Biochemical Response of <0.1 ng/ml Predicts Therapy-free Survival of Prostate Cancer Patients following Prostate-specific Membrane Antigen-targeted Salvage Surgery.

BACKGROUND: In a subset of patients with oligorecurrent prostate cancer (PCa), salvage surgery with prostate-specific membrane antigen (PSMA) radioguided surgery (PSMA-RGS) seems to be of value. OBJECTIVE: To evaluate whether a lower level of postoperative prostate-specific antigen (PSA; <0.1 ng/ml) is predictive of therapy-free survival (TFS) following salvage PSMA-RGS. DESIGN, SETTING, AND PARTICIPANTS: This cohort study evaluated patients with biochemical recurrence after radical prostatectomy and oligorecurrent PCa on PSMA positron emission tomography treated with PSMA-RGS in three tertiary care centers (2014-2022). INTERVENTION: PSMA-RGS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Postsalvage surgery PSA response was categorized as <0.1, 0.1-<0.2, or >0.2 ng/ml. Kaplan-Meier and multivariable Cox regression models evaluated TFS according to PSA response. RESULTS AND LIMITATIONS: Among 553 patients assessed, 522 (94%) had metastatic soft tissue lesions removed during PSMA-RGS. At 2-16 wk after PSMA-RGS, 192, 62, and 190 patients achieved PSA levels of <0.1, 0.1-<0.2, and >0.2 ng/ml, respectively. At 2 yr of follow-up, TFS rate was 81.1% versus 56.1% versus 43.1% (p < 0.001) for patients with PSA <0.1 versus 0.1-<0.2 versus >0.2 ng/ml. In multivariable analyses, PSA levels of 0.1-0.2 ng/ml (hazard ratio [HR]: 1.9, confidence interval [CI]: 1.1-3.1) and ≥0.2 ng/ml (HR: 3.2, CI: 2.2-4.6, p < 0.001) independently predicted the need for additional therapy after PSMA-RGS. The main limitation is the lack of a control group. CONCLUSIONS: For patients after salvage PSMA-RGS, a lower biochemical response (PSA <0.1 ng/ml) seems to predict longer TFS. This insight may help in counseling patients postoperatively as well as guiding the timely selection of additional therapy. PATIENT SUMMARY: We studied what happened to prostate cancer patients in three European centers who had salvage surgery using a special method called prostate-specific membrane antigen-targeted radioguidance. We found that patients who had low prostate-specific antigen levels soon after surgery were less likely to need further treatment for a longer time.

Impact of COVID-19 on the time to counseling and treatment of prostate cancer.

PURPOSE: This study investigates how the COVID-19 pandemic (CP) impacted the timeline between initial diagnosis (ID) of prostate carcinoma and subsequent therapy consultation (TC) or radical prostatectomy (RP) due to the implementation of a "minimal contact concept," which postponed clinical examinations until the day of admission. METHODS: We analyzed patient data from a tertiary care center from 2018 to September 2021. The focus was on comparing the time intervals from ID to TC and from ID to RP before and during the CP. RESULTS: Of 12,255 patients, 6,073 (61.6%) were treated before and 3,791 (38.4%) during the CP. The median time from ID to TC reduced from 37 days (IQR: 21 - 58d) pre-CP to 32 days (IQR: 20 - 50d) during CP (p < 0.001). Similarly, the time from ID to RP decreased from 98 days (IQR: 70 - 141d) to 75 days (IQR: 55 - 108d; p < 0.001) during the CP. There was a significant decrease in low-risk tumor cases at ID (18.9% vs. 21.4%; p = 0.003) and post-RP (4% vs. 6.7%; p < 0.001) during the CP. CONCLUSION: Our findings suggest that the COVID-19 pandemic facilitated more timely treatment of prostate cancer, suggesting potential benefits for both low-risk and aggressive tumor management through expedited clinical procedures.

Feasibility of Next-generation Sequencing of Liquid Biopsy (Circulating Tumor DNA) Samples and Tumor Tissue from Patients with Metastatic Prostate Cancer in a Real-world Clinical Setting in Germany.

