Survival analysis of radical prostatectomy and brachytherapy in the treatment of early-stage localized prostate cancer

Objective Brachytherapy is minimally invasive with few complications, so may be a good alternative to surgery for patients with prostate cancer. This study aimed to compare the therapeutic effects of brachytherapy and radical prostatectomy in the treatment of localized prostate cancer at different stages. Methods A total of 16532 patients pathologically diagnosed with prostate cancer who underwent radical prostatectomy and 16627 patients who underwent brachytherapy between 2010 and 2012 were collected through the Surveillance, Epidemiology, and End Results (SEER) Stat software. These patients were randomly matched based on age and prostate specific antigen (PSA) level at first diagnosis, and were divided into five subgroups, including G2T1c, G3T1c, G2T2a, G3T2a and G3T3b. Differences in survival were analyzed by Kaplan-Meier survival curves and compared by log-rank test. Results The overall survival (OS) and prostate cancer-specific death time (PCSDT) in the radical prostatectomy group at G3T1c stage were significantly longer than in the brachytherapy group (P<0.05), and OS, but not PCSDT, was longer than the brachytherapy group at G2T2a stage (P=0.02). But at the G2T1c, G3T2a and G3T3b stages OS and PCSDT were not significantly different between the two treatments (P>0.05). The radical was superior to brachytherapy in the treatment of early-stage low-risk localized prostate cancer, whereas there was no significant difference in the prognosis of patients with moderate or high-risk localized prostate cancer.


Abstract
Objective Brachytherapy is minimally invasive with few complications, so may be a good alternative to surgery for patients with prostate cancer. This study aimed to compare the therapeutic effects of brachytherapy and radical prostatectomy in the treatment of localized prostate cancer at different stages.

Methods
A total of 16532 patients pathologically diagnosed with prostate cancer who underwent radical prostatectomy and 16627 patients who underwent brachytherapy between 2010 and 2012 were collected through the Surveillance, Epidemiology, and End Results (SEER) Stat software. These patients were randomly matched based on age and prostate specific antigen (PSA) level at first diagnosis, and were divided into five subgroups, including G2T1c, G3T1c, G2T2a, G3T2a and G3T3b.
Differences in survival were analyzed by Kaplan-Meier survival curves and compared by log-rank test.

Results
The overall survival (OS) and prostate cancer-specific death time (PCSDT) in the radical prostatectomy group at G3T1c stage were significantly longer than in the brachytherapy group (P<0.05), and OS, but not PCSDT, was longer than the brachytherapy group at G2T2a stage (P=0.02).
But at the G2T1c, G3T2a and G3T3b stages OS and PCSDT were not significantly different between the two treatments (P>0.05).

Conclusion
The radical prostatectomy prognosis was superior to brachytherapy in the treatment of early-stage low-risk localized prostate cancer, whereas there was no significant difference in the prognosis of patients with moderate or high-risk localized prostate cancer.

Background
With economic development, advanced aging and steady improvement in public health, prostate cancer has become a global problem threatening middle-aged and elderly males. Over one million males are diagnosed with prostate cancer, and over 300,000 people die of prostate cancer each year.
( 1) Early diagnosis of early-stage localized prostate cancer may improve this by screening programs for prostate specific antigen (PSA).( 2) According to the American Association for the Study of the Prostate Cancer Strategy (CaPSURE), patients with low-risk prostate cancer account for 70% of the total patients with prostate cancer.(

