The role of PSMA PET/CT in predicting downgrading in patients with Gleason score 4+4 prostate cancer in prostate biopsy.

BACKGROUND: To investigate the predictable parameters associated with downgrading in patients with a Gleason score (GS) 8 (4+4) in prostate biopsy after radical prostatectomy. METHODS: We retrospectively analyzed 62 patients with a GS of 4+4 on prostate biopsy who underwent robotic radical prostatectomy between 2017 and 2022. RESULTS: 38 of 62 (61.2%) were downgraded. In multivariable logistic regression model, Ga-68 prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) SUV max was independent predictor of downgrading (OR 0.904; p = 0.011) and a Logistic Regression model was constructed using the following formula: Y = 1.465-0.95 (PSMA PET/CT SUV max). The model using this variable correctly predicted the downgrading in 72.6% of patients. The AUC for PSMA PET/CT SUV max was 0.709 the cut off being 8.8. A subgroup analysis was performed in 37 patients who had no other European Association of Urology (EAU) high risk features. 25 out of 37 (67.5%) were downgraded, and 21 of these 25 had organ confined disease. Low PSMA SUV max (<8.1) and percentage of GS 4+4 biopsy cores to cancer bearing cores (45.0%) were independently associated with downgrading to GS 7. CONCLUSION: PSMA PET/CT can be used to predict downgrading in patients with GS 4+4 PCa. Patients with GS 4+4 disease, but no other EAU high risk features, low percentage of GS 4+4 biopsy cores to cancer bearing cores, and a low PSMA PET/CT SUV max are associated with a high likelihood of the cancer reclassification to intermediate risk group.

Radioligand Therapy With 177 Lu-PSMA-I&T in Patients With Metastatic Prostate Cancer : Oncological Outcomes and Toxicity Profile.

INTRODUCTION: This study aimed to investigate the oncological outcomes and toxicity profile of 177 Lu-PSMA-I&T radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC), as well as our initial experience in metastatic hormone-sensitive prostate cancer (mHSPC). PATIENTS AND METHODS: A total of 38 consecutive patients with metastatic prostate cancer (33 mCRPC and 5 mHSPC) received 177 Lu-PSMA-I&T RLT, with a median of 2 cycles per patient (range, 1-7). Response to RLT was evaluated based on prostate-specific antigen (PSA) changes and imaging response. Clinical progression-free survival and overall survival were used to report oncological outcomes. Toxicity was assessed using the Common Toxicity Criteria for Adverse Events criteria. RESULTS: In mCRPC, 22 (69%), 18 (56%), and 11 (34%) patients achieved any PSA decline, PSA response of ≥30%, and PSA response of ≥50%, respectively. The clinical progression-free survival and overall survival after the first cycle of RLT were 6.3 and 21.4 months, respectively. In mHSPC, 177 Lu-PSMA-I&T RLT resulted in excellent PSA response (93.0%-99.9%) in all cases. Clinical progression and cancer-related mortality occurred in only 1 case. Toxicity profile was favorable in both mHSPC and mCRPC. CONCLUSIONS: 177 Lu-PSMA-I&T RLT demonstrated favorable PSA response (≥30%) in over half of the patients with mCRPC and excellent PSA response in all patients with mHSPC. Toxicity profile was favorable in both mHSPC and mCRPC settings. Further studies are needed to evaluate the role of 177 Lu-PSMA-I&T RLT in the management of metastatic prostate cancer.

Intraoperative Frozen Section via Neurosafe During Robotic Radical Prostatectomy in the Era of Preoperative Risk Stratifications and Primary Staging With mpMRI and PSMA-PET CT: Is There a Perfect Candidate?

