Edited by: Sifeng Qu, Shandong University, China
Reviewed by: Yu Gao, Chinese PLA General Hospital, China; Ming Zong, Tongji University, China
*Correspondence: Hongqian Guo,
†These authors have contributed equally to this work
This article was submitted to Genitourinary Oncology, a section of the journal Frontiers in Oncology
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
To evaluate whether different preoperative hormonal therapy options affect postoperative continence and to identify risk/protective factors for continence recovery.
This is a retrospective analysis of several clinical trials (NCT04356430, NCT04869371, NCT04992026 and NCT05406999). Data from patients treated with hormonal therapy followed by RARP were collected and analyzed. Continence was defined as 0 pad/day or one safety pad.
The study included 230 patients with adequate information. The median time to continence recovery is 8 weeks. A total of 216 (93.9%) participants recovered to urinary continence within 12 months after surgery. 21 (9.1%) participants achieved immediate continence. 69, 85, 27 and 14 participants restored continence at 1 month, 1-3 month, 3-6 month, 6-12 month, accounting for 30.0%, 40.0%, 11.7% and 6.1% accordingly. No difference in continence recovery was found among different preoperative hormonal treatment options (
There is no difference in postoperative continence recovery among ADT, ADT+Docetaxel and ADT+Abiraterone preoperative treatment options. More advanced T stage indicated poor immediate continence recovery. Longer membranous urethral length was a promotional factor for both short-time and long-time continence recovery.
香京julia种子在线播放
Urinary incontinence following robot-assisted radical prostatectomy (RARP) is a significant and perhaps under-reported consequence that substantially decreases quality of life (QOL) (
Androgen deprivation therapy (ADT) has been the standard of care for over 50 years for metastatic PCa (
The effects of neoadjuvant hormonal therapy (NHT) for high risk PCa have been a popular concern for many years, though the oncological results remained controversial. As for functional aspects, researchers found that neoadjuvant hormonal therapy resulted in immediate impairment of vitality and sexual quality of life (
Several clinical trials at our center focusing on hormonal therapy followed by RARP for localized, locally advanced and metastatic PCa with hundreds of participants were under way, which happened to be suitable for the continence research. The purpose of this study was to evaluate whether different preoperative hormonal therapy options affect postoperative continence and to identify risk/protective factors for incontinence.
From December 2018 to May 2021, a total of 235 consecutive PCa patients from several phase 2 clinical trials (
According to the inclusion and exclusion criteria of the trials, patients with high risk localized (T1-2, N0, M0), locally advanced (T3-4, N0-1, M0) or oligometastatic PCa (no more than 5 metastatic lesions, no visceral metastasis) were all included in this analysis. All patients were diagnosed PCa with biopsy and went through careful examination including 1) Transrectal prostate ultrasonography; 2) prostate multi-parameter magnetic resonance imaging (mpMRI); 3) ECT plus CT scan of the whole abdomen or 68Ga-labeled molecular imaging with PET-targeted prostate-specific membrane antigen (68Ga-PSMA PET). Ultrasonography and mpMRI of prostate were carried out again after preoperative hormonal therapy to re-evaluated tumor conditions before surgery.
The duration of preoperative hormonal therapy is 6 months. Regarding medication modality, it can be divided into the following three cases 1) ADT, hypodermic injection of luteinizing hormone-releasing hormone analog (LHRHa) every 12 weeks; 2) ADT+Docetaxel, ADT with additional intravenous administration of docetaxel 75 mg/m2 body surface area every 3 weeks for 6 cycles; 3) ADT+Abiraterone, ADT with additional daily 1000 mg of abiraterone acetate orally.
The surgical technique was accomplished using da Vinci Surgical System. Robot-assisted radical prostatectomy (RARP) plus enlarged pelvic lymph node dissection (ePLND) within 2 weeks after the end of the therapy were performed by the same experienced surgeon (Dr. HG). Conventional robot-assisted radical prostatectomy (C-RARP), also known as anterior approach or Retzius-sparing robot-assisted radical prostatectomy (RS-RARP), also known as posterior approach was carefully chosen based on tumor conditions (tumor location, tumor stage and tumor lesion volume) and physical conditions (age and systematic complications). Other techniques, which could possibly improve continence were also applied including preserving maximal urethral length, dorsal venous complex ligation (DVCL) and posterior reconstruction (PR). Nerve sparing was not applied due to oncologic consideration.
Patients were discharged 4-6 days after surgery and the urinary catheter was removed on the 14th postoperative day. All patients were encouraged to practice Kegels exercise. The follow-up was continued until urinary continence, which was defined as 0 pad/day or one safety pad. Immediate continence was defined as continence within 7 days after the removal of catheter.
