Abstract
Background
Cytoreductive radical prostatectomy (CRP) may improved outcomes in men with low-volume metastatic hormone-sensitive prostate cancer (mHSPC), but its roles in high-volume disease remains controversial. Contemporary systemic therapy has enabled an increasing proportion of patients with high metastatic burden to achieve deep disease remission, creating a potential window to assess additional benefit from primary tumor resection. We aimed to investigate the feasibility and oncological outcomes of CRP in patients with mHSPC, including those with high-volume disease.
Methods
This multicentre, prospective study recruited patients with histologically diagnosed mHSPC from September, 2018 to October, 2023. All eligible patients received lifelong androgen deprivation therapy combined with novel androgen receptor pathway inhibitors and achieved a deep biochemical response (prostate-specific antigen [PSA] < 0.2 ng/ml). Patients either underwent CRP plus standard of care (SOC) or received SOC only. The primary endpoint was radiographic progression-free survival (rPFS). Secondary endpoints were overall survival (OS) and PSA progression-free survival (PSA-PFS). Multivariable Cox proportional hazards models, incorporating CRP as a time-dependent covariate, were used to evaluate associations with outcomes. Propensity score matching (PSM) was applied to balance baseline characteristics between groups.
Results
Of 126 patients enrolled, 62 underwent CRP + SOC and 64 received SOC. At a median follow-up of 46.7 months, patients in the CRP + SOC group demonstrated prolonged survival compared with those receiving SOC alone. Among 74 patients with high-volume diseases, CRP remained associated with significant longer rPFS (hazard ratio [HR] 0.36, p = 0.035), OS (HR 0.10, p = 0.006), and PSA-PFS (HR 0.32, p = 0.017). Multivariate Cox regression analysis identified CRP as an independent prognostic factor (all p < 0.05). After PSM, 30 well-balanced pairs were identified. In the matched cohort, CRP + SOC was consistently showed improved rPFS (HR 0.31, p = 0.036), OS (HR 0.22, p = 0.031), and PSA-PFS (HR 0.25, p = 0.009) compared with SOC alone.
Conclusions
CRP is feasible and associated with improved oncological outcomes in well-selected patients with mHSPC who achieved deep biochemical response to contemporary systemic therapy, including those with high-volume metastatic disease. However, these findings require validation in larger, prospective, randomized controlled trials.
Supplementary Information
The online version contains supplementary material available at https://doi.org/10.1186/s12916-026-04961-2.
Keywords: Cytoreductive radical prostatectomy, Metastatic hormone-sensitive prostate cancer, High-volume, Standard of care, Oncological outcomes
Background
Metastatic hormone-sensitive prostate cancer (mHSPC) remains an incurable disease [1]. Over the past decade, the therapeutic landscape has changed dramatically. The current standard of care (SOC) for systemic treatment in mHSPC consists of androgen deprivation therapy (ADT) plus novel androgen receptor pathway inhibitors (ARPIs), with or without docetaxel [2, 3]. Upfront administration of ARPIs has been associated with durable prostate-specific antigen (PSA) response, deeper metastatic remission, and improved oncological outcomes [4]. These advances have created an oncological “window of opportunity” to explore the benefit of treating the residual primary tumor to achieve further disease control [5].
Since 2018, the European Association of Urology (EAU) guidelines have included local radiotherapy as a reasonable treatment option in men with low-volume metastatic burden [6–9]. More recently, several prospective studies have suggested that cytoreductive radical prostatectomy (CRP) is a feasible, safe, and potentially effective therapy in selected patients with mHSPC [10–14]. However, the role of CRP in combination with contemporary SOC therapy remains poorly understood, particularly in men who presented with high-volume metastatic diseases.
In this study, we evaluated the feasibility and oncological outcomes of CRP in men with mHSPC who achieved a deep biochemical response to systemic therapy, including those with high metastatic burden, to investigate the clinical efficacy of cytoreductive surgery in this population.
