Robot-assisted PSMA-radioguided Surgery to Assess Surgical Margins and Nodal Metastases in Prostate Cancer Patients: Report on Three Cases Using an Intraoperative PET-CT Specimen Imager.

INTRODUCTION: The aim of this feasibility study was to test the intraoperative use of this brand-new specimen PET/CT to guide robot-assisted radical prostatectomy and pelvic lymph node dissection. MATERIALS AND METHODS: Three cases of robot-assisted radical prostatectomy and pelvic lymph node dissection were performed with intraoperative use of the specimen imager. Surgeries were performed with Da Vinci Xi robot. An intravenous injection of 68Ga-PSMA-11 was performed in the OR and after complete excision, the specimens were analyzed with the imager. RESULTS: The average nodal yield was 17.3 (5.8 SD) nodes per patient. Specimen PET/CT images showed a focal uptake in a metastatic node (TBR 13.6), and no uptake or diffuse, faint uptake in negative nodes (TBR range: 1-5.3). The specimen imager provided intraoperative PET/CT images that clearly showed negative surgical margins in two patients, whereas the results were uncertain in a locally advanced case. CONCLUSION: The intraoperative use of the specimen PET/CT imager is safe and feasible and could improve the evaluation of prostate surgical margins and lymph node status.

Predictors of Prostate Cancer at Fusion Biopsy: The Role of Positive Family History, Hypertension, Diabetes, and Body Mass Index.

BACKGROUND: PSA density and an elevated PI-RADS score are among the strongest predictors of prostate cancer (PCa) in a fusion biopsy. Positive family history, hypertension, diabetes, and obesity have also been associated with the risk of developing PCa. We aim to identify predictors of the prostate cancer detection rate (CDR) in a series of patients undergoing a fusion biopsy. METHODS: We retrospectively evaluated 736 consecutive patients who underwent an elastic fusion biopsy from 2020 to 2022. Targeted biopsies (2-4 cores per MRI target) were followed by systematic mapping (10-12 cores). Clinically significant PCa (csPCa) was defined as ISUP score ≥ 2. Uni- and multi-variable logistic regression analyses were performed to identify predictors of CDR among age, body mass index (BMI), hypertension, diabetes, positive family history, PSA, a positive digital rectal examination (DRE), PSA density ≥ 0.15, previous negative biopsy status, PI-RADS score, and size of MRI lesion. RESULTS: The median patients' age was 71 years, and median PSA was 6.6 ng/mL. A total of 20% of patients had a positive digital rectal examination. Suspicious lesions in mpMRI were scored as 3, 4, and 5 in 14.9%, 55.0%, and 17.5% of cases, respectively. The CDR was 63.2% for all cancers and 58.7% for csPCa. Only age (OR 1.04, p < 0.001), a positive DRE (OR 1.75, p = 0.04), PSA density (OR 2.68, p < 0.001), and elevated PI-RADS score (OR 4.02, p = 0.003) were significant predictors of the CDR in the multivariable analysis for overall PCa. The same associations were found for csPCa. The size of an MRI lesion was associated with the CDR only in uni-variable analysis (OR 1.07, p < 0.001). BMI, hypertension, diabetes, and a positive family history were not predictors of PCa. CONCLUSIONS: In a series of patients selected for a fusion biopsy, positive family history, hypertension, diabetes, or BMI are not predictors of PCa detection. PSA-density and PI-RADS score are confirmed to be strong predictors of the CDR.

Topography of Prostate Cancer Recurrence: A Single-centre Analysis of Salvage Radical Prostatectomy Specimens and Implications for Focal Salvage Treatments.

Background: Most prostate cancer (PCa) recurrences after nonsurgical first-line treatment are managed with androgen deprivation therapy (ADT). When local treatment is indicated, salvage focal treatment (FT) may achieve outcomes similar to those after salvage radical prostatectomy (sRP), with lower morbidity. However, descriptions of the topography of PCa recurrence are scarce. Objective: To describe the characteristics and topography of recurrent PCa at sRP. Design setting and participants: We performed a review of the final pathology for consecutive men undergoing sRP at a single centre between 2007 and 2021. Outcome measurements and statistical analysis: Clinical and pathological outcomes and recurrence localisation (standardised map) were recorded. Suitability for salvage FT was evaluated using criteria defined a priori. Results and limitations: We included 41 men who underwent sRP after whole-gland treatment (82.9% primary radiotherapy). Of these, 68.3% had grade group ≥3 and 46.3% had pT3 disease, including nine men (22%) with seminal vesicle involvement >1 cm. The pN+ rate was 29.3%. Surgical margins were positive in 39% (mostly at the apex, 21.9%). PCa was located at <3 mm from the apex in 68% of cases. The segment most frequently involved was the mid-gland (93%). The median prostate and index lesion (IL) volume was 31.4 cm3 (interquartile range [IQR] 23-37) and 2 cm3 (IQR 0.5-6), respectively. A solitary IL was present in 63.4% of cases, while 7.3% had whole-gland PCa involvement. Overall, 56% of the men (n = 23) were deemed suitable for salvage FT (although seven had pN+ disease). The sample size, single-centre retrospective design, and unavailability of magnetic resonance imaging data are the main limitations. Conclusions: According to sRP pathology, radiorecurrent PCa is an aggressive disease, frequently showing extraprostatic extension, positive margins, and apical involvement. The majority of cases still harbour a solitary index lesion and a consistent proportion may be suitable for a gland-preserving strategy. Patient summary: In this report we looked at the location of prostate cancer recurrence within the prostate gland after radiotherapy or ablation, in which energy (such as heat, cold, or laser energy) is used to kill cells. We found that although these recurrences are often high-grade locally advanced disease, around half of cases might be suitable for a gland-preserving salvage treatment.

