Journal of Men's Health,2023,19(7):39-44 DOI:10.22514/jomh.2023.056
Original Research

Enhancing androgen ablation response in metastatic hormone-sensitive prostate cancer: the benefits of transurethral resection of the prostate

Yan Zhao1,2,†, Jie Liang2,†, Qian Wang2, Jing-Yi Cao2, Zhi-Xiang Yin1, Han-Yong Feng1, Yu-Hao Peng1, Nian-Xin Gai1, Chang-Song Pei1,*,

1Department of Urology, The First Affiliated Hospital of Soochow University, 215006 Suzhou, Jiangsu, China

2Department of Urology, Xuzhou Cancer Hospital, Affiliated Hospital of Jiangsu University, 221000 Xuzhou, Jiangsu, China

*Corresponding Author(s):20224132064@stu.suda.edu.cn (Chang-Song Pei)

† These authors contributed equally.

History Submitted: 25 November 2022 | Accepted: 15 March 2023 | Published: 30 July 2023
Copyright:  ©2023  The Author(s). Published by MRE Press.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

Collapse table of contents

Abstract

Presently, there is limited data on the potential survival benefits of transurethral resection of the prostate (TURP) in patients with metastatic hormone-sensitive prostate cancer (mHSPCa). In this study, we aimed to assess the effects of TURP on the survival of mHSPCa patients. Of the 59 patients diagnosed with mHSPCa included, 28 received androgen deprivation therapy (ADT) alone, and the remaining received TURP plus ADT. Their time to biochemical progression (TBCP) and progression-free survival (PFS) were analyzed. Our results showed that for a median follow-up time of 15 (range, 3–40) months and 21 (range, 6–39) months for the ADT group and the TURP group, respectively, the TURP group exhibited significantly longer TBCP than the ADT group (p = 0.020). In addition, patients in the TURP group had numerically longer PFS, although the difference between the two groups was not significantly different (p = 0.110). Cox multivariate analysis indicated that longer TBCP was independently associated with TURP (p = 0.032) and lower Gleason scores (p = 0.001). Altogether this study showed that TURP could prolong TBCP and potentially improve the PFS of mHSPCa patients. However, further studies with a larger sample size are needed to confirm these findings.

Keywords:Metastasis prostate cancer;Hormone sensitive;Transurethral resection of the prostate;Progression-free survival;Time to castration resistance
PDF(2.02 MB)|EndNote (RIS)|BibTeX|RefMan|RefWorks

Cite this article

Yan Zhao, Jie Liang, Qian Wang, Jing-Yi Cao, Zhi-Xiang Yin, Han-Yong Feng, et al.Enhancing androgen ablation response in metastatic hormone-sensitive prostate cancer: the benefits of transurethral resection of the prostate.Journal of Men's Health,2023,19(7):39-44 DOI:10.22514/jomh.2023.056

1. Introduction

Prostate cancer remains a highly prevalent malignancy, comprising about 29% of all cancer diagnoses in men [1]. Despite advances in treatment, patients with metastatic prostate cancer (mPCa) still have poor survival prospects [2]. Although androgen deprivation therapy (ADT) remains the traditionally recommended therapy for metastatic hormone-sensitive prostate cancer (mHSPCa) [3], most of these patients eventually develop biochemical or clinical progression, resulting in a significant decline in survival outcomes [4]. Moreover, the growth of cancer cells and the occurrence of local complications such as bladder outlet obstruction (BOO) and hematuria are also contributory factors that further reduce their quality of life and survival [5]. In such instances, TURP is often performed to relieve these local complications [6].

Cytoreductive surgery of the primary tumor has been shown to confer survival benefits in several malignancies [7, 8, 9, 10]. The potential for a similar impact on prostate cancer has been demonstrated with cytoreductive radical prostatectomy (CRP) in mPCa patients [11, 12, 13]. Mechanistically, reducing the overall tumor burden has been proposed to improve survival outcomes following CRP in mPCa patients [12]. Similar to CRP, TURP can be performed to manage local complications in mPCa patients to a certain extent, making it a form of cytoreductive surgery that could theoretically lead to better survival outcomes.

