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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.

Zusammenfassung Hintergrund Die Osteoprotektion bei Prostatakarzinompatienten spielt nicht nur in der ossär metastasierten kastrationsresistenten (mCRPC) Situation eine Rolle. Auch im ossär metastasiertem hormonsensitiven Stadium (mHSPC) und im Allgemeinen begleitend zur Androgendeprivationstherapie (ADT) wird eine Osteoprotektion empfohlen. Diese Studie soll die Anwendungsrealität der verschiedenen Arten der Osteoprotektion beim metastasierten Prostatakarzinom in Deutschland aufzeigen. Material und Methoden Es wurde ein Online-Fragebogen bestehend aus 16 Fragen zur Erfassung der Behandlungsrealität in Deutschland entwickelt und an Mitglieder der Arbeitskreise Onkologie und urologische Onkologie (AKO/AUO) sowie an Kollegen der Klinik für Urologie des Universitätsklinikums Schleswig-Holstein (Campus Lübeck), des Klinikums Braunschweig und der Technischen Universität München verschickt. Mithilfe der aktuellen Studienlage, Fachinformationen und Leitlinien wurden ferner Entscheidungspfade für das ossär metastasierte Prostatakarzinom und für den ADT-induzierten Knochenschwund entwickelt. Ergebnisse Zusammenfassend ergab die Auswertung, dass die Osteoprotektion beim ossär mCRPC zur Routine gehört. Beim ossär mHSPC hingegen wird eine Osteoprotektion seltener indiziert und ist zur Reduktion eines ADT-induzierten Knochenschwundes noch weniger im Einsatz. Denosumab wird häufiger genutzt als Zoledronsäure. Die vorgestellten Entscheidungspfade illustrieren die verschiedenen Dosierungs- und Applikationsschemata in den verschiedenen Stadien des metastasierten Prostatakarzinoms. Schlussfolgerung Die Osteoprotektion beim Prostatakarzinom ist facettenreich und nicht nur auf das ossär mCRPC beschränkt. Osteoprotektive Maßnahmen sind ein wichtiger Baustein im ganzheitlichen Therapiekonzept des metastasierten Prostatakarzinoms.

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.

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Benefit of the 3-level DNA score beyond the CAPRA-S nomogram for prediction of early biochemical recurrence. A) Prognostic impact of different levels of the CAPRA-S score. B)-F) Additional prognostic impact of the 3-level DNA score in subsets of cancers with B) CAPRA-S score 0-1, C) CAPRA-S score 2-3, D) CAPRA-S score 4-5, E) CAPRA-S score 6-8, F) CAPRA-S score 9-12. The 3-level DNA score combines cancers according to the following criteria: negative, DNA diploid and no deletion; intermediate, DNA diploid with deletion (of at least one of PTEN and 6q) or DNA tetraploid without deletion; high, DNA tetraploid with deletion or DNA aneuploidy.

Purpose: Aberrant DNA content has been discussed as a potential prognostic feature in prostate cancer.Experimental Design: We analyzed the clinical significance of DNA ploidy in combination with prognostic relevant deletions of PTEN and 6q15 in 3,845 prostate cancers.Result: The DNA status was diploid in 67.8%, tetraploid in 25.6%, and aneuploid in 6.8% of tumors, and deletions of PTEN and 6q15 occurred in 17.8% and 20.3% of tumors. Abnormal DNA content and deletions were linked to high Gleason score, advanced tumor stage, and positive nodal stage (P < 0.0001 each). The risk of PSA recurrence increased from diploid to tetraploid and from tetraploid to aneuploid DNA status (P < 0.0001 each). However, 40% of patients with Gleason score ≥4+4 and 55% of patients with PSA recurrence had diploid cancers. This fraction decreased to 21% (Gleason ≥4+4) and 29% (PSA recurrence) if PTEN and/or 6q deletion data were added to ploidy data to identify cancers with an aberrant DNA status. The significance of combining both deletions and ploidy was further demonstrated in a combined recurrence analysis. Presence of deletions increased the risk of PSA recurrence in diploid (P < 0.0001), tetraploid (P < 0.0001), and aneuploid cancers (P = 0.0049), and the combination of ploidy data and deletions provided clinically relevant information beyond the CAPRA-S nomogram. Multivariate modeling including preoperatively and postoperatively available parameters identified the “combined DNA status” as a strong independent predictor of poor patient outcome.Conclusions: The combinatorial DNA content analysis involving general (ploidy) and specific events (deletions) has the potential for clinical utility in prostate cancer. Clin Cancer Res; 22(11); 2802–11. ©2016 AACR.