BACKGROUND AND OBJECTIVE: With European Medicines Agency approval of PARP inhibitors in metastatic castration-resistant prostate cancer and ongoing trials in metastatic hormone-sensitive prostate cancer, detection of genetic alterations in BRCA1/2 and other homologous recombination repair genes has gained an important role. Our aim was to investigate the feasibility and comparability of comprehensive next-generation sequencing (NGS) of liquid biopsy (LB; circulating tumor DNA) and tumor tissue (TT) samples in a real-world clinical setting. METHODS: The study cohort consisted of 50 patients with metastatic prostate cancer (mPC) who had TT NGS performed for BRCA1/2 alterations and consent for additional LB NGS. The Oncomine Comprehensive Assay v3 (Thermo Fisher Scientific, Waltham, MA, USA) was used for TT NGS. The Guardant360 83-gene assay (Guardant Health, Palo Alto, CA, USA) was used for LB NGS, including all types of somatic alterations, microsatellite instability, and blood tumor mutational burden. We calculated BRCA1/2 alteration rates and the negative percentage agreement (NPA) and positive percentage agreement (PPA) between TT and LB results. KEY FINDINGS AND LIMITATIONS: TT NGS was successful in 44/50 patients (88%), with pathogenic BRCA1/2 alterations detected in four (9%). LB NGS was successful in all 50 patients (100%), with BRCA1/2 alterations detected in ten (20%). In a subgroup analysis for the 44 patients with successful TT NGS, NPA was 85% and PPA was 50%. The median time between TT sample collection and blood sampling for NGS was 132 wk (IQR 94-186). The limited sample size and differences in the time of NGS assessment are limitations. CONCLUSIONS AND CLINICAL IMPLICATIONS: LB NGS resulted in a higher detection rate for BRCA1/2 alterations in comparison to conventional TT NGS (20% vs 9%). Ideally, BRCA1/2 testing should be based on both approaches to identify all patients with mPC eligible for PARP inhibitor therapy. PATIENT SUMMARY: Our study shows that genetic tests for both tumor tissue and blood samples results in higher rates of detection of BRCA1/2 gene alterations in patients with metastatic prostate cancer.

Robot-assisted vs open retropubic radical prostatectomy: a propensity score-matched comparative analysis based on 15 years and 18,805 patients.

PURPOSE: To compare oncological, functional, and surgical outcomes of a large cohort of patients who underwent open retropubic radical prostatectomy (ORP) or robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: Data from 18,805 RPs performed with either the open or the robot-assisted approaches at a single tertiary referral center between 2008 and 2022 were analyzed. The impact of surgical approach on biochemical recurrence-free survival, salvage radiotherapy-free survival, and metastasis-free survival was analyzed by log-rank test and Kaplan-Meier analysis in a propensity score (PS)-based matched cohort. Intraoperative and postoperative surgical outcomes were assessed. One-week, 3-month, and 12-month continence rates and 12-month erectile function (EF) were analyzed. RESULTS: No statistically significant differences in oncological outcomes were found between ORP and RARP. A slight statistically significant difference in favor of RARP was noted in urinary continence at 3 months (RARP vs. ORP: 81% vs. 77%, p = 0.007) and 12 months (91% vs. 89.3%, p = 0.008), respectively. The rate of EF was statistically significantly higher (60%) after RARP than after ORP (45%, p < 0.001). CONCLUSION: Both RARP and ORP yielded similar oncological outcomes. RARP offered a slight advantage in terms of continence recovery, but its clinical significance may be less meaningful. RARP resulted in significantly improved postoperative EF, suggesting a potential influence of both surgical experience and minimally invasive approach.

[Local therapies for oligometastatic hormone-sensitive prostate cancer]. / Stellenwert der lokalen Therapien beim oligometastasierten, hormonsensitiven Prostatakarzinom.

