Contextualizing Olaparib and Abiraterone in the Current Treatment Landscape for Metastatic Castration-resistant Prostate Cancer

The PROpel trial assessed the combination of olaparib + abiraterone acetate (AA) plus prednisone and androgen deprivation therapy (ADT) versus AA plus prednisone and ADT alone as first-line treatment for metastatic castration-resistant prostate cancer (mCPRP). To contextualize the progression free survival (PFS) benefit in PROpel, we performed a systematic review and quasi-individual patient data network meta-analysis on randomized controlled trials of first-line hormonal treatments for mCPRC. Meta-analysis was performed for the PROpel control arm and PREVAIL (enzalutamide) and COU-AA-302 (AA) treatment arms. Kaplan-Meier PFS curves were digitally reconstructed and differences in restricted mean survival time (ΔRMST) were computed. Combination therapy yielded longer PFS (24-mo ΔRMST 1.5 mo, 95% confidence interval 0.6-2.4) in comparison to novel hormonal treatments alone. However, the lack of mature overall survival data, higher complication rates, and higher health care costs are limitations of combination therapy. Ultimately, combining treatments, rather than molecularly targeted sequencing in cases of failure, might not be justified in unselected patients with mCRPC.Patient summaryA recent trial showed that for metastatic prostate cancer that does not respond to hormone treatment, combined therapy with two drugs (olaparib and abiraterone) may prolong survival free from cancer progression. We included these data in an analysis of three trials that confirmed a small benefit. This combination approach has higher complication rates and is more expensive, and longer-term results for overall survival are needed

The Impact of Implementation of the European Association of Urology Guidelines Panel Recommendations on Reporting and Grading Complications on Perioperative Outcomes after Robot-assisted Radical Prostatectomy

Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.Peer reviewedPostprin

The Impact of PSMA-PET on Oncologic Control in Prostate Cancer Patients Who Experienced PSA Persistence or Recurrence

Simple Summary PSMA-PET is currently recommended to restage PCa and to guide salvage treatments. We aim to evaluate the oncologic outcomes of patients with recurrent PCa who received PSMA-PET. PSMA-PET may be a prognostic tool in BCR patients after PR. In recurrent PCa patients who never received previous salvage therapies, men with positive PSMA-PET had similar oncologic outcomes compared to those with negative PSMA-PET. PCa patients who already had previous salvage therapies with positive PSMA-PET experienced worse oncologic outcomes compared to those with negative PSMA-PET. In a PSMA-PET positive population no significant differences were found in terms of progression and metastasis between patients with oligometastatic vs. polimetastatic disease and local/N1 vs. M1 at PSMA-PET. Background: Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is currently recommended to restage prostate cancer (PCa) and to guide the delivery of salvage treatments. We aim to evaluate the oncologic outcomes of patients with recurrent PCa who received PSMA-PET. Methods: 324 hormone-sensitive PCa with PSA relapse after radical prostatectomy who underwent PSMA-PET in three high-volume European Centres. Patients have been stratified as pre-salvage who never received salvage treatments (n = 134), and post-salvage, including patients who received previous salvage therapies (n = 190). Patients with oligorecurrent (<= 3 lesions), PSMA-positive disease underwent PSMA-directed treatments: salvage radiotherapy (sRT) or Metastases-directed therapy (MDT). Patients with polirecurrent (>3 lesions) PSMA-positive disease were treated with systemic therapy. Patients with negative PSMA-PET were treated with sRT or systemic therapies or observation. The primary outcome of the study was Progression-free survival (PFS). Secondary outcomes were: Metastases-free survival (MFS) and Castration Resistant Pca free survival (CRPC-FS). Results: median follow up was 23 months. In the pre-salvage setting, the PFS, MFS and CRPC-FS estimates at 3 years were 66.2% vs. 38.9%, 95.2% vs. 73.7% and 94.9% vs. 93.1% in patients with negative vs. positive PSMA-PET, respectively (all p >= 0.2). In the post-salvage setting, the PFS, MFS and CRPC-FS estimates at 3 years were 59.5% vs. 29.1%, 92.7% vs. 65.1% and 98.8% vs. 88.8% in patients with negative vs. positive PSMA-PET, respectively (all p <= 0.01). At multivariable analyses, a positive PSMA-PET was an independent predictor of progression (HR = 2.15) and metastatic disease (HR 2.37; all p <= 0.03). Conclusion: PSMA-PET in recurrent PCa detects the site of recurrence guiding salvage treatments and has a prognostic role in patients who received previous salvage treatments

