Outcomes of robotic prostatectomy with lymph node removal and early hormone therapy for locally advanced prostate cancer (pT3-4N0-1M0)

Abstract

Background

To investigate the efficacy and safety of robot-assisted radical prostatectomy (RARP) combined with extended pelvic lymph node dissection (ePLND) and immediate androgen deprivation therapy (ADT) for patients with locally advanced or lymph node metastatic prostate cancer (pT3-4N0-1M0).

Methods

We retrospectively analyzed clinical data from 40 patients with pT3-4N0-1M0 prostate cancer treated between April 2021 and April 2024. All patients had preoperative PSA > 20 ng/mL and received RARP + ePLND followed by immediate ADT. Postoperative follow-up ranged from 12 to 48 months, with records of surgical parameters, complications, urinary continence recovery, and biochemical recurrence.

Results

Operative time (207.4 ± 70.7 min), intraoperative blood loss (111.7 ± 127.8 mL), positive surgical margin rate (17.5%), and overall complication rate (10.0%) were all within acceptable ranges. Median postoperative hospitalization and catheter indwelling times were 7 and 22 days, respectively. Urinary continence recovery rates at 1, 3, 6, and 12 months were 62.5%, 85.0%, 90.0%, and 95.0%. During follow-up, one patient with positive margins (R1) and positive lymph nodes (N1) experienced biochemical recurrence at 3 years postoperatively, while one R1 but node-negative (N0) patient recurred at 4 years.

Conclusions

RARP + ePLND combined with immediate ADT is safe and feasible for treating locally advanced or lymph node metastatic prostate cancer (pT3-4N0-1M0), providing patients with favorable functional recovery and oncological outcomes.

Trial registration

Not applicable. (This study is a retrospective analysis and was not registered in a clinical trials registry.)

Background

Prostate cancer is one of the most common malignancies in men worldwide, with its incidence showing an increasing trend in recent years [1]. For patients with locally advanced (pT3-4) or lymph node metastatic (N1) prostate cancer, the choice of treatment strategy is particularly critical. Robot-assisted laparoscopic radical prostatectomy (RARP) has become an important surgical approach for localized prostate cancer due to its precision and minimally invasive advantages [2]. However, for pT3-4N0-1M0 patients, surgery alone has limited efficacy, often requiring combined extended lymph node dissection (ePLND) and adjuvant therapy to improve prognosis [3]. Androgen deprivation therapy (ADT) serves as the foundation of management for advanced prostate cancer, but its optimal timing and efficacy when combined with RARP require further investigation [4]. Currently, there are few studies worldwide on RARP combined with ePLND and immediate ADT for pT3-4N0-1M0 prostate cancer, and long-term follow-up data are lacking. This study retrospectively analyzed clinical data from 40 patients to evaluate the efficacy and safety of this combined treatment modality, providing references for clinical practice.

Methods

Patient selection

We retrospectively reviewed the medical records of 40 patients with pT3-4N0-1M0 prostate cancer who underwent RARP + ePLND combined with immediate ADT between April 2021 and April 2024. All patients had a preoperative PSA level > 20 ng/mL, with no distant metastasis detected by MRI or bone ECT. All patients received neoadjuvant endocrine therapy with “Goserelin 10.8 mg subcutaneous injection” three months before surgery, followed by immediate ADT with “Goserelin” postoperatively. All surgeries were performed by one fixed surgeon and two non-fixed assistants. Detailed clinicopathological data are shown in Table 1.

Table 1.

Characteristics of the patients

Total number of patients	40
Preoperative maximum PSA (mean ± SD, ng/mL)	46.9 ± 31.8
Biopsy Gleason score (n)
3 + 4	8
4 + 3	11
4 + 4	9
4 + 5	6
5 + 4	4
5 + 5	2
Clinical stage (n)
T1c	10
T2a	6
T2b	9
T2c	15
Operative time (mean ± SD, min)	207.4 ± 70.7
Blood loss (mean ± SD, mL)	111.7 ± 127.8
Nerve-sparing (n)	0
Postoperative Gleason score (n)
3 + 4	3
4 + 3	10
4 + 4	13
4 + 5	6
5 + 4	6
5 + 5	2
Pathological stage (n)
T3a	18
T3b	19
T4	3
Positive surgical margins (n, %)	7 (17.5)
Positive lymph nodes (n, %)	4 (10.0)
Postoperative hospital stays [median (range), days]	7 (7–14)
Postoperative catheterization duration [median (range), days]	22 (21–28)

PSA Prostate-specific antigen, SD Standard deviation

This study was approved by the Clinical Research Ethics Committee of Shenzhen Second People’s Hospital, and all patients provided informed consent.