BACKGROUND: Oligometastatic, hormone-sensitive prostate cancer (omHSPC) is increasingly diagnosed due to the implementation of molecular imaging. OmHSPC is mostly defined as a maximum of four bone metastases without visceral metastases on conventional imaging. OBJECTIVES: This study highlights the existing evidence regarding local treatment of omHSPC, taking into account molecular imaging and modern therapies. MATERIALS AND METHODS: Narrative review article based on expert consensus and national/international guideline recommendations, supported by a nonsystematic literature search in PubMed (MEDLINE). The authors consider the cited studies as the most significant works in this regard and these were selected to illustrate developments and fundamental concepts, without claiming completeness. RESULTS: Initially, the STAMPEDE study prospectively demonstrated an oncologic benefit of radiotherapy (RT) to the prostate in addition to androgen deprivation therapy for omHSPC. At 3 years, overall survival (OS) was 81% with RT versus 73% without RT (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.52-0.90; p = 0.007). However, this benefit was not observed in polymetastatic HSPC (HR 1.07; 95% CI 0.90-1.28; p = 0.4). In a study by Dai et al., local therapy for omHSPC was performed surgically in 85% of cases, also demonstrating an OS advantage (HR 0.44; 95% CI 0.24-0.81; p = 0.008). CONCLUSION: OmHSPC should be treated using adjunctive RT. Preliminary prospective evidence shows comparable efficacy with prostatectomy. Modern systemic combination therapies challenge the role of local therapy.

[Androgen deprivation therapy and cardiovascular morbidity in prostate cancer: a narrative review]. / Androgendeprivationstherapie und kardiovaskuläre Morbidität beim Prostatakarzinom: ein narratives Review.

Prostate cancer is the most common malignancy in men, mostly affecting older men who harbor an increased prevalence of cardiovascular disease and metabolic syndrome. Androgen deprivation therapy (ADT), the standard therapy for various stages of prostate cancer, further increases the risk for cardiovascular disease and for metabolic syndrome. Therefore, screening for cardiovascular risk factors should be performed prior to the initiation of ADT, and, if necessary, cardiological evaluation and interdisciplinary management should be provided during and after completion of ADT. Moreover, the use of a gonadotropin-releasing hormone (GnRH) antagonist may help reduce cardiovascular risk in patients with cardiovascular disease.

PSMA PET-directed surgical metastasis-directed therapy in metachronous prostate cancer.

We present the case of a patient who underwent an open radical prostatectomy with pelvic lymph node dissection (Gleason 4+3, pT3a pN1 R0) in March 2017. In November 2020, prostate-specific membrane antigen (PSMA)-radioguided salvage lymph node dissection was planned due to a single left para-rectal lymph node at a [68Ga] Ga-PSMA-I&T PET. In January 2022, the [68Ga] Ga-PSMA-I&T PET showed an isolated liver lesion. Biopsy confirmed prostate adenocarcinoma. A liver segmentectomy was performed. A complete biochemical response was reported until the last follow-up (December 2022). Prostate-specific membrane antigen positron emission tomography (PSMA PET)-directed metastasis-directed therapy may be an effective treatment in selected cases, allowing a benefit in the oncological outcome.

Impact of persistent PSA after salvage radical prostatectomy: a multicenter study.

BACKGROUND AND OBJECTIVE: Persistent prostatic specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). However, the impact of persistent PSA on oncologic outcomes in patients undergoing salvage RP is unknown. To investigate the impact of persistent PSA after salvage RP on long-term oncologic outcomes. MATERIAL AND METHODS: Patients who underwent salvage RP for recurrent prostate cancer between 2000 and 2021 were identified from twelve high-volume centers. Only patients with available PSA after salvage RP were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of persistent PSA on biochemical recurrence (BCR), metastasis and any death after salvage RP. Persistent PSA was defined as a PSA-value ≥ 0.1 ng/ml, at first PSA-measurement after salvage RP. RESULTS: Overall, 580 patients were identified. Of those, 42% (n = 242) harbored persistent PSA. Median follow-up after salvage RP was 38 months, median time to salvage RP was 64 months and median time to first PSA after salvage RP was 2.2 months. At 84 months after salvage RP, BCR-free, metastasis-free, and overall survival was 6.6 vs. 59%, 71 vs. 88% and 77 vs. 94% for patients with persistent vs. undetectable PSA after salvage RP (all p < 0.01). In multivariable Cox models persistent PSA was an independent predictor for BCR (HR: 5.47, p < 0.001) and death (HR: 3.07, p < 0.01). CONCLUSION: Persistent PSA is common after salvage RP and represents an independent predictor for worse oncologic outcomes. Patients undergoing salvage RP should be closely monitored after surgery to identify those with persistent PSA.

