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15 pages, 780 KB  
Article
Pathological Predictors of Limited Salvage Radiotherapy Efficacy After Radical Prostatectomy: Central Review of JCOG0401
by Masashi Kato, Toyonori Tsuzuki, Akira Yokomizo, Takahiro Kimura, Keita Sasaki, Masaki Shiota, Keiichiro Mori, Takuma Kato, Takashi Kawahara, Dai Koguchi, Katsuyoshi Hashine, Mikio Sugimoto, Masatoshi Eto, Hiroyuki Nishiyama and Hiroshi Kitamura
Cancers 2026, 18(12), 1868; https://doi.org/10.3390/cancers18121868 - 8 Jun 2026
Viewed by 259
Abstract
Background/Objectives: The multicenter randomized trial JCOG0401 showed that initial salvage radiotherapy (SRT) before salvage hormonal therapy (SHT) significantly prolonged time to treatment failure (TTF) compared with SHT alone. This central pathology analysis aimed to explore pathological features potentially associated with reduced relative benefit [...] Read more.
Background/Objectives: The multicenter randomized trial JCOG0401 showed that initial salvage radiotherapy (SRT) before salvage hormonal therapy (SHT) significantly prolonged time to treatment failure (TTF) compared with SHT alone. This central pathology analysis aimed to explore pathological features potentially associated with reduced relative benefit from SRT, while distinguishing prognostic from predictive effects. Methods: We re-analyzed 167 patients from JCOG0401 (SHT: 81, SRT ± SHT: 86). Prostatectomy specimens were re-evaluated, focusing on tertiary Gleason pattern (GP) 5 and intraductal carcinoma of the prostate (IDC-P). Cox proportional hazards models assessed exploratory interaction effects between pathological features and the treatment effect of bicalutamide on TTF. Pathological subgroups in which SRT failed to improve TTF over SHT alone were defined as having reduced benefit from SRT. Results: Adverse pathological features associated with shorter TTF with limited SRT included Gleason score (≥8), GP5, tertiary GP5, IDC-P, positive surgical margins, lymphovascular invasion, and advanced pathological T stage. Exploratory Interaction analyses suggested that IDC-P and tertiary GP5 may be associated with reduced relative benefit from SRT. Among patients without IDC-P, SRT significantly improved TTF (HR 0.330, 95%CI 0.161–0.673), whereas no significant benefit was observed in those with IDC-P (HR: 0.771, 95% CI: 0.446–1.332). Similarly, the absence of tertiary GP5 was associated with a marked benefit from SRT (HR: 0.099, 95% CI: 0.021–0.466), whereas this effect was not observed with tertiary GP5 (HR: 0.760, 95% CI: 0.400–1.443). Conclusions: IDC-P and tertiary GP5 may represent pathological features associated with reduced relative benefit from SRT after radical prostatectomy. These findings are exploratory and hypothesis-generating and require prospective validation in independent cohorts. Careful pathological evaluation may help identify patients who could benefit from treatment intensification or alternative postoperative strategies. Full article
(This article belongs to the Section Clinical Research of Cancer)
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14 pages, 1004 KB  
Systematic Review
The Outcome of Immediate Adjuvant Postoperative External Beam Radiotherapy Versus Observation Alone After Radical Prostatectomy in High-Risk Prostate Cancer: A Meta Analysis
by Walaa Borhan and Emad Rajih
J. Clin. Med. 2026, 15(8), 3149; https://doi.org/10.3390/jcm15083149 - 20 Apr 2026
Viewed by 597
Abstract
Background/Objectives: High-risk prostate cancer patients undergoing radical prostatectomy remain at significant risk of biochemical recurrence and metastasis. Immediate adjuvant external beam radiotherapy (EBRT) has been proposed to improve outcomes, but its role compared to observation remains debated due to potential [...] Read more.