BACKGROUND: We aimed to analyze the effect of preoperative risk assessment including Ga-68 PSMA PET and multiparametric magnetic resonance imaging (mpMRI) on nerve sparing practices, positive surgical margin (PSM) rates and oncological outcomes based on a comparison between patients underwent RARP with and without Neurosafe (NS). METHODS: Patients underwent RARP with NS (RARP-NS) or without (RARP-only) NS retrospectively evaluated. Suspicion for extracapsular extension on mpMRI and/or Ga-68 PSMA PET was recorded as i(imaging)T3. NS was performed according to the Martini-Klinik technique. PSM at preserved bundle side were called PSM at region of interest (ROI) while the others were elsewhere. RESULTS: A total of 208 patients (90 in RARP-NS, 118 in RARP-only groups) were included. Preoperatively the RARP-only group showed significantly higher mean PSA (p = .01) and PIRADS 5 (p = .002) findings and had more D'Amico high risk (DAHR) patients (p = .08). The overall PSM rates for pT2 versus pT3 disease were 7.5% versus 21.6 and 15.6% versus 55% in RARP-NS and RARP-only groups, respectively. NS resulted in more bilaterally preserved bundles (81.1% vs. 66.3%) and less PSM at the ROI (3.3% vs. 23.4%) than RARP-only group. NS outperformed RARP-only in all clinical settings had its highest differential benefit in more bilateral nerve sparing and less PSM at ROI in patients with both DAHR and iT3 disease. BCR rates were 2.2% and 2.5% for RARP-NS and RARP only groups, respectively (p = .4). One patient in RARP-NS and 9 in RARP-only groups had PSA persistence (p = .02). CONCLUSION: RARP-NS led to more preserved bundles with less PSM. It was especially useful in DAHR patients with preoperative extracapsular extension suspicion in imaging simultaneously.

Diagnostic Performance of 68Ga-PSMA-11 Positron Emission Tomography/Computed Tomography to Monitor Treatment Response in Patients with Metastatic Prostate Cancer: The Concordance Between Biochemical Response and Prostate-specific Membrane Antigen Results.

BACKGROUND: Treatment response is traditionally monitored using prostate-specific antigen (PSA) and conventional imaging in patients with metastatic prostate cancer (mPCa). OBJECTIVE: To assess the diagnostic performance of prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) when monitoring mPCa patients receiving systemic treatment and also to investigate the concordance between PSMA PET response according to the PSMA PET progression (PPP) criteria and biochemical response. DESIGN, SETTING, AND PARTICIPANTS: A total of 96 patients with 68Ga-PSMA-11 PET/CT-detected mPCa at baseline PSMA PET/CT (bPSMA) who underwent at least one follow-up scan after receiving systemic treatment were included in the study. PSA levels at bPSMA and follow-up PSMA PET (fPSMA) scans were recorded. The PPP criteria were used to define PSMA progression. Biochemical progression was defined as ≥25% increase in PSA. PSMA PET and PSA responses were dichotomized into progressive disease (PD) versus non-PD, and the concordance between PSA and PSMA responses was evaluated. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The concordance between PSA and PSMA PET responses was presented using frequencies, percentages, and Cohen's kappa test. RESULTS AND LIMITATIONS: A total of 345 serial PSMA PET/CT (96 bPSMA and 249 fPSMA) scans were evaluated. The positivity rates of PSMA PET scans for PSA levels of <0.01, 0.01-0.2, 0.2-4, and >4 ng/ml were 55.6%, 75.0%, 100%, and 98.8%, respectively. PSA and PSMA responses showed moderate-to-high concordance (Cohen's κ = 0.623, p < 0.001). PSA-PSMA discordance was detected in 39 scans (17%). The most common cause of discordance was the discordant results between different metastatic lesions (16/28, 57.1%) in patients with PPP without PSA progression and local progression in prostate (n = 7/11, 63.6%) in patients with PSA progression without PPP. CONCLUSIONS: PSMA PET/CT showed very high detection rates of malignant lesions even at very low PSA values and showed significant concordance with PSA response when monitoring treatment response in patients receiving systemic treatment for mPCa. PATIENT SUMMARY: This study describes that prostate-specific membrane antigen positron emission tomography (PSMA PET), a new sensitive imaging tool, can detect malignant lesions even at very low prostate-specific antigen values when monitoring metastatic prostate cancer. The PSMA PET response and biochemical response showed significant concordance, and the reason for discordant results seems to be the different responses of metastatic lesions and prostatic lesions to systemic treatment.

