As 2024 concludes, the field of minimally invasive urological surgery has made remarkable strides, particularly in prostate cancer surgery, which often serves as a testing ground for innovative surgical approaches. With the advancement of precision medicine and multidisciplinary team (MDT) management, prostate cancer surgery now extends beyond simple tumor removal, incorporating preoperative diagnostic optimization, postoperative systemic therapy, and alternative local treatment approaches. In this annual review, Dr. Yao Zhu from Fudan University Shanghai Cancer Center summarizes the key developments in prostate cancer surgery over the past year.

Preoperative Diagnosis

Q1: Can Targeted Biopsies Reduce Overtreatment?

NEJM Göteborg-2 Study: MRI-Targeted Biopsy Reduces Detection of Clinically Insignificant Prostate Cancer by 57% Eur Urol Multicenter Study: The Overall Risk of Overtreatment with Targeted Biopsy is 2.7%

Accurate diagnosis is the cornerstone of optimal treatment decisions, and prostate biopsy remains the gold standard for prostate cancer diagnosis. However, the traditional systematic biopsy approach frequently detects low-risk (ISUP grade 1) prostate cancer, leading to unnecessary active surveillance, increased healthcare burden, and heightened patient anxiety. This has led researchers to explore ways to optimize biopsy strategies and reduce overtreatment.

The Göteborg-2 trial in Sweden aimed to evaluate the differences between systematic biopsy and MRI-targeted biopsy. This large-scale, population-based study included over 13,000 men aged 50-60, randomly assigned to either a systematic biopsy group (with MRI-targeted biopsy only for suspicious findings) or an MRI-targeted biopsy group.

Two years ago, NEJM published results showing that MRI-targeted biopsy halved the risk of overdiagnosing low-risk tumors, at the expense of slightly delaying the diagnosis of some intermediate-risk (ISUP ≥2) tumors. In September 2024, the four-year follow-up data confirmed these findings:

• MRI-targeted biopsy reduced the detection of ISUP 1 cancers by 57% (RR 0.43, P<0.001)
• MRI-targeted biopsy also slightly reduced the detection of ISUP 2+ cancers by 16% (RR 0.84)
• For every 1,000 men, MRI-targeted screening resulted in 51 fewer biopsies and 14 fewer ISUP 1 diagnoses
• However, 3 men had delayed detection of ISUP 2 or higher cancers

While MRI-targeted biopsy effectively reduces the detection of clinically insignificant prostate cancer, one concern remains: Could this approach lead to overestimation of cancer stage and grade, ultimately causing overtreatment?

To address this, a multicenter retrospective study in France analyzed 1,020 men diagnosed with Gleason grade group (GG) ≥2 cancers via MRI-targeted biopsy and compared their biopsy results with postoperative pathology. Only 2.7% of cases (28 patients) met the study’s definition of overtreatment risk, meaning their surgical pathology was downgraded to GG 1 or GG 2. This suggests that the risk of biopsy-induced overtreatment remains low.

Q2: How Can We Reduce Unnecessary Prostate Biopsies?

JAMA Netw Open STHLM3-MRI Study: Limited Benefit of Repeat Screening for Low-Grade Prostate Cancer J Clin Oncol SEPTA Study: Stockholm3 Outperforms PSA in Reducing Unnecessary Biopsies

The Göteborg-2 study demonstrated that one or more rounds of MRI-targeted biopsy could reduce ISUP 1 detection rates by 57-75%. But does repeat MRI-targeted biopsy provide additional benefit, or does it lead to unnecessary procedures?

The STHLM3-MRI study, conducted in Stockholm, Sweden, enrolled 12,743 men and randomized them into a standard biopsy group or an MRI-targeted biopsy group. Those in the MRI group who had negative findings were re-screened after 2-3 years.

Key findings from the 1,500 men who underwent repeat screening:

• 44.5% (667 men) had PSA levels ≥3 ng/mL
• 51 men (7.6%) had PI-RADS scores of 3, while 33 men (4.9%) had PI-RADS scores ≥4
• Among 383 men with initially negative MRI results, only 10 (2.6%) later developed PI-RADS scores ≥4

These findings suggest that although nearly half of men showed PSA elevations upon repeat screening, the majority did not have significant prostate cancer, and the likelihood of developing PI-RADS 4+ lesions remained low. This suggests that repeat MRI-targeted biopsy may not be necessary for all patients, and more refined criteria should be developed to identify patients who can safely forgo repeat biopsy.