Background/Objectives: High-risk prostate cancer patients undergoing radical prostatectomy remain at significant risk of biochemical recurrence and metastasis. Immediate adjuvant external beam radiotherapy (EBRT) has been proposed to improve outcomes, but its role compared to observation remains debated due to potential toxicity and uncertain overall survival benefit. To evaluate the efficacy and safety of immediate adjuvant EBRT versus observation following radical prostatectomy in men with high-risk prostate cancer. Methods: A meta-analysis was conducted according to PRISMA guidelines. We sought to include both randomized controlled trials (RCTs) and observational studies published between 2005 and 2025; however, no observational studies meeting the predefined criteria were identified. Therefore, only RCTs comparing immediate adjuvant EBRT with observation in patients with adverse pathological features and undetectable postoperative PSA were included. Primary outcomes were biochemical recurrence-free survival (BCR-FS), metastasis-free survival (MFS), and overall survival (OS). Secondary outcomes included toxicity and quality of life (QoL). Data were pooled using Mantel–Haenszel and inverse variance methods, and heterogeneity was assessed with I2 statistics. Results: Four RCTs (n = 1987) met the inclusion criteria. Adjuvant EBRT significantly improved progression-free survival (PFS) (HR = 0.38; 95% CI: 0.20–0.74; p = 0.004) and metastasis-free survival (HR = 0.70; 95% CI: 0.54–0.92; p = 0.01). However, OS benefit was not statistically significant (HR = 0.88; 95% CI: 0.59–1.32; p = 0.55). Heterogeneity was substantial for some outcomes (I2 up to 71%). Adjuvant EBRT was associated with higher genitourinary and gastrointestinal toxicity compared to observation. Conclusions: Immediate adjuvant EBRT after radical prostatectomy improves PFS and MFS in high-risk prostate cancer but does not confer a clear OS advantage. Treatment decisions should be individualized, balancing disease-control benefits against toxicity risks. Observation with early salvage RT remains a reasonable alternative in selected patients. Full article
(This article belongs to the Special Issue Urologic Neoplasms: Recent Advances and Future Perspectives)
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17 pages, 460 KB  
Review
Nerve-Sparing in High-Risk Prostate Cancer: Advantages and Pitfalls of Current Strategies and Technologies
by Daniele Robesti, Pierluigi Russo, Giuseppe Fallara, Fernando Blank, Massimo Valerio, Ashutosh K. Tewari, Francesco Montorsi, Guillaume Ploussard, Nilesh Patil and Alberto Martini
Cancers 2026, 18(6), 945; https://doi.org/10.3390/cancers18060945 - 13 Mar 2026
Viewed by 1030
Abstract
Background and Objective: Positive surgical margins (PSMs) remain a major challenge during radical prostatectomy, particularly in patients with high-risk prostate cancer (HR-PCa), where extracapsular extension, multifocal disease, and aggressive tumor biology substantially increase the likelihood of incomplete resection. In this setting, PSMs [...] Read more.
Background and Objective: Positive surgical margins (PSMs) remain a major challenge during radical prostatectomy, particularly in patients with high-risk prostate cancer (HR-PCa), where extracapsular extension, multifocal disease, and aggressive tumor biology substantially increase the likelihood of incomplete resection. In this setting, PSMs are strongly associated with early biochemical recurrence and frequently prompt adjuvant or salvage treatments, potentially exposing patients to overtreatment and added morbidity. Materials and Methods: To review and critically appraise established and emerging intraoperative technologies for surgical margin assessment during radical prostatectomy, with a specific focus on their potential role and relevance in patients with HR-PCa. Evidence Acquisition: A non-systematic literature review was performed using Pubmed, MEDLINE, Web of Science, and Google Scholar, focusing on preoperative, intraoperative ex vivo, and intraoperative in vivo technologies for margin assessment. Emphasis was placed on techniques with potential applicability to HR-PCa, where real-time intraoperative decision-making is particularly consequential. Evidence Synthesis: Preoperative tools, including multiparametric MRI, PSMA-PET imaging, and predictive nomograms, aid surgical planning but show limited sensitivity for microscopic extracapsular extension, especially in high-risk disease. Intraoperative frozen section analysis reduces positive surgical margin rates while enabling selective nerve-sparing (defined as a side-specific, risk-adapted preservation strategy); however, its widespread adoption is constrained by substantial logistical and resource requirements, and robust oncological outcome data in high-risk populations remain limited. Novel ex vivo approaches, such as fluorescence confocal microscopy and specimen-based PSMA PET/CT imaging, offer rapid whole-gland or targeted margin assessment with reduced dependency on dedicated pathology workflows. In parallel, emerging in vivo technologies, particularly PSMA-targeted near-infrared-fluorescence-guided surgery, enable real-time detection of residual tumor and facilitate selective re-resection, representing a biology-driven approach that may be especially suited to HR-PCa. Conclusions: In high-risk prostate cancer, intraoperative margin assessment technologies may extend beyond functional preservation and play a central role in optimizing oncological radicality and multimodal treatment sequencing. While NeuroSAFE remains the reference standard, PSMA-based ex vivo and in vivo technologies are particularly promising in HR-PCa due to their ability to integrate tumor biology into surgical decision-making. Prospective studies focusing on high-risk-specific oncological and patient-reported outcomes are needed before widespread clinical implementation. Full article
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13 pages, 3625 KB  
Article
Reirradiation of Local Recurrences of Prostate Cancer: PROSTARE (PROstate Cancer STereotActic REirradiation) Early Safety Analysis of a Phase 2 Study with a Limited Cohort
by Wojciech Majewski, Aleksandra Napieralska, Marcin Miszczyk, Anna Misiorowska-Gołosz, Marcela Krzempek, Małgorzata Stąpór-Fudzińska, Justyna Rembak-Szynkiewicz and Jerzy Wydmański
Cancers 2026, 18(5), 848; https://doi.org/10.3390/cancers18050848 - 6 Mar 2026
Viewed by 878
Abstract
Objective: This study aims to report the early safety outcomes from an ongoing single-center, non-randomized phase 2 trial on focal salvage stereotactic radiotherapy (s-SBRT) for local prostate cancer recurrence. Materials and methods: This prospective phase 2 study includes patients with local [...] Read more.