In this present study, we evaluated the survival of a well-selected cohort of mHSPCa patients who underwent TURP and ADT compared to ADT alone to shed light on strategies for improving the prognosis of patients with mPCa.

2. Methods

In this prospective study, 59 mHSPCa patients receiving ADT with or without TURP from Jun 2019 to July 2022 were assessed. Of them, 31 underwent TURP due to the indications of hematuria or BOO before ADT (TURP group), while the others received ADT alone (ADT group). TURP was performed by the same doctor. The procedure was the same as TURP for benign prostate hyperplasia, and the prostate tissues were resected till the level of the capsule. The diagnosis of PCa was confirmed by biopsy. Tissues were sampled during routine transrectal ultrasound-guided 12 to 18-core biopsy of the prostate. Then, several parameters, including the number of positive biopsy cores and the Gleason score, were assessed. Metastatic disease was confirmed via routine imaging, including skeletal scintigraphy, magnetic resonance imaging (MRI), or abdominal/pelvic/chest computed tomography (CT). Positron emission tomography-computed tomography (PET/CT) was performed for unequivocal findings on skeletal scintigraphy, MRI or CT.

Study eligibility criteria were: (1) the diagnosis of PCa was based on tissue samples taken during transrectal-ultrasound guided core biopsy; (2) had metastasis to the bone or viscera including liver, cerebrum, or lung; (3) were initially hormone-sensitive; (4) had no prior radiation and systemic therapy; (5) provided written informed consent; and (6) had a life expectancy >1 year from the time of diagnosis.

2.1 TURP group

Thirty-one mHSPCa patients with BOO or hematuria who underwent transrectal-ultrasound-guided core biopsy were elected to receive TURP as the initial local therapy and were recommended ADT (3.6 mg goserelin once every month and 50 mg bicalutamide per day) as adjuvant therapy.

2.2 ADT group

Twenty-eight mHSPCa patients without local complications underwent ADT alone. Once diagnosed, they were started on goserelin (3.6 mg, s.c. AstraZeneca; once every month) and bicalutamide (50 mg, p.o. AstraZeneca; once every day).

2.3 Following-up

All patients were followed-up until biochemical progression, clinical progression, or death. In the first year, they were followed-up every month. Following successful ADT intervention, they were followed-up every 3 months for the next two years, then annually afterward. At each follow-up, the patients underwent testosterone, alkaline phosphatase, prostate-specific antigen (PSA), and digital rectal examinations. Prostate magnetic resonance imaging (MRI), skeletal scintigraphy, abdominal/pelvic/chest CT, or PET/CT were performed every three months to evaluate radiographic changes.

2.4 Definition of progression

Biochemical progression was described as a continuous increase in PSA levels, resulting in a 50% increase above the nadir value. The onset of new symptoms due to PCa progression or radiographic evidence of disease progression alone were used as indications for determining clinical progression. Time to biochemical progression (TBCP) was measured from the start of ADT until biochemistry progression. Progression-free survival (PFS) was defined as the time interval from the initiation of ADT to the first occurrence of biochemical progression and clinical progression.

2.5 Statistical analysis

The SPSS v18.0 (IBM Corp., Armonk, NY, USA) software was used for statistical analysis. Continuous variables were analyzed using independent-samples Student’s t-test. The chi-square test was used for categorical variables. The primary endpoint was TBCP, and the secondary endpoint was PFS. Kaplan-Meier survival analysis and log-rank test were performed for survival analysis. Cox univariate and multivariate proportional hazard analyses were also performed to identify factors independently associated with patients’ survival. A two-sided p-value < 0.05 was considered for statistical significance.

3. Results

3.1 Baseline characteristics of the patients

Our analysis showed no significant difference in baseline characteristics between the two study groups in regard to age, PSA at diagnosis, American joint Committee on cancer (AJCC) clinical stage, and biopsy Gleason score (Table 1).

