The direct prognosis comparison of ¹²⁵I low-dose-rate brachytherapy versus laparoscopic radical prostatectomy for patients with intermediate-risk prostate cancer

A total of 361 consecutive IRPC patients treated with curative intent between January 2014 and August 2021 at the Peking Union Medical College Hospital were identified, of which 160 (44.3%) underwent RP, and 201 (55.7%) received LDR. Patients were categorized according to the NCCN risk classification criteria [8], which defines IRPC by clinical stage T2b-c, Gleason score (GS) 3 + 4 (group 2) or 4 + 3 (group 3), and/or initial PSA (iPSA) of 10.1–20.0 ng/ml. Percentage positive biopsy cores (PPBC) > 50% was calculated from the pathology report. Favorable IRPC was described as patients with no more than one intermediate adverse risk factor, such as GS 3 + 4 (group 2), iPSA 10.1–20.0 ng/ml, or clinical stage T2b-c, PPBC ≤ 50%. On the other hand, those with multiple intermediate adverse risk factors, which included PPBC > 50%, or any IRPC with GS 4 + 3 (group 3), were classified as unfavorable IRPC [12]. Institutional Review Board has approved our protocols.

The following information of all patients was evaluated: medical history, physical examination, digital rectal examination, prostate volume (PV), iPSA. Clinical stages for both RP and LDR groups are determined using a standardized TNM classification system which is evaluated according to the combination of prostate biopsy pathology report, chest radiography, bone scintigraphy, CT-scan and magnetic resonance imaging (MRI) of the pelvis before biopsy. The staging was carried out by at least two surgeons at our institution. PV was calculated as anteroposterior diameter × vertical diameter × transverse diameter × 0.52 based on MRI [13].

The treatment option, LDR versus RP, was decided collaboratively by both doctors and patients after discussions. The clinics will initially introduce the advantages and disadvantages, prognosis and possible complications of each treatment plan to the patient in detail. After the patient has preliminary understanding of each treatment plan, they can decide the treatment plan based on their own perspectives. Patients with relative contraindications for LDR (e.g., LUTS with International Prostate Symptom Score > 12–20, transurethral resection of the prostate defects, large median lobes, and/or gland size > 50-60 ml) were recommended to undergo RP. Patients who could not tolerate RP would be directed towards LDR. Written informed consent was obtained from all participants included in the present study. According to NCCN guidelines, patients with unfavorable risk IRPC would receive adjuvant EBRT plus ADT after LDR; whereas, patients with favorable risk IRPC would undergo LDR monotherapy. In RP group, considering the low amount of lymph node metastasis found in the favorable IRPC group, the extent of pelvic lymph node dissection (PLND) was not regularly performed based on NCCN guidelines. In unfavorable IRPC group, an extended PLND would be performed when the estimated risk for pN + exceeds 5% [14]. If a patient was diagnosed with positive margins based on whole mount pathology report obtained through RP, an adjuvant EBRT plus ADT was then conducted. EBRT was delivered through 3D-conformal radiation therapy, intensity-modulated radiation therapy, or volumetric-modulated arc therapy to the primary prostate field [15]. The planning target volume for EBRT was generated through adding an 8 mm margin surrounding the clinical target volume, except posteriorly, where the margin was limited to 3 mm. Radiotherapy dosing regimen ranged from 66 to 74 Gy. Patients with positive lymph nodes or have contraindications to radiotherapy of EBRT were treated by adjuvant ADT immediately after obtaining the RP pathology report (approximately 2 weeks after surgery) until three months after PSA nadir [16]. Patients suffered from BF would be treated by salvage ADT. The ADT type we chose is the combination of bicalutamide and goserelin.

The RP was conducted through a pure laparoscopic RP technique described by Guillonneau [17] with an extraperitoneal approach and five trocar technique by two experienced surgeons both of whom had an average of RP cases of 100 per year (WY and ZZ). The vesico-urethral anastomosis was accomplished with a running suture with Y604 (Ethicon, USA). Treatment with LDR was planned for the prostate and proximal seminal vesicles to receive 145 Gy with a 5-mm margin laterally, anteriorly, and inferiorly by two urologist with over 10 years of brachytherapy experience [18]. No margin was planned superiorly (bladder) and posteriorly (rectum). ¹²⁵I seeds were accurately introduced into preplanned positions by a brachytherapy stepping unit MICK200 (Computerized Medical Systems, Inc, St. Louis, MO, USA) using a standard 0.5 cm brachytherapy template placed over the perineum. 1 week after implantation, dosimetric analysis was conducted by CT scan, and the D90 (defined as the minimum dose covering 90% of the prostate) was obtained for each patient.