Comparative analysis of robot-assisted and open approach for PSMA-radioguided surgery in recurrent prostate cancer.

PURPOSE: To compare the oncological and surgical outcomes of patients with recurrent prostate cancer (PCa) who underwent either open or newly established robot-assisted salvage prostate-specific membrane antigen-radioguided surgery (PSMA-RGS). MATERIALS AND METHODS: Patients who consecutively underwent PSMA-RGS for PCa recurrence between January 2021 and December 2022 were identified. The rate of complete biochemical response, biochemical recurrence-free survival [BFS], and the rate of salvage therapy were evaluated. Univariable and multivariable regression models tested the association between the surgical approach and surgical outcomes. RESULTS: Overall, 85 patients were selected, with 61 patients (72%) undergoing open PSMA-RGS and 24 patients (28%) receiving a robot-assisted approach. The oncological outcomes of the two groups were comparable (12-month BFS: 41% (Confidence interval (CI): 29-58%) vs. 39% (CI: 19-79%), p = 0.9, respectively). According to multivariable regression models, the robotic approach did not significantly influence estimated blood loss (EBL) (ß = -40, 95% CI: -103, 22; p = 0.2) and significantly increased operative time (OT) (ß = 28, 95% CI: 10, 46; p = 0.002). No Clavien-Dindo III-V complications were reported in the robotic group. CONCLUSION: Both, the open as well as the robot-assisted approach for PSMA-RGS had comparable oncological outcomes. No safety concerns arose for the robotic-assisted approach offering a potentially improved quality of life for patients.

Safety and efficiency of repeat salvage lymph node dissection for recurrence of prostate cancer using PSMA-radioguided surgery (RGS) after prior salvage lymph node dissection with or without initial RGS support.

BACKGROUND AND OBJECTIVE: Metastasis-directed therapy is a feasible option for low PSA, recurrent locoregional metastatic prostate cancer. After initial salvage surgery, patients with good response might consider a repeat salvage surgery in case of recurrent, isolated, and PSMA-positive metastases. This analysis aimed to evaluate the oncological outcome and safety of repeat PSMA-targeted radioguided surgery (RGS) after either prior RGS or "standard" salvage lymph node dissection (SLND). MATERIALS AND METHODS: We identified 37 patients undergoing repeat RGS after prior SLND (n = 21) (SLND-RGS) or prior RGS (n = 16) (RGS-RGS) between 2014 and 2021 after initial radical prostatectomy with or without pelvic radiation therapy at two German tertiary referral centers. Kaplan-Meier analyses and uni-/multivariable Cox regression models were used to investigate factors associated with biochemical recurrence-free survival (BRFS) and treatment-free survival (TFS) after repeat salvage surgery. RESULTS AND LIMITATIONS: Complete Biochemical Response (cBR, PSA < 0.2 ng/ml) was observed in 20/32 patients (5 NA). Median overall BRFS [95% confidence interval (CI)] after repeat salvage surgery was 10.8 months (mo) (5.3-22). On multivariable regression, only age (HR 1.09, 95% CI 1.01-1.17) and preoperative PSA (HR 1.23, 95% CI 1.01-1.50) were associated with shorter BRFS, although PSA (HR 1.16, 95% CI 0.99-1.36) did not achieve significant predictor status in univariable analysis before (p value = 0.07). Overall, one year after second salvage surgery, 89% of the patients (number at risk: 19) did not receive additional treatment and median TFS was not reached. Clavien-Dindo grade > 3a complications were observed in 8% (3/37 patients). Limitations are the retrospective evaluation, heterogeneous SLND procedures, lack of long-term follow-up data, and small cohort size. CONCLUSION: In this study, repeat RGS was safe and provided clinically meaningful biochemical recurrence- and treatment-free intervals for selected cases. Patients having low preoperative PSA seemed to benefit most of repeat RGS, irrespective of prior SLND or RGS or the time from initial RP/first salvage surgery.

Outcome of patients with epithelialized cavity formation after excessive vesicourethral anastomotic leak post radical prostatectomy.