Objective: This study aims to report the early safety outcomes from an ongoing single-center, non-randomized phase 2 trial on focal salvage stereotactic radiotherapy (s-SBRT) for local prostate cancer recurrence. Materials and methods: This prospective phase 2 study includes patients with local recurrence after conventional or hypofractionated radiotherapy, ultrahypofractionated radiotherapy, or post-prostatectomy radiotherapy. The present analysis includes an initial subset of 21 out of 55 planned patients. All patients undergo mpMRI and PSMA-PET; biopsy is not required if imaging results are unambiguous. Focal s-SBRT is delivered to the recurrent lesion with a dose of 5 × 6.75 Gy. The primary endpoint is the rate of treatment-related CTCAE v5.0 grade ≥ 3 genitourinary (GU) or gastrointestinal (GI) toxicity. Secondary endpoints include early biochemical response (BR), defined as any PSA decline at 3 months. Results: With a median follow-up of 14 months (range: 4.5–25), one patient (4.8%) experienced both early and persistent late Grade 3 GU toxicity (bladder bleeding). Late Grade 2 GU and GI toxicities occurred in five (23.8%) and one (4.8%) patients, respectively. In exploratory univariable analysis, PTV volume 13 cc was identified as a marginal predictor for increased GU/GI radiation reactions (p < 0.1). Regarding efficacy, all 21 patients (100%) demonstrated an early biochemical response, with 15 patients (71.4%) achieving a PSA reduction of 50%. Conclusions: Focal s-SBRT demonstrates a favorable early safety profile and consistent biochemical response, supporting the preliminary safety of this ongoing study. Full article
(This article belongs to the Special Issue Radiation Therapy in Oncology)
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16 pages, 866 KB  
Article
Observational Management for Patients with Biochemical Recurrence Following Radical Prostatectomy, in the Absence of Detectable Disease on Restaging PSMA PET/CT Imaging
by Katelijne C. C. de Bie, Jan-Jaap J. Mellema, Dennie Meijer, Frederik R. Teunissen, Pim J. van Leeuwen, Daniela E. Oprea-Lager, Maarten L. Donswijk, Roderick C. N. van den Bergh and André N. Vis
Diagnostics 2026, 16(1), 32; https://doi.org/10.3390/diagnostics16010032 - 22 Dec 2025
Viewed by 1523
Abstract
Background/Objectives: In men with biochemical recurrence (BCR) after a radical prostatectomy (RP), salvage radiotherapy (SRT) is commonly recommended when imaging shows no metastases. The optimal management for patients with negative prostate-specific membrane antigen (PSMA) PET/CT findings at BCR remains uncertain. This study evaluated [...] Read more.
Background/Objectives: In men with biochemical recurrence (BCR) after a radical prostatectomy (RP), salvage radiotherapy (SRT) is commonly recommended when imaging shows no metastases. The optimal management for patients with negative prostate-specific membrane antigen (PSMA) PET/CT findings at BCR remains uncertain. This study evaluated outcomes of patients with BCR and negative PSMA PET/CT to identify who may be safely observed and who may benefit from early SRT. Methods: This retrospective multicentre cohort study included 89 patients with BCR and negative PSMA PET/CT findings after a RP (2015–2022) who were managed with observation. The exclusion criteria were PSA levels ≥ 0.8 ng/mL at baseline, prior SRT, or prior or ongoing hormonal therapy. Minimum follow-up was 3 years. Biochemical progression (PSA rise > 0.2 ng/mL above baseline or initiation of additional treatment) and radiological progression (local or metastatic disease on follow-up PSMA PET/CT) were assessed. Patients were stratified by EAU BCR-risk classification. Multivariable Cox regression included age, biochemical persistence (BCP) after a RP, pathological tumour stage (pT), pathological ISUP grade group (pISUP), node status (pN), margin status (R), and PSA doubling time (PSAdt). Results: The median age was 66 years (IQR 60–69) and the median PSA measurement at BCR was 0.2 ng/mL (IQR 0.2–0.3). A total of 27/89 (30%) patients were EAU BCR low-risk and 62/89 (70%) were high-risk. At three years, biochemical progression occurred in 14/27 (52%) low-risk vs. 51/62 (83%) high-risk patients, with time to progression being 21 vs. 12 months (p = 0.01). A pISUP grade group ≥ 4 (HR 2.04 [95%-CI 1.11–3.74]; p = 0.022) and a PSAdt < 20 months (HR 5.72 [95%-CI 2.41–13,56]; p < 0.01) independently predicted biochemical progression. Radiological progression occurred in 43/68 (66%) rescanned patients, with 32/43 (74%) showing disease outside the prostatic fossa. Conclusions: Nearly half of patients with BCR and negative PSMA PET/CT findings who were classified as EAU BCR low-risk remained progression-free at three years. These results support a risk-adapted approach, indicating that SRT may be deferred in selected low-risk patients. Full article
(This article belongs to the Special Issue Diagnostic Imaging in Urologic Disorders)
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13 pages, 594 KB  
Article
Outcome and Toxicity of Moderately Hypofractionated Post-Prostatectomy Radiotherapy: A Retrospective Study
by Rocchina Vilella, Fiorella D’Auria, Luciana Valvano, Barbara D’Andrea, Antonietta Montagna, Giovanni Castaldo, Ilaria Benevento, Angela Pia Solazzo, Manuela Botte, Grazia Lazzari, Teodora Statuto and Luciana Rago
Med. Sci. 2025, 13(4), 315; https://doi.org/10.3390/medsci13040315 - 12 Dec 2025
Cited by 1 | Viewed by 1016
Abstract
Background: In this study, we retrospectively analyzed clinical and toxicity outcomes of 67 prostate cancer (PCa) patients undergoing moderately hypofractionated radiotherapy (RT) after prostatectomy, with adjuvant or salvage intent. Methods: Irradiation was delivered by volumetric modulated arc therapy. The median follow-up [...] Read more.