Table 1.Baseline patient characteristics.
Baseline characteristicsTURP and ADTADT alonep value
(n = 31)(n = 28)
Mean age at diagnosis (range)75.7 (56–89)75.6 (55–89)0.978
No. age (%)
<601 (3.2)1 (3.6)
60–705 (16.1)5 (17.8)
Greater than 7025 (80.7)22 (78.6)
Mean PSA level at diagnosis, ng/mL (range)119.3 (2.37–416.0)213.2 (4.16–654.0)0.092
Mean PSA nadir, ng/mL (range)0.33 (0.01–1.52)0.87 (0.01–3.60)0.015
Gleason score (%):0.066
6 or less10 (32.3)5 (17.9)
77 (22.6)7 (25.0)
8 or greater14 (45.1)16 (57.1)
Clinical T stage (%):0.082
≤cT222 (70.9)18 (64.3)
cT36 (19.4)4 (14.3)
cT43 (9.7)6 (21.4)
Lymph nodes status (%):0.351
N027 (87.1)22 (78.6)
N14 (12.9)6 (21.4)
Clinical M stage (%):0.062
M1a0 (0)0 (0)
M1b ≤5a21 (67.7)14 (50.0)
M1b >5b6 (19.4)9 (32.1)
M1c4 (12.9)5 (17.9)
a: skeletal metastases number is no more than five; b: skeletal metastases number is greater than five. TURP: transurethral resection of the prostate; ADT: androgen deprivation therapy; PSA: prostate-specific antigen.

3.2 Histopathology, clinical T stages, and complications related to TURP

The diagnosis of PCa was confirmed in all patients via pathological examination (Fig. 1).

Representative pathology image of prostate cancer. The arrow indicates the tumor on gross histological slides.

Fig. 1.Representative pathology image of prostate cancer. The arrow indicates the tumor on gross histological slides.

Imaging examinations showed that 22 (70.9%) patients were staged as cT1 and cT2, six (19.4%) as cT3, and three (9.7%) as cT4 in the TURP group. In the ADT group, there were 18 (64.3%) patients staged as cT1 and cT2, four (14.3%) as cT3, and six (21.4) as cT4. Additionally, four (12.0%) in the TURP group and six (21.4%) in the ADT group had lymph node metastases (Table 1). No serious TURP complications, such as perineum hematoma, rectal injury or urethra-rectal fistula, occurred in any of the investigated patients. However, one patient in the TURP group suffered from stress incontinence, but symptoms resolved within 3 months. All patients in the TURP group could urinate after removing the catheter.

3.3 Follow-up of oncologic parameters

3.3.1 TURP plus ADT

The overall follow-up time of the TURP group was 21 months (range, 6–39 months). Three patients died during follow-up, including one due to stroke and two from PCa progression. The mean TBCP was 12.6 months (95% confidence interval (CI): 10.5 to 14.6), and the mean PFS was 23.9 months (95% CI: 19.8 to 28.0). Of the 28 patients who developed biochemical progression, 18 underwent second-line treatment, and the remaining 10 received chemotherapy with docetaxel. Mean PSA at diagnosis was 119.3 ng/mL (range, 2.37–416.0 ng/mL). The mean nadir PSA in the TURP group during follow-up was 0.33 ng/mL (range, 0.01–1.52 ng/mL), which was significantly lower than that in the ADT group (p = 0.015) (Table 1).

3.3.2 ADT alone

The median follow-up time for this cohort of patients was 15 months (range, 3–40 months). Two patients died of prostate cancer progression during the follow-up period. The mean TBCP was 9.2 months (95% CI: 6.3 to 12.0), and the mean PFS was 17.4 months (95% CI: 13.0 to 21.8 months). Additionally, the mean PSA at diagnosis was 213.2 ng/mL (range, 4.16–654.0 ng/mL), and the mean nadir PSA during follow-up was 0.87 ng/mL (range, 0.01–3.60 ng/mL) (Table 1).

