Summa1. Intry of: Biochemical Recurrence in High-Risk Localized Prostate Caoductioncer

This retrospective study by Rybar et al. (2025) investigates biochemical recurrence (BCR) in high-risk localized prostate cancer, comparing two primary curative treatment modalities: laparoscopic radical prostatectomy (LRP) and external beam radiotherapy combined with androgen deprivation therapy (EBRT+ADT). Conducted at the University Hospital Bratislava between 2016 and 2023, the study aims to determine predictors of BCR and to evaluate recurrence-free survival (RFS) outcomes over a five-year follow-up.

A total of 107 male patients with high-risk localized prostate cancer were enrolled. Of these, 61 underwent LRP and 46 received EBRT+ADT. High-risk was defined in line with EAU guidelines, including elevated PSA (>20 ng/mL), high Gleason/ISUP score, and clinical stage up to cT2c. Median follow-up was 60 months in the LRP group and 66 months in the EBRT group. All patients were treated by a single urologic team to minimize bias, and ethical approval (EK 2/3/2023) along with informed consent was obtained.

Biochemical recurrence was defined differently for each treatment arm: PSA > 0.2 ng/mL after LRP, and PSA > 2 ng/mL above nadir after EBRT, reflecting standard clinical definitions. Kaplan–Meier analysis and Cox regression models were used for statistical assessment (significance set at p < 0.05).

2. Key Results

Key Results:

• Positive surgical margins (
• p
• < 0.001),
• Intermediate PSA levels (10–20 ng/mL;
• p
• = 0.080).

• BCR occurred in 34.4% of LRP patients and 21.7% of EBRT patients.
• Five-year BCR-free survival was 65.6% for LRP vs. 71.7% for EBRT, a difference that approached statistical significance (log-rank p = 0.089).
• Median time to BCR was shorter in LRP (30 months) than EBRT (48 months).
• In the LRP group, BCR was significantly associated with:
• Higher ISUP grade (p = 0.001),
• Advanced pathological stage (p < 0.001),
• Positive surgical margins (p < 0.001),
• Intermediate PSA levels (10–20 ng/mL; p = 0.080).
• BCR occurred in 34.4% of LRP patients and 21.7% of EBRT patients.
• Five-year BCR-free survival was 65.6% for LRP vs. 71.7% for EBRT, a difference that approached statistical significance (log-rank p = 0.089).
• Median time to BCR was shorter in LRP (30 months) than EBRT (48 months).
• In the LRP group, BCR was significantly associated with:
• Higher ISUP grade (p = 0.001),
• Advanced pathological stage (p < 0.001),

No independent predictors of BCR were found in the EBRT group, potentially due to smaller event numbers.

Histological analysis revealed a 23% discordance between clinical and pathological tumor staging and an 18% discrepancy in Gleason scoring, highlighting limitations in biopsy-based diagnostics. Interestingly, the group with iPSA levels of 10–20 ng/mL showed a higher recurrence rate than those with PSA > 20 ng/mL—contradicting prior expectations and aligning with findings from larger U.S. datasets.

3. Clinical Implications

Clinical Implications:

The findings of this study have meaningful clinical implications for the management of high-risk localized prostate cancer. Although both LRP and EBRT+ADT offer comparable five-year biochemical recurrence-free survival, LRP was associated with a notably higher recurrence rate. This underscores the importance of carefully selecting patients for surgical treatment and recognizing the limitations of prostatectomy in certain risk groups.

For patients undergoing LRP, the presence of adverse histopathological features—such as high ISUP grade, advanced pathological stage, and positive surgical margins—strongly predicted BCR. These patients may benefit from more aggressive post-operative surveillance strategies, early consideration of adjuvant or salvage radiotherapy, and potential enrollment in clinical trials targeting high-risk postoperative populations. Identifying these risk factors preoperatively, when possible, could aid in shared decision-making and may shift treatment preference toward radiotherapy in select cases.