18F-FDG PET/CT texture analysis of anthracotic lymph nodes detected with EBUS and comparison with cytological findings.

OBJECTIVE: Lymph node metastasis is the most important factor both in the selection of treatment since many alternatives have been created in recent years, and in the evaluation of prognosis in lung cancer. The most unpredictable cause of lymph node false positivity in fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is anthracosis. The aim of this study is to compare 18F-FDG PET/CT texture information of anthracotic (ALN) and metastatic (MLN) lymph nodes, after re-evaluation of the cytological samples obtained from anthracotic lymph nodes by EBUS-TBNA. SUBJECTS AND METHODS: Ninety nine patients, 78 of whom had primary lung cancer were included in the study. Two hundred and three lymph nodes from 99 patients sampled by EBUS-TBNA and diagnosed cytologically as ALN or MLN were evaluated retrospectively. All ALN were classified as grades 1, 2 and 3 cytologically. Volume of interest (VOI) of 203 lymph nodes was re-drawn and maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) values were recorded. RESULTS: There was a statistically significant difference in MTV and TLG values in MLN and all ALN grades. However, only grade 1-2 ALNs could be differentiated from MLNs with SUVmax, and no statistically significant difference was found in grade 3 ALN and MLN. Metabolic tumor volume and TLG values over 4.10cm3 and 26.57 showed 60% and 59% sensitivity and 83% and 94 specificity respectively for the identification of MLN. CONCLUSION: The contribution of MTV and TLG values of 18F-FDG PET/CT to the differential diagnosis of ALN is much more valuable than SUVmax values, especially for grade 3 anthracosis. It was thought that cytological reporting of only grade 3 ALN could make a better contribution to the 18F-FDG PET/CT evaluation analysis.

68Ga-PSMA-11 Positron Emission Tomography/Computed Tomography for Primary Lymph Node Staging Before Radical Prostatectomy: Central Review of Imaging and Comparison with Histopathology of Extended Lymphadenectomy.

BACKGROUND: Results from prospective trials have shown higher accuracy of prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) in detection of lymph node metastasis (LNM) compared to conventional imaging. OBJECTIVE: To evaluate the accuracy of 68Ga-PSMA-11 PET/CT for LNM detection in patients undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (PLND). DESIGN, SETTING, AND PARTICIPANTS: Between June 2014 and November 2020, 96 patients with 68Ga-PSMA PET/CT for primary staging underwent RP and extended PLND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The results from 68Ga-PSMA PET/CT were compared with histologic data from primary PLND in 96 patients. All 68Ga-PSMA PET/CT scans were centrally reviewed. RESULTS AND LIMITATIONS: Of 96 patients, 15.6% (n = 15) harbored LNMs. The median prostate-specific antigen at 68Ga-PSMA PET/CT was 8.0 ng/ml (interquartile range 5.5-11.7). The majority of patients had intermediate- (52.1%) or high-risk disease (41.7%). Biopsy grade group 4 and 5 was present in 22.9% and 15.6%, respectively. The 68Ga-PSMA PET/CT scans identified eight of 15 patients (53.3%) as LN-positive (true positive). The calculated per-patient sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 68Ga-PSMA PET/CT in the detection of LNM were 53.3%, 98.8%, 88.9%, 92.0%, and 91.7%, respectively. The per-patient sensitivity and specificity in the detection of LNMs larger than 2 mm were 61.5% and 98.8%, respectively. The main limitation is the retrospective design of the study. CONCLUSIONS: 68Ga-PSMA PET/CT is accurate in lymph node staging and the results support its use for primary staging of prostate cancer. PATIENT SUMMARY: We compared prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) findings with histopathology results after extended lymph node dissection and showed that it is accurate in detecting lymph node metastases. Our results support the use of PSMA PET/CT for primary staging of prostate cancer.

Diagnostic ability of Ga-68 PSMA PET to detect dominant and non-dominant tumors, upgrading and adverse pathology in patients with PIRADS 4-5 index lesions undergoing radical prostatectomy.

