Administering [177Lu]Lu-PSMA-617 Prior to Radical Prostatectomy in Men with High-risk Localised Prostate Cancer (LuTectomy): A Single-centre, Single-arm, Phase 1/2 Study.

BACKGROUND: High-risk localised prostate cancer (HRCaP) has high rates of biochemical recurrence; [177Lu]Lu-PSMA-617 is effective in men with advanced prostate cancer. OBJECTIVE: To investigate the dosimetry, safety, and efficacy of upfront [177Lu]Lu-PSMA-617 in men with HRCaP prior to robotic radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: In this single-arm, phase I/II trial, we recruited men with HRCaP (any of prostate-specific antigen [PSA] >20 ng/ml, International Society of Urological Pathology (ISUP) grade group [GG] 3-5, and ≥cT2c), with high tumour uptake on [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PSMA PET/CT), and scheduled for RP. INTERVENTION: Cohort A (n = 10) received one cycle and cohort B (n = 10) received two cycles of [177Lu]Lu-PSMA-617 (5 GBq) followed by surgery 6 weeks later. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was tumour radiation absorbed dose. Adverse events (AEs; Common Terminology Criteria for Adverse Events (CTCAE) version 5.0), surgical safety (Clavien-Dindo), imaging, and biochemical responses were evaluated (ClinicalTrials.gov: NCT04430192). RESULTS AND LIMITATIONS: Between May 29, 2020 and April 28, 2022, 20 patients were enrolled. The median PSA was 18 ng/ml (interquartile range [IQR] 11-35), Eighteen (90%) had GG ≥3, and six (30%) had N1 disease. The median (IQR) highest tumour radiation absorbed dose after cycle 1 for all lesions was 35.5 Gy (19.5-50.1), with 19.6 Gy (11.3-48.4) delivered to the prostate. Five patients received radiation to lymph nodes. Nine (45%) patients achieved >50% PSA decline. The most common AEs related to [177Lu]Lu-PSMA-617 were grade 1 fatigue in eight (40%), nausea in seven (35%), dry mouth in six (30%), and thrombocytopenia in four (20%) patients. No grade 3/4 toxicities or Clavien 3-5 complications occurred. Limitations include small a sample size. CONCLUSIONS: In men with HRCaP and high prostate-specific membrane antigen (PSMA) expression, [177Lu]Lu-PSMA-617 delivered high levels of targeted radiation doses with few toxicities and without compromising surgical safety. Further studies of [177Lu]Lu-PSMA-617 in this population are worthwhile to determine whether meaningful long-term oncological benefits can be demonstrated. PATIENT SUMMARY: In this study, we demonstrate that up to two cycles of [177Lu]Lu-PSMA-617 given prior to radical prostatectomy in patients with high-risk localised prostate cancer are safe and deliver targeted doses of radiation to tumour-affected tissues. It is tolerated well with minimal treatment-related adverse events, and surgery is safe with a low rate of complications. Activity measured through PSA reduction, repeat PSMA PET/CT, and histological response is promising.

Combination treatment in metastatic prostate cancer: is the bar too high or have we fallen short?

Androgen deprivation therapy (ADT) alone has been the cornerstone of treatment for patients with newly diagnosed metastatic prostate cancer for the past century. Based on results from landmark trials in the past decade, combination approaches of ADT with chemotherapy or novel hormonal agents have established a new standard of care for these patients. This paradigm shift in treatment has been reflected in the updates to guideline recommendations of major professional associations. However, real-world data from around the world have highlighted the dismal adoption of combination therapy, despite evidence-based recommendations. The disparity between evidence and practice is concerning, especially with emerging evidence of survival benefit with further treatment intensification using triplet combinations (ADT, docetaxel and novel hormonal agents). Thus, a pressing need to raise awareness and call the uro-oncology community to action exists to deliver evidence-based care for these patients.

Oncologic outcomes of patients with lymph node invasion at prostatectomy and post-prostatectomy biochemical persistence.