Background: In this study, we retrospectively analyzed clinical and toxicity outcomes of 67 prostate cancer (PCa) patients undergoing moderately hypofractionated radiotherapy (RT) after prostatectomy, with adjuvant or salvage intent. Methods: Irradiation was delivered by volumetric modulated arc therapy. The median follow-up was 48 months. The 3- and 5-year biochemical relapse-free survival rates were 80% and 69%. The RT schedule consisted of a median total dose of 67.5 Gy with a median number of 25 fractions and a median fraction dose of 2.7 Gy to the prostate bed (PB) and 60% of patients simultaneously received whole pelvis irradiation (WP; fraction dose: 1.8 Gy, median total dose of 46.8 Gy). Results: The rate of acute toxicity was 54% for gastrointestinal (GI) and 36% for genitourinary (GU). No grade 3 acute toxicity was observed. Late toxicity was as follows: G1, G2, and G3 GI events in 25.5%, 3.6%, and 1.8% of the cases, respectively; G1, G2, and G3 GU events in 37.1%, 11.1%, and 7.4%, respectively. The toxicity-free survival (TFS) curves showed a different trend for acute and late toxicity. TFS was significantly associated with RT volume, except for acute GI toxicity. Specifically, the concomitant irradiation of PB and WP appeared to be a significant risk factor for late GI and GU toxicity (p = 0.029 and p = 0.012, respectively). Conclusions: At the 48-month median timepoint considered by our study, postoperative hypofractionated RT achieved promising results in terms of clinical outcomes with acceptable toxicity. Only the irradiated volume seems to be an important predictor for toxicity. Full article
(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)
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13 pages, 462 KB  
Review
Androgen Deprivation Therapy and Salvage Radiotherapy in Post-Radical Prostatectomy Biochemical Recurrence of Prostate Cancer: Current Evidence
by Paula Simon-Silva, Rocio del Castillo-Acuña, Jonathan Saavedra-Bejarano, Angeles Sanchez-Galvez, Antonio Lazo-Prados and Manuel Luis Blanco-Villar
Therapeutics 2025, 2(4), 16; https://doi.org/10.3390/therapeutics2040016 - 24 Sep 2025
Viewed by 5657
Abstract
Background/Objectives: Biochemical recurrence (BCR) occurs in 15–40% of men within five years of radical prostatectomy (RP), presenting a major challenge for long-term disease control. While salvage radiotherapy (SRT) and androgen deprivation therapy (ADT) are established post-RP interventions, the optimal integration of ADT [...] Read more.
Background/Objectives: Biochemical recurrence (BCR) occurs in 15–40% of men within five years of radical prostatectomy (RP), presenting a major challenge for long-term disease control. While salvage radiotherapy (SRT) and androgen deprivation therapy (ADT) are established post-RP interventions, the optimal integration of ADT with SRT—regarding timing, duration, and patient selection—remains unclear. We aimed to synthesize current clinical evidence on the efficacy and safety of combining ADT with SRT in patients experiencing BCR after RP. Methods: A narrative review was conducted, encompassing retrospective cohort studies, prospective randomized controlled trials (notably RTOG 9601, GETUG-AFU 16, RADICALS-HD, and SPPORT), and meta-analyses. Studies were selected based on relevance to combined ADT + SRT versus SRT alone, with outcomes of interest including biochemical progression-free survival (bPFS), metastasis-free survival (MFS), and overall survival (OS). Trial characteristics, ADT duration (short-term [4–6 months] versus long-term [≥24 months]), radiation scheme, and prostate specific antigen (PSA) thresholds at SRT initiation were extracted and compared. Results: The combination of ADT and SRT represents a promising strategy for the treatment of prostate cancer with BCR after RP. Current evidence supports its benefit in terms of disease control and survival, particularly in high-risk patients. Conclusions: Differences in inclusion criteria, ADT duration, and the heterogeneous quality of the available studies limit the formulation of universal recommendations. Well-designed prospective trials are needed to optimize therapeutic approaches and personalize treatment based on each patient’s risk profile. Full article
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14 pages, 248 KB  
Review
A Narrative Review of Treatment Options for Patients with Node-Positive Disease After Radical Prostatectomy: Current Evidence and Controversies
by Paolo Zaurito, Andrea Cosenza, Leonardo Quarta, Pietro Scilipoti, Mattia Longoni, Alfonso Santangelo, Alessandro Viti, Abigail Gettman, Francesco Barletta, Simone Scuderi, Vito Cucchiara, Armando Stabile, Francesco Montorsi, Alberto Briganti and Giorgio Gandaglia
Cancers 2025, 17(17), 2792; https://doi.org/10.3390/cancers17172792 - 27 Aug 2025
Cited by 2 | Viewed by 2279
Abstract
Purpose of Review: In approximately 10–15% of patients with prostate cancer (PCa), pathological lymph node metastases (pN1) are detected at radical prostatectomy (RP). The aim of this review is to describe the various treatment options for pN1 patients, with a focus on [...] Read more.