The observation that intermediate PSA levels (10–20 ng/mL) were associated with higher recurrence risk than even the >20 ng/mL group challenges traditional PSA-based stratification and supports the need for a more nuanced approach. Relying solely on PSA as a predictor may lead to underestimation of recurrence risk in this intermediate subgroup. Therefore, incorporating ISUP grade, radiologic findings, and potentially genomic classifiers should be considered essential in pre-treatment planning.

In the EBRT group, the absence of statistically significant predictors of recurrence may reflect both the relatively smaller sample size and the therapeutic buffering effect of combined modality treatment (radiation plus long-term hormonal suppression). This might support the consideration of EBRT+ADT as a safer option for patients with multiple risk factors or those unfit for surgery, particularly when long-term control is a priority over immediate PSA kinetics.

Finally, these findings emphasize the broader trend toward personalized oncology. The integration of clinical, pathological, and potentially molecular information into treatment algorithms can improve outcomes and avoid both overtreatment and undertreatment. Moving forward, clinicians should adopt a multidisciplinary, risk-adapted model for managing high-risk localized prostate cancer that leverages all available data sources to guide individualized therapeutic decisions.

4. Limitations

Limitations:

This study has several limitations that should be considered when interpreting the findings. First, its retrospective design inherently introduces the risk of selection bias and limits causal inferences. The single-center setting also reduces generalizability across different populations and healthcare systems. The relatively small sample size—particularly in the EBRT+ADT group—limits statistical power, especially for multivariate analyses of predictors of biochemical recurrence. Additionally, the choice of treatment modality was patient-driven rather than randomized, potentially introducing further bias related to patient characteristics or comorbidities.

Another significant limitation is the differing definitions of BCR used for the LRP and EBRT groups (PSA > 0.2 ng/mL vs. PSA nadir + 2 ng/mL, respectively). While these definitions are clinically standard, they complicate direct comparisons of recurrence rates and may influence apparent outcome disparities. Moreover, only surgical patients had access to complete histopathological data such as margin status, pT stage, and lymph node involvement. These data were not available for EBRT patients, limiting cross-modality comparisons in terms of pathologic risk factors.

Furthermore, a small subset of patients in the surgical arm was found to have pT3 disease postoperatively, raising concerns about staging accuracy and possible misclassification at baseline. The discrepancy between clinical and pathological staging (23%) and Gleason scoring (18%) underscores the limitations of current diagnostic modalities such as biopsy and multiparametric MRI. Finally, the study did not account for molecular or genomic tumor profiling, which could offer more precise risk stratification and treatment prediction in the era of personalized oncology.

5. Conclusion

Conclusion:

This study confirms that both laparoscopic radical prostatectomy and EBRT with androgen deprivation therapy offer effective long-term cancer control for high-risk localized prostate cancer. However, LRP was associated with a higher rate of biochemical recurrence, particularly among patients with high ISUP grade, advanced pathological stage, positive surgical margins, or intermediate-range PSA levels (10–20 ng/mL). These findings reinforce the importance of pathological assessment and suggest that even patients not classified as highest-risk by PSA alone may warrant intensified monitoring or adjuvant treatment.

Importantly, the study raises concerns about relying solely on PSA levels for risk stratification. The unexpected BCR trends among intermediate PSA levels highlight the need for improved prognostic models. Integration of advanced diagnostic tools—including molecular biomarkers, genomic risk scores, and functional imaging—could enhance personalized decision-making and post-treatment surveillance strategies.

Overall, the study supports a risk-adapted, multimodal approach to patient management and highlights the importance of future prospective studies to validate these findings in larger and more diverse populations.

Based on: Rybar, L.; Hesko, P.; Miko, M.; Bujdak, P.; Harsanyi, S. Biochemical Recurrence in High-Risk Localized Prostate Cancer: A Comparison of Laparoscopic Prostatectomy and External Radiotherapy. Medicina 2025, 61, 928. https://doi.org/10.3390/medicina61050928