Beyond MRI-based screening, researchers are also investigating biomarker-driven risk stratification. The Stockholm3 risk score is a multi-marker prediction model that incorporates:

• Clinical variables (age, family history, prior biopsy results)
• Biomarkers (PSA, KLK2, and others)

The SEPTA trial, a prospective multicenter study from the U.S., included 2,129 men undergoing biopsy and compared Stockholm3 with traditional PSA screening (PSA ≥4 ng/mL).

Key results:

• Stockholm3 had comparable sensitivity to PSA (relative sensitivity = 0.95) but was nearly three times more specific (relative specificity = 2.91)
• Stockholm3 could reduce unnecessary biopsies by 45% compared to PSA alone

These findings suggest that Stockholm3 could serve as a valuable tool in reducing unnecessary biopsies and refining prostate cancer risk stratification.

Advancements in prostate cancer preoperative diagnosis in 2024 focused on reducing unnecessary biopsies and minimizing overtreatment. MRI-targeted biopsy has proven effective in avoiding the detection of low-risk prostate cancer, and emerging biomarker-based risk assessment tools such as Stockholm3 are further refining screening strategies.

Moving forward, the integration of imaging, biomarkers, and AI-driven prediction models will likely revolutionize prostate cancer diagnosis, ensuring that high-risk cancers are identified early while avoiding unnecessary interventions for indolent cases.

Q3: Is Preventive Antibiotic Use Necessary for Prostate Biopsy?

The PREVENT study, published in European Urology, examined whether transperineal biopsy without prophylactic antibiotics differs from transrectal biopsy with prophylactic antibiotics in terms of infection rates and cancer detection. Prostate biopsy is mainly performed using two approaches: transrectal biopsy, which is commonly performed under local anesthesia and typically requires prophylactic antibiotics, and transperineal biopsy, which is usually conducted under general anesthesia and has been suggested as a safer option that may not require antibiotics.

The NORAPP study previously confirmed that transperineal prostate biopsy does not necessitate prophylactic antibiotic use. However, in clinical practice, transrectal biopsies still commonly involve antibiotic prophylaxis. The PREVENT trial aimed to determine whether transperineal biopsy without antibiotics and transrectal biopsy with antibiotics yield different outcomes in terms of infection rates and cancer detection. The study enrolled 658 men who were randomly assigned to either transperineal biopsy without prophylactic antibiotics or transrectal biopsy with antibiotic prophylaxis.

The results showed that no infections occurred in the transperineal group, whereas four cases (1.4%) of infection were recorded in the transrectal group. Additionally, the detection rates of clinically significant prostate cancer were comparable between the two groups, with 53% in the transperineal group and 50% in the transrectal group. Although patients in the transperineal group reported more perioperative pain, symptoms resolved within seven days. These findings further support that transperineal biopsy can be performed safely without the need for prophylactic antibiotics, without compromising cancer detection rates.

Preoperative Treatment

Q4: Can Novel Therapies Improve Preoperative Outcomes?

The LuTectomy study, published in European Urology, explored the efficacy of two cycles of 177Lu-PSMA-617 as a neoadjuvant treatment for high-risk localized prostate cancer. The study included 20 patients who received two cycles of 177Lu-PSMA-617 (5 GBq) before surgery. Results showed that 45% of patients experienced a PSA reduction of at least 50%, and no grade 3 or 4 adverse events were reported.

The FAST-PC study, presented at the 2024 ESMO conference, investigated a combination of androgen receptor signal inhibitors (ARSi) and PARP inhibitors (PARPi) as a neoadjuvant treatment for high-risk or very high-risk prostate cancer. In this single-arm phase 2 trial, 35 patients received six cycles of fluzoparib, abiraterone, prednisone, and medical castration therapy. Three patients achieved a pathological complete response (pCR), and 13 had minimal residual disease (MRD), resulting in a combined pCR/MRD rate of 45.7%. Furthermore, patients who achieved pCR/MRD had significantly longer biochemical progression-free survival (bPFS) compared to those who did not. Only six patients (17.1%) experienced grade 3 or higher treatment-related adverse events. These findings indicate that ARSi plus PARPi neoadjuvant therapy offers promising efficacy with manageable toxicity, warranting further large-scale trials.

