Prostate cancer is one of the most common malignancies threatening men's health worldwide. With population aging and lifestyle changes, the incidence of prostate cancer in China has been steadily increasing in recent years. As an early-stage disease, localized prostate cancer generally has a favorable prognosis, with curative potential through comprehensive treatment primarily centered on local interventions such as surgery. Enhancing the diagnosis and treatment of localized prostate cancer is key to improving overall survival rates for prostate cancer patients. Looking back at 2024, what were the major research advances in this field? This review will summarize key developments in screening and diagnosis, neoadjuvant therapy, surgical treatment, and the management of biochemical recurrence after surgery.

01 Screening and Diagnosis

In recent years, the discussion around prostate cancer screening and diagnosis has focused on improving screening strategies to enhance diagnostic accuracy while avoiding overtreatment or undertreatment. In the era of systematic biopsies, many clinically insignificant low-risk (ISUP Grade 1) prostate cancers were detected, leading to unnecessary active surveillance, increasing the burden on healthcare resources, and causing psychological distress for patients.

GÖTEBORG-2 Study: Targeted Biopsy Reduces the Detection of Clinically Insignificant Prostate Cancer

GÖTEBORG-2 is a large-scale population-based screening study from Sweden designed to compare systematic biopsy with MRI-targeted biopsy. The study enrolled over 13,000 men aged 50-60, who were randomly assigned to a systematic biopsy group (where MRI-targeted biopsy was performed only if suspicious lesions were found) or an MRI-targeted biopsy group.

Previous findings published in The New England Journal of Medicine (NEJM) reported that after two years of follow-up, targeted biopsy reduced the risk of overdiagnosing low-risk tumors by half. In September 2024, NEJM published the four-year follow-up results, showing that in the first round of screening, compared with the systematic biopsy group, the MRI-targeted biopsy group had a 57% reduction in ISUP Grade 1 cancer detection (RR 0.43, P<0.001) and a 16% reduction in ISUP Grade 2 or higher cancers (RR 0.84).

Both updates from the GÖTEBORG-2 study indicate that MRI-negative patients can safely avoid biopsy, reducing the detection of clinically insignificant prostate cancer by more than half. Moreover, the risk of these patients developing high-grade disease during follow-up remained low.

STHLM3-MRI Study: Limited Effectiveness of Repeat MRI and PSA Screening

Findings from this study suggest that PSA and MRI-based prostate cancer screening every two years has limited effectiveness in detecting cancer during the second screening round. The detection rate for low-grade tumors remained low, and many individuals underwent unnecessary MRI scans. Future research should focus on refining screening strategies to optimize MRI resource utilization.

New Targeted Diagnostic Agents

Beyond traditional biomarkers such as PSA, prostate-specific membrane antigen (PSMA)-based functional imaging has already been integrated into prostate cancer diagnosis and monitoring. In 2024, Lancet Oncology published findings on another molecular imaging approach targeting gastrin-releasing peptide receptor (GRPR).

This single-center, single-arm Phase 2/3 clinical study from the U.S. evaluated the diagnostic performance of the GRPR-targeted radiotracer 68Ga-RM2 in patients with biochemical recurrence of prostate cancer who had no detectable lesions on conventional imaging. All participants underwent 68Ga-RM2 PET-MRI. The results showed that among 100 patients, 69% had positive lesions on 68Ga-RM2 PET-MRI, compared to only 40% on MRI alone (P<0.0001).

This study highlights the potential of GRPR as a novel diagnostic target for prostate cancer, demonstrating that 68Ga-RM2 PET-MRI provides higher diagnostic accuracy than MRI alone in patients with biochemical recurrence.

02 Neoadjuvant Therapy

There is currently no standard neoadjuvant therapy for prostate cancer. Research in this area has traditionally focused on neoadjuvant chemotherapy, androgen deprivation therapy (ADT), and radiotherapy. In recent years, new-generation androgen receptor pathway inhibitors (ARi) and PARP inhibitors have also been explored in neoadjuvant settings. However, these approaches have not significantly improved pathologic complete response (pCR) rates or minimal residual disease (MRD) rates. This raises the question of whether PSMA-targeted radionuclide therapy could further enhance neoadjuvant efficacy.

LuTectomy Study: Radioligand Therapy as a Neoadjuvant Approach for High-Risk Patients

The LuTectomy study is a single-center, single-arm, Phase 1/2 clinical trial designed to evaluate the dosimetry, safety, and efficacy of preoperative ¹⁷⁷Lu-PSMA-617 in high-risk localized prostate cancer.

Findings showed that in nine patients, PSA levels decreased by more than 50% following ¹⁷⁷Lu-PSMA-617. The most common treatment-related adverse events included Grade 1 fatigue (40%), nausea (35%), dry mouth (30%), and thrombocytopenia (20%). No Grade 3/4 toxicities or Clavien-Dindo Grade 3-5 complications were observed.

