Ac-PSMA-617 RLT of chemotherapy-naïve patients with advanced metastatic prostate carcinoma led to a ≥ 90% decline in serum PSA in 82% of patients including 41% of patients with undetectable serum PSA who remained in remission 12 months after therapy. The remarkable therapeutic efficacy reported in this study could be achieved with reduced toxicity to salivary glands due to de-escalation of administered activities in subsequent treatment cycles. This necessitates further exploration for informing clinical practice and clinical trial design.

Metastatic prostate carcinoma overexpresses prostate-specific membrane antigen (PSMA), making this antigen a suitable target for radioligand therapy of the disease. Here we report on our experience with a series of 73 castration-resistant prostate carcinoma patients treated with 225 Ac-PSMA-617, identifying variables predictive for overall survival (OS) and progression-free survival (PFS) after 225 Ac-PSMA-617 treatment. Methods: 225 Ac-PSMA-617 was administered to patients who had metastatic castration-resistant prostate carcinoma and who had exhausted available therapy options for their disease. Full blood count, glomerular filtration rate, and liver function test were obtained at baseline and on follow-up for evaluation of toxicity. 68 Ga-PSMA PET/CT was obtained at baseline, before every treatment cycle, and on follow-up for selection of patients for treatment, to determine the activity of the treatment agent to be administered, and for response assessment. Serial prostatespecific antigen (PSA) was obtained for PSA response assessment. Results: Seventy-three men (mean age, 69 y; range, 45-85 y) with metastatic castration-resistant prostate carcinoma were treated with 210 cycles of 225 Ac-PSMA-617. In 70% of patients, a PSA decline of greater than or equal to 50% was obtained; 82% of patients had any PSA decline. In 29% of patients, all lesions on 68 Ga-PSMA PET resolved in response to treatment. During follow-up, 23 patients experienced disease progression, whereas 13 patients died from their disease. The estimated median PFS and OS were 15.2 mo (95% CI, 13.1-17.4) and 18 mo (95% CI, 16.2-19.9), respectively. In univariate analyses, factors such as baseline PSA, any PSA decline, PSA decline of greater than or equal to 50%, prior chemotherapy, prior radiation therapy, and baseline hemoglobin level were associated with longer PFS and OS (all Ps , 0.05). In multivariate analyses, there was a negative association between prior 177 Lu-PSMA therapy and PFS, and a positive association between PSA decline of greater or equal to 50% and PFS. Only a PSA decline of greater than or equal to 50% remained significantly associated with OS on multivariate analyses. Xerostomia was seen in 85% of patients but was not severe enough to warrant discontinuing treatment. Anemia was seen in 27 patients; no patients had grade IV bone marrow toxicity. Renal failure of grade III or IV was seen in 5 patients with baseline renal impairment. Conclusion: In this study, a PSA decline of greater than or equal to 50% after treatment with 225 Ac-PSMA-617 was proven by multivariate analyses to be significantly associated with OS and PFS. Furthermore, previous 177 Lu-PSMA treatment was negatively associated with PFS in both univariate and multivariate analyses.

Papillary lesions of the breast continue to be a diagnostic challenge because of the wide morphologic spectrum that may be encountered in these lesions. A rare entity termed "breast tumor resembling the tall cell variant of papillary thyroid carcinoma" is considered to be a subtype of papillary carcinoma of the breast. It is characterized by distinct morphologic features, setting it apart from typical papillary carcinoma of the breast. Its resemblance to papillary thyroid carcinoma in conjunction with the established terminology may cause confusion, resulting in unnecessary ancillary studies to exclude the association of this lesion with papillary thyroid carcinoma. As immunohistochemical and molecular studies have shown no evidence to support any association between this entity and papillary thyroid carcinoma, we propose to change the current terminology of "breast tumor resembling the tall cell variant of papillary thyroid carcinoma" to the term "tall cell variant of papillary breast carcinoma."