Purpose of Review: In approximately 10–15% of patients with prostate cancer (PCa), pathological lymph node metastases (pN1) are detected at radical prostatectomy (RP). The aim of this review is to describe the various treatment options for pN1 patients, with a focus on the most recent evidence reported in the literature. Evidence Synthesis: Due to the lack of prospective studies, several retrospective analyses were conducted according to different types of treatment. Most common strategies are represented by observation plus early salvage radiotherapy (RT) in case of PSA rising, adjuvant androgen deprivation therapy (ADT) alone, or adjuvant RT with or without ADT. Patients with pN1 disease and favorable disease characteristics (lower T stage and ISUP ≤ 2 at RP, <3 metastatic nodes at pathology) have a similar overall mortality risk if observed with PSA testing and eventual use of early salvage RT compared to patients directly treated with adjuvant RT with or without ADT. While conflicting results in terms of survival benefit were reported for the use of adjuvant ADT only, several studies showed an overall survival benefit in patients with pN1 disease treated with adjuvant RT when high-risk features (such as an increasing number of positive nodes, ISUP > 3) were detected at RP. Lastly, few studies analyzed the rate of adverse events following adjuvant ADT or RT, leaving the issue of treatment-related side effects still open. Summary: There is no clearly established standard of care for men with pN1 PCa, and disease characteristics should guide the choice of optimal post-operative management for these patients. Prospective data and clinical trials are clearly needed to define the most effective therapeutic strategy. Full article
15 pages, 587 KB  
Perspective
The Surgical Imprint: How Operative Trauma May Shape Radiation Tolerance After Prostatectomy
by Alessio G. Morganti, Gabriella Macchia, Filippo Mammini, Arina A. Zamfir, Milly Buwenge, Francesco Cellini, Lorenzo Bianchi, Riccardo Schiavina, Eugenio Brunocilla, Francesco Deodato and Savino Cilla
Cancers 2025, 17(16), 2685; https://doi.org/10.3390/cancers17162685 - 18 Aug 2025
Cited by 1 | Viewed by 1207
Abstract
In a recent multicenter analysis of 454 patients undergoing post-prostatectomy salvage radiotherapy, the open surgical approach, as opposed to minimally invasive surgery, emerged, unexpectedly, as the strongest predictor of acute gastrointestinal and genitourinary toxicity. Patients treated with laparoscopic or robotic prostatectomy experienced significantly [...] Read more.
In a recent multicenter analysis of 454 patients undergoing post-prostatectomy salvage radiotherapy, the open surgical approach, as opposed to minimally invasive surgery, emerged, unexpectedly, as the strongest predictor of acute gastrointestinal and genitourinary toxicity. Patients treated with laparoscopic or robotic prostatectomy experienced significantly lower rates of ≥grade 2 toxicity compared to those who had undergone open retropubic surgery, irrespective of total dose, treatment margins, or radiation delivery platform. This finding, which to our knowledge has not been previously reported, raises the hypothesis that surgical technique leaves a lasting biological imprint on irradiated tissues. Drawing on current knowledge in radiobiology, cytokine signaling, wound healing, and pelvic dosimetry, we explore potential mechanisms by which open surgery may create a more hypoxic, inflamed, and fibrotic microenvironment, thereby amplifying radiation damage. We further discuss how target volume margins may biologically interact with this tissue state to increase normal tissue exposure. This Perspective aims to provide a conceptual framework for understanding this unexpected association, highlighting its clinical relevance for individualizing margins, counselling high-risk patients, and designing future studies at the interface of surgery and radiation oncology. This paper does not introduce additional patients or statistical models; instead, it offers an in-depth clinical and mechanistic interpretation of previously published ICAROS findings. Full article
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14 pages, 1517 KB  
Article
Adverse Pathology After Radical Prostatectomy in Low- and Intermediate-Risk Prostate Cancer: A Propensity Score-Matched Analysis of Long-Term Health-Related Quality of Life
by Michael Chaloupka, Alexander Buchner, Marc Kidess, Benedikt Ebner, Yannic Volz, Nikolaos Pyrgidis, Stephan Timo Ledderose, Dirk-André Clevert, Julian Marcon, Philipp Weinhold, Christian G. Stief and Maria Apfelbeck
Diagnostics 2025, 15(15), 1969; https://doi.org/10.3390/diagnostics15151969 - 6 Aug 2025
Viewed by 1728
Abstract
Background and Objective: Adverse pathology to high-risk prostate cancer (PCa) after radical prostatectomy (upgrading) poses a threat to risk stratification and treatment planning. The impact on sexual function, urinary continence, and health-related quality of life (HRQOL) remains unclear. Methods: From 2004 [...] Read more.
