Long-term outcomes of prostate cancer patients with metastases in the anterior fat pad and pelvic lymph nodes: Nodal upstaging without worse long-term outcomes.

To compare perioperative and early oncological outcomes of robotic radical prostatectomy (RP) with and without extended pelvic lymph node dissection (PLND) in a cohort of intermediate (IR)-to-high-risk (HR) prostate cancer (PCa) patients. Data was prospectively collected from 88 patients (47 PLND, 41 no-PLND) with unfavorable intermediate- and high-risk miN0M0 PCa, all staged preoperatively with PSMA-PET/CT. Outcomes were assessed using Kaplan-Meier curves, uni-and multivariable Cox regression, for biochemical recurrence-free survival (BCRFS) and biochemical failure-free survival (BCFFS). A propensity score matched analysis with Cox regression was undertaken matching 1:1 for potential confounders (age, iPSA, preoperative ISUP, cT stage at MRI). Both groups (PLND and no-PLND) had the same proportion of HR patients (p = 1.0). The no-PLND group had a shorter median operative time by 50min (p < 0.01). Conversely, the PLND group experienced significantly higher rates of 90-day high-grade complications (p = 0.03) and lymphoceles (p < 0.01). Over a median 20.5-month follow-up, no significant differences emerged in BCRFS (p = 0.59) or BCFFS (p = 0.76). Uni- and multivariable analyses adjusted for UCSF CAPRA and CAPRA-S variables, as well as propensity score matching, confirmed PLND was not associated with improved BCFFS. In patients who did recur, the sites of recurrence did not differ between the two groups (p = 0.62), with pelvic nodal recurrence being the most common site of recurrence in both groups (6, 50% for PLND and 3, 60% for no-PLND). In this short-term follow-up, performing PLND increased high-grade postoperative complications without providing a clear early oncological benefit regarding BCRFS, PSA persistence, or recurrence location.

Positive surgical margins (PSMs) after robot-assisted radical prostatectomy (RARP) are consistently associated with biochemical recurrence (BCR), yet their prognostic heterogeneity and functional implications remain debated. This study aimed to evaluate the oncological and functional impact of PSMs and to explore clinicopathological predictors of margin positivity. We conducted a retrospective single-center study including 93 patients undergoing RARP. Surgical margin status, length, focality, and location were recorded. BCR was defined as PSA ≥0.2 ng/mL confirmed by two measurements. Functional outcomes (urinary continence and erectile function) were assessed at 6 months. Multivariable logistic regression identified predictors of PSM, and Kaplan-Meier analysis evaluated BCR-free survival. PSMs were identified in 48 patients (51.6%). During a median follow-up of 11 months, BCR occurred more frequently in patients with PSMs than in those with negative margins (20.8% vs 4.4%, p=0.018). PSMs were associated with significantly worse early BCR-free survival (log-rank p=0.013). Margin length ≥3 mm did not stratify early BCR risk. In multivariable analysis, ISUP Grade Group 3-5 was the only independent predictor of PSM (OR 0.25, p=0.044). No significant differences in urinary continence or erectile function at 6 months were observed according to margin status. PSMs are associated with an increased risk of early biochemical recurrence, while early functional outcomes appear independent of margin status. Tumor biology, rather than surgical factors, emerges as the main determinant of margin positivity. These findings support a risk-adapted interpretation of PSMs and align with current guidelines favoring close surveillance and early salvage treatment over routine adjuvant therapy.