3)
Radical prostatectomy is still the gold standard for the treatment of low-risk prostate cancer. It is one of the most effective ways to treat localized prostate cancer, and 30-50% of newly diagnosed patients are physically eligible to undergo the risk of surgery.( 4) In addition, laparoscopic and robot-assisted laparoscopic radical prostatectomy has improved prognosis after prostatectomy.( 5) These modern developments also effectively control treatment side-effects. (   6) However, brachytherapy brings hope to elderly patients with prostate cancer who have poorer physical condition and significant surgical contraindications. Brachytherapy is a good choice for patients who are unsuitable or unwilling to undergo surgery, and this method has been accepted in North America and some European countries.  Survival rate was calculated using Kaplan-Meier graphs, comparison of survival rates was made by log-rank test. Continuous variables that met normal distribution were expressed as mean ± standard deviation (SD), and comparison between groups used independent t-test. Continuous variables that did not meet normal distribution were expressed as median (range), and comparison between groups used Mann-Whitney U test. Categorical data were expressed as frequency and percentage, and comparison between groups used Chi-square test. P <0.05 was considered to be statistically significant.

baseline characteristics in the two treatment groups
The selection of patients from the SEER database for inclusion in the study, their grouping and subgrouping were shown in the Figure 1. The comparison of baseline characteristics between the two groups was shown in Table 1. There were significant differences of race, PSA level, marital status and staging between the two groups (P <0.001). After random matching, the baseline characteristics of subgroups at T1-T3 stages were with no significant difference (P >0.05). were not significantly different between the radical prostatectomy group and the brachytherapy group (P >0.05, Fig.6).

Discussion
The aim of this study was to compare the survival of patients with early-stage localized prostate cancer treated with either radical prostatectomy or brachytherapy. The results showed no significant difference in the OS and PCSDT between the two treatment methods in patients with G2T1c, G2T2a and G3T3b stage prostate cancer. But there was a significant difference in OS and PCSDT of patients with G3T1c stage and in OS of patients with G3T2a stage prostate cancer, with those treated with radical prostatectomy surviving longer. These results suggest that radical prostatectomy may be superior to brachytherapy in the treatment of low-risk localized prostate cancer.
Previous studies that compared the survival of patients with localized prostate cancer treated with these two methods have shown similar survival times.( 9, 10) However, the aim of this study was to investigate the influence of cancer stages on the survival of patients. The TNM staging system of prostate cancer was designed by AJCC and UICC in 1992, aiming to determine the prognosis of patients and develop treatment regimen.( 12) Patients in this study were divided into 5 subgroups according to pathological staging and T staging. Random matching was performed based on age and PSA level. In this study, a total of 33159 patients diagnosed with prostate cancer between 2010 and 2012 were analyzed, including 16532 cases of radical prostatectomy and 16627 of brachytherapy. The percentage of patients at T1 stage was higher, and OS as well as PCSDT at G3T1c stage in the radical prostatectomy group were both longer than those in the brachytherapy group, indicating that radical prostatectomy was still advantageous in the treatment of most patients with localized prostate cancer, whereas brachytherapy was also a good choice for patients at G2T1c stage. For patients at T2 and T3 stages, prognosis was not significantly different between the two treatments regardless of poorly-or welldifferentiated prostate cancer. These patients may benefit from the use of external radiotherapy and chemotherapy. These results are partially supported by a previous study that also used the SEER database. [13] In that study patients ≥65 years old with clinically localized prostate cancer were classified by their predicted life expectancy. The study found that patients with 10+ years life expectancy at diagnosis showed longer survival times after radical prostatectomy than radiotherapy (including brachytherapy) or observation, but this benefit was not seen in the patients with shorter life expectancy. However, although life expectancy and cancer stage are related, the study did not indicate any association between the two variables.  17) The radiobiological data suggest that α/β ratio is low in prostate cancer tissue, at 1.2-3.0Gy, indicating that sustained and low-dose radiation is lethal to prostate cancer.( 18) Brachytherapy can perform low-dose and sustained radiation to prostate tissue and part of the surrounding tissues. α/β ratio of the tissues surrounding the prostate is high. Moreover, dose distribution around the radiation source decreases inversely proportionally to the square of the distance from the radiation source, which means that dose at the center is the highest, and the dose decreases with the increase in the distance from the radiation source. Thereby, brachytherapy can achieve higher local control rate, protect most of the bladder and rectum, as well as reduce