BACKGROUND: To evaluate the additive role of Ga-68 PSMA PET as a primary staging tool in patients bearing prostate cancer in single PIRADS 4 or 5 index lesions. METHODS: Eighty-one biopsy-naive patients with preoperative mpMRI and Ga-68 PSMA PET who underwent radical prostatectomy (RP) were evaluated retrospectively. Forty-nine patients had PIRADS 4 and 32 had PIRADS 5 index lesions. The localization, grade, and volumetric properties of dominant (DT) and non-dominant tumors (NDT) in RP were compared to the index lesions of mpMRI and Ga-68 PSMA PET. RESULTS: The median age and PSA level were 62 (IQR; 59-69) years and 7 (IQR; 2-8) ng/ml, respectively. Ga-68 PSMA PET detected DTs in 100% of the patients including 13 patients in whom mpMR failed. In 45 patients an NDT was reported in RP. Ga-68 PSMA PET accurately detected NDT in 24 of 45 (53.3%) patients. Six patients (12.2%) in PIRADS 4 and 8 (25%) in PIRADS 5 group showed upgrading. In PIRADS 4, Ga-68 PSMA PET localized DT in all patients with upgraded tumors whereas mpMRI missed exact location in 2 of 6 (33.3%). In PIRADS 5 both mpMRI and Ga-68 PSMA PET accurately located all DTs. Overall detection rates of extracapsular extension (ECE) and seminal vesicle invasion (SVI) by mpMRI were 51.1% and 53.8%, respectively. Ga-68 PSMA PET detected ECE and SVI in 27.9% and 30.7%, respectively. When mpMRI and Ga-68 PSMA PET were used in combination detection rates of ECE and SVI increased to 65.1 and 61.5%. Ga-68 PSMA PET-detected six of ten patients with positive lymph nodes whereas mpMRI could not identify any. CONCLUSIONS: Ga-68 PSMA PET has a better diagnostic accuracy in detecting DT, NDT, upgrading, adverse pathology in patients with PIRADS 4 index lesions. However, mpMRI better predicted ECE and SVI than Ga-68 PSMA PET.

Diagnostic Accuracy of Ultrasound for the Evaluation of Lateral Compartment Lymph Nodes in Papillary Thyroid Carcinoma.

AIMS: To evaluate the diagnostic accuracy of ultrasound (US) assessing the lateral compartment lymph node metastasis in patients with primary papillary thyroid carcinoma (PTC), and to demonstrate the incidence and patterns of the lateral lymph node metastasis. METHODS: We retrospectively reviewed 198 patients with primary PTC who underwent thyroidectomy in addition to modified lateral neck dissections (MLND) involving level II to level V due to clinically positive lateral neck disease. A skilled and experienced single operator performed all US examinations. Surgical pathology results were accepted as the reference method and sensitivity, specificity, and diagnostic accuracy of US in detecting metastatic lymph nodes established using level-by-level analysis. RESULTS: In the study cohort, 10.1% of the patients had lateral compartment lymph node metastases without any central compartment involvement. For the lateral compartment, 48.5% had level II, 74.7% had level III, 64.6% had level IV, and 29.3% of the patients had level V metastasis. None of the patients had isolated level V metastasis. The sensitivity, specificity, and diagnostic accuracy of US in identifying lateral lymph compartment metastasis ranged from 87% to 91.4%, 92% to 98.6% 92.4% to 96%, respectively. However, the sensitivity (74.7%) and diagnostic accuracy (76.2%) of US significantly decreased for the central compartment while specificity (90%) remained similar. CONCLUSION: US performed by a skilled operator has an excellent diagnostic accuracy for the evaluation of lateral cervical lymph nodes in primary PTC; thus, might enable precise tailoring of the management strategies. Moreover, the high incidence of level V involvement favors MLND over selective approaches.

Posttherapeutic Critical Organ Dosimetry of Extensive 177Lu-PSMA Inhibitor Therapy With Metastatic Castration-Resistant Prostate Cancer: One Center Results.