366 Background: To evaluate the prognostic value of histologic variants of prostate cancer (PCa) in men treated with radical prostatectomy (RP) and external beam radiation therapy (EBRT). Methods: We identified patients with localized PCa treated with EBRT (n=221) or RP (n=2,039) at West China Hospital between 2011 and 2023. 1:3 propensity score matching was performed to adjust the patients’ backgrounds. Histologic variants of PCa included intraductal carcinoma of the prostate (IDCP), ductal adenocarcinoma of the prostate (DA), and neuroendocrine differentiation (NED), all biopsy-confirmed. We compared the biochemical recurrence (BCR)-free survival using the Phoenix definition (prostate-specific antigen [PSA] nadir plus 2 ng/mL) for EBRT and the surgical definition (PSA cut-off value of 0.2 ng/mL) for RP. We also directly compared the BCR-free survival using the same PSA cut-off value of 0.2 ng/mL for both EBRT and RP. Results: Totally, 884 patients were included. Patients with histologic variants of PCa harbored the worst prognosis compared with adenocarcinoma of the prostate (PAC) in both RP and EBRT cohort (RP: 23-Mo vs 138-Mo, p &lt; 0.001; EBRT: neither reached the median BCR-free survival, p &lt; 0.001). Subsequent multivariate cox regression analysis further established histologic variants of PCa as an independent risk factor in RP and EBRT cohort (RP: HR: 2.00, 95%CI: 1.55-2.60, p &lt; 0.001; EBRT: HR: 2.19, 95%CI: 1.03-4.66, p = 0.042;). Comparing the BCR-free survival using the above definitions for RP and EBRT showed that EBRT yielded a significantly better BCR-free survival than did RP whether in PAC or histologic variants of PCa (PAC: RP vs EBRT: 138-Mo vs not reached, p &lt; 0.001; Histologic variants of PCa: RP vs EBRT: 23.3-Mo vs not reached, p &lt; 0.001;). When the surgical definition was applied to both treatments, there was no significant difference between EBRT and RP in PAC (138 months vs not reached, p=0.062), whereas EBRT remained superior in histologic variants of PCa (23.3 months vs not reached, p=0.001). Conclusions: Histologic variants of PCa is associated with inferior prognosis after both RP and EBRT. EBRT was linked to longer BCR-free survival than RP, including under a uniform surgical definition, among patients with histologic variants of PCa. EBRT should be strongly considered when selecting definitive therapy for localized histologic variants of PCa.

P0628 Prognostic impact of surgical margin status on biochemical recurrence-free survival after robot-assisted radical prostatectomy: Stratification by stage, grade, and nodal involvement

P0932 PSMA PET/CT vs. Conventional imaging: Biochemical recurrence-free survival after radical prostatectomy

P0835 Racial impact (Asians vs. Caucasians/Whites) on biochemical recurrence-free survival after robot-assisted radical prostatectomy: A propensity score matching study from 2012 to 2018

Perineural Invasion in Radical Prostatectomy Specimens and Its Association with Biochemical Recurrence and Survival in Prostate Cancer: A Systematic Review and Meta-analysis.

TPS415 Background: Of the estimated 31,000 high risk localized prostate cancer (PC) cases in 2025, up to 46% have a risk of biochemical recurrence after definitive treatment (Falgario U, JAMA Netw Open 2023). A pooled analysis showed 3-year biochemical recurrence-free survival (bRFS) was robustly correlated to pathologic complete response (pCR) plus minimal residual disease (MRD) in patients treated neoadjuvantly (NAJ) with androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI) (McKay R, J Urol 2021). A separate study of localized high-risk PC revealed increased glucocorticoid receptor (GR) expression in residual tumors of PC patients (pts) treated with NAJ ARPI plus ADT (Efstathiou E, Eur Urol 2019). Resistance to the ARPI enzalutamide (Enz) is mitigated by targeting GR (Isikbay M, Horm Cancer 2014). We previously demonstrated the safety of the combination of the selective GR antagonist (SGRA) relacorilant (Rel) plus Enz (Desai, CCR , 2024). We have thus initiated a trial to evaluate the NAJ efficacy of this combination. Methods: This phase 2 placebo-controlled 2:1 randomized trial of NAJ LHRH agonist/antagonist and Enz (160 mg daily) plus Rel (150 mg daily)/placebo has a primary objective of response, measured by pCR and MRD at radical prostatectomy (RP). Eligible pts include those with high risk or very high-risk localized prostatic adenocarcinoma per NCCN guidelines, allowing lymph nodes below the iliac bifurcation. After randomization pts will be treated with 6 mo of LHRH agonist/antagonist plus Enz plus Rel/placebo and undergo RP 1 month later. The total sample size is 90 patients with an interim analysis for futility conducted after 45 pts undergo RP. As of October 2025, 30 pts have enrolled, with 23 in follow up and 7 on treatment. A chi-square test will be used to compare the proportion of pts achieving pCR/MRD. Assuming a true CR/MRD rate of 15% in the control group, 90 pts total would yield a power of 80% with a hypothesized CR/MRD of 32% in the Rel group, based on a one-sided test at the alpha=0.15 significance level. Secondary endpoints include evaluating radiographic response within the prostate with multiparametric MRI (mpMRI) and the 3-year bRFS and metastasis-free survival (MFS) rates in both arms. For correlatives, we will demonstrate decreased nuclear hormone receptor-driven proliferative gene expression in viable PC due to NAJ ARPI combined with GR antagonism versus ARPI alone, as well as correlation between pathologic response and enhanced mpMRI imaging. The study is open and seeking additional sites (currently 3 open). ClinicalTrials.gov Identifier: NCT05726292. Clinical trial information: NCT05726292 .