Q5: What Are the Best Surrogate Endpoints for Neoadjuvant Therapy?

A meta-analysis of phase 2 trials, presented at ASCO 2024, examined the association between residual cancer burden (RCB) and metastasis-free survival (MFS) in patients receiving ARSi-based neoadjuvant therapy. While median survival for localized prostate cancer patients can exceed 15 years, making long-term outcomes difficult to measure, surrogate endpoints such as pCR and MRD have been widely used in other solid tumors like breast and lung cancer. The FDA has adopted metastasis-free survival (MFS) as an endpoint for evaluating neoadjuvant therapies in prostate cancer.

The meta-analysis found that the five-year MFS rate for the overall cohort was 83%. Stratification based on RCB scores showed distinct prognostic differences: patients with RCB-0 (complete response) had a 100% five-year MFS rate, while those with RCB-1 had a rate of 90%, RCB-2 had 82%, and RCB-3 had 63%. These findings suggest that RCB classification has significant prognostic value for MFS and could serve as a potential surrogate endpoint for future neoadjuvant therapy trials in prostate cancer.

The advancements in prostate cancer preoperative strategies in 2024 reflect significant progress in biopsy techniques, infection prevention, and neoadjuvant therapies. The evidence now strongly supports transperineal biopsy without prophylactic antibiotics as a safe and effective approach. Additionally, new treatment strategies, such as ARSi combined with PARPi and PSMA-targeted radioligand therapy, have demonstrated promising efficacy in high-risk prostate cancer, improving pathological response rates and prolonging biochemical progression-free survival. The validation of residual cancer burden (RCB) as a prognostic marker further enhances its potential as a surrogate endpoint for future clinical trials. These findings are shaping the future of prostate cancer diagnosis and treatment, optimizing surgical outcomes while minimizing unnecessary interventions.

Surgical Treatment

Q6: How to Choose the Best Local Treatment Approach?

The treatment of localized prostate cancer includes surgery, radiotherapy, and ablative techniques, which can serve as curative treatments for early-stage patients and as palliative cytoreductive therapies for advanced cases. For localized disease, in addition to tumor control, functional outcomes and quality of life are major concerns for patients.

A long-term follow-up study published in JAMA involving nearly 2,500 men with localized prostate cancer over 10 years examined the functional outcomes of different treatment approaches. Among patients with favorable prognoses, surgery resulted in more severe urinary incontinence (Prostate Cancer Composite Index score difference: -12.1) and sexual dysfunction (-7.2) compared to active surveillance. In patients with poorer prognoses, surgery also caused more severe urinary incontinence compared to external beam radiotherapy (EBRT) (-26.6), although there was no significant difference in sexual function (-1.4). However, EBRT was associated with greater impairment in bowel function (-4.9) and hormonal function (-4.9). Another study in JAMA Oncology analyzed data from nearly 30,000 prostate cancer patients over 12 years, showing that complications from surgery were twice as frequent as those from radiotherapy (124.26 vs. 62.15 per 1,000 person-years).

The debate over active surveillance versus definitive treatment gained attention in 2023 when NEJM published 15-year follow-up data from the ProtecT study. The study showed that while radical treatment reduced the risk of disease progression, it did not significantly lower prostate cancer-related mortality. However, the 2024 SPCG-4 study, also published in NEJM, presented contrasting findings. This 30-year follow-up trial demonstrated that radical prostatectomy reduced prostate cancer mortality risk by 48% (RR 0.52) and all-cause mortality risk by 26% (RR 0.74) compared to active surveillance, extending life expectancy by an average of 2.2 years. It is important to note that the two studies were conducted in different eras—SPCG-4 was initiated when PSA screening was not yet widely implemented.

While most of these studies are based on population-level observational data, European Urology reported findings from PACE-A, a direct randomized controlled trial comparing stereotactic body radiotherapy (SBRT) and radical prostatectomy (RP). In this trial, which enrolled 123 patients, SBRT resulted in fewer reports of urinary incontinence and sexual dysfunction, though bowel issues were slightly more common compared to RP. At the two-year mark, 6.5% of patients in the SBRT group used at least one pad daily for urinary incontinence, compared to 50% in the RP group. Bowel function scores were 87.5 for SBRT and 100 for RP, while sexual function scores were 62.5 for SBRT and 19 for RP.