Patients’ data were extracted from their medical records. To be specific, basic information (age, BMI), information at initial diagnosis (PSA, TNM stage, biopsy Gleason, apex invasion or not), preoperative characteristics (membranous urethral length, PSA, prostate volume), preoperative therapy, surgery approach, post-surgery information (pathological T and N stage, surgical margin, post-surgery treatment) were collected. The membranous urethral length (MUL) (
The measurement of membranous urethral length (MUL). The membranous urethral length (MUL) was measured from the prostate apex to penile bulb on the preoperative sagittal plane of T2-weighted MRI.
Statistical analysis was realized by SPSS version 22.0 (IBM SPSS, Chicago, IL, USA). Continuous variables were presented as mean ± standard deviation (SD) or median and interquartile range (IQR). Categorical variables were reported as absolute frequency (percentage). One-way ANOVA (Analysis of Variance) or Kruskal-Wallis test was used to compare continuous variables between groups while Chi-square test or Fisher’s exact test was used to compare categorical variables between groups. Cox regression as well as logistic regression analysis were then sequentially applied for univariate and multivariate analysis. Age, BMI, initial T stage, apex invasion, preoperative PSA, preoperative volume, membranous urethral length, preoperative T, preoperative therapy, surgery approach and post-surgery ADT were included as evaluated variables. P < 0.05 was considered statistically significant.
Data from 235 consecutive PCa patients who received preoperative hormonal therapy followed by RARP were collected from December 2018 to May 2021. 5 patients were then excluded due to refusal of phone interview. The average age was 69.00 ± 6.90 years and the average BMI was 24.50 ± 2.94 kg/m2. Participants’ basic characteristics were summarized in
Summary of Characteristics.
Total | ADT (N=45) | ADT+Docetaxel (N=50) | ADT+Abiraterone (N=135) |
|
|
---|---|---|---|---|---|
Basic characteristic | |||||
Age, y, Mean ± SD | 69.00 ± 6.90 | 70.58 ± 5.89 | 68.26 ± 7.28 | 68.75 ± 6.59 | 0.237 |
BMI, kg/m2, Mean ± SD | 24.50 ± 2.94 | 23.76 ± 3.01 | 24.40 ± 2.88 | 24.78 ± 3.13 | 0.358 |
Characteristic at initial diagnosis | |||||
PSA, ng/ml, IQR | 40.17 (18.94-75.13) | 40.9 (13.70-56.99) | 57.26 (19.76-100) | 38.80 (19.46-69.76) | 0.103 |
T stage, n(%) | 0.756 | ||||
T2 | 47 (20.4) | 10 (22.2) | 10 (20.0) | 27 (20.0) | |
T3a | 54 (23.5) | 9 (20.0) | 14 (28.0) | 31 (23.0) | |
T3b | 88 (38.3) | 16 (35.6) | 21 (42.0) | 51 (37.8) | |
T4 | 41 (17.8) | 10 (22.2) | 5 (10.0) | 26 (19.3) | |
N stage, n(%) | <0.001** | ||||
N0 | 149 (64.8) | 40 (88.9) | 50 (100.0) | 59 (43.7) | |
N1 | 81 (35.2) | 5 (11.1) | 0 (0.0) | 76 (56.3) | |
M stage, n(%) | <0.001** | ||||
M0 | 204 (88.7) | 45 (100.0) | 50 (100.0) | 109 (80.7) | |
M1 | 26 (11.3) | 0 (0.0) | 0 (0.0) | 26 (19.3) | |
ISUP, n(%) | 0.845 | ||||
1 | 40 (17.4) | 10 (22.2) | 10 (20.0) | 20 (14.8) | |
2 | 5 (2.2) | 1 (2.2) | 2 (4.0) | 2 (1.5) | |
3 | 53 (23.0) | 10 (22.2) | 13 (26.0) | 30 (22.2) | |
4 | 106 (46.1) | 19 (42.2) | 20 (40.0) | 67 (49.6) | |
5 | 26 (11.3) | 5 (11.1) | 5 (10.0) | 16 (11.9) | |
Apex invasion, n(%) | 0.013* | ||||
Yes | 103 (44.8) | 23 (51.1) | 30 (60.0) | 50 (37.0) | |
No | 127 (55.2) | 22 (48.9) | 20 (40.0) | 85 (63.0) | |
Preoperative characteristic | |||||