The impact of neoadjuvant chemohormonal therapy (NCHT) on biochemical recurrence-free survival (BRFS) in patients with very-high risk localized prostate cancer remains uncertain, particularly because previous studies have included heterogeneous populations with locally advanced disease. This retrospective study evaluated the clinical significance of NCHT in patients with strictly defined T2-T3a very-high risk disease. A total of 49 patients treated between 2017 and 2024 were analyzed; 25 received NCHT consisting of androgen deprivation therapy and estramustine phosphate, while 24 underwent radical prostatectomy without NCHT. All patients received robot-assisted radical prostatectomy with extended lymph node dissection. Baseline characteristics and pathological outcomes were comparable between the two groups, with a median follow-up period of 19 months in the NCHT group and 29 months in the non-NCHT group. Kaplan-Meier analysis demonstrated no significant difference in BRFS between the groups (p=0.397). In multivariable Cox analysis, primary Gleason pattern 5 was the only independent predictor of BRFS (hazard ratio=3.72; 95% confidence interval=1.19-11.58), whereas NCHT did not confer an oncological benefit. These findings suggest that for patients with very-high risk prostate cancer limited to T2-T3a disease, NCHT does not improve biochemical recurrence outcomes, and tumor biology-particularly primary Gleason pattern 5-plays a more decisive role in prognosis than neoadjuvant systemic intensification. While cytotoxic therapy combined with androgen deprivation remains of investigational interest, its utility in organ-confined but biologically aggressive prostate cancer appears limited based on current evidence. Further large-scale, prospective studies are warranted to clarify the optimal patient selection for neoadjuvant approaches.

Background High-risk and locally advanced prostate cancer (HRPC/LAPC) continues to present significant therapeutic challenges. Although conventional neoadjuvant therapy combining androgen deprivation therapy (ADT) with first-generation antiandrogens [e.g., bicalutamide (BICA)] has been widely adopted, this approach’s limited efficacy in achieving durable pathological responses and improving long-term survival underscores the need for more effective strategies. The emergence of novel hormonal therapies (NHTs), such as abiraterone and next-generation androgen receptor inhibitors (e.g., darolutamide), has revolutionized the treatment for patients with advanced disease by enabling marked suppression of the androgen signaling pathway. However, evidence regarding the perioperative benefits of ADT plus NHT relative to those of conventional ADT + BICA remains scarce, particularly in terms of pathological outcomes [e.g., complete response and minimal residual disease (MRD)] and early efficacy indicators. This study thus aimed to compare these treatment approaches through a retrospective analysis of real-world data in order to better inform the optimization of neoadjuvant strategies for this high-risk population. The objective of this study was to compare the pathological and early oncological outcomes of neoadjuvant ADT plus NHT to those of conventional ADT plus BICA in patients with high-risk or LAPC undergoing radical prostatectomy (RP).Methods A retrospective cohort study was conducted that included 87 patients who received neoadjuvant therapy followed by RP. Patients were stratified into two groups: an ADT + BICA group (n=35) and an ADT + NHT group (n=52). The primary endpoints included the pathological complete response (pCR) rate, incidence of MRD, the pathological downstaging rate (based on American Joint Committee on Cancer eighth edition staging), and positive surgical margin (PSM) rate. The secondary endpoints included the rate of ≥50% decline in prostate-specific antigen level (PSA50 response rate), PSA90 response rate, and biochemical recurrence (BCR) rate.Results The ADT + NHT group, compared to the ADT + BICA group, demonstrated significantly higher rates of pCR (15.4% vs. 0%, P=0.04), MRD (30.8% vs. 8.6%; P=0.01), and pathological downstaging (44.2% vs. 22.9%; P=0.04). Although both groups achieved 100% PSA50 and high PSA90 response rates (97.1% vs. 94.2%), no significant differences were observed in PSM rates (32.7% vs. 48.6%; P=0.14) or BCR-free survival (log-rank P=0.90). Among NHT agents, darolutamide showed the most favorable performance. All regimens were well-tolerated, with no grade 3–4 adverse events being reported.Conclusions Neoadjuvant ADT + NHT was associated with improved pathological responses compared to ADT + BICA, although this advantage did not translate into significant differences in surgical margins or short-term survival outcomes. These findings support the superior pathological efficacy of NHT-containing regimens and underscore the need for longer-term follow-up to evaluate their survival benefits.