The day of the operation of RP/LDP was counted as the day 0. Patients were followed up monthly during the first three months and at three-month intervals thereafter. If PSA level was stable, routine follow-up was scheduled every six months from 2 years after surgery. Imaging result for each patient was generally reviewed once a year and rechecked at any time if any signs of disease progression or biochemical recurrence were observed. Biochemical relapse-free survival (bRFS) and clinical relapse-free survival (cRFS) were the primary endpoints of this study, whereas cancer-specific survival (CSS) and overall survival (OS) were the secondary endpoints. BF was defined as a PSA value ≥ 0.2 ng/mL for patients who underwent RP [19] and an increase of 2 ng/mL or > nadir PSA value (Phoenix definition) [20] for patients treated by LDR. Clinical relapse was defined as metastases identified by medical imaging, with or without localizing symptoms, or biopsy-proven local recurrence. Both distant metastasis and regional lymph node metastasis were defined as clinical recurrence in cRFS analysis. Cancer-specific mortality was defined as mortality due to PCa, noted on the death certificate alongside the biochemical and clinical information, or the presence of uncontrolled metastatic disease when the patient succumbed.

Tables 1, 2 present complete pretreatment characteristics of enrolled patients. A total of 361 patients were included in the present study, comprising 201 LDR patients (55.7%) and 160 RP patients (44.3%). A total of 370 participants were initially selected retrospectively, and nine patients have been lost during follow-up: two in the RP group and seven in LDR group. The median age of the study population was 70 (IQR 65–75) years. Patients in Group RP were slightly younger 66 (IQR: 62–71) than those in Group LDR 74 (IQR: 69–77), P < 0.001. The median follow-up for RP and LDR was 54 and 69 months, respectively. The median duration of ADT in arms LDR and RP were 183 days (IQR 176–190) and 60 days (IQR: 58–62) (P < 0.001). At baseline, the median PSA level was 12.29 ng/mL (IQR 9.53–15.01). The median follow-up duration for surviving patients was 63 months (IQR 44–86). According to biopsy results, in LDR group, 42 patients (20.8%), 36 patients (17.9%), 32 patients (15.9%) and 91 patients (45.2%) were diagnosed with stages T1c, T2a, T2b, and T2c, respectively; whereas, in RP group, 15 patients (9.4%), 40 patients (25.0%), 41 patients (25.6%) and 64 patients (40.0%) were diagnosed with stages T1c, T2a, T2b, and T2c, respectively. The clinical TNM staging in RP Group is significantly higher than LDR group. In patients underwent RP, according to whole mount pathology report, positive margins were found in 55 (34.4%) patients; the extracapsular extension was found in 31 (19.3%) patients and seminal vesicle invasion in 18 (11.3%) patients, resulting in 49 (30.2%) RP patients upstaged to pathologic T3. Biochemical recurrence was observed in 46 patients in the RP group and 42 patients in the LDR group (P = 0.004). The median age for BF was 68 years (IQR 62–75), median PSA was 11.82 ng/ml (IQR 9.02–15.01) and the median PV was 20.96 ml (IQR 18.95–33.02). As for the clinical recurrence aspect, nine patients were found to have metastasis for both the RP group and the LDR group (P = 0.628). The median age of metastasis onset was 69 years (61–75), with a median PSA of 10.01 ng/ml (7.03–17.38) and a median PV of 19.72 ml (18.15–25.35); the mean D90 for the LDR group was 144 Gy (1 standard deviation = 20.58 Gy). 31.2% of patients in RP group received ADT while 94.5% in LDR, (P < 0.001). Adjuvant EBRT was used for 15 patients (9.4%) in the RP group and 5 (2.5%) in the LDR group, respectively (P = 0.004).

The median time to BF was 61 months (IQR 51–81) and 44 months (IQR 27–66) for RP and LDR, respectively (P = 0.327). As for the median time to clinical recurrence for RP and LDR, it was 67 months (IQR 49–90) and 51 months (IQR 35–66), respectively (P = 0.974). The 5- and 8-year bRFS rates were 70.2% and 63.1% in the RP group and 83.2% and 68.9% in the LDR group, respectively (Fig. 1A). The log-rank test indicated that the 5- and 8-year bRFS rates for the RP group were both lower than the LDR group with P = 0.003 and P < 0.001, (Fig. 1A). The 5- and 8-year cRFS rates were 94.2% and 92.1% in the RP group and 95.1% and 93.7% in the LDR group, respectively, with P = 0.404 and P = 0.128 (Fig. 1B). The 5- and 8-year CSS rates were 99.2% and 97.4% in the RP group and 98.9% and 97% in the LDR group with P = 0.774 and P = 0.385 (Fig. 1C). The 5- and 8-year OS rates were 98.6% and 97.0% in the RP group and 97.7% and 95.4.5% in the LDR group, respectively, with P = 0.951 and P = 0.412 (Fig. 1D).