PDF file - 163K, Homozygous CHD1 deletion in areas of prostatic intraepithelial neoplasia (PIN) and invasive cancer cells. Overwiew of a hematoxylin- and eosin stained tissue section containing areas of PIN (a, b) and invasive cancer (c). Corresponding FISH images show complete loss of CHD1 FISH signals (red) in PIN and cancer cells but not in stroma cells indicated by an asterix. The control FISH signals (green) correspond to centromere 6.

PDF file - 101K, GISTIC analysis of genomic rearrangements (cytoband) significantly associated with 5q21 deletion. The cytobands, significance (q value) and peak boundaries are indicated.

PDF file - 155K, Baseline CHD1 mRNA (a) and protein (b) expression levels in prostate cancer cell lines cells. Efficacy of ectopic overexpression of CHD1 in PC-3 cells on mRNA (c) and protein level (d) by Taqman PCR and immunoblot analysis, respectively.

PDF file - 44K, Overexpression of RB1 and PTEN in PC-3 cells transfected with PSG5L-RB1 and PSG5L-PTEN as compared to the control vector PLNGY. Lysates were analysed for RB1 (a) and PTEN (b) by immunoblot analysis. Tubulin immunoblot served as loading control.

PDF file - 92K, Impact of sh-RNA mediated knockdown of CHD1 (a), RB1 (b), PTEN (c) and mTOR (d) knockdown on mRNA and protein levels in BPH-1 cells by Taqman.

PDF file - 57K, COX regression multivariate analysis for the predictive factor biochemical recurrence (BCR).

PDF file - 68K, Localization of the CHD1 FISH probe made from two BAC clones relative to the CHD1 gene.

PDF file - 636K, Impact of CHD1 on colony formation, soft agar growth and cell invasiveness. a) Effect of CHD1 overexpression on cell growth. DU-145 cells were transfected with expression vectors encoding CHD1, PLNGY (control) and the known tumor suppressor genes RB1 and PTEN. Effect of CHD1 depletion on cell growth. DU-145 cells were transfected with shCHD1 vector. The control group consisted of shGFP, shRB1 and shPTEN vectors. Cells were selected with puromycin and cultured for two weeks, and colonies were fixed with methanol and stained with Giemsa. b) Soft agar assay showing the impaired anchorage-independent growth of shCHD1 PC-3 cells and control shNeg cells. Representative images of the stained colonies are shown. The bars represent the average number of colonies. c) CHD1 knockdown impairs invasion of PC-3 (shCHD1) cells through matrigel as compared to shNeg control cells. Photographs show representative fields of crystal-violet stained invading cells.