A retrospective study in European Urology Focus compared partial gland cryoablation (PGC) with robotic-assisted radical prostatectomy (RARP) in terms of oncological control. The findings indicated that the two-year (33% vs. 11%, P<0.001) and four-year (43% vs. 14%, P<0.001) treatment failure rates were significantly higher in the PGC group compared to the RARP group. These results highlight the potential risks of focal therapies and reinforce the need for careful patient selection when considering non-surgical options.

Q7: How to Refine Patient Selection for Salvage Surgery?

While surgical treatment is not the only option for localized prostate cancer, it remains an important strategy for tumor control. Treatment selection should consider factors such as age, patient preferences, and potential side effects.

For patients who undergo non-surgical treatments such as ablative therapy or radiotherapy but later experience recurrence, salvage radical prostatectomy (sRP) is a potential treatment option. A multicenter retrospective study in European Urology Focus examined patients who experienced recurrence following radiotherapy or focal ablation and were classified as having Gleason Score (GS) 6 disease. The study divided patients into two groups: those with biopsy-confirmed GS 6 before undergoing sRP and those directly undergoing sRP. The results showed that in the biopsy-confirmed group, the 10-year metastasis rate, cancer-specific survival (CSS), and overall survival (OS) were 79%, 98%, and 89%, respectively, while the direct surgery group had rates of 100%, 100%, and 90%, respectively.

However, the study also revealed that 69% of patients in the biopsy-confirmed group experienced pathological upgrading after surgery, indicating that their disease was more aggressive than initially diagnosed. Furthermore, complications were significant—over 50% of patients experienced overall complications, more than 10% had severe complications, and over 15% developed severe urinary incontinence. These findings highlight the need for improved biopsy accuracy before salvage surgery and emphasize the importance of refining selection criteria for sRP to balance oncological benefits with potential morbidity.

Q8: Should Pelvic Lymph Node Dissection Be Performed in Prostate Cancer Surgery?

The 2024 European Association of Urology (EAU) guidelines removed the recommendation for pelvic lymph node dissection (PLND) in intermediate-risk patients but continued to recommend extended PLND (ePLND) for high-risk cases. This update aligns with recent evidence questioning the oncological benefits of ePLND while acknowledging its associated surgical risks.

A randomized controlled trial published in European Urology assessed the impact of ePLND on biochemical recurrence (BCR) and metastasis risk. The study found that while ePLND did not significantly reduce the risk of BCR, it did lead to a significant decrease in the risk of metastasis. These findings suggest that while ePLND may not influence early biochemical outcomes, it could play a role in preventing disease progression in selected high-risk patients.

Conversely, a meta-analysis published in International Journal of Surgery evaluated the outcomes of ePLND and concluded that it does not reduce the risk of BCR but increases the likelihood of perioperative complications. This reinforces the notion that ePLND should be reserved for carefully selected high-risk patients rather than performed routinely.

Overall, these findings indicate a shift in surgical strategy toward a more individualized approach to lymph node dissection, emphasizing oncological benefits while minimizing unnecessary surgical morbidity. As research continues, optimizing patient selection for ePLND will be crucial in refining prostate cancer surgical protocols.

Pelvic Lymph Node Dissection in Prostate Cancer: An Ongoing Debate

Pelvic lymph node dissection (PLND) in prostate cancer remains a topic of debate in urological surgery. The updated 2024 EAU guidelines removed the previous recommendation for performing PLND in intermediate-risk prostate cancer and now only advise PLND for high-risk patients, specifically recommending extended pelvic lymph node dissection (ePLND). This shift reflects a more selective and aggressive approach targeting high-risk cases.

A 2022 prospective study reported that among intermediate-risk patients undergoing PLND, only 2.9% had lymph node metastases. With the advancements in functional imaging techniques such as PSMA-PET/CT and the introduction of novel therapies at the biochemical recurrence (BCR) stage, alternative treatment strategies can now provide effective disease management for these patients.

There is still no consensus on whether standard PLND (sPLND) or ePLND is superior. A randomized controlled trial published in European Urology included 1,432 patients undergoing radical prostatectomy (RP), randomly assigning them to either limited PLND (removal of external iliac nodes) or extended PLND (removal of external iliac, obturator, and lower abdominal nodes). The study found no significant difference in BCR rates between the two groups (HR 1.05, P=0.3). However, ePLND showed a clear advantage in reducing metastatic disease risk, with a 18% reduction in any metastasis risk (HR 0.82, P=0.003) and a 25% reduction in distant metastasis risk (HR 0.75, P<0.001). These findings suggest that while ePLND does not necessarily lower BCR rates, it may have clinical significance in reducing the risk of disease progression.