BACKGROUND: Pathologic nodal invasion at prostatectomy is frequently associated with persistently elevated prostate-specific antigen (PSA) and with increased risk of disease recurrence. Management strategies for these patients are poorly defined. We aimed to explore the long-term oncologic outcomes and patterns of disease progression. METHODS: We included men treated between 2000 and 2017 who had lymph node invasion at radical prostatectomy and persistently detectable prostate-specific antigen post-prostatectomy. Postoperative imaging and management strategies were collated. Patterns of recurrence and probability of metastasis-free survival, prostate cancer-specific survival, and overall survival (OS) were assessed. RESULTS: Among our cohort of 253 patients, 126 developed metastasis. Twenty-five had a positive scan within 6 months of surgery; of these, 15 (60%) had a nodal metastasis, 10 (40%) had a bone metastasis, and 4 (16%) had local recurrence. For metastasis-free survival, 5- and 10-year probabilities were 52% (95% CI 45%, 58%) and 37% (95% CI 28%, 46%), respectively. For prostate cancer-specific survival, 5- and 10-year probabilities were 89% (95% CI 84%, 93%) and 67% (95% CI 57%, 76%), respectively. A total of 221 patients proceeded to hormonal deprivation treatment alone. Ten patients received postoperative radiotherapy. CONCLUSIONS: Biochemical persistence in patients with lymph node invasion is associated with high risk of disease progression and reduced prostate cancer-specific survival. Management was hindered by the limitation of imaging modalities utilized during the study period in accurately detecting residual disease. Novel molecular imaging may improve staging and help design a therapeutic strategy adapted to patients' specific needs.

Prevalence of High-Risk Prostate Cancer Metastasis to Cloquet's Ilioinguinal Lymph Node.

PURPOSE: Cloquet's node, located at the junction between the deep inguinal nodes and the external iliac chain, is easily accessible and commonly excised during pelvic lymph node dissection for prostate cancer. However, we hypothesize that Cloquet's node is not part of lymphatic metastatic spread of prostate cancer. MATERIALS AND METHODS: Between September 2016 and June 2019, 105 consecutive patients with high-risk prostate cancer (cT3a or Grade Group 4/5, or prostate specific antigen >20 ng/ml) underwent a laparoscopic radical prostatectomy and pelvic lymph node dissection. First, Cloquet's node was identified, retrieved and submitted separately to pathology as right and left Cloquet's node. Next, a pelvic lymph node dissection was completed including the external iliac, obturator fossa and hypogastric nodal packets. Each lymph node was cut into 3 mm slices which were separately embedded in paraffin, stained with hematoxylin and eosin, and examined microscopically. RESULTS: The final analysis included 95 patients. In this high-risk population, the median number of nodes removed was 22 (IQR 18-29); 39/95 patients (41%) had lymph node metastasis. The median number of Cloquet's nodes removed was 2 (IQR 2-3). Cloquet's node was negative in all but 1 patient (1.1%), who had very high-risk features and high metastatic burden in the lymph nodes. CONCLUSIONS: In high-risk prostate cancer, metastasis to the ilioinguinal node of Cloquet is rare. Given this low prevalence, Cloquet's node can be safely excluded from the pelvic lymph node dissection template.

Comparative Outcomes and Predictive Assessment of Trifecta in Open, Laparoscopic, and Robotic-Assisted Partial Nephrectomy Cases with Renal Cell Carcinoma: A 10-Year Experience at Ramathibodi Hospital.

PURPOSE: To compare perioperative and trifecta outcomes of open partial nephrectomy (OPN), laparoscopic partial nephrectomy (LPN), and robotic-assisted laparoscopic partial nephrectomy (RPN) in patients with small renal mass at Ramathibodi Hospital, and to determine predictive factors in connection with trifecta. METHODS: We retrospectively reviewed 141 patients who underwent partial nephrectomy by eight experienced surgeons from January 2009 to December 2018. Baseline preoperative characteristics, postoperative and trifecta outcomes of the three treatment modalities were compared and analyzed. Univariate analysis was performed to determine predictive factors for trifecta achievement. RESULTS: A total of 70 patients had complete data available. Eighteen OPN, 11 LPN and 41 RPN cases were identified and reviewed. All preoperative and perioperative parameters were similar, except for operative time, which was significantly shorter in the OPN group compared with those undergoing LPN and RPN (135 vs 189 and 225 min, respectively; p-value = 0.001). Of these 70 patients, 59 were deemed eligible for and included in trifecta analysis, which revealed similar trifecta outcomes (64.29%, 45.45%, and 64.71% in the OPN, LPN, and RPN groups, respectively; p-value = 0.388). Univariate analysis showed that length of hospital stay was a negative associated factor for trifecta achievement (p-value = 0.007, 95% CI = 0.619 (0.44-0.88)). CONCLUSION: Although OPN displayed the shortest operative time, the trifecta achievement rate was not significantly different among the three groups. The sole parameter, which was negatively associated with trifecta outcome achievement, was the length of hospital stay.

Radical prostatectomy outcomes in renal transplant recipients: a retrospective case series of Thai patients.