Due to the small sample size, the study’s conclusions remain preliminary. However, results suggest that in high-risk localized prostate cancer patients with PSMA expression, ¹⁷⁷Lu-PSMA-617 can deliver a high radiation dose with minimal toxicity while preserving surgical safety. Further studies are needed to determine its long-term benefits.

03 Surgical Treatment

Radical prostatectomy (RP) remains one of the primary curative treatment options for localized prostate cancer. In addition to surgery, radiotherapy and focal therapy are also key local treatment modalities. Recent discussions in the field have centered on whether active surveillance can replace surgery in certain low-risk patients and whether some carefully selected localized prostate cancer patients could benefit from radiotherapy or ablative techniques instead of RP.

SPCG-4 Study: RP Surgery Extends Survival Compared to Active Surveillance

The debate on whether early-stage, relatively low-risk prostate cancer can be managed with active surveillance instead of surgery remains unresolved. The ProtecT study, published in NEJM in 2023, reported 15-year follow-up results showing that radical treatment reduces the risk of disease progression compared to active surveillance. However, it did not demonstrate a significant reduction in prostate cancer-specific mortality.

In contrast, findings from the SPCG-4 study, published in NEJM in 2024 with 30 years of follow-up, presented a different perspective. The study revealed that radical prostatectomy reduced prostate cancer-specific mortality by 48% (RR 0.52) and all-cause mortality by 26% (RR 0.74), extending patient survival by an average of 2.2 years. It is important to note that these studies were conducted in different eras—when the SPCG-4 study was initiated, PSA screening was not yet widely implemented.

EAU Robotic Urology Group’s 20-Year Report on RARP

The debate surrounding radiotherapy, ablative therapies, and surgery must consider the trade-offs between treatment-related adverse effects and quality of life, allowing for personalized treatment selection. With the evolution of robot-assisted radical prostatectomy (RARP), the surgical approach has progressed from achieving three key treatment goals to five, improving both oncological control and functional outcomes.

The European Association of Urology (EAU) Robotic Urology Section conducted a retrospective analysis of 9,876 patients who underwent RARP between 2002 and 2012 at seven leading robotic urology centers in Europe and the U.S.

Key findings from this 15-year follow-up study:

• The cancer-specific survival (CSS) rate was 97.6% (97.2%-98.0%), and the overall survival (OS) rate was 85.5% (84.6%-86.4%).
• The 15-year CSS rates for low-risk, intermediate-risk, and high-risk patients were 99%, 98%, and 90%, respectively.
• Patients with pT3a disease had survival outcomes comparable to those with pT2 disease, whereas pT3b patients had significantly worse CSS (98.9% vs. 97.4% vs. 86.5%).

These multicenter retrospective data reinforce that RARP provides excellent survival outcomes for localized prostate cancer. Notably, low-risk and intermediate-risk patients had a higher likelihood of dying from non-prostate cancer causes, whereas high-risk patients had a significantly increased prostate cancer-specific mortality rate.

Retrospective Study: Cryoablation Failure Risk is Five Times Higher than RARP

Partial gland cryoablation (PGC) is often considered for elderly patients, those with poor surgical tolerance, or individuals prioritizing quality-of-life factors such as sexual function and urinary continence. However, there is limited high-quality evidence supporting its oncologic efficacy.

A single-center retrospective study from Weill Cornell Medicine, Department of Urology, compared oncological outcomes between PGC and RARP.

The study analyzed patients treated between January 2017 and December 2022, including:

• 98 patients in the PGC group
• 536 patients in the RARP group

Results showed:

• PGC had a significantly higher 2-year treatment failure rate (33% vs. 11%; P<0.001) and 4-year failure rate (43% vs. 14%; P<0.001).
• Cox regression analysis, adjusting for confounding factors, demonstrated that PGC was associated with a 4.6-fold higher risk of treatment failure (RR 4.6; 95% CI: 2.7-7.9; P<0.001).

This is the first retrospective study comparing PGC and RARP for cancer control. Findings indicate that PGC carries a nearly fivefold increased risk of failure within 2-4 years compared to RARP. Clinicians should clearly communicate the potential survival trade-offs associated with focal therapies when counseling patients.

04 Systemic Therapy for Biochemical Recurrence (BCR)

Biochemical recurrence (BCR) refers to a rise in PSA levels after radical treatment, without evidence of metastatic disease on imaging. It serves as a precursor to local recurrence or distant metastasis. Current international guidelines primarily recommend salvage radiotherapy to reduce the risk of recurrence and metastasis.