PSA, ng/ml, IQR | 0.05 (0.01-0.19) | 0.12 (0.04-0.41) | 0.14 (0.03-0.53) | 0.03 (0.01-0.10) | <0.001** |
Prostate volume, ml, Mean ± SD | 17.50 (13.60-22.73) | 18.90 (14.50-25.25) | 18.00 (14.60-23.05) | 18.00 (14.63-23.05) | 0.286 |
Membranous urethral length, mm, Mean ± SD | 15.19 ± 1.87 | 14.77 ± 2.01 | 15.34 ± 2.03 | 15.28 ± 1.75 | 0.243 |
T stage, n(%) | 0.170 | ||||
T2 | 91 (39.6) | 20 (44.4) | 12 (24.0) | 59 (43.7) | |
T3a | 61 (26.5) | 14 (37.1) | 16 (32.0) | 31 (23.0) | |
T3b | 65 (28.3) | 8 (17.8) | 19 (38.0) | 38 (28.1) | |
T4 | 13 (5.7) | 3 (6.7) | 3 (6.0) | 7 (5.2) | |
Surgery | 0.768 | ||||
Anterior approach RARP | 149 (64.8) | 30 (66.7) | 34 (68.0) | 85 (63.0) | |
Posterior approach RARP | 81 (35.2) | 15 (33.3) | 16 (32.0) | 50 (37.0) | |
Post-surgery information | |||||
Pathological T | 0.302 | ||||
T0 | 12 (5.2) | 1 (2.2) | 3 (6.0) | 8 (5.9) | |
T2 | 103 (44.8) | 19 (42.2) | 20 (40.0) | 64 (47.4) | |
T3a | 61 (26.5) | 18 (40.0) | 13 (26.0) | 30 (22.2) | |
T3b | 54 (23.5) | 7 (15.6) | 14 (28.0) | 33 (24.4) | |
Margin | 0.918 | ||||
Positive | 46 (20.0) | 9 (20.0) | 9 (18.0) | 28 (20.7) | |
Negative | 184 (80.0) | 36 (80.0) | 41 (82.0) | 107 (79.3) | |
Pathological N stage | 0.352 | ||||
N0 | 177 (77.0) | 38 (84.4) | 39 (78.0) | 100 (74.1) | |
N1 | 53 (23.0) | 7 (15.6) | 11 (22.0) | 35 (25.9) | |
Post-surgery ADT, n (%) | 0.391 | ||||
Yes | 47 (20.4) | 6 (13.3) | 12 (24.0) | 29 (21.5) | |
No | 183 (79.6) | 39 (86.7) | 38 (76.0) | 106 (78.5) |
**p < 0.01
BMI, Body mass index; PSA, Prostate specific antigen; ISUP, International Society of Urological Pathology; RARP, Robot-assisted radical prostatectomy; ADT, Androgen deprivation therapy.
The median time to continence recovery is 8 weeks. A total of 216 (93.9%) participants recovered to urinary continence within 12 months after surgery, leaving 14 (6.1%) not recovered at one year follow-up. 21 (9.1%) participants achieved immediate continence. 69, 85, 27 and 14 participants restored continence at 1 month, 1-3 month, 3-6 month, 6-12 month, accounting for 30.0%, 40.0%, 11.7% and 6.1% accordingly. More detailed information regarding time to continence recovery were illustrated in
Time to urinary continence.
Absolute Number | Accumulated Number | Absolute Percentage (%) | Accumulated Percentage (%) | |
---|---|---|---|---|
Immediate | 21 | 21 | 9.1 | 9.1 |
1 month | 69 | 90 | 30.0 | 39.1 |
3 month | 85 | 175 | 40.0 | 76.1 |
6 month | 27 | 202 | 11.7 | 87.8 |
12 month | 14 | 216 | 6.1 | 93.9 |
>12month | 14 | 230 | 6.1 | 100 |
Kaplan-Meier failure graph of continence recovery. The Kaplan-Meier failure graph demonstrates continence results under different preoperative treatment conditions. No difference was found among the ADT, ADT + Docetaxel and ADT + Abiraterone groups (Log rank
After including evaluated variables in the Cox regression analysis (
Cox regression model for urinary continence.
Factor | Univariate | Multivariate | ||
---|---|---|---|---|
OR (95% CI) |
|
OR (95% CI) |
|
|
Age | 0.99 (0.97-1.01) | 0.240 | – | – |
BMI | 1.00 (0.95-1.06) | 0.963 | – | – |
Initial T | 0.88 (0.74-1.06) | 0.184 | – | – |
Apex invasion | 1.03 (0.78-1.36) | 0.820 | – | – |
Preoperative PSA | 0.99 (0.95-1.03) | 0.632 | – | – |
Preoperative volume | 1.00 (0.98-1.02) | 0.844 | – | – |
Membranous urethral length | 1.13 (1.04-1.22) | 0.002** | 1.12 (1.04-1.20) | 0.002** |