We have compiled stratigraphic ranges of genera of calcareous nannofossils, calcispheres, planktonic foraminifers, larger benthic foraminifers, corals and rudists bivalves, and species of dasycladalean green algae. These taxa comprise the main planktonic and benthic carbonate producers of the Cretaceous, a period of exceptionally high sea level and palaeotemperatures that was characterized by unique assemblages of benthic carbonate producers and the significant rise in pelagic carbonate sedimentation. The autecology, physiological control on calcification, and carbonate-production potential of these groups is summarized. The observed diversity patterns are compared with proxy data of Cretaceous climate and seawater chemistry to elucidate the effect of environmental change on carbonate production and sedimentation. Two characteristic patterns are recognized. Diversity of calcareous nannofossils, calcispheres, planktonic foraminifers and corals trace the evolution of Cretaceous sea-level, while the diversity of dasycladalean algae, larger benthic foraminifers, corals and rudist bivalves show significant reductions at the level of oceanic anoxic events (OAEs). Benthic carbonate producers except for corals thus appear to have been more vulnerable to environmental change, and these general patterns appear to be unrelated to the autecology of the taxa investigated. The expansion of suitable habitats during episodes of high sea level and high temperatures appears to have been a more important control of diversity in calcareous nannofossils, planktonic foraminifers, and corals than changes in seawater chemistry. Aragonitic or aragonite-dominated benthic carbonate producers are most affected during extinction events related to OAEs, and there is a general trend of decreasing aragonite dominance throughout the Cretaceous. This is compensated by the extensive formation of calcitic hemipelagic chalk since the Cenomanian. The trend of decreasing aragonite dominance is independent of the level of biological control on calcification in the different taxa affected. The demise of aragonitic or aragonite-dominated carbonate producers at OAE1a (early Aptian) and OAE2 (Cenomanian–Turonian boundary interval) may be related to short episodes of reduced seawater carbonate-saturation caused by short-lived injections of CO2 from large igneous provinces that initiated OAEs. For OAE1a, this scenario also explains the retreat of carbonate platforms to low latitudes in the early Aptian, as sea-surface water typically has a higher carbonate saturation in warm, lower than in cooler, higher latitude waters. The gradual decrease of aragonite throughout the Cretaceous matches model simulations of seawater carbonate-saturation. An increase in the relative number of azooxanthellate coral genera following OAE1a and OAE2 suggests a disruption of photosymbiosis in the course of these global events due to high temperatures. However, the relative numbers of azooxanthellate genera continued to increase during the Late Cretaceous, when global temperatures declined. Due to the short residence time of major nutrients in seawater, these may have affected carbonate-producing ecosystems regionally. The recent patterns of benthic carbonate production being highest in oligotrophic environments cannot confidently be extrapolated to the Cretaceous. Our database records ranges of genera at the substage level. Higher-resolution stratigraphical studies of neritic carbonate sequences are required to understand what aspect of environmental change in the sequences are required to understand what aspect of environmental change in the sequence of events that unfolded in the context of OAEs caused the demise of benthic carbonate producers.

Contains fulltext : 291600.pdf (Publisher’s version ) (Open Access) BACKGROUND: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. OBJECTIVE: To present consensus voting results for select questions from APCCC 2022. DESIGN, SETTING, AND PARTICIPANTS: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members ("panellists") who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1-3. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. RESULTS AND LIMITATIONS: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. CONCLUSIONS: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.

Prostate health index (PHI) and, more recently, Proclarix have been proposed as serum biomarkers for prostate cancer (PCa). In this study, we aimed to evaluate Proclarix and PHI for predicting clinically significant prostate cancer (csPCa).Proclarix and PHI were measured using samples of 344 men from two different centers. All patients underwent prostate biopsy, and among those, 188 men with PCa on biopsy had an additional radical prostatectomy (RP). All men had a prostate-specific antigen (PSA) between 2 and 10 ng/ml. Evaluation of area under the curve (AUC) and performance at predefined cut-offs of Proclarix and PHI risk scores as well as the linear combination thereof was performed to predict csPCa. PSA density was used as an independent comparator.The cohort median age and PSA were 65 (interquartile range [IQR]: 60-71) and 5.6 (IQR: 4.3-7.2) ng/ml, respectively. CsPCa was diagnosed in 161 (47%) men based on the RP specimen. ROC analysis showed that Proclarix and PHI accurately predicted csPCa with no significant difference (AUC of 0.79 and 0.76, p = 0.378) but significantly better when compared to PSA density (AUC of 0.66, p 0.001). When using specific cut-offs, Proclarix (cut-off 10) revealed higher specificity and positive predictive value than PHI (cut-off 27) at similar sensitivities. The combination of Proclarix and PHI provided a significant increase in the AUC (p ≤ 0.007) compared to the individual tests alone and the highest clinical benefit was achieved.Results of this study show that both Proclarix and PHI accurately detect the presence of csPCa. The model combining Proclarix and PHI revealed the synergistic effect and improved the diagnostic performance of the individual tests.

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.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.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.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).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.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.