PURPOSE: Excessive vesicourethral anastomotic leak (EVAL) is a rare but severe complication after radical prostatectomy (RP). Epithelialized vesicourethral cavity formation (EVCF) usually develops during prolonged catheterization. To our knowledge, there is no description of postoperative outcomes, complications, or functional assessment of these patients who received conservative therapy after EVAL. METHODS: We identified 70 patients (0.56%) with radiographic evidence of EVCF out of 12,434 patients who received RP in 2016-2020 at our tertiary care center. Postoperative radiographic cystograms (CG) were retrospectively re-examined by two urologists individually. We assessed urinary continence (UC), the need for intervention due to anastomotic stricture formation, urinary tract infection (UTI), and symphysitis during the first year of follow-up post-RP. RESULTS: The median age was 66 years [interquartile range (IQR) 61-70 years], the median body mass index was 27.8 kg/m2 (IQR 25.5-30.3 kg/m2), and the median prostate specific antigen before RP was 7.1 ng/ml (IQR 4.7-11.8 ng/ml). The median catheter insertion time was 44.5 days (IQR 35.2-54 days). One-year continence follow-up was available for 27 patients (38.6%), of which 22 (81.5%) reported the use of ≤ one pad, two patients reported the use of two (7.4%) pads/24 h, and three (11.1%) patients reported use > two pads/24 h. Overall, four (5.7%) patients needed surgical reintervention for anastomotic stricture, eight (11.5%) patients presented with symphysitis, and 55 (77.1%) presented with UTI. CONCLUSION: UC in 81.5% 1-year post-RP suggests that conservative treatment in EVAL is a treatment option with an acceptable outcome on UC and should be considered before reintervention for anastomotic insufficiency.

Impact of Age on Long-Term Urinary Continence after Robotic-Assisted Radical Prostatectomy.

Aim and Objectives: We aimed to test the impact of age on long-term urinary continence (≥12 months) in patients undergoing robotic-assisted radical prostatectomy. Methods and Materials: We relied on an institutional tertiary-care database to identify the patients who underwent robotic-assisted radical prostatectomy between January 2014 and January 2021. Patients were divided into three age groups: age group one (≤60 years), age group two (61-69 years) and age group three (≥70 years). Multivariable logistic regression models tested the differences between the age groups in the analyses addressing long-term urinary continence after robotic-assisted radical prostatectomy. Results: Of the 201 prostate cancer patients treated with robotic-assisted radical prostatectomy, 49 (24%) were assigned to age group one (≤60 years), 93 (46%) to age group two (61-69 years) and 59 (29%) to age group three (≥70 years). The three age groups differed according to long-term urinary continence: 90% vs. 84% vs. 69% for, respectively, age group one vs. two vs. three (p = 0.018). In the multivariable logistic regression, age group one (Odds Ratio (OR) 4.73, 95% CI 1.44-18.65, p = 0.015) and 2 (OR 2.94; 95% CI 1.23-7.29; p = 0.017) were independent predictors for urinary continence, compared to age group three. Conclusion: Younger age, especially ≤60 years, was associated with better urinary continence after robotic-assisted radical prostatectomy. This observation is important at the point of patient education and should be discussed in informed consent.

Triplet or Doublet Therapy in Metastatic Hormone-sensitive Prostate Cancer: Updated Network Meta-analysis Stratified by Disease Volume.