Lymphovascular invasion is an adverse pathologic feature in prostate cancer, but its independent molecular drivers remain unclear due to strong confounding by tumor grade and stage. We performed a confounder-adjusted transcriptomic analysis of 403 TCGA-PRAD samples. Differential expression was adjusted for Gleason score and pathological T stage. A transcriptional profile associated with LVI was derived and tested in multivariable logistic and Cox proportional hazards models for biochemical recurrence-free survival, with bootstrap internal validation. After multivariable adjustment, 129 genes were independently associated with LVI. This gene set was overwhelmingly enriched for interferon-alpha/beta signaling and antiviral response pathways. A continuous composite score derived from this profile predicted a reduced risk of biochemical recurrence independently of standard clinicopathological factors (adjusted HR per unit = 0.911, 95% CI: 0.835-0.993, p = 0.033). Multi-omics integration revealed subtle promoter hypomethylation and strong correlations between methylation and expression for key interferon genes, supporting transcriptional regulation. We identify a robust, interferon-response transcriptional profile that specifically defines LVI in prostate cancer after accounting for major clinical confounders. This transcriptional signature provides independent prognostic information, refines the biological understanding of LVI, and presents a novel targetable pathway for further investigation.

This study investigates a short-course, intensified regimen combining apalutamide, abiraterone acetate and prednisone (AAP), and stereotactic body radiotherapy to reduce treatment burden and improve disease control in a very high-risk population (VHR) inadequately represented in prior trials. This multi-institutional, single-arm phase 2 trial enrolled patients with VHR localized prostate cancer, defined per NCCN as histologically confirmed adenocarcinoma with ≥2 high-risk features: Gleason 8-10, PSA ≥20, clinical/radiographic ≥T3, or >4 cores of Gleason 8 disease. Patients received 6 months of apalutamide, abiraterone acetate and leuprolide plus prostate/seminal vesicle-directed ultra-fractionated SBRT. The primary endpoint was 3-year biochemical recurrence (BCR) rate by Phoenix criteria, with a prespecified superiority threshold of <10%. Secondary endpoints included PSA ≥ 0.2, metastasis-free survival (MFS), and time to testosterone recovery >150 ng/dL. Between 08/2016 to 12/2022, 63 patients were treated. At 3 years, the Phoenix-defined BCR rate was 19.0%. Biochemical recurrence-free survival (bRFS) was 84.2% (95 CI, 75.6-93.7) with median follow-up of 41 months (34-43). Three-year MFS was 93.6% (95% CI, 87.8%-99.8%), with no deaths observed. Median time to testosterone recovery >150 ng/dL was 6 months (range, 3-24). No new safety signals emerged, and the only significant quality-of-life decline was in the EPIC sexual sub-domain at 12 months. Treatment intensification with apalutamide, AAP, ADT and SBRT well-tolerated with limited impact on quality of life. While BCR rates exceed the superiority threshold, outcomes aligned with historical benchmarks, supporting further evaluation of the regimen in prospective trials.

Evidence for neoadjuvant androgen deprivation therapy (ADT) before radical prostatectomy (RP) remains inconclusive, and current guidelines do not endorse its routine use. We aimed to evaluate the impact of neoadjuvant ADT on surgical and oncologic outcomes in a Singaporean cohort undergoing radical prostatectomy. In this retrospective study, 1091 men underwent RP between 2013 and 2024; a total of 105 received neoadjuvant ADT and 986 did not. A 1:1 propensity score-matched analysis was performed on age, PSA, PSA density, Gleason score, clinical T-stage, and receipt of adjuvant therapies, yielding 105 matched pairs. The primary outcome was biochemical recurrence (BCR). Secondary surgical outcomes included operative time, estimated blood loss, length of stay, catheter duration, and postoperative complications. Secondary oncologic outcomes included extracapsular extension, margin status, seminal vesicle invasion, lymph node involvement, clinical-to-pathological T-stage downstaging, Gleason score decrease, and PSA decrease. Kaplan-Meier survival and univariable linear and logistic regression analyses were used. Subgroup analysis was performed using stratified odds ratios to identify clinical subgroups that derived the greatest benefit from neoadjuvant ADT in terms of biochemical recurrence reduction. After matching, neoadjuvant ADT was associated with a lower rate of extracapsular extension (30.8% vs. 51.4%, p = 0.004), positive surgical margins (18.4% vs. 39.4%, p = 0.002), lymph node involvement (1.0% vs. 13.0%, p = 0.002), and biochemical recurrence (4.8% vs. 18.1%, p = 0.005). There were no significant differences in operative time, blood loss, length of stay, or complication rates. Before matching, 2-year biochemical recurrence-free survival (BCR-FS) did not differ significantly (93.0% vs. 88.2%, log-rank p = 0.26), but after matching, BCR-FS favored ADT (93.0% vs. 81.8%, log-rank p = 0.02). Subgroup analysis showed that the reduction in biochemical recurrence with neoadjuvant ADT was more pronounced in patients with PSA density ≥ 0.20 ng/mL2, Gleason score ≥ 8, and clinical T3 disease. Limitations include the retrospective design and potential residual confounding. Neoadjuvant ADT prior to RP significantly reduces locoregional spread and biochemical recurrence without increasing perioperative morbidity. Prospective trials are needed to confirm its benefit in high-risk prostate cancer.