Methods
Study design and participants
This multicentre, prospective, and controlled feasibility study enrolled patients diagnosed with de novo synchronous mHSPC from five tertiary hospitals in China between September 10, 2018 and October 5, 2023 (Fig. 1). Eligible men were 18–80 years old, had histologically confirmed prostate adenocarcinoma, and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1 score. Metastatic disease was confirmed by bone scintigraphy and/or PSMA PET/CT. Patients were considered candidates who achieved a deep biochemical response (PSA < 0.2 ng/ml), remission or stable osseous, lymph node, or visceral metastases, and no evidence of new lesions. Exclusion criteria included neuroendocrine or small-cell differentiation at biopsy, prior chemotherapy, or any previous local treatment of the primary tumor.
Fig. 1.
Consort flow diagram of patient enrollment. SOC standard of care, PSA prostate-specific antigen, CRP cytoreductive radical prostatectomy
This study was approved by the ethics committees of Peking University First Hospital (2018-R-177), the Second Affiliated Hospital of Tianjin Medical University (KY2019K002), and Beijing Friendship Hospital (2018-030). All procedures involving human participants were undertaken in accordance with the International Conference on Harmonisation for Good Clinical Practice guidance and the Declaration of Helsinki. Written informed consent was obtained from all participants.
All patients received contemporary SOC in accordance with the EAU guidelines, including lifelong ADT plus a novel-generation ARPI, with or without docetaxel. Patients were categorized into either the CRP + SOC group or the SOC group according to whether they underwent CRP. Treatment decisions were made on shared clinical judgement between physicians and patients after a detailed discussion of the probable benefits and adverse effects of each treatment option. CRP was considered only in carefully selected patients who had no symptoms related to metastatic lesions, were deemed fit for surgery following evaluation by urologist and anaesthesiologist, and had a resectable primary tumor. Operability was assessed using digital rectal examination and multiparametric MRI. CRP was performed using a non-nerve-sparing approach as previously described [15, 16], with or without pelvic lymph node dissection.
Patient characteristics
Clinicopathological characteristics, including age, PSA level at biopsy, biopsy International Society of Urological Pathology (ISUP) grade group, clinical stage, and number of metastases were collected. The TNM stage was determined according to the 7th edition of the American Joint Committee on Cancer (AJCC) staging system. Tumor burden was stratified as low- or high-volume based on the CHAARTED criteria, with high-volume disease defined as the presence of visceral metastasis and/or ≥ 4 bone metastases, including ≥ 1 outside vertebral column or pelvis [17]. For patients who underwent CRP, preoperative and postoperative parameters including operating time, estimated blood loss, blood transfusions, length of hospital stays, catheter maintenance period, complications (stratified according to the Clavien–Dindo classification system), and pathology of the surgical specimen were evaluated.
Follow-up
Patients were followed at 3-month intervals for the first two years and every 6 months thereafter. Follow-up examinations included PSA testing and clinical examination. Further radiological diagnosis was performed when clinically indicated, based on rising PSA, symptomatic progression, or physician discretion.
Propensity score matching
Propensity score matching (PSM) was performed using a 1:1 nearest-neighbour algorithm with a caliper width of 0.1 of the standard deviation of the logit of the propensity score. This approach yielded two comparable cohorts (CRP + SOC: n = 30; SOC: n = 30), effectively emulating a randomized trial design, minimizing residual confounding, and increasing the precision of estimated treatment effects. Adjustment variables included age, biopsy ISUP grade group, clinical T stage, clinical N stage, and metastatic burden. Standardized mean differences were calculated to confirm adequate covariate balance between the two groups.