Safety and Feasibility of Transperineal Targeted Microwave Ablation for Low- to Intermediate-risk Prostate Cancer.

Background: Focal therapy has emerged as an interesting option for localized low- to intermediate-risk prostate cancer (PCa). Targeted microwave ablation (TMA) is a novel FT modality involving targeted delivery of microwave energy under multiparametric magnetic resonance imaging (MRI)/ultrasound guidance. Objective: To describe the step-by-step procedure for TMA and report early functional outcomes. Design setting and participants: This was an experimental phase 1-2 trial in 11 patients diagnosed with a single, MRI-visible PCa lesion of up to 12 mm, scored as International Society of Urological Pathology grade group (GG) 1 or 2. Surgical procedure: Transperineal TMA under MRI/ultrasound image fusion guidance. Measurements: We recorded patient and PCa features; intraoperative and postoperative parameters; pain (Visual Analog Scale [VAS]) and adverse events (Common Terminology Criteria for Adverse Events v5.0); and prostate-specific antigen (PSA), International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) scores at 1 wk and 1, 3, and 6 mo. Results and limitations: The median patient age was 67 yr (interquartile range [IQR] 18). Median PSA was 5.4 ng/ml (IQR 1.8), median prostate volume was 51 cm3 (IQR 35), and median lesion size on MRI was 10 mm (IQR 4). Ten patients had GG 2 PCa and one had GG 1 disease. The median procedure time was 40 min (IQR 30). No intraoperative complications were reported. All treatments were performed on a day-case basis and no patients were discharged with a urinary catheter. Postoperatively, no grade ≥2 complications were reported. No significant changes in PSA (p = 0.46), IPSS (p = 0.39), or IIEF-5 scores (p = 0.18) scores were reported. The postoperative VAS score at 24 h was 0 for all patients. Conclusions: TMA is safe, feasible, and well tolerated in patients with low- to intermediate-risk PCa. Oncological outcomes are still awaited. Patient summary: Targeted microwave therapy is safe and feasible for selected patients with low- to intermediate-risk prostate cancer. The procedure is well tolerated and does not require a urinary catheter after the procedure. Cancer control outcomes are still awaited.

Nightmares in Salvage Robot-assisted Radical Prostatectomy After Primary Radiation Therapy for Prostate Cancer: A Step by Step Tutorial.

Salvage radical prostatectomy after primary radiotherapy (sRP) is considered a challenging procedure. We highlight the complications of sRP and detail critical surgical steps to help prevent them. A nonsystematic literature review in PubMed using the term "salvage radical prostatectomy" was performed on December 1, 2021. Salvage robot-assisted RP (sRARP) cases and imaging materials were used to create an educational video providing practical examples. Owing to radiation-induced changes in the prostate and surrounding tissues after radiotherapy, sRP is typically more challenging than primary RP. Among its critical steps are incision of the endopelvic fascia, bladder neck dissection with attempts at sparing the neck, development of posterior planes between the prostate and rectum, and dissection of the prostatic apex. Complication rates are significant, in particular for bladder neck contracture (0-16%) and anastomotic leakage (10-33%). Rectal injury is now rare (<2%) but still feared; careful adherence to surgical principles is required to avoid this complication. Functional outcomes are nonoptimal, with a high risk of urinary incontinence (severe incontinence in ∼25% of men). sRARP is a challenging urological procedure and should be performed by experienced surgeons. Thorough knowledge of the surgical anatomy and a meticulous technique for the most difficult surgical steps are crucial to minimise complications and to improve patient outcomes. Patient summary: In patients with prostate cancer, removal of the prostate because of cancer recurrence after primary treatment with radiotherapy can be difficult because of radiation-induced tissue damage. This challenging procedure should be performed by experienced surgeons to minimise the risk of complications.