Biochemical recurrence (BCR) is a critical factor affecting the prognosis of prostate cancer (PCa) patients, while T cell exhaustion and metastatic prostate cancer (mPC)-related genes play significant roles in tumor progression. This study aims to identify key genes associated with BCR by integrating single-cell transcriptomics and deep learning techniques, and to validate their clinical significance. First, we identified highly expressed genes in CD8+ T cell exhaustion clusters from single-cell RNA sequencing data (scRNA-seq) of PCa and intersected them with mPC-related genes. Based on these genes, significant prognostic factors were screened using Cox regression analysis, and a deep learning neural network model was constructed to predict the risk of biochemical recurrence in prostate cancer patients. The tumor-infiltrating lymphocyte (TILs) infiltration was predicted by stratifying patients into high- and low-risk groups. ERBB2 was identified as the most predictive gene through model analysis. Subsequently, ERBB2 expression was validated in an independent PCa cohort using immunohistochemistry (IHC), and its association with biochemical recurrence and clinicopathological features was evaluated through survival analysis and statistical methods. The deep learning model demonstrated excellent performance in predicting BCR, with ERBB2 identified as the most important predictive factor. IHC results revealed that patients with high ERBB2 expression had significantly shorter biochemical recurrence-free survival (bRFS) (P < 0.05). Moreover, high ERBB2 expression was significantly associated with higher prostate-specific antigen (PSA) levels, Node-Metastasis (NM) stage, and International Society of Urological Pathology (ISUP) grade (P < 0.05). This study, for the first time, integrates single-cell transcriptomics, deep learning, and IHC to reveal the critical role of ERBB2 in biochemical recurrence of PCa. High ERBB2 expression is not only a potential biomarker for poor prognosis in PCa patients but may also provide a novel target for personalized therapy.

Prostate-specific membrane antigen (PSMA) PET/CT offers excellent accuracy in the staging of high-risk prostate cancer (PCa), yet outcomes-based evidence of the clinical benefit remains limited. We aimed to determine whether the rates of biochemical recurrence-free survival (BRFS) are influenced by PSMA-based staging compared with that of conventional imaging among patients undergoing radical prostatectomy (RP), using real-world data and exploiting regional variation in the adoption of PSMA PET/CT across Denmark. Methods: This nationwide cohort study included men with high-risk PCa who underwent RP between 2016 and 2023. Patients were classified on the basis of whether they underwent PSMA PET/CT or conventional imaging before surgery. The primary outcome was BRFS, with overall survival as the secondary outcome. The outcomes were analyzed by inverse probability weighting and adjusted Cox proportional hazards regression analyses. Results: Among 3,279 eligible patients with high-risk PCa who underwent RP, 959 (29.3%) underwent preoperative PSMA PET/CT. This group had a higher 5-y BRFS rate than did the conventional imaging group (65.1%; 95% CI, 61.4%-68.7% vs. 61.1%; 95% CI, 58.9%-63.2%, respectively; weighted hazard ratio, 0.82; 95% CI, 0.70-0.96; P = 0.014). The difference was most pronounced in patients with Gleason scores of 8-10, with 62.5% in the PSMA PET/CT group (95% CI, 57.7%-67.2%) versus 48.9% in the conventional imaging group (95% CI, 44.9%-52.9%; hazard ratio, 0.61; 95% CI, 0.51-0.74; P < 0.001). Overall survival was also greater in the PSMA PET/CT group; however, the limited follow-up prohibited any firm conclusions. The main limitation of this study was its observational design. Conclusion: The use of PSMA PET/CT for high-risk PCa staging was associated with increased BRFS rates.