Which Patients with Clinically Node-positive Prostate Cancer Should Be Considered for Radical Prostatectomy as Part of Multimodal Treatment? The Impact of Nodal Burden on Long-term Outcomes

BACKGROUND: A role for local therapies including radical prostatectomy (RP) in prostate cancer (PCa) patients with clinical lymphadenopathies has been proposed. However, no data are available to identify men who would benefit from RP in this setting. OBJECTIVE: To identify predictors of clinical recurrence (CR) in surgically managed PCa patients with clinical lymphadenopathies. DESIGN, SETTING, AND PARTICIPANTS: We identified 162 patients with lymphadenopathies treated with RP and lymph node dissection at three referral centers. OUTCOME MEASURES AND STATISTICAL ANALYSES: CR was defined as the onset of metastases detected by conventional imaging. Kaplan-Maier analyses assessed time to CR after stratifying patients according to the site of lymphadenopathies and nodal burden. Regression tree analysis stratified patients into risk groups on the basis of their preoperative characteristics. RESULTS AND LIMITATIONS: Overall, 80% of patients had lymphadenopathies in the pelvis alone and 20% in the retroperitoneum±pelvis. The median size of positive nodes was 13mm. A total of 84 patients (52%) received neoadjuvant androgen deprivation therapy and 127 (78%) had pathological lymph node invasion. The median follow-up for survivors was 64 mo. The 8-yr CR-free and CSM-free survival rates were 59% and 80%, respectively. Biopsy grade group and preoperative nodal burden should identify patients more likely to experience CR. While <10% of men with biopsy grade group 1-3 and two or fewer clinical lymphadenopathies developed CR, up to 60% of patients with biopsy grade group 4-5 and retroperitoneal node involvement ultimately experienced CR at 8 yr after RP. The discrimination of the regression tree was 76% according to the area under the receiver operating characteristic curve. Our study is limited by potential unmeasured confounders and the relatively small sample size. CONCLUSIONS: Surgery in a multimodal setting might play a role in PCa patients with biopsy grade group 1-3 and/or enlarged nodes in the pelvis. Conversely, grade group 4-5 PCa and lymphadenopathies in the retroperitoneum are associated with worse oncologic outcomes. PATIENT SUMMARY: Approximately half of prostate cancer patients with clinical lymphadenopathies treated with radical prostatectomy are free from metastases at 8-yr follow-up. Radical prostatectomy with or without systemic therapies might play a role in selected patients with biopsy grade group 1-3 disease and/or enlarged nodes in the pelvis. Conversely, a higher grade group and the presence of lymphadenopathies in the retroperitoneum should identify candidates for systemic therapies upfront.status: publishe

Defining Clinically Meaningful Positive Surgical Margins in Patients Undergoing Radical Prostatectomy for Localised Prostate Cancer

The impact of positive surgical margins (PSMs) on the risk of metastases in prostate cancer (PCa) patients treated with radical prostatectomy (RP) is still debated

Understanding the Role of Ureteral Access Sheath in Preventing Post-Operative Infectious Complications in Stone Patients Treated with Ureteroscopy and Ho:YAG Laser Lithotripsy: Results from a Tertiary Care Referral Center