Statistical analysis
The primary endpoint was radiographic progression-free survival (rPFS), defined as the time from diagnosis to first documented radiographic progression or death, whichever occurred first. Radiographic progression was evaluated according to Prostate Cancer Working Group 3 (PCWG3) criteria for bone lesions and the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for soft-tissue lesions. Secondary endpoints included overall survival (OS) and PSA progression-free survival (PSA-PFS). OS was defined as the time from diagnosis to death from any cause. PSA-PFS was defined as the time from diagnosis to the earliest PSA progression according to the PCWG3 criteria as a ≥ 25% increase and an absolute ≥ 2 ng/ml above the nadir, confirmed by a second measurement.
Statistical analyses were performed using SPSS version 26.0 (SPSS Inc, Chicago, IL, USA) and R version 4.2.2 (The R Project for Statistical Computing, Vienna, Austria). Continuous variables were presented as medians (interquartile ranges, IQRs) and categorical variables as frequencies (percentages). Baseline characteristics were compared using Student’s t test or the Mann–Whitney U test for continuous variables, and Pearson’s chi-square test or Fisher’s exact test for categorical variables. Survival curves were generated via the Kaplan‒Meier method, and differences were assessed with the log-rank tests. Multivariable Cox proportional hazards models, incorporating CRP as a time-dependent covariate, were used to investigate associations between variables and the risks of oncological outcomes. All statistical tests were two-sided, and p < 0.05. was considered statistically significant.
Results
Baseline characteristics of patients
Between September 10, 2018 and October 5, 2023, a total of 126 patients were enrolled, including 62 who underwent CRP + SOC and 64 received SOC alone. The median age was 68 years (IQR 61–72), and the median PSA at diagnosis were 80.0 ng/ml (IQR 26.7–179.9). The clinicopathological characteristics are summarized in Table 1. Patients treated with CRP + SOC were younger (p = 0.002), had lower PSA at diagnosis (p = 0.010), and fewer bone metastases (p = 0.011) than those receiving SOC, while other baseline characteristics and systemic treatment strategies were comparable between groups (all p > 0.05).
Table 1.
Baseline characteristics before and after propensity score matching
| Variables | Before PSM | After PSM | ||||
|---|---|---|---|---|---|---|
| CRP + SOC (n = 62) |
SOC alone (n = 64) |
p value | CRP + SOC (n = 30) |
SOC alone (n = 30) |
p value | |
| Age, years (IQR) | 64 (59–71) | 69 (64–73) | 0.002 | 67 (59–72) | 68 (58–72) | 0.129 |
| PSA at diagnosis, ng/ml (IQR) | 46.4 (24.6–125.3) | 100.0 (42.5–279.0) | 0.010 | 63.9 (29.4–112.5) | 73.1 (26.1–124.3) | 0.935 |
| Follow–up period, months (IQR) | 50.5 (33.1–68.0) | 45.4 (28.7–56.0) | 0.118 | 46.6 (32.2–60.9) | 47.9 (32.2–55.5) | 0.605 |
| Year of diagnosis, n (%) | 0.272 | 0.550 | ||||