Two randomized controlled trials recently demonstrated an overall survival benefit with triplet therapy (androgen receptor axis-targeted agent [ARAT] + docetaxel + androgen deprivation therapy [ADT]) over doublet therapy (docetaxel + ADT) in metastatic hormone-sensitive prostate cancer (mHSPC), broadening the treatment options. In our previous systematic review and network meta-analysis on the role of triplet versus doublet therapy, we focused on ARAT + ADT, as this is the actual standard of care in many countries for mHSPC. However, survival data by disease volume were only available for one triplet therapy regimen (PEACE-1). Survival data stratified by disease volume for a second triplet regimen (ARASENS) are now available, hence we updated our meta-analysis for low- and high-volume mHSPC. Consistent with previous findings, ADT alone no longer represents a valid treatment option for mHSPC. Similar considerations apply to doublet therapy with docetaxel + ADT. For low-volume mHSPC, in comparison to ADT, the benefit of combination therapies other than ARAT + ADT was not substantial. For high-volume mHSPC, darolutamide + docetaxel + ADT ranked first (P score 0.92), followed by abiraterone + docetaxel + ADT (P score 0.85) and then ARAT + ADT combination therapies. In high-volume mHSPC, only darolutamide + docetaxel + ADT demonstrated superior overall survival (hazard ratio 0.76, 95% confidence interval 0.59-0.97) versus (pooled) ARAT + ADT, confirming the importance of triplet therapy in (high-volume) mHSPC. PATIENT SUMMARY: We performed an updated comparison of double and triple therapy options for metastatic prostate cancer that still responds to hormone treatment. For patients with low-volume cancer, there was no significant survival benefit from addition of a third drug. For patients with high-volume cancer, the best survival was obtained with darolutamide + docetaxel + androgen deprivation therapy.

A Neural Network Model Combining [-2]proPSA, freePSA, Total PSA, Cathepsin D, and Thrombospondin-1 Showed Increased Accuracy in the Identification of Clinically Significant Prostate Cancer.

BACKGROUND: The Prostate Health Index (PHI) and Proclarix (PCLX) have been proposed as blood-based tests for prostate cancer (PCa). In this study, we evaluated the feasibility of an artificial neural network (ANN)-based approach to develop a combinatorial model including PHI and PCLX biomarkers to recognize clinically significant PCa (csPCa) at initial diagnosis. METHODS: To this aim, we prospectively enrolled 344 men from two different centres. All patients underwent radical prostatectomy (RP). All men had a prostate-specific antigen (PSA) between 2 and 10 ng/mL. We used an artificial neural network to develop models that can identify csPCa efficiently. As inputs, the model uses [-2]proPSA, freePSA, total PSA, cathepsin D, thrombospondin, and age. RESULTS: The output of the model is an estimate of the presence of a low or high Gleason score PCa defined at RP. After training on a dataset of up to 220 samples and optimization of the variables, the model achieved values as high as 78% for sensitivity and 62% for specificity for all-cancer detection compared with those of PHI and PCLX alone. For csPCa detection, the model showed 66% (95% CI 66-68%) for sensitivity and 68% (95% CI 66-68%) for specificity. These values were significantly different compared with those of PHI (p < 0.0001 and 0.0001, respectively) and PCLX (p = 0.0003 and 0.0006, respectively) alone. CONCLUSIONS: Our preliminary study suggests that combining PHI and PCLX biomarkers may help to estimate, with higher accuracy, the presence of csPCa at initial diagnosis, allowing a personalized treatment approach. Further studies training the model on larger datasets are strongly encouraged to support the efficiency of this approach.

Histopathological results of radical prostatectomy specimen of men younger than 50 years of age at the time of surgery: possible implications for prostate cancer screening programs?

INTRODUCTION: Prostate cancer (PCa) detection is usually achieved by PSA measurement and, if indicated, further diagnostics. The recent EAU guidelines recommend a first PSA test at the age of 50 years, if no family history of PCa or BRCA2 mutation exists. However, some men might harbor significant PCa at younger age; thus we evaluated the histopathological results of men treated with radical prostatectomy (RP) in their 40 s at our institution. MATERIALS AND METHODS: We relied on the data of all patients who underwent RP in our institution between 1992 and 2020 and were younger than 50 years at the time of surgery. The histopathological results are descriptively presented. Moreover, we tested the effect of a positive family history on the descriptive results. RESULTS: Overall, 1225 patients younger than 50 years underwent RP at our institution. Median age was 47 years. Most patients showed favorable histopathological characteristics. However, 20% of patients had extraprostatic disease (≥ pT3a), 15% had ISUP Gleason grade group ≥ 3, and 7% had positive lymph nodes (pN1). Patients with a known positive family history did not have a higher rate of adverse disease as their counterparts with a negative family history. DISCUSSION: Our data show that the majority of patients who were diagnosed with PCa at a very young age had favorable histopathological RP characteristics. However, a non-negligible proportion of patients already showed locally advanced disease and would have probably benefited from earlier PCa detection. This should be kept in mind when PCa screening recommendations are proposed.