3.4 Survival and Regression analyses of TBCP

Kaplan-Meier survival analysis and log-rank test were conducted for survival analysis. The results showed that the TBCP of the TURP group was significantly longer than that of the ADT group (p = 0.020) (Fig. 2).

Time to biochemical progression of TURP plus ADT versus ADT alone. TURP: transurethral resection of the prostate; ADT: androgen deprivation therapy.

Fig. 2.Time to biochemical progression of TURP plus ADT versus ADT alone. TURP: transurethral resection of the prostate; ADT: androgen deprivation therapy.

However, we found no significant difference in PFS between the two groups, though the TURP group tended to exhibit a longer PFS (p = 0.110) (Fig. 3).

Progression-free survival of TURP plus ADT versus ADT alone. TURP: transurethral resection of the prostate; ADT: androgen deprivation therapy.

Fig. 3.Progression-free survival of TURP plus ADT versus ADT alone. TURP: transurethral resection of the prostate; ADT: androgen deprivation therapy.

Univariate analysis showed longer TBCP was associated with TURP, lower Gleason score, lower PSA at diagnosis, and lower clinical M staging. Subsequently, multivariate analysis indicated that longer TBCP was independently associated with TURP (HR (hazard ratio), 2.735; 95% CI: 1.091–6.858, p = 0.032) and lower Gleason score (HR, 1.947; 95% CI: 1.375–2.756) (p = 0.001) (Table 2).

Table 2.Multivariate analyses of time to castration resistance prostate cancer.
VariablesHR95% CIp value
TURP (yes)2.7351.091–6.8580.032
PSA at diagnosis0.9990.997–1.0020.532
Biopsy Gleason score1.9471.375–2.7560.001
M staging
M1b ≤5a1.6030.339–7.5800.551
M1b >5b0.3420.103–1.1400.081
M1c0.5800.168–2.0050.389
Note: a, skeletal metastases number ≤5; b, skeletal metastases number >5; HR, hazard ratio; CI, confidence interval; TURP, transurethral resection of the prostate; PSA, prostate-specific antigen.

4. Discussion

Prostate cancer is one of the most common malignancies of the male genitourinary system. According to epidemiological analyses, 268,490 new cases of prostate cancer were diagnosed in the United States in 2022, and 34,500 men died from this disease [14]. mPCa often leads to poor prognosis. Although systemic therapy remains the traditional treatment of mPCa, the therapeutic efficacy remains far from satisfactory [15]. In recent years, new therapeutic strategies have been explored for mPCa. In 2014, Antwi et al. [16] reported that CRP could reduce the mortality of mPCa patients. Recently, a meta-analysis and our previous results confirmed the survival benefit of CRP for mPCa [11, 17]. Collectively, these suggest that primary tumor reduction might be a promising approach that could improve the survival of mPCa patients.

Researchers have explored the underlying mechanisms influencing the outcomes of cytoreductive surgery in mPCa. They discovered that the “seed and soil” hypothesis might be pivotal during this process. Specifically, cytoreductive surgery offered a compelling advantage for mPCa by reducing the tumor load, shedding and metastasis of primary tumor cells, indicating the ideology that this intervention could effectively decrease the dissemination of prostate cancer (“seeds”) to other organs (“soil”), whereby eliminating the tumor bank decreases the potential for future metastasis [18]. A similar phenomenon was reported in colorectal cancer, breast cancer, gastric cancer and renal cell carcinoma [7, 8, 9, 10].

TURP has been proven to be safe and effective and is usually performed for relieving local complications such as BOO and hematuria in patients with mPCa [6, 19, 20]. As a special type of cytoreductive surgery, TURP may theoretically lead to a better prognosis for mPCa patients. Qin et al. [21] first explored the survival benefits of TURP in patients with mPCa. The results showed that TURP was associated with a significantly longer time to castration-resistance prostate cancer (CRPC) and trended toward better overall survival (OS) and cancer-specific survival (CSS). However, another study [22] revealed a worse CRPC-free survival, CSS and OS when TURP was performed in mPCa patients, suggesting that the oncological outcomes of TURP in advanced mPCa remain controversial. Hence, we performed this current research. Our results showed that mHSPCa patients in the TURP group benefitted from a significantly longer TBCP than the ADT group, indicating that TURP may result in a better prognosis.