Introduction and objectives: The use of ureteral access sheaths (UAS) limits the irrigation-induced increase in intrarenal pressure during ureteroscopy (URS). We investigated the relationship between UAS and rates of postoperative infectious complications in stone patients treated with URS. Materials and methods: Data from 369 stone patients treated with URS from September 2016 to December 2021 at a single institution were analyzed. UAS (10/12 Fr) placement was attempted in case of intrarenal surgery. The chi-square test was used to assess the relationship between the use of UAS and fever, sepsis, and septic shock. Univariable and multivariable logistic regression analyses tested the association of patients’ characteristics and operative data and the rate of postoperative infectious complications. Results: Full data collection of 451 URS procedures was available. Overall, UAS was used in 220 (48.8%) procedures. As for postoperative infectious sequalae, we recorded fever (n = 52; 11.5%), sepsis (n = 10; 2.2%), and septic shock (n = 6; 1.3%). Of those, UAS was not used in 29 (55.8%), 7 (70%), and 5 (83.3%) cases, respectively (all p > 0.05). At multivariable logistic regression analysis, performing URS without UAS was not associated with the risk of having fever and sepsis, but it increased the risk of septic shock (OR = 14.6; 95% CI = 1.08–197.1). Moreover, age-adjusted CCI score (for fever-OR = 1.23; 95% CI = 1.07–1.42, sepsis-OR = 1.47; 95% CI = 1.09–1.99, and septic shock-OR = 1.61; 95% CI = 1.08–2.42, respectively), history of fever secondary to stones (for fever-OR = 2.23; 95% CI = 1.02–4.90) and preoperative positive urine culture (for sepsis-OR = 4.87; 95% CI = 1.12–21.25) did emerge as further associated risk factors. Conclusions: The use of UAS emerged to prevent the onset of septic shock in patients treated with URS, with no clear benefit in terms of fever and sepsis. Further studies may help clarify whether the reduction in fluid reabsorption load mediated by UAS is protective against life-threatening conditions in case of infectious complications. The patients’ baseline characteristics remain the main predictors of infectious sequelae in a clinical setting

PSMA-PET Guided Treatment in Prostate Cancer Patients with Oligorecurrent Progression after Previous Salvage Treatment

Background: Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is used to select recurrent prostate cancer (PCa) patients for metastases-directed therapy (MDT). We aimed to evaluate the oncologic outcomes of second-line PSMA-guided MDT in oligo-recurrent PCa patients. Methods: we performed a retrospective analysis of 113 recurrent PCa after previous radical prostatectomy and salvage therapies with oligorecurrent disease at PSMA-PET (≤3 lesions in N1/M1a-b) in three high-volume European centres. Patients underwent second-line salvage treatments: MDT targeted to PSMA (including surgery and/or radiotherapy), and the conventional approach (observation or Androgen Deprivation Therapy [ADT]). Patients were stratified according to treatments (MDT vs. conventional approach). Patients who underwent MDT were stratified according to stage in PSMA-PET (N1 vs. M1a-b). The primary outcome of the study was Progression-free survival (PFS). Secondary outcomes were Metastases-free survival (MFS) and Castration Resistant PCa free survival (CRPC-FS). Kaplan-Meier analyses assessed PFS, MFS and CRPC-FS. Multivariable Cox regression models identified predictors of progression and metastatic disease. Results: Overall, 91 (80%) and 22 (20%) patients were treated with MDT and the conventional approach, respectively. The median follow-up after PSMA-PET was 31 months. Patients who underwent MDT had a similar PFS compared to the conventional approach (p = 0.3). Individuals referred to MDT had significantly higher MFS and CRPC-FS compared to those who were treated with the conventional approach (73.5% and 94.7% vs. 30.5% and 79.5%; all p ≤ 0.001). In patients undergoing MDT, no significant differences were found for PFS and MFS according to N1 vs. M1a-b disease, while CRPC-FS estimates were significantly higher in patients with N1 vs. M1a-b (100% vs. 86.1%; p = 0.02). At multivariable analyses, age (HR = 0.96) and ADT during second line salvage treatment (HR = 0.5) were independent predictors of PFS; MDT (HR 0.27) was the only independent predictor of MFS (all p ≤ 0.04) Conclusion: Patients who underwent second-line PSMA-guided MDT experienced higher MFS and CRPC-FS compared to men who received conventional management