The SAFE Pilot Trial-SAlvage Focal Irreversible Electroporation-For Recurrent Localized Prostate Cancer: Rationale and Study Protocol.

Introduction: Currently, the majority of prostate cancer (PCa) recurrences after non-surgical first-line treatment are managed with androgen-deprivation therapy (ADT). Salvage radical prostatectomy (sRP) is a curative alternative to ADT but yields significant morbidity. Preliminary evidence from focal salvage treatments shows similar oncological control but lower morbidity compared to sRP. Among available ablative focal energies, irreversible electroporation (IRE) is a treatment modality that proved promising, especially in treating apical lesions, where PCa most often recurs. Our aim is to test the safety of salvage IRE for recurrent PCa. Methods: We performed a single-arm pilot feasibility study (IDEAL stage 2a): SAFE, SAlvage Focal irreversible Electroporation for recurrent localized PCa. Twenty patients with biopsy-proven PCa recurrence after primary non-surgical (radiation or ablation) treatment were included. All men will undergo mpMRI ± targeted biopsies, pre-operative PSMA-PET staging before inclusion and sIRE. Outcomes will be evaluated through internationally validated questionnaires and morbidity scales. All men will undergo a control biopsy at one year. Results: Primary objectives were the evaluation of the safety of sIRE (and patients' quality of life) after treatment. Secondary objectives were the evaluation of functional outcomes, namely, continence and erectile function changes and evaluation of short-term oncological efficacy. Conclusions: SAFE is the second pilot study to evaluate sIRE and the first one performed according to the most recent diagnostic and staging imaging standards. sIRE may provide a curative option for recurrent PCa together with lower comorbidities compared to sRP.

Risk of recurrence after nephrectomy: Comparison of predictive ability of validated risk models.

OBJECTIVE: To assess accuracy of University of California Los Angeles Integrated Staging System (UISS), Stage, Size, Grade and Necrosis (SSIGN) score, Leibovich score and GRade, Age, Nodes and Tumor (GRANT) score, the ASSURE (Adjuvant Sunitinib or Sorafenib vs. placebo in resected Unfavorable REnal cell carcinoma) score models and seventh American Joint Committee on Cancer (AJCC)/TNM staging system in predicting recurrence-free survival (RFS) in surgically-treated non-metastatic clear cell renal cell carcinoma (ccRCC) patients. MATERIALS AND METHODS: Kaplan-Meier curves and the log-rank test tested RFS according to risk groups among the UISS, SSIGN, Leibovich and GRANT models and the AJCC/TNM system. The Heagerty's C-index for survival tested for discrimination of each model at different time points after nephrectomy. RESULTS: Three hundred and fifty-eight M0 ccRCC patients were included. RFS significantly differed among each risk category for all models (P < 0.001). SSIGN showed the highest c-index over time (from 0.89 at 6-month to 0.82 at 60-month), followed by Leibovich (from 0.89-0.82), AJCC/TNM stage (from 0.82-0.77), ASSURE (from 0.81 to 0.76), GRANT (from 0.83-0.73) and UISS (from 0.76-0.72). For all models, peak discriminatory ability was reached before 12 months. The most prominent decline occurred within 24 months and reaches the lowest discriminatory ability at 60 months. CONCLUSIONS: Predictive models, with preference for SSIGN and Leibovich scores, are reliable to predict recurrence after nephrectomy and should be recommended to tailor postoperative surveillance protocols.

Assessment of predictors of renal cell carcinoma progression after nephrectomy at short- and medium-term follow-up and implication on surveillance protocols.