RARP + ePLND and ADT

RARP + ePLND: Prior to extrafascial RARP, ePLND was performed via a transperitoneal approach. The lymph node dissection included the external iliac, internal iliac, obturator, and presacral lymph node groups. Following ePLND, the RARP procedure included: (1) Surgical exposure of the anterior bladder, prostate, and endopelvic fascia.; (2) Mobilization of the bilateral prostate, division of the puboprostatic ligaments, and ligation of the dorsal venous complex; (3) Transaction of bladder neck, isolation of seminal vesicles and vas deferens, and anterior dissection of Denonvilliers’ fascia; (4) Division of the urethra and prostatic apex; (5) Tension-free anastomosis of the bladder and urethral stumps [5, 6].

ADT: All patients began receiving Goserelin 10.8 mg (subcutaneous injection every 3 months) starting from the third postoperative month, continuing for 2 years (for node-negative, N0 patients) or longer (for node-positive, N1 patients) [3].

Evaluation and follow-up

Urinary continence was assessed using the International Continence Society (ICS) questionnaire. Recovery of continence was defined as not requiring pads [7]. Biochemical recurrence was characterized by two successive PSA measurements exceeding 0.2 ng/mL, obtained at minimum one-week intervals [8, 9].

All patients were followed up for at least 12 months postoperatively. For N1 patients, follow-up was conducted every 3 months; for N0 patients, follow-up was every 3 months for the first two years, every 6 months in the third year, and annually thereafter. Follow-up included clinical evaluation and testing of PSA, testosterone, hemoglobin, transaminase, and creatinine levels. Chest X-ray and bone ECT were performed annually postoperatively.

For patients with biochemical recurrence, PSMA PET-CT was performed to assess distant metastasis. Individualized treatment plans (e.g., secondary ADT or ADT + apalutamide) were formulated based on the patient’s condition.

Statistical analysis

Data were analyzed using SPSS 26.0 software. Continuous variables were expressed as mean ± standard deviation or median (range), while categorical variables were expressed as counts.

Results

The clinicopathological characteristics of the patients are shown in Table 1. The operative time for RARP + ePLND was 207.4 ± 70.7 min, and the intraoperative blood loss was 111.7 ± 127.8 mL. None of the patients underwent nerve-sparing surgery. Postoperative pathology revealed 7 cases (17.5%) with positive surgical margins and 4 cases (10.0%) with positive lymph nodes. The median postoperative hospital stay was 7 days, and the median duration of catheterization was 22 days.

Patient complications, urinary continence recovery, and biochemical recurrence are summarized in Table 2. Four patients (10.0%) experienced postoperative complications (including one case each of blood transfusion, urinary tract infection, urinary leakage, and bladder-urethral anastomotic stenosis). The urinary continence recovery rates at 1, 3, 6, and 12 months postoperatively were 62.5%, 85.0%, 90.0%, and 95.0%, respectively. During follow-up, one patient with positive margins (R1) and positive lymph nodes (N1) experienced biochemical recurrence in the third postoperative year, and one R1 but node-negative (N0) patient experienced biochemical recurrence in the fourth postoperative year. The overall biochemical recurrence rate was 5.0%. For these two patients with biochemical recurrence, PSMA PET-CT imaging demonstrated localized micro-metastatic disease. The treatment regimen was subsequently modified to ADT combined with apalutamide (240 mg PO QD). Currently, this therapeutic approach has achieved effective PSA control in both cases.

Table 2.

Complications, continence, and biochemical recurrence

	n (%)
Complications (n, %)	4 (10.0)
Blood transfusion	1 (2.5)
Urinary tract infection	1 (2.5)
Urinary leakage	1 (2.5)
Bladder-urethral anastomotic stricture	1 (2.5)
Postoperative continence recovery
1 month	25 (62.5)
3 months	34 (85.0)
6 months	36 (90.0)
12 months	38 (95.0)
Biochemical recurrence	2 (5.0)

Discussion

This retrospective study evaluated the efficacy and safety of RARP + ePLND combined with immediate ADT in 40 patients with pT3-4N0-1M0 prostate cancer. The results demonstrated favorable clinical outcomes in terms of surgical metrics, complication rates, urinary continence recovery, and biochemical recurrence, providing patients with excellent functional recovery and oncological prognosis.

Surgical efficacy and safety

The operative time (207.4 ± 70.7 min) and blood loss (111.7 ± 127.8 mL) in this study align with previous reports on RARP for high-risk prostate cancer [10]. The positive surgical margin rate (17.5%) is consistent with rates observed in other studies involving locally advanced disease, where margins are often challenging to achieve due to tumor extent [11]. The overall complication rate (10.0%) was comparable to large series reporting complications after RARP, further supporting the safety of this approach [12]. Notably, the absence of nerve-sparing procedures in our cohort reflects the high-risk nature of the included cases, as nerve preservation is often avoided in such scenarios to ensure oncological safety [13].

