Neuroendocrine differentiation in castration resistant prostate cancer. Nuclear medicine radiopharmaceuticals and imaging techniques: A narrative review.

BACKGROUND: Androgen Deprivation Therapy (ADT) is the primary treatment for patients suffering from relapsing or advanced prostate cancer (PC). Hormone therapy generally guarantees adequate clinical control of the disease for some years, even in those patients affected by widespread skeletal and soft tissue metastases. Despite ADT, however, most patients treated with hormones eventually progress to castration-resistant prostate cancer (CRPC), for which there are no effective treatments. This clinical reality is an open challenge to the oncologist because of those neoplasms which elaborate neuroendocrine differentiation (NED). METHODS: An online search of current and past literature on NED in CRPC was performed. Relevant articles dealing with the biological and pathological basis of NED, with nuclear medicine imaging in CRPC and somatostatin treatment in NED were analyzed. EVIDENCE FROM THE LITERATURE: NED may arise in prostate cancer patients in the late stages of ADT. The onset of NED offers prognostic insight because it reflects a dramatic increase in the aggressive nature of the neoplasm. Several genetic, molecular, cytological and immunohistochemical markers are associated with this transformation. Among these, overexpression of somatostatin receptors, seen through Nuclear Medicine testing, is one of the most studied. CONCLUSIONS: Preliminary studies show that the overexpression of somatostatin receptors related to NED in CRPC may easily be studied in vivo with PET/CT. This finding offers a potentially useful objective for targeted therapy in CRPC. If the overexpression of SSTRs is shown to afflict a significant segment of patients with CRPC, this will open further study of possible therapeutic options based on this marker.

Will Stone Density Stop Being a Key Factor in Endourology? The Impact of Stone Density on Laser Time Using Lumenis Laser p120w and Standard 20 W Laser: A Comparative Study.

Introduction and Objectives: Ureteroscopy is the gold standard for most urinary tract calculi. Our institute recently incorporated a powerful 120 W holmium laser machine integrating innovative technology (Lumenis® MOSES PulseTM120H Holmium:YAG laser; Lumenis Ltd.). In this retrospective comparative study, we evaluated the influence of stone density on laser dusting time in a high-power 120 W laser machine vs a standard 20 W machine (Dornier Medilas® H20 Holmium:YAG laser; Dornier Ltd.) Methods: We conducted a retrospective review of medical records of patients who underwent ureteroscopy during the years 2013-2018 for a solitary stone. Stone and clinical characteristics, among other parameters, have been evaluated, including the total laser time until complete stone dusting. Results: Among 631 eligible patients, 462 were treated with a 20 W standard laser and 169 patients with a p120w laser machine. Overall laser time was less than half with p120w laser vs d20w (195 seconds vs 397.14 seconds, p-value <0.001). Multivariate regression demonstrated 234.91 seconds shorter laser time with a p120w laser while controlling confounders such as stone volume, hydronephrosis, and location (p value <0.0001). This pattern was demonstrated in all stone densities. The association between laser dusting time per stone volume and stone density demonstrated relatively constant laser time when using p120w laser, even for hard stones. When the standard 20 W laser was used, laser time was longer in each stone density. Moreover, a stone density of 1164 HU and more demonstrated an upward shift of laser time to stone density curve in standard d20w laser group only. Conclusions: Time to complete stone dusting using p120w laser is extremely shorter, approximately half, comparing with the standard 20 W laser. This pattern is robust and even exponential when evaluating laser time per stone density, especially in hard stones. A new horizon of powerful innovative laser technology will enable to improve endourology practice and patients' care.

PET/CT With 68Ga-DOTA-TATE for Diagnosis of Neuroendocrine: Differentiation in Patients With Castrate-Resistant Prostate Cancer.

AIM: Castrate-resistant prostate cancer (CRPC) often shows histological evidence of neuroendocrine differentiation (NED). To evaluate the extent of NED in patients with CRPC, we used PET/CT with Ga-[DOTA-Tyr]-octreotate (Ga-DOTA-TATE), a somatostatin analog that binds somatostatin receptor 2 with high affinity. This radiotracer is used in imaging of neuroendocrine tumors. METHODS: Twelve patients (mean age, 65 [SD, 12] years) with CRPC were studied. Their mean prostate-specific antigen level at scanning was 85.6 (SD, 144.6) ng/mL. PET/CT images were obtained after the injection of 120 to 200 MBq of Ga-DOTA-TATE. RESULTS: All participants had at least 1 blastic metastasis demonstrating uptake of Ga-DOTA-TATE (mean SUVmax of 5.3 [SD, 2.3]). In 6 patients, moderately high to high uptakes (SUVmax, >5) were seen. Patients with multiple bone metastases had a significantly higher SUVmax compared with patients with few metastases (mean of 5.8 vs 3.8, P = 0.05). In 4 patients, lytic bone lesions or lymph node metastases also showed uptake of the tracer (mean SUVmax of 7.2 [SD, 3.2]). Uptake of the radiotracer was also observed in bones showing normal architecture in CT, suggesting that NED cells appear early during metastases development. CONCLUSIONS: Uptake of Ga-DOTA-TATE is a common finding in metastases of CRPC patients, suggesting that NED is frequent in these patients. In half of the patients, widespread uptake of Ga-DOTA-TATE was observed. This suggests that the possibility of treating selected CRCP patients with anti-neuroendocrine tumor therapies should be explored and that Ga-DOTA-TATE scanning could have a role in predicting the efficacy of these treatments.