BACKGROUND: Prediction of risk of RCC progression after surgery is important for follow-up planning. We identified predictors of progression-free survival (PFS) and cancer-specific survival (CSS) in a large single institutional cohort and investigated patterns and sites of progression according to stage and grade. METHODS: Node-negative non-metastatic clear-cell RCC (ccRCC) patients treated with radical or partial nephrectomy from 2000 to 2020 were included. Sites of progression were defined as thoracic, abdominal and others (bone/brain). Kaplan-Meier curves and multivariable Cox regression (MCR) models tested for PFS and CSS. RESULTS: Of 384 clear cell RCC N0M0 patients, 301 (78.4%) vs. 83 (21.6%) were pT1-2 vs. pT3-4, respectively; 253 (65.9%) vs. 130 (33.9%) were G1-G2 vs. G3-G4. Thoracic progressions occurred in 2.7% pT1-T2 vs. 21.7% pT3-T4 and 2.8% G1-G2 vs. 14.6% G3-G4 tumors. Abdominal progressions occurred in 4.0% pT1-T2 vs. 13.3% pT3-T4 and 4.3% G1-G2 vs. 9.2% G3-G4. Other progressions occurred in 0.3% pT1-T2 vs. 9.6% pT3-T4 and 0.8% G1-G2 vs. 5.4% G3-G4 (5.4%). Five-year PFS and CSS were 81.7 and 90.6%, respectively. At MCR models, pT3-4 (HR 9.1, P<0.001), G3-G4 (HR 2.7, P=0.003) and PSMs (HR 6.1, P<0.001) independently predicted PFS. Similarly, pT3-4 (HR 10.1, P<0.001), G3-G4 (HR 4.1, P=0.02), and PSMs (HR 5.2, P=0.04) independently predicted CSS. CONCLUSIONS: In ccRCC N0M0 patients, G3-G4, pT3-4, PSMs were independent predictors of progression after surgery. Lower stage and grade ccRCCs progress predominantly in the abdominal sites and may be followed with less frequent extra-abdominal imaging compared to more advanced/aggressive tumors.

Intraoperative 3D-US-mpMRI Elastic Fusion Imaging-Guided Robotic Radical Prostatectomy: A Pilot Study.

INTRODUCTION: When performing a nerve-sparing (NS) robotic radical prostatectomy (RARP), cancer location based on multiparametric MRI (mpMRI) is essential, as well as the location of positive biopsy cores outside mpMRI targets. The aim of this pilot study was to assess the feasibility of intraoperative 3D-TRUS-mpMRI elastic fusion imaging to guide RARP and to evaluate its impact on the surgical strategy. METHODS: We prospectively enrolled 11 patients with organ-confined mpMRI-visible prostate cancer (PCa), histologically confirmed at transperineal fusion biopsy using Koelis Trinity. Before surgery, the 3D model of the prostate generated at biopsy was updated, showing both mpMRI lesions and positive biopsy cores, and was displayed on the Da Vinci robotic console using TilePro™ function. RESULTS: Intraoperative 3D modeling was feasible in all patients (median of 6 min). The use of 3D models led to a major change in surgical strategy in six cases (54%), allowing bilateral instead of monolateral NS, or monolateral NS instead of non-NS, to be performed. At pathologic examination, no positive surgical margins (PSMs) were reported. Bilateral PCa presence was detected in one (9%), four (36%), and nine (81%) patients after mpMRI, biopsy, and RARP, respectively. Extracapsular extension was found in two patients (18%) even if it was not suspected at MRI. CONCLUSIONS: Intraoperative 3D-TRUS-mpMRI modeling with Koelis Trinity is feasible and reliable, helping the surgeon to maximize functional outcomes without increasing the risk of positive surgical margins. The location of positive biopsy cores must be registered in 3D models, given the rates of bilateral involvement not seen at mpMRI.

Transperineal Free-hand mpMRI Fusion-targeted Biopsies Under Local Anesthesia: Technique and Feasibility From a Single-center Prospective Study.

OBJECTIVE: To evaluate the feasibility of "in-office" TPFBx under local anesthesia (LA). MATERIALS AND METHODS: We prospectively screened for eligibility data of 724 consecutive men undergoing either TPFBx (target and systematic cores) or TPSBx (systematic cores only) from September 2016 to June 2018 due to suspicion of prostate cancer (CaP), according to predefined exclusion criteria. RESULTS: We included 459 men (TPFBx n = 279 including n = 338 mpMRI lesions, Pi-RADS 4 in 63.6%; TPSBx n = 180). Median procedural time and maximum pain were 19 minutes and 5 numeric rating scale (NRS) points; pain was highest at the time of LA. Only 1 major complication occurred (Clavien 3a). Hematuria and hematospermia were frequent (72.6% and 54.2%). Vaso-vagal reactions and AUR were rare (0.7% and 0.4%). No cases of UTI and 1 case of fever were recorded. No significant changes in erectile and urinary functions were noted from baseline compared to 40 days after TPFBx (P = .86 and P = .89). In comparison with TPSBx the sole differences were pain during prostatic sampling (P = .03), duration of hematospermia (P <.0001) and procedural time (P <.001) all higher for TPFBx. Clinically significant (cs) CaP was detected in n = 150 (53.8%) patients in the TPFBx group (34.9%, 51.7%, and 75% of Pirads 3, 4, and 5, respectively). Addition of systematic cores detected n = 25 csCaP that were missed by targeted cores (17.4% of all csCaP). CONCLUSION: TPFBx under LA are feasible, yielding high tolerability, low complications, no impact on erectile and urinary function and good csCaP detection. Addition of systematic to targeted cores remains recommended. Further studies are needed to confirm our findings.