [3.0%], P = 0.3; thrombocytopenia, 3/43 [7.0%] vs. 3/68 [4.4%], P = 0.3; renal, 2/43 [4.7%] vs. 5/68 [7.4%], P = 0.2). Conclusion: Extended therapy with [177Lu]Lu-PSMA is safe and has not been associated with increased grades 3-4 toxicity. Patient candidates for extended treatment experienced a favorable median survival of 31.3 mo from the first administration. Response under [177Lu]Lu-PSMA rechallenge demonstrated preserved efficacy of [177Lu]Lu-PSMA after a treatment break.

Prostate-specific Membrane Antigen Positron Emission Tomography-detected Disease Extent and Overall Survival of Patients with High-risk Nonmetastatic Castration-resistant Prostate Cancer: An International Multicenter Retrospective Study.

Previously, we demonstrated that prostate-specific membrane antigen positron emission tomography (PSMA-PET) revealed distant metastases in 109/200 patients (39% distant nodes, 24% bone, and 6% visceral organ) with nonmetastatic castration-resistant prostate cancer (nmCRPC) and high-risk features (International Society of Urological Pathology score ≥4 and/or prostate-specific antigen doubling time ≤10 mo) without metastases by conventional imaging. However, the impact of disease extent determined by PSMA-PET on patient outcomes is unknown. We followed these 200 patients for a median of 43 mo after PSMA-PET and retrospectively assessed the association between patient characteristics, PSMA-PET findings, treatment management, and outcomes using a Kaplan-Meier model and Cox multivariable regressions. Among assessed disease characteristics, polymetastatic disease (five or more distant lesions on PET) was independently associated with shorter overall survival (OS; median 61 mo vs not reached; hazard ratio [95% confidence interval], 1.81 [1.00-3.27]; p = 0.050) and time to new metastases (median 38 vs 60 mo; 1.80 [1.10-2.96]; p = 0.019), and initial pN1 status with shorter OS (55 mo vs not reached; 1.94 [1.12-3.37]; p = 0.019). Following PSMA-PET, locoregional salvage therapies were used most commonly in no/local disease (58%), and androgen receptor signaling inhibitors were used in distant metastatic disease (51%). PSMA-PET provides additional risk stratification for patients with nmCRPC. Polymetastatic disease (five or more distant lesions) is associated with worse outcomes. PATIENT SUMMARY: A novel sensitive imaging technology, called prostate-specific membrane antigen positron emission tomography (PSMA-PET), allows doctors to detect the spread of prostate cancer, known as distant metastases, earlier and more accurately than in the past. In our study, PSMA-PET detected none to many metastases in patients who were considered free of distant metastasis by conventional imaging. These findings predicted outcomes and were used to select appropriate treatment.

PET/CT With 68Ga-PSMA and 18F-FDG in Metastatic Adenoid Cystic Carcinoma: Report of 2 Cases.

ABSTRACT: Adenoid cystic carcinoma (ACC) is a rare and slow-growing tumor, originating from salivary glands. Locoregional recurrence and distant metastasis of ACC can be visualized not only with 18F-FDG but also with 68Ga-PSMA PET/CT due to its high prostate-specific membrane antigen (PSMA) expression. We report 2 cases of metastatic ACC who underwent first 18F-FDG and then 68Ga-PSMA for staging and restaging.

Urinary Reflux Into the Prostate Gland and Seminal Vesicles: A Potential Pitfall in 18F-FDG and 68Ga-PSMA PET/CT.

A 64-year-old man with lung cancer underwent F-FDG PET/CT for restaging, which demonstrated intense F-FDG uptake in the right lobe of prostate gland and seminal vesicles, indicating a potential prostate cancer. In Ga-PSMA PET/CT, intense uptake in the right lobe of prostate gland and seminal vesicles was also observed but decreased in postmictional delayed images. Magnetic resonance imaging showed high signal intensity of urine in the same areas of uptakes. F-FDG and Ga-PSMA PET/CT findings in the prostate gland and seminal vesicles were considered to be a result of urinary reflux possibly because of the patient's previous transurethral resection.

Uptake of an Acrochordon Incidentally Detected on 68Ga Prostate-Specific Membrane Antigen PET/CT.

Ga prostate-specific membrane antigen (PSMA) PET/CT is a promising tool for imaging of prostate cancer. Ga-PSMA PET/CT uptake of prostate cancer and its metastases are reflective of significant overexpression of PSMA. However, PSMA expression of benign neoplasms and nonprostate epithelial malignancies is not very well defined. We report a moderate Ga-PSMA uptake of an acrochordon (skin tag), which was incidentally found in a patient referred for staging prostate cancer. Acrochordon is a frequent, small, soft, skin-colored or hyperpigmented, benign, and usually pedunculated neoplasm of the skin. Nuclear medicine physicians should be aware of it while reporting a Ga-PSMA PET/CT.