Background and Objective: Adverse pathology to high-risk prostate cancer (PCa) after radical prostatectomy (upgrading) poses a threat to risk stratification and treatment planning. The impact on sexual function, urinary continence, and health-related quality of life (HRQOL) remains unclear. Methods: From 2004 to 2024, 4189 patients with preop low-/intermediate-risk PCa (Gleason score 6 or 7a, PSA ≤ 20 ng/mL) underwent radical prostatectomy at our department and were analyzed. Primary endpoint was HRQOL, erectile function, and urinary continence. Secondary endpoint was rate of salvage therapies and biochemical-free survival. Propensity score matching was performed using “operative time”, “robot-assisted surgery”, “blood loss”, “nerve-sparing surgery”, “age”, and “BMI” to represent comparable surgical approach. Median follow-up was 39 months (Interquartile-range (IQR) 15–60). Key Findings and Limitations: Patients who were upgraded to high-risk PCa showed a higher rate of postoperative radiotherapy and androgen-deprivation therapy compared to patients who were not upgraded (21% vs. 7%, p < 0.001; 9% vs. 3%, p = 0.002). Five-year biochemical recurrence-free survival was 68% in the upgrading group vs. 84% in the no-upgrading group (p < 0.001). We saw no difference in patient-reported HRQOL, urinary continence, or erectile function. Multivariable analysis showed that postoperative upgrading was a significant risk for not achieving good overall HRQOL (OR: 0.77, 95% CI: 0.61–0.97, p = 0.028) during the follow-up. Conclusions and Clinical Implications: Although postoperative upgrading to high-risk PCa leads to worse oncologic outcomes and higher salvage therapy rates, this study indicates that its impact on health-related quality of life is minimal and should not deter a cautious approach to radical prostatectomy. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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17 pages, 3010 KB  
Article
A Multicenter Machine Learning-Based Predictive Model of Acute Toxicity in Prostate Cancer Patients Undergoing Salvage Radiotherapy (ICAROS Study)
by Francesco Deodato, Gabriella Macchia, Patrick Duhanxhiu, Filippo Mammini, Letizia Cavallini, Maria Ntreta, Arina Alexandra Zamfir, Milly Buwenge, Francesco Cellini, Selena Ciabatti, Lorenzo Bianchi, Riccardo Schiavina, Eugenio Brunocilla, Elisa D’Angelo, Alessio Giuseppe Morganti and Savino Cilla
Cancers 2025, 17(13), 2142; https://doi.org/10.3390/cancers17132142 - 25 Jun 2025
Cited by 3 | Viewed by 1625
Abstract
Background: This study aimed to develop a predictive model for acute gastrointestinal (GI) and genitourinary (GU) toxicity in prostate cancer patients treated with salvage radiotherapy (SRT) post-prostatectomy, using machine learning techniques to identify key prognostic factors. Methods: A multicenter retrospective study analyzed 454 [...] Read more.
Background: This study aimed to develop a predictive model for acute gastrointestinal (GI) and genitourinary (GU) toxicity in prostate cancer patients treated with salvage radiotherapy (SRT) post-prostatectomy, using machine learning techniques to identify key prognostic factors. Methods: A multicenter retrospective study analyzed 454 patients treated with SRT from three Italian radiotherapy centers. Acute toxicity was assessed using Radiation Therapy Oncology Group criteria. Predictors of grade ≥ 2 toxicity were identified through Least Absolute Shrinkage and Selection Operator (LASSO) regression and Classification and Regression Tree (CART) modeling. The analyzed variables included surgical technique, clinical target volume (CTV) to planning target volume (PTV) margins, extent of lymphadenectomy, radiotherapy technique, and androgen-deprivation therapy (ADT). Results: No patients experienced grade ≥ 4 toxicity, and grade 3 toxicity was below 1% for both GI and GU events. The primary determinant of acute toxicity was the surgical technique. Open prostatectomy was associated with significantly higher grade ≥ 2 GI (41.8%) and GU (35.9%) toxicity compared to laparoscopic/robotic approaches (18.9% and 12.2%, respectively). A CTV-to-PTV margin ≥ 10 mm further increased toxicity, particularly when combined with extensive lymphadenectomy. SRT technique and ADT were additional predictors in some subgroups. Conclusions: SRT demonstrated excellent tolerability. Surgical technique, CTV-to-PTV margin, and treatment parameters were key predictors of toxicity. These findings emphasize the need for personalized treatment strategies integrating surgical and radiotherapy factors to minimize toxicity and optimize outcomes in prostate cancer patients. Full article
(This article belongs to the Special Issue Application of Artificial Intelligence in Radiation Oncology)
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12 pages, 810 KB  
Article
Stereotactic Salvage Radiotherapy for Macroscopic Prostate Bed Recurrence After Prostatectomy: STARR (NCT05455736): An Early Analysis from the STARR Trial
by Niccolo’ Bertini, Giulio Francolini, Vanessa Di Cataldo, Pietro Garlatti, Michele Aquilano, Giulio Frosini, Olga Ruggieri, Laura Masi, Raffaela Doro, Mauro Loi, Pierluigi Bonomo, Daniela Greto, Isacco Desideri, Gabriele Simontacchi, Icro Meattini, Riccardo Campi, Lorenzo Masieri and Lorenzo Livi
Cancers 2025, 17(13), 2092; https://doi.org/10.3390/cancers17132092 - 23 Jun 2025
Viewed by 1895
Abstract
Purpose/Objectives: Salvage radiotherapy (SRT) after a radical prostatectomy is a curative approach for patients with biochemical recurrence (BR). However, outcomes are often less favorable when imaging reveals macroscopic local recurrence. In such cases, dose escalation through stereotactic salvage radiotherapy (SSRT) may offer improved [...] Read more.