Introduction: This study aimed to evaluate the harms and oncological benefits of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) in prostate cancer patients at risk for regional lymph node invasion. Methods: Patients with cN0M0 prostate cancer who underwent RP between January 2013 and February 2023 were included. Patients were categorized into two groups: 334 patients who underwent RP with PLND (group A) and 161 without PLND (group B). Perioperative and oncologic outcomes were assessed, and multivariate analysis identified independent prognostic factors. Inverse probability of treatment weighting (IPTW) was applied to account for baseline differences. Results: Group A had more advanced disease, longer operation times, and higher complication rates, with 58.3% of complications related to PLND. After a median follow-up of 56 months, there were no significant differences in 4-year biochemical recurrence-free survival (BRFS) (68.9% vs. 75.4%), metastasis-free survival, or overall survival between the groups. Positive surgical margins and tumor grade were independent risk factors for biochemical recurrence, while PLND was not. Cox regression in the IPTW-adjusted cohort confirmed no significant impact of PLND on BRFS (HR: 0.70, p = 0.09). Conclusion: PLND during RP increases postoperative complications without improving short-term oncologic outcomes, serving mainly as a staging procedure to inform management.

Magnetic resonance-guided stereotactic body radiotherapy (MRgSBRT) combines high-precision SBRT with superior soft tissue visualization and daily adaptive planning. While prospective studies suggest reduced toxicity compared to CT-based SBRT, data on oncologic outcomes and PSA kinetics in the MR-guided setting remain limited. We retrospectively reviewed 150 prostate cancer patients treated with MRgSBRT (ViewRay MRIdian) between September 2018 and April 2024. Patients received 36.25 Gy radiotherapy in 5fractions with or without androgen deprivation therapy (ADT). Outcomes included biochemical recurrence free survival (bRFS), local progression free survival (LPFS), regional recurrence free survival (RRFS), distant metastases free survival (DMFS), event-free survival (EFS), PSA kinetics, and toxicity (CTCAE v5.0). The median follow-up was 27.2 months (range: 4-73months). The estimated 5‑year bRFS, LPFS, RRFS, DMFS and EFS rates were 81.8%, 91.4%, 99.2%, 98.3% and 77.3% respectively. All patients were alive at the time of analysis. The estimated EFS was lowest for the very high-risk group (2-year EFS: 55.6%). The median time to nadir PSA (nPSA) was 12months (range: 3-54months), with amedian value of 0.46 ng/mL, for all cohort. PSA bounce occurred in 15.3% of patients and was associated with numerically higher 5‑year EFS (95% vs. 73.8%). No acute or late grade ≥ 3GU or GI toxicities were observed. MRgSBRT for localized prostate cancer provides favorable tumor control with minimal toxicity. Although not statistically significant, PSA bounce was associated with improved outcomes, warranting further investigation as apotential prognostic marker.

Identification of Biomarkers Predictive of Successful Salvage Surgery in Prostate-specific Membrane Antigen Positron Emission Tomography-positive Oligorecurrent Prostate Cancer: Results from the BioPoP Trial.

In 2025, the National Comprehensive Cancer Network (NCCN) updated the definition of very high-risk (VHR) prostate cancer to include individuals meeting at least two of the following: clinical stage ≥ T3, prostate-specific antigen ≥ 40 ng/mL, and Gleason Grade Group (GG) ≥ 4. This revision alters group classification and may impact surgical outcomes. We aimed to compare oncological outcomes under the earlier and 2025 definitions in individuals undergoing robot-assisted radical prostatectomy (RARP) without perioperative systemic therapy. We retrospectively reviewed 1879 individuals who underwent RARP at two institutions between July 2012 and November 2022. Of these, 641 classified as high risk or above were analyzed: historical high risk (Group 1: n = 377), reclassified from VHR to high risk (Group 2: n = 119), and VHR per 2025 criteria (Group 3: n = 145). The median follow-up was 59.8 months. Five-year biochemical recurrence-free survival rates were 71.1%, 44.7%, and 29.8%; metastasis-free survival rates were 99.6%, 94.1%, and 88.9% for the three groups, respectively. Group 2 showed worse outcomes than Group 1. Exploratory analyses indicated that within Group 3, having > 4 biopsy cores with GG 4-5 was associated with significantly worse recurrence outcomes, whereas those without this factor had results closer to Group 2. In conclusion, both the revised high-risk and VHR categories include heterogeneous populations. Refinement of risk stratification in the surgical setting may help identify subsets requiring tailored perioperative and multimodal strategies.