According to the “seed and soil” hypothesis, the total amount of prostate tissues removed during TURP significantly impacts the survival and prognosis of mPCa patients. Therefore, when we performed TURP in mHSPCa patients, the prostate tissues were resected till the level of the capsule to achieve the greatest tumor reduction, which might be a reason for our reported different biochemical progression results between the two groups. In addition, though biochemical progression can explain the deterioration of mPCa to some extent, it is still insufficient. The impact on patient survival can be more fully explained when biochemical and clinical progression occurs. Thus, in this study, we defined PFS as the period from the start of ADT to the confirmed co-occurrence of biochemical and clinical progression. Our results showed that although there was a difference in TBCP between the two groups, no difference was observed between the PFS of both groups, suggesting that TURP might only benefit biochemical progression but not improve patient survival. Thus, more investigations are needed to clarify the underlying mechanisms to shed more light on this topic.

Recently, a prospective study [23] comprising 188 patients investigated the impact of TURP combined with ADT versus ADT alone on the survival of mHSPCa. The researchers revealed that TURP could prolong the CSS of mHSPCa patients, with PSA value, Gleason score and the number of bone metastases being the influencing factors, which were concordant with our findings and demonstrated the survival benefit of TURP in mHSPCa.

There were several limitations in this current study that should be considered. The investigated cohort size was relatively small, and the follow-up period was relatively short. Besides, only a few deaths were recorded. Due to these initially determined limitations, we chose TBCP and PFS as the outcome variables of this study.

5. Conclusions

Our results demonstrated that TURP could prolong TBCP and potentially improve the survival of mHSPCa patients. Further research using a larger sample size is needed to confirm our findings.

Availability of data and materials

The data are contained within this article.

Author contributions

YZ, JL and CSP—conceived and designed the experiments; QW, JYC, ZXY and HYF—performed the experiments; YHP and NXG—analyzed the data; YZ—wrote the paper.

Ethics approval and consent to participate

This study was reviewed and approved by the Ethics Committee of Xuzhou Cancer Hospital (XCH20190016x). All study potential risks and procedures have been explained to the patients, and they gave their written informed consent.

Acknowledgment

Not applicable.

Funding

This study was funded by the Science and Technology Program of Suzhou City (grant no. SLJ201906 and P112206121).

Conflict of interest

The authors declare no conflict of interest.

References

Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA: A Cancer Journal for Clinicians. 2023; 73: 17–48.

[Google Scholar]

Achard V, Putora PM, Omlin A, Zilli T, Fischer S. Metastatic prostate cancer: treatment options. Oncology. 2022; 100: 48–59.

[Google Scholar]

Cornford P, van den Bergh RCN, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M. EAU-EANM-ESTRO-ESUR-SIOG guidelines on prostate cancer. Part II—2020 update: treatment of relapsing and metastatic prostate cancer. European Urology. 2021; 79: 263–282.

[Google Scholar]

Ryan CJ, Tindall DJ. Androgen receptor rediscovered: the new biology and targeting the androgen receptor therapeutically. Journal of Clinical Oncology. 2011; 29: 3651–3658.

[Google Scholar]

Wiegand LR, Hernandez M, Pisters LL, Spiess PE. Surgical management of lymph-node-positive prostate cancer: improves symptomatic control. BJU International. 2011; 107: 1238–1242.

[Google Scholar]

Crain DS, Amling CL, Kane CJ. Palliative transurethral prostate resection for bladder outlet obstruction in patients with locally advanced prostate cancer. Journal of Urology. 2004; 171: 668–671.

[Google Scholar]

Rapiti E, Verkooijen HM, Vlastos G, Fioretta G, Neyroud-Caspar I, Sappino A. Complete excision of primary breast tumor improves survival of patients with metastatic breast cancer at diagnosis. Journal of Clinical Oncology. 2006; 24: 2743–2749.