Purpose/Objectives: Salvage radiotherapy (SRT) after a radical prostatectomy is a curative approach for patients with biochemical recurrence (BR). However, outcomes are often less favorable when imaging reveals macroscopic local recurrence. In such cases, dose escalation through stereotactic salvage radiotherapy (SSRT) may offer improved disease control. The STARR trial (NCT05455736) is a prospective, multicenter study evaluating the efficacy and safety of SSRT in patients with macroscopic prostate bed recurrence. This interim analysis reports early findings from the initial patient cohort. Materials and Methods: Patients with BR (PSA > 0.2 ng/mL) post-prostatectomy and PET-confirmed macroscopic recurrence (PSMA or Choline PET, confirmed by MRI) were eligible. Treatment involved CyberKnife®-based SSRT delivering 35 Gy in five fractions to the visible lesion. Androgen deprivation therapy (ADT) was not permitted. Complete biochemical response (CBR) was defined as PSA < 0.2 ng/mL, and biochemical response (BR) as a ≥50% PSA reduction. Additional outcomes included biochemical, radiological, and ADT-free survival (bPFS, rPFS, aPFS). Results: As of analysis, 51 patients were enrolled, with a median follow-up of 16 months (95% CI: 16–22). CBR and BR were achieved in 45.1% and 80.4% of patients, respectively. Events affecting bPFS, rPFS, and aPFS occurred in 12, 5, and 6 patients, with median values not yet reached. Toxicity was minimal, with two cases each of acute grade 2 GI and GU events, and one late grade 2 GI event. No grade ≥ 3 toxicities were reported. Conclusion: Early data support SSRT as a safe and a promising option for macroscopic local recurrence, with encouraging response rates and minimal toxicity. Full article
(This article belongs to the Special Issue The Role of Robot‐Assisted Radical Prostatectomy in Prostate Cancer)
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10 pages, 961 KB  
Article
Biochemical Recurrence in High-Risk Localized Prostate Cancer: A Comparison of Laparoscopic Prostatectomy and External Radiotherapy
by Lubos Rybar, Patrik Hesko, Michal Miko, Peter Bujdak and Stefan Harsanyi
Medicina 2025, 61(5), 928; https://doi.org/10.3390/medicina61050928 - 20 May 2025
Viewed by 3525
Abstract
Background: This retrospective study evaluated and compared oncological outcomes in patients with localized prostate cancer treated either by laparoscopic radical prostatectomy (LRP) or by external beam radiotherapy (EBRT) combined with androgen deprivation therapy (ADT). The primary aim was to identify predictors of [...] Read more.
Background: This retrospective study evaluated and compared oncological outcomes in patients with localized prostate cancer treated either by laparoscopic radical prostatectomy (LRP) or by external beam radiotherapy (EBRT) combined with androgen deprivation therapy (ADT). The primary aim was to identify predictors of biochemical recurrence (BCR) and to assess recurrence-free survival. Subjects and methods: A total of 107 patients diagnosed with localized prostate cancer and treated between 2016 and 2023 were included in the analysis. Of these, 61 patients underwent LRP, and 46 patients received EBRT+ADT. The median follow-up period was 60 months for the LRP group (IQR 24–72) and 66 months for the EBRT group (IQR 49.5–72). Biochemical recurrence (BCR) was defined as a PSA level > 0.2 ng/mL after LRP or an increase > 2 ng/mL above nadir following EBRT. Kaplan–Meier survival curves, log-rank tests, Pearson’s chi-square, and Cox regression models were used to evaluate outcomes and identify predictors of recurrence, with significance set at p < 0.05. Results: Biochemical recurrence occurred in 21 (34.4%) of LRP patients and 10 (21.7%) of EBRT patients. The five-year BCR-free survival was 40 (65.6%) patients in the LRP group and 33 (71.7%) for EBRT, with a trend toward improved outcomes in the EBRT group that approached statistical significance (log-rank p = 0.089). Median time to recurrence was 30 months for LRP (IQR 12.75–60) and 48 months for EBRT (IQR 30–60). Predictive analysis revealed that in the LRP group, higher ISUP grade at biopsy (p = 0.001), advanced pathological stage (p < 0.001), positive surgical margins (p < 0.001), and intermediate initial PSA levels (10–20 ng/mL; p = 0.080) were associated with increased risk of BCR. No independent predictors of recurrence were identified in the EBRT group. Conclusions: Both LRP and EBRT+ADT provide effective cancer control with similar five-year BCR-free survival. However, LRP was associated with a higher recurrence rate, particularly among patients with intermediate-risk features such as iPSA 10–20 ng/mL, high ISUP grade, advanced pathological stage, or positive surgical margins. These findings highlight the need for risk-adapted follow-up and timely salvage treatment in high-risk LRP patients to improve long-term outcomes. Full article
(This article belongs to the Special Issue Urologic Oncology: Current Issues and Future Directions)
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16 pages, 265 KB  
Review
The Role of Robot-Assisted, Imaging-Guided Surgery in Prostate Cancer Patients
by Leonardo Quarta, Donato Cannoletta, Francesco Pellegrino, Francesco Barletta, Simone Scuderi, Elio Mazzone, Armando Stabile, Francesco Montorsi, Giorgio Gandaglia and Alberto Briganti
Cancers 2025, 17(9), 1401; https://doi.org/10.3390/cancers17091401 - 23 Apr 2025
Cited by 8 | Viewed by 2922
Abstract
Emerging imaging-guided technologies, such as prostate-specific membrane antigen radioguided surgery (PSMA-RGS) and augmented reality (AR), could enhance the precision and efficacy of robot-assisted prostate cancer (PCa) surgical approaches, maximizing the surgeons’ ability to remove all cancer sites and thus patients’ outcomes. Sentinel node [...] Read more.