Cohort Study of Oligorecurrent Prostate Cancer Patients: Oncological Outcomes of Patients Treated with Salvage Lymph Node Dissection via Prostate-specific Membrane Antigen-radioguided Surgery.

BACKGROUND: In a subset of patients with recurrent oligometastatic prostate cancer (PCa) salvage surgery with prostate-specific membrane antigen (PSMA)-targeted radioguidance (PSMA-RGS) might be of value. OBJECTIVE: To evaluate the oncological outcomes of salvage PSMA-RGS and determine the predictive preoperative factors of improved outcomes. DESIGN, SETTING, AND PARTICIPANTS: A cohort study of oligorecurrent PCa patients with biochemical recurrence (BCR) after radical prostatectomy and imaging with PSMA positron emission tomography (PET), treated with PSMA-RGS in two tertiary care centers (2014-2020), was conducted. INTERVENTION: PSMA-RGS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier and multivariable Cox regression models were used to assess BCR-free (BFS) and therapy-free (TFS) survival. Postoperative complications were classified according to Clavien-Dindo. RESULTS AND LIMITATIONS: Overall, 364 patients without concomitant treatment were assessed. At PSMA-RGS, metastatic soft-tissue PCa lesions were removed in 343 (94%) patients. At 2-16 wk after PSMA-RGS, 165 patients reached a prostate-specific antigen (PSA) level of <0.2 ng/ml. Within 3 mo, 24 (6.6%) patients suffered from Clavien-Dindo complications grade III-IV. At 2 yr, BFS and TFS rates were 32% and 58%, respectively. In multivariable analyses, higher preoperative PSA (hazard ratio [HR]: 1.07, 95% confidence interval [CI]: 1.02-1.12), higher number of PSMA-avid lesions (HR: 1.23, CI: 1.08-1.40), multiple (pelvic plus retroperitoneal) localizations (HR: 1.90, CI: 1.23-2.95), and retroperitoneal localization (HR: 2.04, CI: 1.31-3.18) of lesions in preoperative imaging were independent predictors of BCR after PSMA-RGS. The main limitation is the lack of a control group. CONCLUSIONS: As salvage surgery in oligorecurrent PCa currently constitutes an experimental treatment approach, careful patient selection is mandatory based on life expectancy, low PSA values, and low number of PSMA PET-avid lesions located in the pelvis. PATIENT SUMMARY: We looked at the outcomes from prostate cancer patients with recurrent disease after radical prostatectomy. We found that surgery may be an opportunity to prolong treatment-free survival, but patient selection criteria need to be very narrow.

Full functional-length urethral sphincter- and neurovascular bundle preservation improves long-term continence rates after robotic-assisted radical prostatectomy.

The objective of the study was to test the impact of implementing standard full functional-length urethral sphincter (FFLU) and neurovascular bundle preservation (NVBP) with intraoperative frozen section technique (IFT) on long-term urinary continence in patients undergoing robotic-assisted radical prostatectomy (RARP). We relied on an institutional tertiary-care database to identify patients who underwent RARP between 01/2014 and 09/2019. Until 10/2017, FFLU was not performed and decision for NVBP was taken without IFT. From 11/2017, FFLU and IFT-guided NVBP was routinely performed in all patients undergoing RARP. Long-term continence (≥ 12 months) was defined as the usage of no or one safety- pad. Uni- and multivariable logistic regression models tested the correlation between surgical approach (standard vs FFLU + NVBP) and long-term continence. Covariates consisted of age, body mass index, prostate volume and extraprostatic extension of tumor. The study cohort consisted of 142 patients, with equally sized groups for standard vs FFLU + NVBP RARP (68 vs 74 patients). Routine FFLU + NVBP implementation resulted in a long-term continence rate of 91%, compared to 63% in standard RARP (p < 0.001). Following FFLU + NVBP RARP, 5% needed 1-2, 4% 3-5 pads/24 h and no patient (0%) suffered severe long-term incontinence (> 5 pads/24 h). No significant differences in patient or tumor characteristics were recorded between both groups. In multivariable logistic regression models, FFLU + NVBP was a robust predictor for continence (Odds ratio [OR]: 7.62; 95% CI 2.51-27.36; p < 0.001). Implementation of FFLU and NVBP in patients undergoing RARP results in improved long-term continence rates of 91%.