BACKGROUND: The incidence of prostate cancer in renal transplant recipients (RTR) is similar to the general population. Radical prostatectomy (RP) is the standard of care in the management of clinically localized cancer, but is considered complicated due to the presence of adhesions, and the location of transplanted ureter/kidney. To date, a few case series or studies on RP in RTR have been published, especially in Asian patients. This study aimed to evaluate the efficacy and safety and report the experience with RP on RTR. METHODS: We retrospectively reviewed data of 1270 patients who underwent RP from January 2008 to March 2020, of which 5 patients were RTR. All available baseline characteristics, perioperative and postoperative data (operative time, estimated blood loss (EBL), complications, length of hospital stay, complication), pathological stage, Gleason score, surgical margin status, and pre/postoperative creatinine were reviewed. RESULTS: Of the 5 RTR who underwent RPs (1 open radical prostatectomy (ORP), 1 laparoscopic radical prostatectomy (LRP), 2 robotic-assisted laparoscopic radical prostatectomies (RALRP), and 1 Retzius-sparing RALRP (RS-RALRP)) prostatectomy, the mean age (± SD) was 70 (± 5.62) years. In LRP and RALRP cases, the standard ports were moved slightly medially to prevent graft injury. The mean operative time ranged from 190 to 365 min. The longest operative time and highest EBL (630 ml) was the ORP case due to severe adhesion in Retzius space. For LRP and RALRP cases, the operative times seemed comparable and had EBL of ≤ 300 ml. All RPs were successful without any major intra-operative complication. There was no significant change in graft function. The restorations of urinary continence were within 1 month in RS-RALRP, approximately 6 months in RALRP, and about 1 year in ORP and LRP. Three patients with positive surgical margins had prostate-specific antigen (PSA) persistence at the first follow-up and 1 had later PSA recurrence. Two patients with negative margins were free from biochemical recurrence at 47 and 3 months after their RP. CONCLUSIONS: Our series suggested that all RP techniques are safe and feasible mode of treatment for localized prostate cancer in RTR.

Neoadjuvant Androgen Deprivation Therapy Effects on Perioperative Outcomes Prior to Radical Prostatectomy: Eleven Years of Experiences at Ramathibodi Hospital.

OBJECTIVE: The aim of this study was to demonstrate the efficacy of neoadjuvant androgen deprivation therapy (NADT) on perioperative outcomes in patients who underwent radical prostatectomy (RP). MATERIALS AND METHODS: From January 2008 to July 2018, we collected retrospective data of patients with clinically localized prostate cancer who underwent RP to assess their perioperative and pathological outcomes. The data included age, body mass index (BMI), serum prostate specific antigen (PSA) level, clinical stage, neoadjuvant ADT usage, operative time, estimated blood loss (EBL), perioperative complications, blood transfusion rate, adjacent organ injury rate, length of hospital stay, pathological stage, Gleason score (GS) of the biopsy and pathological specimen, specimen weight (g), and margin status. RESULTS: Of the 718 RPs performed, 138 (19.22%) were NADT and 580 (80.78%) were non-NADT. Patients who underwent NADT had a significant benefit in operative time (185 vs 195 mins), EBL (300 vs 500 mL) and specimen weight. These benefits were more obvious in non-low risk prostate cancer with less operative time, EBL, blood transfusion rate, length of hospital stay and specimen weight. However, the margin status and adjacent organ injury rate were similar in the NADT and non-NADT groups. CONCLUSION: NADT provides significantly better perioperative outcomes, especially in non-low risk prostate cancer, and has comparable pathological outcomes.

Risk Factors for Anastomosis Leakage After Kidney Transplantation.

PURPOSE: Kidney transplantation is one of the best treatment options for end-stage renal disease with an incidence of urologic complications of 2.5 to 30%. One of the most serious and frequent urological complications is urinary leakage from ureteroneocystostomy anastomosis. The purpose of this study was to evaluate risk factors of urinary leakage from ureteroneocystostomy anastomosis after kidney transplantation. PATIENTS AND METHODS: A retrospective study was performed on patients who received kidney transplantation and were diagnosed with urinary leakage thereafter based on renal scan or drain creatinine per serum creatinine compared with patients in control group. Risk factor assessment was based on inpatient and outpatient information from hospital database. RESULTS: From 459 patients who received kidney transplantation in 2016-2018, there were 20 patients who were diagnosed with urinary leakage after they underwent ureteroneocystostomy anastomosis. The significant risk factors for anastomosis leakage were size of suture materials and duration of ureteral stent insertion. No statistically significant difference in other factors such as underlying disease, surgical technique or duration of urinary catheter was found. About overall urological complication, gender and body mass index significantly affected the outcome. CONCLUSION: The rate of urinary leakage complications was found to be about 4.36%. The risk factors of overall complication comprised gender and body mass index. Although a lot of previous studies revealed many risk factors that could affect urinary leakage, size of suture materials and duration of ureteral stent insertion were the significant risk factors in our study. Proper consideration should be given to the size of suture materials and optimal duration of ureteral stent.