PURPOSE: Lu-PSMA inhibitor peptide receptor radioligand therapy (RLT) is playing an increasing role in metastatic castration-resistant prostate cancer. We aimed to estimate the absorbed radiation doses for critical organs (eg, kidneys, parotid glands, submandibular glands, and lacrimal glands) of patients treated with 4 to 6 cycles by Lu-PSMA inhibitor RLT, retrospectively, and to evaluate the findings extensively in order to determine the critical organ radiation-absorbed limitations and the number of prospective RLT. MATERIALS AND METHODS: A total of 51 cycles Lu-PSMA inhibitor RLT in 10 patients was analyzed. Therapies have been applied in 4 to 6 cycles with 8 to 10 weeks' intervals. Dosimetric estimates of kidneys, parotid glands, submandibular glands, and lacrimal glands have been calculated based on MIRD scheme pamphlet no. 16. Regions of interest were drawn with GE Xeleris Functional Imaging Workstation. OLINDA/EXM 1.1 simulation software was used to calculate radiation-absorbed doses. RESULTS: Mean radiation-absorbed doses were 0.70 ± 0.24 Gy/GBq for kidneys, 1.34 ± 0.78 Gy/GBq for parotid glands, 0.94 ± 0.45 Gy/GBq for submandibular glands, and 2.28 ± 1.29 Gy/GBq for lacrimal glands. CONCLUSIONS: Due to the critical target organ risks and the optimal therapy doses, patient-specific dosimetry is a deterministic factor in radionuclide therapy. Even when the absorbed kidney doses were above the ICRP critical dose limits in patients who had 4 to 6 cycles of therapy, mortality due to nephrotoxicity has not been observed. Mild increased tolerated radiation dose is acceptable for the patient groups with very low survival rate.

Can Ga-68 PSMA PET/CT replace conventional imaging modalities for primary lymph node and bone staging of prostate cancer?

Imaging is critical for primary staging of prostate cancer. Traditional imaging modalities (computerized tomography scan and nuclear medicine bone scans) are limited by their suboptimal diagnostic performance. Recent meta-analyses have demonstrated that nuclear imaging with 68Ga-labeled prostate-specific membrane antigen ligand (68Ga-PSMA) using positron emission tomography/computed tomography (PET/CT) has higher sensitivity and specificity in this setting compared to conventional imaging techniques. 68Ga-PSMA PET/CT for whole-body assessment can be used as the sole imaging modality for primary lymph node and bone staging of prostate cancer. PATIENT SUMMARY: There is a rapidly growing body of evidence that nuclear imaging with 68Ga-labeled prostate-specific membrane antigen ligand using positron emission tomography/computed tomography has a higher detection rate for lymph node and bone metastases in prostate cancer patients. This approach has strong potential to replace conventional techniques in the primary setting in the near future.

Effect on gastric emptying and weight reduction of botulinum toxin-A injection into the gastric antral layer: an experimental study in the obese rat model.

BACKGROUND: We investigated the effects of Botox-A on weight loss and gastric emptying in an experimental obese rat model. Although there is evidence of weight loss in normal-weight rats after Botox-A injection, there are no studies indicating the effect of Botox-A injection on weight loss and gastric emptying time in obese rats. METHODS: 37 female Wistar Albino rats were given high calorie diet for 90 days. They were separated into 3 groups. The first group (Botox group) consisted of 15 obese rats whose gastric antrum was injected with 20 U of Botulinum Toxin Type A. The second group (Saline group) consisted of 15 obese rats whose gastric antrum was injected with 20 U of saline. The third group (Control group) had no surgical intervention. Gastric scintigraphy was performed in the 3 groups pre- and postoperatively. RESULTS: The saline group had a weight reduction in the early postoperative days but began to gain weight thereafter. The mean weight of the Botox group between the 16th and 28th days postoperatively was significantly lower than the mean weights of the control and the saline groups (P<0.05, P<0.001). The results of gastric emptying scintigraphy in all 3 groups at day 20 revealed significantly higher T1/2 values in the Botox-A group when compared to the results of the control and saline groups (P<0.001). CONCLUSION: Botox-A application to the gastric antrum in obese rats leads to weight loss by increasing the gastric emptying time.