Triplet or Doublet Therapy in Metastatic Hormone-sensitive Prostate Cancer Patients: A Systematic Review and Network Meta-analysis.

CONTEXT: Two recent randomized controlled trials (RCTs) reported overall survival benefit of triplet therapy (androgen receptor axis-targeted therapy agent [ARAT], docetaxel, and androgen deprivation therapy [ADT]) over that of doublet therapy (docetaxel and ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Ranking of therapy options and comparisons between triplet therapy and doublet ARAT and ADT therapy are scarce. OBJECTIVE: To rank therapy options (triplet vs doublet [docetaxel and ADT] vs doublet [ARAT and ADT]) and address them within formal network meta-analyses (NMAs); subsequently, NMAs were refitted following stratification according to (1) low- and high-volume tumor burden and (2) doublet versus triplet therapy. EVIDENCE ACQUISITION: A systematic literature review (PubMed, MEDLINE, Embase, Web of Science, Scopus, and Cochrane database) of RCT trials that investigated the overall survival efficacy of systemic treatment in the setting of mHSPC was conducted. The study search and inclusion criteria were in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. EVIDENCE SYNTHESIS: Ten RCTs (n = 9702) were identified. The NMA focusing on the overall cohort of mHSPC demonstrated that triplet therapies (darolutamide, docetaxel, and ADT, and abiraterone, docetaxel, and ADT) were ranked first and second (hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.44-0.66; HR: 0.60; 95% CI: 0.46-0.78), followed by doublet therapy (ARAT and ADT) and lastly docetaxel and ADT. Owing to missing data within one RCT, the NMA for low- and high-volume mHSPC focused on nine trials. In high-volume disease, triplet therapy (abiraterone, docetaxel, and ADT) was ranked first (HR: 0.52, 95% CI: 0.38-0.71). CONCLUSIONS: Triplet therapy, consisting of an ARAT, docetaxel, and ADT, ranked first in systematic treatment in mHSPC. Moreover, triplet therapy might result in more pronounced overall survival benefit than doublet ARAT and ADT therapy in high-volume mHSPC. PATIENT SUMMARY: We compared different systemic therapy options for metastatic hormone-sensitive prostate cancer and concluded that triplet therapy, consisting of androgen receptor axis-targeted therapy agent, docetaxel, and androgen deprivation therapy, seems to be most beneficial for overall survival. Back to top.

Diabetes mellitus lowers the chance of short-term urinary continence recovery in prostate cancer patients undergoing radical prostatectomy.

Introduction: The aim of this article was to test the impact of diabetes mellitus (DM) on short-term urinary continence in patients undergoing radical prostatectomy (RP). Material and methods: We relied on an institutional tertiary-care database to identify patients who underwent RP between 11/2018 and 02/2021 with data available on short-term urinary continence status (30-90 days post-surgery). Continence was defined as the usage of no or one safety-pad within 24 hours. Univariable and multivariable logistic regression models tested the correlation between DM and short-term continence. Covariates consisted of pathological T-stage, body mass index, prostate volume, surgical approach and nerve-sparing. Results: Of 142 eligible patients, 15 (11%) patients exhibited concomitant DM. Patients diagnosed with DM exhibited lower continence rates at short-term follow-up compared to patients without DM (33 vs 63%, p = 0.03). In univariable and multivariable logistic regression models, DM was strongly associated with reduced chances of short-term urinary continence recovery (multivariable odds ratio [OR]: 0.26, 95%-CI: 0.07-0.86; p = 0.03). Furthermore, pathological T-stage (pT3/pT4) was additionally associated with reduced chance of urinary continence in logistic regression models (multivariable OR: 0.43, 95%-CI: 0.19-0.94; p = 0.04). Other covariables failed to reach statistical significance in multivariable logistic regression analyses predicting urinary continence. Conclusions: DM was associated with lower chances of short-term urinary continence recovery in a contemporary cohort of patients undergoing radical prostatectomy. Patients with DM should be preoperatively informed and intensified, postoperative pelvic floor training should be considered in this subgroup of RP patients.