| 2018 | 9 (14.5) | 3 (4.7) | 3 (10.0) | 1 (3.3) | ||
| 2019 | 8 (12.9) | 7 (10.9) | 5 (16.7) | 4 (13.3) | ||
| 2020 | 10 (16.1) | 14 (21.9) | 4 (13.3) | 6 (20.0) | ||
| 2021 | 9 (14.5) | 17 (26.6) | 4 (13.3) | 9 (30.0) | ||
| 2022 | 13 (21.0) | 11 (17.2) | 8 (26.7) | 5 (16.7) | ||
| 2023 | 13 (21.0) | 12 (18.8) | 6 (20.0) | 5 (16.7) | ||
| ECOG performance status, n (%) | 0.640 | 0.718 | ||||
| 0 | 55 (88.7) | 55 (85.9) | 26 (86.7) | 25 (83.3) | ||
| 1 | 7 (11.3) | 9 (14.1) | 4 (13.3) | 5 (16.7) | ||
| Biopsy ISUP grade group, n (%) | 0.149 | 0.818 | ||||
| 2 | 10 (16.1) | 3 (4.7) | 3 (10.0) | 2 (6.7) | ||
| 3 | 6 (9.7) | 4 (6.3) | 2 (6.7) | 1 (3.3) | ||
| 4 | 18 (29.0) | 23 (35.9) | 11 (36.7) | 14 (46.7) | ||
| 5 | 28 (45.2) | 34 (53.1) | 14 (46.7) | 13 (43.3) | ||
| Clinical T stage, n (%) | 0.416 | 0.429 | ||||
| ≤ T2c | 13 (21.0) | 13 (20.3) | 5 (16.7) | 7 (23.3) | ||
| T3a–T3b | 35 (56.5) | 30 (46.9) | 19 (63.3) | 14 (46.7) | ||
| T4 | 14 (22.6) | 21 (32.8) | 6 (20.0) | 9 (30.0) | ||
| Clinical N stage, n (%) | 0.594 | 0.592 | ||||
| N0 | 20 (32.3) | 19 (29.7) | 12 (40.0) | 10 (33.3) | ||
| N1 | 42 (67.7) | 44 (68.8) | 18 (60.0) | 20 (67.7) | ||
| Nx | 0 (0.0) | 1 (1.6) | 0 (0.0) | 0 (0.0) | ||
| Clinical M stage, n (%) | 0.372 | 0.815 | ||||
| M1a | 4 (6.5) | 1 (1.6) | 2 (6.7) | 1 (3.3) | ||
| M1b | 49 (79.0) | 53 (82.8) | 22 (73.3) | 22 (73.3) | ||
| M1c | 9 (14.5) | 10 (15.6) | 6 (20.0) | 7 (23.3) | ||
| PET used for initial staging, n (%) | 21 (33.9) | 20 (31.3) | 0.754 | 10 (33.3) | 9 (30.0) | 0.781 |
| Number of bone metastases, n (%) | 0.011 | 0.165 | ||||
| 1 | 17 (29.8) | 7 (11.5) | 5 (18.5) | 3 (10.7) | ||
| 2 | 8 (14.0) | 3 (4.9) | 3 (11.1) | 2 (7.1) | ||
| 3 | 7 (12.3) | 9 (14.8) | 1 (3.7) | 7 (25.0) | ||
| 4 | 5 (8.8) | 3 (4.9) | 5 (18.5) | 2 (7.1) | ||
| 5 | 1 (1.8) | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||
| ≥ 6 | 19 (33.3) | 39 (63.9) | 13 (48.1) | 14 (50.0) | ||
| Metastatic burden, n (%) | 0.002 | 1.000 | ||||
| Low | 34 (54.8) | 18 (28.1) | 11 (36.7) | 11 (36.7) | ||
| High | 28 (45.2) | 46 (71.9) | 19 (63.3) | 19 (63.3) | ||
| Antiandrogen agent, n (%) | 0.929 | 0.958 | ||||
| Abiraterone acetate | 30 (47.6) | 28 (43.8) | 15 (50.0) | 14 (46.7) | ||
| Enzalutamide | 4 (6.3) | 6 (9.4) | 2 (6.7) | 4 (13.3) | ||
| Apalutamide | 16 (25.4) | 15 (23.4) | 7 (23.3) | 6 (20.0) | ||
| Darolutamide | 12 (19.0) | 13 (20.3) | 5 (16.7) | 5 (16.7) | ||
| Rezvilutamide | 1 (1.6) | 2 (3.1) | 1 (3.3) | 1 (3.3) | ||
| PET used for follow-up, n (%) | 44 (71.0) | 41 (64.1) | 0.408 | 19 (63.3) | 18 (60.0) | 0.791 |
| Chemotherapy, n (%) | 14 (22.6) | 15 (23.4) | 0.909 | 6 (20.0) | 5 (16.7) | 0.739 |
| Metastasis-directed radiotherapy, n (%) | 12 (19.4) | 8 (12.5) | 0.292 | 5 (16.7) | 4 (13.3) | 0.718 |
PSM propensity score matching, CRP cytoreductive radical prostatectomy, SOC standard of care, PSA prostate-specific antigen, ISUP International Society of Urological Pathology, Metastatic burden metastatic disease as per CHAARTED definition “high’’ versus ‘‘low’’