[Google Scholar]

Temple LKF, Hsieh L, Wong WD, Saltz L, Schrag D. Use of surgery among elderly patients with stage IV colorectal cancer. Journal of Clinical Oncology. 2004; 22: 3475–3484.

[Google Scholar]

Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, et al. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. New England Journal of Medicine. 2001; 345: 1655–1659.

[Google Scholar]

Hallissey MT, Allum WH, Fielding JWL, Roginski C. Palliative surgery for gastric cancer. Cancer. 1988; 62: 440–444.

[Google Scholar]

Wang Y, Qin Z, Wang Y, Chen C, Wang Y, Meng X, et al. The role of radical prostatectomy for the treatment of metastatic prostate cancer: a systematic review and meta-analysis. Bioscience Reports. 2018; 38: BSR20171379.

[Google Scholar]

Heidenreich A, Pfister D, Porres D. Cytoreductive radical prostatectomy in patients with prostate cancer and low volume skeletal metastases: results of a feasibility and case-control study. Journal of Urology. 2015; 193: 832–838.

[Google Scholar]

Fossati N, Trinh Q, Sammon J, Sood A, Larcher A, Sun M, et al. Identifying optimal candidates for local treatment of the primary tumor among patients diagnosed with metastatic prostate cancer: a SEER-based study. European Urology. 2015; 67: 3–6.

[Google Scholar]

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA: A Cancer Journal for Clinicians. 2022; 72: 7–33.

[Google Scholar]

Wang L, Paller CJ, Hong H, De Felice A, Alexander GC, Brawley O. Comparison of systemic treatments for metastatic castration-sensitive prostate cancer: a systematic review and network meta-analysis. JAMA Oncology. 2021; 7: 412–420.

[Google Scholar]

Antwi S, Everson TM. Prognostic impact of definitive local therapy of the primary tumor in men with metastatic prostate cancer at diagnosis: a population-based, propensity score analysis. Cancer Epidemiology. 2014; 38: 435–441.

[Google Scholar]

Zhao Y, Peng DS, Liang J, Lin YL, Qi JG. A systematic review and meta-analysis of comparative studies on the efficacy of cytoreductive prostatectomy in patients with metastatic prostate cancer. International Journal of Clinical and Experimental Medicine. 2020; 13: 330–339.

[Google Scholar]

Fidler IJ. The pathogenesis of cancer metastasis: the “seed and soil” hypothesis revisited. Nature Reviews Cancer. 2003; 3: 453–458.

[Google Scholar]

Poelaert F, Verbaeys C, Rappe B, Kimpe B, Billiet I, Plancke H. Cytoreductive prostatectomy for metastatic prostate cancer: first lessons learned from the multicentric prospective local treatment of metastatic prostate cancer (LoMP) trial. Urology. 2017; 106: 146–152.

[Google Scholar]

Marszalek M, Ponholzer A, Rauchenwald M, Madersbacher S. Palliative transurethral resection of the prostate: functional outcome and impact on survival. BJU International. 2007; 99: 56–59.

[Google Scholar]

Qin X, Ma C, Ye D, Yao X, Zhang S, Dai B, et al. Tumor cytoreduction results in better response to androgen ablation—a preliminary report of palliative transurethral resection of the prostate in metastatic hormone sensitive prostate cancer. Urologic Oncology: Seminars and Original Investigations. 2012; 30: 145–149.

[Google Scholar]

Choi SY, Ryu J, You D, Jeong IG, Hong JH, Ahn H. Oncological effect of palliative transurethral resection of the prostate in patients with advanced prostate cancer: a propensity score matching study. Journal of Cancer Research and Clinical Oncology. 2018; 144: 751–758.

[Google Scholar]

Qu M, Zhu F, Chen H, Lian B, Jia Z, Shi Z. Palliative transurethral resection of the prostate in patients with metastatic prostate cancer: a prospective study of 188 patients. Journal of Endourology. 2019; 33: 570–575.

[Google Scholar]