Background: To test the impact of urethral sphincter length (USL) and anatomic variants of prostatic apex (Lee-type classification) in preoperative multiparametric magnet resonance imaging (mpMRI) on mid-term continence in prostate cancer patients treated with radical prostatectomy (RP). Methods: We relied on an institutional tertiary-care database to identify patients who underwent RP between 03/2018 and 12/2019 with preoperative mpMRI and data available on mid-term (>6 months post-surgery) urinary continence, defined as usage 0/1 (-safety) pad/24 h. Univariable and multivariable logistic regression models were fitted to test for predictor status of USL and prostatic apex variants, defined in mpMRI measurements. Results: Of 68 eligible patients, rate of mid-term urinary continence was 81% (n = 55). Median coronal (15.1 vs. 12.5 mm) and sagittal (15.4 vs. 11.1 mm) USL were longer in patients reporting urinary continence in mid-term follow-up (both p < 0.01). No difference was recorded for prostatic apex variants distribution (Lee-type) between continent vs. incontinent patients (p = 0.4). In separate multivariable logistic regression models, coronal (odds ratio (OR): 1.35) and sagittal (OR: 1.67) USL, but not Lee-type, were independent predictors for mid-term continence. Conclusion: USL, but not apex anatomy, in preoperative mpMRI was associated with higher rates of urinary continence at mid-term follow-up.

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.

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.To evaluate the oncological outcomes of salvage PSMA-RGS and determine the predictive preoperative factors of improved outcomes.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.PSMA-RGS.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.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 of0.2 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.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.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.

5009 Background: Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) allows detection of small and/or atypically localized metastatic prostate cancer (PCa) lesions. In a subset of patients with recurrent oligometastatic PCa salvage surgery with PSMA-targeted radioguidance (PSMA-RGS) may be of value. We aimed to evaluate the oncological outcomes of salvage PSMA-RGS for oligo-recurrent PCa and determine predictive preoperative factors of improved outcomes. Methods: In this cohort study within two tertiary care centers, patients with biochemical recurrence (BCR) after radical prostatectomy (RP) and imaging with PSMA PET receiving salvage PSMA-RGS between 2014 and 2020 were analyzed. Kaplan-Meier and multivariable Cox regression models adjusted for various parameters were used to test for BCR-free survival (BFS) and therapy-free survival (TFS) differences. Postoperative complications were classified according to Clavien-Dindo. Results: Overall, 364 patients were assessed. At PSMA-RGS, median (IQR) age and preoperative PSA was 67 (61-71) years and 1.0 (0.5-1.9) ng/ml. Metastatic soft-tissue lesions from PCa metastases could be removed in 343 (94.2%) patients. Within three months from surgery, 24 (6.6%) patients suffered from Clavien-Dindo complications grade III-IV. During follow-up, 225 patients experienced BCR and 121 patients received further therapy. Median follow-up for patients who did not experience BCR and who did not receive further therapy was 10.8 months and 10.3 months, respectively. Median (IQR) BFS and TFS was 7.8 (5.4-10.5) and 35.5 months (25.9-45.9 months). At two years of follow-up, BFS rate was 31.9% and TFS rate was 58.0%. In multivariable analyses, higher preoperative PSA (HR: 1.1), higher number of PSMA-avid lesions on preoperative imaging (HR: 1.2) and multiple (pelvic plus retroperitoneal) localizations (HR: 1.9), as well as retroperitoneal localization (HR: 2.0) of lesions in PSMA PET imaging were independent predictors of BCR after PSMA-RGS. Limitations are the retrospective design and lack of a control group. Conclusions: As salvage surgery in oligo-recurrent 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. Further studies are needed to confirm our findings and define the oncological value of salvage surgical procedures in oligo-recurrent PCa.