Preoperative T | 1.05 (0.87-1.27) | 0.590 | – | – |
Preoperative therapy | – | |||
ADT + Docetaxel vs ADT | 0.81 (0.52-1.26) | 0.352 | – | – |
ADT + Abiraterone vs ADT | 0.95 (0.66-1.38) | 0.794 | – | – |
Surgery approach | 1.04 (0.78-1.39) | 0.781 | – | – |
Post-surgery ADT | 0.79 (0.55-1.15) | 0.781 | 0.76 (0.54-1.06) | 0.109 |
**p < 0.01.
BMI, Body mass index; PSA, Prostate specific antigen; ADT, Androgen deprivation therapy; OR, Odds ratio; CI, Confidence Interval.
Deeper digging into the potential risk or protective factors for urinary continence at different time were then carried out using logistic regression (
A portion of the patients continued to receive ADT shortly after surgery (
The results of the study showed that 9.1% and 93.9% of patients restored continence immediately and 1 year after removal of catheter. No difference was found in postoperative continence recovery among ADT, ADT+Docetaxel and ADT+Abiraterone preoperative treatment options. More advanced T stage increased the risk of immediate incontinence and longer membranous urethral length (MUL) promoted continence at 1, 3, 6 and 12 month.
Radical prostatectomy leads to anatomical impairment to urethral sphincter complex, its surrounding tissue and innervation, which cause incontinence (
Current evidence exhibited significant advantage of RS-RARP over C-RARP in terms of immediate continence recovery while not in long-term continence recovery (
Preoperative membranous urethral length (MUL) was shown to be a crucial factor influencing continence recovery, which is consistent with former researches (
Though our research demonstrated that different preoperative treatment options did not make a difference on continence recovery, it did show that sustained postoperative hormonal therapy might impair continence recovery. The impact of occurent or previous hormonal therapy on postoperative continence still needs to be further discussed.
There are several limitations of this study. Firstly, this is a single center, single surgeon retrospective study. The learning curve and retrospective nature might undermine the general implication of the study. Secondly, the varying and complicated patients’ characteristics might cause potential bias. Despite the limitations, this study provided evidence of the impact of different preoperative pharmacotherapy on postoperative urinary continence, which was scarcely ever mentioned in existing research.
In the study, 93.9% participants recovered to urinary continence within 12 months after surgery. There is no difference in postoperative continence recovery among ADT, ADT+Docetaxel and ADT+Abiraterone preoperative treatment options. More advanced T stage indicated poor immediate continence recovery. Longer membranous urethral length was a promotional factor for short-time and long-time continence recovery.
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
The studies involving human participants were reviewed and approved by Medical Ethics Committee of Nanjing Drum Tower Hospital, China. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements. Written informed consent was not obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
JZ and YW designed and planned the study protocol. HG and LX supervised the work. YW, SZ and XL collected patients’ clinical data while YF provided pathology reports. YW and HH performed the analysis, drafted the manuscript and designed the figures. JZ and XQ aided in interpreting the results and worked on the manuscript. All authors contributed to the article and approved the submitted version.
This work was funded by the National Natural Science Foundation of China (81974394 to JZ, 82172639 to XQ, and 81972388 to HG), Natural Science Foundation of Jiangsu Province for Excellent Young Scholars (BK20200051 to JZ), Nanjing Medical Science and technique Development Foundation (GRX17127 to JZ), the Project of Invigorating Health Care through Science, Technology, and Education, Jiangsu Provincial Key Medical Discipline (Laboratory) (ZDXKB2016014 to HG).
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
The Supplementary Material for this article can be found online at:
RARP, Robot-assisted radical prostatectomy; QOL, Quality of life; PCa, Prostate cancer; ADT, Androgen deprivation therapy; CRP, Cytoreductive prostatectomy; NHT, Neoadjuvant hormonal therapy; mpMRI, multi-parameter magnetic resonance imaging; 68Ga-PSMA PET, 68Ga-labeled molecular imaging with PET-targeted prostate-specific membrane antigen; LHRHa, Luteinizing hormone-releasing hormone analog; ePLND, Enlarged pelvic lymph node dissection; C-RARP, Conventional robot-assisted radical prostatectomy; RS-RARP, Retzius-sparing robot-assisted radical prostatectomy; DVCL, Dorsal venous complex ligation; PR, Posterior reconstruction; PSA, Prostate specific antigen; MUL, Membranous urethral length; BMI, Body mass index; SD, Standard deviation ; IQR, Interquartile range; ANOVA, Analysis of variance; CI, Confidence interval; OR, Odds ratio; NVB, Neurovascular bundle; PSM, Positive surgical margin.