Estimates were given as median (quartile 1, quartile 3) or frequency (percentage)
p Values were calculated using Wilcoxon rank-sum test for continuous and Fisher’s exact test for categorical variables
Histopathology and complications
Among CRP + SOC patients, 15 (24.2%) underwent laparoscopic and 47 (75.8%) robot-assisted RP. Median duration of preoperative ADT was 6.9 months (IQR 3.7–9.3), with a median PSA at surgery of 0.047 ng/ml (IQR 0.006–0.122). Histopathological analysis revealed that two patients (3.2%) achieved a complete pathological response (pT0). The median operative time was 113 min (IQR 88–138), estimated blood loss 50 ml (IQR 20–100), and postoperative hospitalization 4 days (IQR 3–6). No severe perioperative complications, abandoned surgical procedures, or blood transfusions were reported (Additional file 1: Table S1). Detailed surgical characteristics and morbidities are presented in Table 2.
Table 2.
Clinicopathological characteristics of 62 patients who underwent CRP
| Variables | |
|---|---|
| Age at CRP, years (IQR) | 65 (59–71) |
| PSA at CRP, ng/ml (IQR) | 0.047 (0.006–0.122) |
| Time from diagnosis to CRP, months (IQR) | 6.85 (3.73–9.29) |
| Prostate volume, ml (IQR) | 22 (14.9–29.0) |
| Surgical procedure, n (%) | |
| LSRP | 15 (24.2) |
| RARP | 47 (75.8) |
| Pelvic lymphadenectomy, n (%) | |
| None | 52 (83.9) |
| Limited | 3 (4.8) |
| Extended | 7 (11.3) |
| Surgical time, min (IQR) | 113 (88–138) |
| Estimated blood loss, ml (IQR) | 50 (20–100) |
| Blood transfusion, n (%) | 0 (0.0) |
| Postoperative hospitalization time, days (IQR) | 4 (3–6) |
| Time to catheter removal, days (IQR) | 14 (14–14) |
| Pathological T stage, n (%) | |
| ≤ T2c | 13 (21.0) |
| T3a–T3b | 41 (66.1) |
| T4 | 2 (3.2) |
| Tx | 6 (9.7) |
| Pathological N stage, n (%) | |
| N0 | 5 (8.1) |
| N1 | 5 (8.1) |
| Nx (without PLND) | 52 (83.9) |
| Positive surgical margins, n (%) | 11 (17.7) |
| Postoperative ISUP grade group, n (%) | |
| No residual cancer | 2 (3.2) |
| Residual cancer cannot be graded | 60 (96.8) |
| Number of lymph nodes removed (IQR) | 10 (7–18) |
| Number of positive lymph nodes (IQR) | 1 (1–2) |
| PSA at 6 wk after CRP, n (%) | |
| < 0.1 | 52 (83.9) |
| ≥ 0.1 and < 0.2 | 4 (6.5) |
| ≥ 0.2 | 6 (9.7) |
| Perioperative complications, n (%) | 1 (1.6) |
| Postoperative continence at 90 d, n (%) | |
| 0–1 pad (for security) | 53 (85.5) |
| 1–2 pads (mild incontinence) | 6 (9.7) |
| ≥ 3 pads (moderate/severe incontinence) | 3 (4.8) |
| Continent after 1 year, n (%) | 58 (93.5) |
CRP cytoreductive radical prostatectomy, PSA prostate-specific antigen, LSRP laparoscopic radical prostatectomy, RARP robot-assisted radical prostatectomy, ISUP International Society of Urological Pathology
Estimates were given as median (quartile 1, quartile 3) or frequency (percentage)
Entire cohort