Urinary continence recovery

The continence recovery rates (62.5% at 1 month, 95.0% at 12 months) are consistent with contemporary RARP studies, highlighting the functional benefits of robotic assistance [14]. These outcomes are particularly encouraging given the extended lymph node dissection, which can theoretically impact urinary function due to disruption of pelvic anatomy. Recent studies suggest that meticulous preservation of the urethral sphincter complex during RARP contributes to such favorable continence outcomes [15].

Biochemical recurrence and oncological outcomes

The low biochemical recurrence rate (5.0%) in our study may reflect the combined benefits of ePLND and immediate ADT. In high-risk cases, extended lymphadenectomy enhances survival through eradication of micrometastases [16]. Immediate ADT, initiated postoperatively, likely contributed to the observed oncological control, as earlier initiation of systemic therapy is associated with better outcomes in node-positive disease [17]. The two recurrence cases occurred in patients with positive margins, underscoring the prognostic significance of margin status despite multimodal therapy [18].

Significance of extended lymph node dissection

The 10.0% lymph node positivity rate in our cohort aligns with prior studies of ePLND in high-risk prostate cancer [19]. Current guidelines recommend ePLND for patients with ≥ 5% risk of nodal involvement, as it provides accurate staging and potential therapeutic benefits [2]. Our findings support this recommendation, as no isolated nodal recurrences were observed during follow-up, suggesting effective local control.

Timing and efficacy of androgen deprivation therapy

Some studies suggest that for patients with locally advanced prostate cancer (e.g., T3-T4) or those facing technically challenging surgeries, short-term (3–6 months) neoadjuvant hormonal therapy (NHT) may help reduce prostate volume and downstage the tumor, thereby lowering surgical difficulty [20]. Meanwhile, the immediate initiation of ADT postoperatively in our protocol also follows emerging evidence that early systemic therapy improves outcomes in high-risk localized or node-positive disease [21]. The Goserelin-based regimen used here is well-established, with studies demonstrating its efficacy in delaying progression when combined with surgery [3]. However, the optimal duration of ADT remains debated, particularly for node-negative patients [22].

Study limitations and future directions

Given that this study employed a descriptive retrospective design with a limited sample size and lacked a control group, which constrained the statistical power and generalizability of the findings, these encouraging results should be interpreted with caution. Larger-scale studies with longer follow-up periods are still needed to validate these outcomes. Furthermore, this study also has the following limitations. Firstly, the assessment of postoperative urinary continence relied solely on the ICS questionnaire rather than more robust PROMs (e.g., EPIC-26). Secondly, since nerve-sparing techniques were not performed during the radical prostatectomy, sexual function assessment was not conducted. Besides, the impact of novel imaging (e.g., PSMA PET-CT) on patient selection and recurrence detection warrants further investigation [23]. Future research should also explore personalized approaches to ADT duration based on molecular risk stratification [24].

Conclusions

In conclusion, RARP + ePLND combined with immediate ADT is a safe and feasible treatment for locally advanced or node-positive prostate cancer (pT3-4N0-1M0), offering patients excellent functional recovery and oncological prognosis.

Abbreviations

RARP

Robot-assisted radical prostatectomy

ePLND

Extended pelvic lymph node dissection

ADT

Androgen deprivation therapy

PSA

Prostate-specific antigen

SD

Standard deviation

ICS

International Continence Society

PSMA

Prostate-specific membrane antigen

PET-CT

Positron emission tomography–computed tomography

NHT

Neoadjuvant hormonal therapy

PROMs

Patient-reported outcome measures

EPIC-26

Expanded Prostate Cancer Index Composite

Authors’ contributions

Yi Yang designed the study. Yi Yang, Jianli Cheng, Xinhui Liao, Jieqing Chen, Jianting Wu, Chenglong Wu, Yuhan Liu, Xiaohong Han, and Hongbing Mei collected and analyzed the data. Yi Yang drafted the manuscript. Hongbing Mei supervised the study and revised the manuscript. All authors read and approved the final manuscript.

Funding

This study was supported by the Sanming Project of Medicine in Shenzhen (No. SZSM202111007), Shenzhen Key Medical Discipline Construction Fund (No. SZXK020), and Shenzhen High-level Hospital Construction Fund.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

This retrospective study was approved by the Ethics Committee of Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University (Ethical approval number: 2025-343-01PJ). The need for informed consent was waived by the Ethics Committee due to the retrospective nature of the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.