142 Background: In ACIS, APA + AAP improved radiographic progression-free survival in mCRPC vs AAP; difference in overall survival (OS) was not statistically significant. We report a prespecified analysis of androgen receptor (AR) or non-AR genomic/transcriptional aberrations, known to be associated with poor prognosis, and their associations with OS in patients (pts) with mCRPC. Methods: Circulating tumor (ct)DNA and aberrations in 17 PC-relevant genes were assessed using next-generation sequencing at baseline (BL; n = 197) and at end of study treatment (EOST; n = 140) (biomarker population). ctDNA was summarized qualitatively; genomic aberrations were normalized by ctDNA detection. AR splice variant version 7 (ARv7) was detected by quantitative RT-PCR. Cox proportional hazards model assessed association of OS with biomarkers in univariate/multivariate analyses overall and in pts receiving subsequent treatment (tx). Results: BL characteristics of biomarker and total study populations were similar. From BL to EOST: ctDNA detection did not differ (123/196 [63%] to 92/140 [66%], p=0.6); significant increases occurred in ARv7, AR mutations, and any AR aberration (Table). Prevalence of aberrations in PI3K and homologous recombination repair (HRR) pathways did not change from BL to EOST (40/123 [33%] to 34/92 [37%], p=0.5 and 18/123 [15%] to 14/92 [15%], p>0.9, respectively). Worse OS was associated with ctDNA detection or HRR pathway inactivation at BL (HR, 2.5 or 2.2; all p < 0.001) or presence of ctDNA, ARv7, AR amplification or inactivation of TP53, RB1, or RB1/TP35 pathway at EOST (2.2, p < 0.001; 2.1, p < 0.001; 2.6, p < 0.001; 1.5, p < 0.05; 1.7, p < 0.05; 2.1, p < 0.001, respectively) in univariate analyses. EOST ARv7, AR amplification, and inactivation of RB1, TP53, or RB1/TP53 pathway was associated with worse OS in pts receiving subsequent tx. Detection of ctDNA and RB1 inactivation at BL and RB1/TP53 pathway inactivation at EOST was strongly associated with worse OS (2.1, 3.3, 2.9, respectively, all p < 0.01) in multivariate analyses. Conclusions: In ACIS, AAP or APA + AAP tx was associated with increased AR mutations and ARv7 expression. Detection of ctDNA and select AR/non-AR aberrations may predict poor survival in mCRPC. These markers may be used to improve tx selection following confirmation of their predictive value. Clinical trial information: NCT02257736. [Table: see text]

106 Background: Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) allows detection of small and/or atypically localized metastatic prostate cancer (PCa) lesions. In a subset of patients with recurrent oligometastatic PCa salvage surgery with PSMA-targeted radioguidance (PSMA-RGS) may be of value. We aimed to evaluate the oncological outcomes of salvage PSMA-RGS for oligorecurrent PCa and determine predictive preoperative factors of improved outcomes. Methods: In this cohort study within two tertiary care centers, patients with biochemical recurrence (BCR) after radical prostatectomy (RP) and imaging with PSMA PET receiving salvage PSMA-RGS between 2014 and 2020 were analyzed. Kaplan-Meier and multivariable Cox regression models adjusted for various parameters were used to test for BCR-free survival (BFS) and therapy-free survival (TFS) differences. Postoperative complications were classified according to Clavien-Dindo. Results: Overall, 364 patients were assessed. At PSMA-RGS, median (IQR) age and preoperative PSA was 67 (61-71) years and 1.0 (0.5-1.9) ng/ml. Metastatic soft-tissue lesions were removed in 356 (94.4%) patients. Within three months from surgery, 25 (6.6%) patients suffered from Clavien-Dindo complications grade III-IV. During follow-up, 235 patients experienced BCR and 129 patients received further therapy. Median follow-up for patients who did not experience BCR and who did not receive further therapy was 11.1 months and 10.5 months, respectively. Median (IQR) BFS and TFS was 7.8 (5.4-10.9) and 34.9 (24.7-43.5) months. At two years of follow-up, BFS rate was 31.9% and TFS rate was 56.6%. In multivariable analyses, higher preoperative PSA (HR: 1.06), higher number of PSMA-avid lesions on preoperative imaging (HR: 1.2) and multiple (pelvic plus retroperitoneal) localizations (HR: 1.7), as well as retroperitoneal localization (HR: 2.0) of lesions in PSMA PET imaging were independent predictors of BCR after PSMA-RGS. Limitations are the retrospective design and 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. Further studies are needed to confirm our findings and define the oncological value of salvage surgical procedures in oligorecurrent PCa.