The median follow-up was 46.7 months (IQR 30.0–59.2). Kaplan-Meier analyses showed significantly longer rPFS in the CRP + SOC group (hazard ratio [HR] 0.20, 95% confidence interval [CI] 0.09–0.42; p < 0.001), with median rPFS not reached versus 47.4 months in the SOC group (Fig. 2A and Additional file 1: Table S2). Four patients in the CRP + SOC group died, including two deaths due to prostate cancer, compared with 15 deaths in the SOC group, of which 14 were prostate cancer–related. OS was also improved in the CRP + SOC group (HR 0.22, 95% CI 0.09–0.54; p = 0.003; Fig. 2A). PSA progression occurred in eight patients in the CRP + SOC group and 27 patients in the SOC group. PSA-PFS was significantly longer with CRP (HR 0.22, 95% CI 0.11–0.42; p < 0.001; Fig. 2A). On multivariate Cox regression analyses, CRP was the only independent prognostic factor for rPFS (HR 0.22, 95% CI 0.08–0.63; p = 0.005, OS (HR 0.25, 95% CI 0.06–0.94; p = 0.041), and PSA-PFS (HR 0.22, 95% CI 0.09–0.55; p = 0.001) in the entire cohort (Additional file 1: Table S3-S5).
Fig. 2.
Kaplan-Meier estimates of rPFS (left), OS (middle), and PSA-PFS (right) in the entire cohort (A), the high-volume subgroup (B), and the matching cohort (C). CRP cytoreductive radical prostatectomy, SOC standard of care, rPFS radiographic progression-free survival, OS overall survival, PSA-PFS prostate specific antigen progression-free survival, PSM propensity score matching
High-volume subgroup
Among 74 patients with high-volume metastatic disease, 28 underwent CRP + SOC and 46 received SOC alone. As showed in Fig. 2B, CRP conferred significant improvements in rPFS (HR 0.36, 95% CI 0.15–0.85; p = 0.035), OS (HR 0.10, 95% CI 0.04–0.29; p = 0.006), and PSA-PFS (HR 0.32, 95% CI 0.15–0.72; p = 0.017). Multivariable Cox analysis identified CRP as the independent predictor (rPFS: HR 0.28, p = 0.040; OS: HR 0.09, p = 0.031; PSA-PFS: HR 0.31, p = 0.038) in the high-volume subgroup (Additional file 1: Table S3-S5).
PSM analysis
To further reduce potential confounding, PSM analysis yielded 30 patients per group with well-balanced baseline clinical and pathological characteristics (Table 1). In the matched cohort, four patients in the CRP + SOC group and 10 in the SOC group experienced radiographic progression. Kaplan–Meier analyses demonstrated prolonged rPFS with CRP (HR 0.31, 95% CI 0.11–0.89; p = 0.036; Fig. 2C). OS was also markedly improved (HR 0.22, 95% CI 0.06–0.76; p = 0.031; Fig. 2C), with two and eight deaths in the CRP + SOC and SOC group, respectively. PSA progression occurred in four patients in the CRP + SOC group versus 13 in the SOC group, resulting in significantly longer PSA-PFS (HR 0.25, 95% CI 0.10–0.66; p = 0.009; Fig. 2C).
Functional outcome
During the entire follow-up period, adverse events (AEs) of any grade was experienced by 30 of 62 patients (48.4%) in the CRP + SOC group and 28 of 64 (43.8%) in the SOC group. Severe AEs were reported by 13 of 62 patients (21.0%) undergoing CRP + SOC and 9 of 64 (14.1%) receiving SOC alone (Additional file 1: Table S6).