What to expect from the novel pulsed thulium:YAG laser? A systematic review of endourological applications

INTRODUCTION Several preclinical studies about a novel pulsed-thulium:yttrium-aluminum-garnet (p-Tm:YAG) device have been published, demonstrating its possible clinical relevance. METHODS We systematically reviewed the reality and expectations for this new p-Tm:YAG technology. A PubMed, Scopus and Embase search were performed. All relevant studies and data identified in the bibliographic search were selected, categorized, and summarized. RESULTS Tm:YAG is a solid state diode-pumped laser that emits at a wavelength of 2013 nm, in the infrared spectrum. Despite being close to the Ho:YAG emission wavelength (2120 nm), Tm:YAG is much closer to the water absorption peak and has higher absorption coefficient in liquid water. At present, there very few evaluations of the commercially available p-Tm:YAG devices. There is a lack of information on how the technical aspects, functionality and pulse mechanism can be maximized for clinical utility. Available preclinical studies suggest that p-Tm:YAG laser may potentially increase the ablated stone weight as compared to Ho:YAG under specific condition and similar laser parameters, showing lower retropulsion as well. Regarding laser safety, a preclinical study observed similar absolute temperature and cumulative equivalent minutes at 43° C as compared to Ho:YAG. Finally, laser-associated soft-tissue damage was assessed at histological level, showing similar extent of alterations due to coagulation and necrosis when compared with the other clinically relevant lasers. CONCLUSIONS The p-Tm:YAG appears to be a potential alternative to the Ho:YAG and TFL according to these preliminary laboratory data. Due to its novelty, further studies are needed to broaden our understanding of its functioning and clinical applicability

The Impact of PSMA-PET on Oncologic Control in Prostate Cancer Patients Who Experienced PSA Persistence or Recurrence

Background: Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is currently recommended to restage prostate cancer (PCa) and to guide the delivery of salvage treatments. We aim to evaluate the oncologic outcomes of patients with recurrent PCa who received PSMA-PET. Methods: 324 hormone-sensitive PCa with PSA relapse after radical prostatectomy who underwent PSMA-PET in three high-volume European Centres. Patients have been stratified as pre-salvage who never received salvage treatments (n = 134), and post-salvage, including patients who received previous salvage therapies (n = 190). Patients with oligorecurrent (&le;3 lesions), PSMA-positive disease underwent PSMA-directed treatments: salvage radiotherapy (sRT) or Metastases-directed therapy (MDT). Patients with polirecurrent (&gt;3 lesions) PSMA-positive disease were treated with systemic therapy. Patients with negative PSMA-PET were treated with sRT or systemic therapies or observation. The primary outcome of the study was Progression-free survival (PFS). Secondary outcomes were: Metastases-free survival (MFS) and Castration Resistant Pca free survival (CRPC-FS). Results: median follow up was 23 months. In the pre-salvage setting, the PFS, MFS and CRPC-FS estimates at 3 years were 66.2% vs. 38.9%, 95.2% vs. 73.7% and 94.9% vs. 93.1% in patients with negative vs. positive PSMA-PET, respectively (all p &ge; 0.2). In the post-salvage setting, the PFS, MFS and CRPC-FS estimates at 3 years were 59.5% vs. 29.1%, 92.7% vs. 65.1% and 98.8% vs. 88.8% in patients with negative vs. positive PSMA-PET, respectively (all p &le; 0.01). At multivariable analyses, a positive PSMA-PET was an independent predictor of progression (HR = 2.15) and metastatic disease (HR 2.37; all p &le; 0.03). Conclusion: PSMA-PET in recurrent PCa detects the site of recurrence guiding salvage treatments and has a prognostic role in patients who received previous salvage treatments