Emerging imaging-guided technologies, such as prostate-specific membrane antigen radioguided surgery (PSMA-RGS) and augmented reality (AR), could enhance the precision and efficacy of robot-assisted prostate cancer (PCa) surgical approaches, maximizing the surgeons’ ability to remove all cancer sites and thus patients’ outcomes. Sentinel node biopsy (SNB) represents an imaging-guided technique that could enhance nodal staging accuracy by leveraging lymphatic mapping with tracers. PSMA-RGS uses radiolabeled tracers with the aim to improve intraoperative lymph node metastases (LNMs) detection. Several studies demonstrated its feasibility and safety, with promising accuracy in nodal staging during robot-assisted radical prostatectomy (RARP) and in recurrence setting during salvage lymph node dissection (sLND) in patients who experience biochemical recurrence (BCR) after primary treatment and have positive PSMA positron emission tomography (PET). Near-infrared PSMA tracers, such as OTL78 and IS-002, have shown potential in intraoperative fluorescence-guided surgery, improving positive surgical margins (PSMs) and LNMs identification. Finally, augmented reality (AR), which integrates preoperative imaging (e.g., multiparametric magnetic resonance imaging [mpMRI] of the prostate and computed tomography [CT]) onto the surgical field, can provide a real-time visualization of anatomical structures through the creation of three-dimensional (3D) models. These technologies may assist surgeons during intraoperative procedures, thus optimizing the balance between oncological control and functional outcomes. However, challenges remain in standardizing these tools and assessing their impact on long-term PCa control. Overall, these advancements represent a paradigm shift toward personalized and precise surgical approaches, emphasizing the integration of innovative strategies to improve outcomes of PCa patients. Full article
(This article belongs to the Special Issue The Role of Robot‐Assisted Radical Prostatectomy in Prostate Cancer)
15 pages, 2086 KB  
Case Report
Salvage Ultrasound-Guided Robot-Assisted Video-Endoscopic Inguinal Lymphadenectomy (RAVEIL) as a Metastasis-Directed Therapy (MDT) in Oligoprogressive Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Case Report and Review of the Literature
by Rafał B. Drobot, Marcin Lipa and Artur A. Antoniewicz
Curr. Oncol. 2025, 32(2), 115; https://doi.org/10.3390/curroncol32020115 - 18 Feb 2025
Viewed by 2702
Abstract
Background: Metastatic castration-resistant prostate cancer (mCRPC) remains challenging due to progression despite androgen deprivation therapy (ADT). Current treatments, including androgen receptor-targeted agents, chemotherapy, bone-targeted agents, and PARP inhibitors, extend survival but face challenges, such as resistance, adverse effects, and limited durability. Metastasis-directed [...] Read more.
Background: Metastatic castration-resistant prostate cancer (mCRPC) remains challenging due to progression despite androgen deprivation therapy (ADT). Current treatments, including androgen receptor-targeted agents, chemotherapy, bone-targeted agents, and PARP inhibitors, extend survival but face challenges, such as resistance, adverse effects, and limited durability. Metastasis-directed therapies (MDTs), such as stereotactic ablative radiotherapy (SABR), show promise in oligometastatic disease, but their role in oligoprogressive mCRPC is unclear. Salvage lymphadenectomy is rarely pursued due to invasiveness and limited data. This is the first report of robotic surgery as an MDT in this setting, demonstrating the potential of salvage robot-assisted video-endoscopic inguinal lymphadenectomy (RAVEIL) to manage oligoprogressive mCRPC and delay systemic progression. Methods: A 47-year-old male with metastatic hormone-sensitive prostate cancer (Gleason 10) underwent ADT, docetaxel chemotherapy, and radical retropubic prostatectomy with super-extended pelvic and retroperitoneal lymphadenectomy. Upon progression to oligoprogressive mCRPC, 68Ga-PSMA PET/CT detected a single metastatic inguinal lymph node. Salvage RAVEIL was performed using the da Vinci X™ Surgical System, guided by preoperative ultrasound mapping. Results: Histopathology confirmed metastasis in one of the eight excised lymph nodes. The patient achieved undetectable PSA levels and prolonged biochemical progression-free survival. Minor complications (lymphorrhea, cellulitis) resolved without sequelae. No further progression was observed for over 14 months. Conclusions: This case highlights RAVEIL as a viable MDT option for oligoprogressive mCRPC, potentially extending progression-free intervals while minimizing systemic treatment. Full article
(This article belongs to the Section Genitourinary Oncology)
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