At 12 months after CRP, urinary continence was maintained with ≤ 1 pad/day in 58 patients (93.5%), while mild incontinence (1–2 pads/day) was observed in 2 patients (3.2%) and severe incontinence (> 2 pads/day) occurred in 2 patients (3.2%).
Discussion
This study reports oncological and functional outcomes of CRP in well-selected men with mHSPC who achieved a deep biochemical response to contemporary SOC therapy. We observed a significant prognostic benefit from addition of CRP to SOC in this population, including in patients with high-volume metastatic burden. To our knowledge, this is the first multicentre, prospective study to demonstrate the feasibility of combining contemporary systemic therapy with CRP in patients with high-tumor-burden mHSPC, compared with SOC alone. These findings support the rational role of CRP in the individualized management for carefully selected patients with mHSPC.
Treatment of the primary tumor in the metastatic setting may improve OS and alleviate local symptoms in several malignancies [18–20]. In prostate cancer, it has been hypothesized that cytoreduction enhances the efficacy of systemic treatment and controlling the primary tumor may delay metastatic progression [21]. Preclinical data further support the “premetastatic niche” hypothesis, whereby persistence of primary tumor propagates cancer cell dissemination and induces microenvironmental changes that facilitate metastatic colonization [22]. Moreover, highly active systemic therapies may drive tumor evolution toward resistant subclones, and cytoreduction of the primary tumor could mitigate this evolutionary pressure and restrict lineage crisis [23].
Although prostate radiotherapy combined with contemporary systemic therapy has been proposed as a local treatment option for patients with low-volume mHSPC, CRP remains an experimental approach [6–8]. Evidence for CRP, despite being highly promising in terms of oncologic outcomes, local control, and quality of life, has largely been shown in retrospective population-based series, which are limited by selection or confounding biases [24–27]. More recently, several prospective trials and cohort studies have provided more reliable data supporting the role of CRP in mHSPC [28]. The RAMPP randomized controlled trail further supports addition of CRP as local treatment to systemic therapy in oligometastatic prostate cancer [14]. However, there are no prospective studies have evaluated survival outcomes after CRP treatment in patients with high-volume metastatic disease, and only limited retrospective data are available to support this strategy [29]. Thus, the efficacy of cytoreductive surgery in this setting is still controversial [30]. In the present study, we specifically enrolled patients who achieved a deep PSA response (< 0.2 ng/ml) following systemic therapy. Within this highly-selected population, the addition of CRP significantly improved outcomes compared with SOC alone, even among patients with high-volume disease. Multivariable analysis further identified CRP as a significantly independent prognostic factor. In addition, our results suggested that CRP is a safe and feasible treatment option for patients with mHSPC, with acceptable rates of perioperative complications.
Urinary incontinence after cytoreductive interventions remains a key concern for both patients and clinicians. Despite over 20% of patients presenting with cT4 disease at baseline, the observed incontinence rate (6.5%) in our cohort was comparable to that of standard radical prostatectomy. These outcomes are in line with those reported in prior cytoreductive surgery trials, which range from 8.2% to 16.7% [10, 11].
Our study is not devoid of limitations. First, although prospectively designed, treatment allocation was not randomized. Cytoreductive surgery with its inherent morbidity should be an informed and shared decision between patients and treating physician after careful discussion of all possible advantages and disadvantages. Despite multivariate analysis identified CRP as the only significant prognostic factor, and propensity score-matched consistently demonstrated improved outcomes in the CRP group, these findings should be interpreted with caution due to the potential for selection bias. Second, comorbidities data were not systematically collected, which could influence prognosis. However, ECOG PS was comparable between the two groups, and the majority of deaths (16/19) observed in our cohort were prostate cancer-specific. Third, the relatively small sample size and limited follow-up duration may have influenced the survival outcomes observed. Fourth, systemic treatment protocols were not fully standardized among the entire cohort. However, the distribution of therapies administered was comparable between groups and generally consistent with contemporary EAU guidelines [31]. Finally, despite the distribution of imaging modalities did not differ significantly between the two groups, radiographic progression was assessed using non-uniform imaging techniques. Patients enrolled earlier underwent conventional imaging, whereas those enrolled later received PSMA PET/CT, which has a relatively higher sensitivity and may have influenced the detection of progression [32].