Perioperative outcomes of robotic-assisted laparoscopic radical prostatectomy, laparoscopic radical prostatectomy and open radical prostatectomy: 10 years of cases at Ramathibodi Hospital.

BACKGROUND: This study aims to compare the perioperative and pathological outcomes of open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP), and robotic-assisted laparoscopic radical prostatectomy (RALRP) at Ramathibodi Hospital within Mahidol University in Thailand. METHODS: From January 2008 to July 2017, 679 RPs were performed. Patients' data were collected retrospectively to evaluate their perioperative and pathological outcomes. This data included the age, body mass index (BMI), serum prostate specific antigen (PSA) level, clinical stage, Gleason score (GS) from biopsy, operative time, estimated blood loss (EBL), perioperative complications, blood transfusion rate, adjacent organ injury rate, length of hospital stay, pathological stage, GS of the biopsy specimen, specimen weight (g), and marginal status of the patients. RESULTS: Of the 679 RPs performed, 128 (19.28%) were ORPs, 241 (36.30%) were LRPs, and 295 (44.43%) were RALRPs. Patients who underwent a RALRP had a significant advantage in EBL (1,600, 500, and 300 mL for ORPs, LRPs, and RALRPs, respectively), overall complications, and blood transfusion rate. As they are minimally invasive techniques, LRP and RALRP presented an advantage in terms of the length of hospital stay (an average of 9, 6, and 6 days for ORPs, LRPs, and RALRPs, respectively) and adjacent organ injury rate. ORPs also had the shortest operative time (160, 210, and 200 min for ORPs, LRPs, and RALRPs, respectively). However, the specimen weight and marginal status were similar in all of the techniques. CONCLUSIONS: Minimally invasive RP techniques, such as LRPs and RALRPs, appear to be safe, have significantly better perioperative outcomes than ORPs, and have comparable pathological outcomes to those of ORPs.

Ultrasmall Renally Clearable Silica Nanoparticles Target Prostate Cancer.

Although important advances have been achieved in the development of radiolabeled prostate-specific membrane antigen (PSMA)-targeting ligand constructs for both diagnosis and therapy of prostate cancer (PCa) over the past decade, challenges related to off-target effects and limited treatment responses persist. In this study, which builds upon the successful clinical translation of a series of ultrasmall, dye-encapsulating core-shell silica nanoparticles, or Cornell Prime Dots (C' dots), for cancer management, we sought to address these limitations by designing a dual-modality, PSMA-targeting platform that evades undesirable accumulations in the salivary glands, kidneys, and reticuloendothelial system, while exhibiting bulk renal clearance. This versatile PCa-targeted particle imaging probe offers significant clinical potential to improve future theranostic applications in a variety of patient care settings.

Role of surgery in oligometastatic prostate cancer.

Androgen deprivation therapy as single modality therapy was the standard management for oligometastatic prostate cancer (PCa). Current paradigm shifts toward a multimodality therapy approach, targeting all sites of disease, including treatment of the primary in the form of radical prostatectomy or radiation therapy. The objective of this article was to reveiw the literature regarding the role of surgery in oligometastatic PCa. PubMed and MEDLINE electronic databases were queried for English language articles from January 1, 1980 to March 31, 2019. Keywords use included oligometastatic PCa, metastatic prostate cancer (mPCa), radical prostatectomy, and cytoreductive prostatectomy. Preclinical, prospective, and retrospective studies were included. There is no published randomized controlled trials, evaluating the role of surgery in mPCa. Preclinical and retrospective data suggest benefit of primary tumor treatment in mPCa. Current literature supports the concept of cytoreductive surgery as it can prevent late symptomatic local progression, has acceptable complications, and may prolong survival in patients with mPCa. Surgery is a feasible procedure in mPCa which may improve outcome in mPCa. However, there is no Level 1 evidence, yet that support the role of surgery in mPCa. The results from well-organized prospective, randomized controlled trials are awaited before performing radical prostatectomy for mPCa in clinical practice.