In recent years, next-generation androgen receptor inhibitors (ARi) have been introduced into the BCR setting, showing promising disease control while avoiding the radiation-induced toxicities of salvage radiotherapy.

Conclusion: Key Advances in Localized Prostate Cancer in 2024

Several breakthrough studies have advanced the diagnosis and treatment of localized prostate cancer in 2024:

1. More precise screening and diagnostic strategies have helped avoid both overtreatment and undertreatment.
2. Radical prostatectomy remains the cornerstone of curative treatment, with robot-assisted prostatectomy (RARP) showing excellent oncologic and functional outcomes.
3. Novel therapies such as ARi and radioligand therapy are expanding beyond late-stage treatment to preoperative and postoperative settings for localized disease in particular ,the introduction of ARi in the BCR stage has demonstrated potential in reducing recurrence and metastasis risk while avoiding radiation-related side effects.

As global research in prostate cancer continues to evolve, we look forward to more practice-changing discoveries that will enhance patient outcomes and contribute to the “Healthy China 2030” vision.

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Reference

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[2]. Hugosson J, Godtman RA, Wallstrom J, et al. Results after Four Years of Screening for Prostate Cancer with PSA and MRI. N Engl J Med. 2024;391(12):1083-1095. doi:10.1056/NEJMoa2406050

[3]. Duan H, Moradi F, Davidzon GA, et al. 68Ga-RM2 PET-MRI versus MRI alone for evaluation of patients with biochemical recurrence of prostate cancer: a single-centre, single-arm, phase 2/3 imaging trial. Lancet Oncol. 2024 Apr;25(4):501-508. doi: 10.1016/S1470-2045(24)00069-X.

[4]. Eapen RS, Buteau JP, Jackson P, et al. Administering [177Lu]Lu-PSMA-617 Prior to Radical Prostatectomy in Men with High-risk Localised Prostate Cancer (LuTectomy): A Single-centre, Single-arm, Phase 1/2 Study. Eur Urol. 2024 Mar;85(3):217-226. doi: 10.1016/j.eururo.2023.08.026.

[5]. Hamdy FC, Donovan JL, Lane JA, et al. Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer [published online ahead of print, 2023 Mar 11]. N Engl J Med. 2023;10.1056/NEJMoa2214122.doi:10.1056/NEJMoa2214122

[6]. Holmberg L, Garmo H, Andersson SO, et al. Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer. N Engl J Med. 2024;391(14):1362-1364. doi:10.1056/NEJMc2406108

[7]. Falagario UG, Knipper S, Pellegrino F, et al. Prostate Cancer-specific and All-cause Mortality After Robot-assisted Radical Prostatectomy: 20 Years’ Report from the European Association of Urology Robotic Urology Section Scientific Working Group. Eur Urol Oncol. 2024;7(4):705-712. doi:10.1016/j.euo.2023.08.005

[8]. Zhu A, Strasser MO, McClure TD, et al. Comparative Effectiveness of Partial Gland Cryoablation Versus Robotic Radical Prostatectomy for Cancer Control. Eur Urol Focus. 2024;10(5):843-850. doi:10.1016/j.euf.2024.04.008

• Professor, PhD Supervisor, Chief Physician
• Deputy Director, Urology Research Institute, Peking University
• Deputy Director, Tumor Translational Center, Peking University First Hospital
• Director,  Scientific Research, Peking University First Hospital
• National High-Level Talent Special Support Program (Ten-Thousand Talents Program)
• Leading Talent in Science and Technology Innovation,  Ministry of Science and Technology
• Outstanding Talent of the New Century, Ministry of Education
• Member, Tumor Group, Chinese Urological Association
• Deputy Leader, Translational Medicine Group, Chinese Urological Association (CUA)
• Member, First Committee on Rare Diseases, Chinese Medical Association
• Vice Chairman, Urology Branch, China Medical Promotion Association
• Head, Genetics and Rare Diseases Collaborative Group, Chinese Urological Association
• Member, Urological Oncology Committee, Chinese Medical Doctor Association
• Standing Member, Hereditary Tumor Committee, Chinese Anti-Cancer Association
• Executive Council Member, Rare Disease Branch, Chinese Research Hospital Association
• Standing Member, Oncology Committee, Beijing Medical Association
• Standing Member, Rare Disease Committee, Beijing Medical Association
• Advisory Member, International VHL Alliance

Professor Gong has been dedicated to the diagnosis, prevention, and treatment of rare and complex urological tumors. He has led over 20 major national projects, including key initiatives from the Ministry of Science and Technology and the National Natural Science Foundation. His research has been published in top-tier journals such as Cancer Discovery, PNAS, and Cancer Research, with over 100 SCI-indexed papers. He holds three granted patents, one of which has successfully been commercialized.