In 2025, the field of prostate cancer management advanced steadily and decisively. From increasingly precise detection of localized lesions and function-preserving radical surgery, to intensified combination strategies for advanced metastatic disease, progress spanned the full continuum of care.In this comprehensive review, Prof. Dingwei Ye from Fudan University Shanghai Cancer Center offers a panoramic perspective on the most impactful clinical advances of 2025. What emerges is not merely a summary of trials, but a narrative of evolution—one that reflects the transformation of prostate cancer care into a truly lifecycle-based management strategy.
Localized Prostate Cancer
See More Clearly, Cut More Precisely, Choose More Wisely
For localized prostate cancer, the enduring challenge is balancing oncologic control with preservation of urinary and sexual function.
Diagnostic Precision: Micro-Ultrasound Enters the Mainstream
Transperineal biopsy remains the diagnostic gold standard. Over the past decade, imaging guidance has evolved from blind transrectal sampling to mpMRI–ultrasound fusion biopsy. In 2025, the OPTIMUM trial published in JAMA demonstrated that 29-MHz high-resolution micro-ultrasound (Micro-US)–guided biopsy was non-inferior to MRI fusion biopsy in detecting clinically significant prostate cancer (csPCa), with a difference of 3.52% (95% CI: –3.95% to 10.92%; P for non-inferiority < .001).
Micro-US provides real-time, high-resolution imaging that allows clearer visualization of tissue architecture. This represents a meaningful advance in achieving diagnostic precision at the earliest stage of care.
Surgical Refinement: NeuroSAFE Enables Real-Time Margin Guidance
In radical prostatectomy, preserving neurovascular bundles without compromising oncologic safety is a persistent challenge.
The prospective NeuroSAFE PROOF study demonstrated that intraoperative frozen-section margin assessment significantly improved functional outcomes:
- Improved erectile function at 12 months (IIEF-6 mean difference 3.92; P<0.0001)
- Improved urinary continence recovery (ICIQ mean difference –1.41; P=0.006)
This approach transforms surgery from empirical excision into pathology-guided precision resection.
High-Risk Localized Disease: Surgery Versus Radiotherapy
The long-standing debate between radical prostatectomy (RP) and radiotherapy (RT) continues. A simulation-based comparison of CALGB 90203 and RTOG 0521 presented at ASCO-GU 2025 suggested:
- Lower 8-year distant metastasis (DM) rate with RT overall (16% vs 23%; P=0.01)
- However, when RP was intensified with neoadjuvant docetaxel, ADT, and individualized postoperative therapy, differences narrowed (8-year DM: 21% vs 18%; P=0.26)
These findings reinforce that surgery in high-risk disease should not be delivered in isolation, but integrated within multimodal perioperative strategies.
Locally Advanced Disease and Biochemical Recurrence
Intensifying Radiotherapy and Advancing Hormonal Therapy
Radiotherapy Plus Systemic Intensification
The ENZARAD trial presented at ESMO 2025 evaluated adding enzalutamide to high-dose RT plus 2 years of ADT. While no overall metastasis-free survival (MFS) benefit was seen, selected subgroups (cN1 disease; pelvic RT recipients) showed potential benefit.
The ICECaP meta-analysis similarly suggested docetaxel added to RT + ADT may benefit very high-risk populations.
Gene Therapy: A Breakthrough Strategy
A phase III study of CAN-2409 (a replication-deficient adenovirus encoding HSV-tk) combined with valacyclovir and radiotherapy demonstrated:
- Significant improvement in prostate cancer–specific disease-free survival
- Higher 2-year pathological complete response (pCR) rate (80.4% vs 63.6%; P=0.0015)
This “suicide gene” approach opens a novel immunogenic pathway to enhance radiotherapy efficacy.
Biochemical Recurrence (BCR): From Observation to Early Intervention
The EMBARK study redefined management of high-risk BCR:
- Enzalutamide + ADT significantly improved metastasis-free survival
- 2025 OS analysis demonstrated >40% reduction in mortality risk (HR 0.597; P=0.0006)
The PRESTO trial similarly showed metastasis delay with apalutamide + ADT.
These findings shift next-generation hormonal therapy earlier in the disease course.
Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
Consolidating the Foundation, Refining Stratification, Advancing Triplet Therapy
Long-term follow-up of ARCHES and ENZAMET confirmed durable survival benefit with AR pathway inhibitors (ARPI) + ADT.
STOPCAP meta-analysis highlighted subgroup nuances:
- Greater OS benefit in younger patients
- Reduced abiraterone benefit in ≥75-year-old patients
- Stable benefit with enzalutamide across age groups
Triplet Intensification Strategies
HRR-mutated population: AMPLITUDE demonstrated niraparib + abiraterone + ADT reduced progression risk by 37% overall and significantly in BRCA2-mutated patients.
PTEN-deficient disease: CAPItello-281 showed capivasertib + abiraterone extended rPFS by 7.5 months.
High metastatic burden: PSMAddition showed 177Lu-PSMA-617 + ARPI + ADT reduced progression risk by 28%.
Oligometastatic setting: The LUNAR study explored 177Lu-PSMA plus SBRT without ADT, suggesting potential for delaying hormonal therapy in selected patients.
Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Multitargeted Counterattack
PARP Inhibitors
Final TALAPRO-2 analysis showed:
- OS benefit in HRR-mutated patients (45.2 vs 31.1 months; HR 0.622; P=0.0005)
- Favorable trend even in unselected population
Chinese participation was pivotal in this trial.
Radioligand Therapy
- ENZA-p: Adding 177Lu-PSMA-617 to enzalutamide extended median OS to 34 months.
- PEACE-3: Radium-223 + enzalutamide improved OS (42.3 vs 35.0 months; HR 0.69) with mandatory bone protection, mitigating fracture risk.
Novel Mechanisms
Bispecific T-cell engager (Pasritamig, KLK2×CD3): Phase I data showed PSA declines ≥50% in ~40% of patients.
EZH2 inhibition (Mevrometostat + enzalutamide): Demonstrated potential to overcome ARPI resistance, with improved response rates compared to monotherapy.
Conclusion
In 2025, the therapeutic arsenal for prostate cancer expanded dramatically. From NeuroSAFE-guided surgery to PARP inhibitors, AKT inhibitors, radioligand therapy, bispecific antibodies, and gene therapy, multidisciplinary integration has become central to care.
The future of prostate cancer management lies in precision stratification, intelligent combination strategies, and data-driven personalization—areas in which Chinese research continues to make meaningful contributions.
Prof. Dingwei Ye