Conclusions
In summary, CRP is feasible and associated with improved oncological outcomes in patients with mHSPC who achieved deep biochemical response to contemporary systemic therapy, including those with high-volume metastatic disease. Nevertheless, the survival benefit observed in this well-selected population requires validation in larger, prospective, and randomized controlled trials in the future.
Supplementary Information
Below is the link to the electronic supplementary material.
Supplementary Material 1: Additional file 1. Table S1–S6. Table S1 – Perioperative complications for patients underwent CRP. Table S2 – Kaplan-Meier analyses. Table S3 – Multivariable Cox regression analyses for rPFS. Table S4 – Multivariable Cox regression analyses for OS. Table S5 – Multivariable Cox regression analyses for PSA-PFS. Table S6 – Adverse events.
Acknowledgements
Not applicable.
Abbreviations
- ADT
Androgen deprivation therapy
- AEs
Adverse events
- ARPIs
Androgen receptor pathway inhibitors
- CRP
Cytoreductive radical prostatectomy
- EAU
European Association of Urology
- ECOG PS
Eastern Cooperative Oncology Group performance status
- HR
Hazard ratio
- IQR
Interquartile range
- mHSPC
Metastatic hormone-sensitive prostate cancer
- OS
Overall survival
- PSA
Prostate-specific antigen
- PSA-PFS
Prostate-specific antigen progression-free survival
- PSM
Propensity score matching
- rPFS
Radiographic progression-free survival
- SOC
standard of care
Author contributions
LQZ and XSL designed the study. CH, HG, WZG, MRH, GJJ, RR, NZ, YT, and YJN collected the data. CH, HG, WZG, MRH and SMH analyzed and interpreted the data. YFY performed the histological examination. CH, HG, WZG, and LQZ critically drafted the manuscript. LQZ and XSL revised the manuscript. All authors read and approved the final manuscript.
Funding
This study was funded by National Natural Science Foundation of China (81872083, 81972379, and 82173216), China Postdoctoral Science Foundation (2024M750127), National High Level Hospital Clinical Research Funding (Interdisciplinary Research Project of Peking University First Hospital, 2024IR30), Peking University Medicine Sailing Program for Young Scholars’ Scientific & Technological Innovation (The Fundamental Research Funds for the Central Universities, BMU2025YFJHPY015), Wuxi “Taihu Talents Program” Medical and Health High-level Talents Project, Sanming Project of Shenzhen Health and Family Planning Commission (SZSM202011017 and SZSM202111007).
Data availability
Individual data will be made available following publication upon reasonable request to the corresponding author.
Declarations
Ethics approval and consent to participate
This study was approved by the ethics committees of Peking University First Hospital (2018-R-177), the Second Affiliated Hospital of Tianjin Medical University (KY2019K002), and Beijing Friendship Hospital (2018-030). Written informed consent was obtained from all participants.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Cong Huang, Heng Guo, Wenzhi Gao and Mingrui Huang contributed equally to this work.
Contributor Information
Xuesong Li, Email: pineneedle@sina.com.
Liqun Zhou, Email: zhoulqmail@sina.com.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplementary Material 1: Additional file 1. Table S1–S6. Table S1 – Perioperative complications for patients underwent CRP. Table S2 – Kaplan-Meier analyses. Table S3 – Multivariable Cox regression analyses for rPFS. Table S4 – Multivariable Cox regression analyses for OS. Table S5 – Multivariable Cox regression analyses for PSA-PFS. Table S6 – Adverse events.
Data Availability Statement
Individual data will be made available following publication upon reasonable request to the corresponding author.