However, the surgical complications associated with ePLND remain a concern for both clinicians and patients. A meta-analysis conducted by the team at Yantai Yuhuangding Hospital, affiliated with Qingdao University, compared ePLND and sPLND. Although the overall perioperative complication rate (RR 0.68, P=0.16) showed no significant difference between the two approaches, ePLND was associated with a markedly higher risk of lymphocele (RR 0.05, P<0.001) and urinary retention (RR 0.30, P=0.04). Moreover, ePLND did not significantly reduce the risk of BCR (RR 0.59, P=0.16). These findings underscore the need for careful patient selection when considering ePLND, balancing oncological benefits with the risk of postoperative complications.

Postoperative Treatment and Follow-Up

Q9: Should ADT Be Added to Postoperative Adjuvant Radiotherapy?

For intermediate- and high-risk prostate cancer, combining radical radiotherapy with androgen deprivation therapy (ADT) is known to enhance treatment efficacy. However, the benefit of adding ADT to postoperative adjuvant radiotherapy after radical prostatectomy (RP) remains unclear. The international multicenter randomized controlled trial RADICALS-HD aimed to address this question.

The study enrolled 1,480 patients from Europe and North America who had undergone RP. They were randomly assigned to receive either adjuvant radiotherapy alone or radiotherapy combined with six months of ADT (short-term ADT). The findings, published in The Lancet, revealed that short-term ADT did not improve metastasis-free survival (MFS) (HR 0.886, P=0.35). An additional analysis published in European Urology, which included patients receiving 24 months of ADT (long-term ADT), also found no MFS benefit (HR 0.948). These results suggest that adding ADT to postoperative radiotherapy does not provide significant survival advantages, challenging the conventional assumption that more aggressive hormonal therapy always leads to better outcomes.

Q10: MRI Surveillance After Focal Therapy

Focal therapies such as high-intensity focused ultrasound (HIFU) and cryoablation are increasingly used in prostate cancer, particularly for older patients or those with poor physical condition who cannot tolerate surgery or radiotherapy. However, there is currently no standardized or consensus-based protocol for post-treatment follow-up.

A panel of experts from the UK recently published the Transatlantic Recommendations on MRI Assessment of the Prostate After Focal Therapy (TARGET), a systematic review and international consensus statement outlining MRI guidelines for monitoring patients after focal therapy.

The recommendations emphasize that a standardized multiparametric MRI (mpMRI) protocol should be performed at 12 months post-treatment, adhering to PI-RADS 2.1 standards. Importantly, PI-RADS classification should not be used to assess recurrence within the ablation zone. Instead, the consensus proposes an alternative five-point scoring system that incorporates a primary dynamic contrast-enhanced (DCE) MRI sequence along with secondary diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI).

For the DCE sequence, the most concerning radiological feature is the presence of focal nodular early enhancement. The consensus also introduces a structured minimum reporting dataset and standardized reporting criteria to improve consistency and reliability in MRI interpretation following focal therapy. These guidelines aim to optimize post-treatment surveillance and enhance the accuracy of recurrence detection, ensuring better long-term disease management for prostate cancer patients.

Professor Zhu Yao is a chief physician, professor, and doctoral supervisor. He serves as the Deputy Director of Urology at Fudan University Shanghai Cancer Center. He is an editorial board member of Journal of Clinical Oncology and Prostate Cancer and Prostatic Diseases, where he is responsible for the MDT Perspective section. Additionally, he is a special consultant for the international urology podcast GUCast.

Professor Zhu is the Vice Chairman of the Youth Council of the Chinese Anti-Cancer Association and a board member of the Chinese Society of Clinical Oncology (CSCO), where he also serves as the Secretary-General of the Prostate Cancer Expert Committee.

Recognized as an outstanding academic leader, he has been selected for Shanghai’s Eastern Talent Program and holds titles such as Distinguished Professor (Eastern Scholar) and Outstanding Young Medical Talent under the Medical Star Program.

Annually, he performs over 460 radical prostatectomy procedures. As a principal investigator, he has led five research projects funded by the National Natural Science Foundation of China