Comparisons of oncological and functional outcomes among radical retropubic prostatectomy, high dose rate brachytherapy, cryoablation and high-intensity focused ultrasound for localized prostate cancer

The dilemma between definitive treatment and observation/watchful waiting for localized prostate cancer is an important question without standard answer. In the PIVOT study, radical prostatectomy did not significantly reduce all-cause or prostate-cancer specific mortality, as compared with observation during at least 12 years of follow-up (Wilt et al. 2012). In contrast, the SPCG-4 study reported that radical prostatectomy significantly reduced all cause mortality by 12.7% (P < 0.001) and prostate-cancer specific mortality by 11.0% (P = 0.001) compared to watchful waiting during 23.2 years of follow-up (Bill-Axelson et al. 2014). Besides, surgical treatment for localized prostate cancer will inevitably result in complications and functional impairments. Therefore, an ideal treatment for localized prostate cancer with acceptable cancer control and less complications can avoid not only overtreatment and negative impact on quality of life but also disease progression and anxiety related to observation/watchful waiting.

With regard to oncological outcome comparisons, the patients of HDRBT experienced the worst cancer control in PSA biochemical recurrence (overall, D’Amico intermediate and high risk), salvage treatment-free rate and metastasis-free rate compared to those of the other three treatments. Even the patient distribution by D’Amico risk group is not equal in the four treatment modalities statistically, this result still reflects the insufficiency of pure HDRBT without androgen deprivation therapy for D’Amico intermediate and high-risk patients. According to NCCN guidelines and previous studies, neoadjuvant/concomitant/adjuvant androgen deprivation therapy is suggested for intermediate-risk (4–6 months) and high-risk patients (2–3 years) (National Comprehensive Cancer N 2014; Zumsteg et al. 2013; Bolla et al. 2010; D’Amico et al. 2008; Bolla et al. 2002). Our results are compatible with this suggestion. In the present study, cryoablation and HIFU demonstrated non-inferior oncologic outcomes to RRP, which is considered as standard treatment for localized prostate cancer. This intermediate-term result appears to be promising and needs further follow-up.

In respect of postoperative complications, RRP resulted in more urinary incontinence (11.3%), urethral stricture (29.9%) and secondary TURP or OIU (28.9%) than did the other three treatments. In the literature review, post-RRP urinary incontinence rate decreased with time (49.5% at 3 months, 9.5% at 24 months). Finally, 1–3% patients needed surgical intervention (Namiki and Arai 2010). Even in the era of robotic surgery, we still cannot find significant improvement of urinary incontinence rate after robotic-assisted laparoscopic radical prostatectomy compared with open radical prostatectomy (Haglind et al. 2015). Although we may expect the possibly partial recovery of urinary incontinence after a long time, post-RRP urinary incontinence is still a major concern for patients’ quality of life, especially for younger patients with longer life expectancy.

In terms of sexual function, the patients of HIFU demonstrated significantly lower de novo erectile dysfunction rate at 12 months (65.5%) and higher serial IIEF-5 scores than did those of the other three treatments, indicating more possibility of sexual function preservation. In a prospective study comparing radical prostatectomy, brachytherapy and cryoablation, brachytherapy led to better sexual function and bother scores than did radical prostatectomy and cryoablation for 3 years (Malcolm et al. 2010). We did not see the trend in this study, probably due to significantly older age in the patients of HDRBT. Another prospective study revealed that patients of HIFU had continuously better postoperative IIEF scores than cryoablation for 3 years (Li et al. 2010). Our results were compatible with this finding. It is worth noting that the real serial IIEF-5 scores of RRP may be underestimated because the neurovascular bundle sparing technique was not intentionally used in this study. In a recent systemic review, mean potency recovery rates at 12 months can reach 55–81% for patients treated with robotic-assisted laparoscopic prostatectomy and 26–63% for patients treated with retropubic radical prostatectomy (Ficarra et al. 2012). Thus, the potency rate may increase with the improvement of surgical device and technique. Besides, the patients of HIFU experienced significantly lower serial IPSS and QoL scores than did those of the other three treatments, implying better urinary function improvement. The previous study comparing radical prostatectomy, brachytherapy and cryoablation reported that the patients of brachytherapy and cryotherapy had better urinary function and bother scores than those undergoing radical prostatectomy (Malcolm et al. 2010). These conclusions were similar to our results. To sum up, the outcomes for sexual and urinary function are convincing and highlight that HIFU may be an alternative choice than the other three treatments with regard to quality of life.

In our experience, the delicate surgical margin is more easily to be controlled by HIFU because of the computer-programmed targeted area by 0.06 mL each time. Therefore, the precise “nerve-sparing” or focal HIFU decreases the erectile dysfunction rate to 22–31% and results in better sexual function preservation (Shoji et al. 2010; Poissonnier et al. 2007). Moreover, we routinely performed TURP before HIFU. The advantages of TURP before HIFU are (1) to reduce the prostate volume, especially ventral, apical or intravesical prostate tissue to avoid incomplete treatment; (2) to remove prostatic calcification or abscess that would attenuate the HIFU energy; and (3) to reduce the postoperative obstruction complication rate (from 31 to 6%) (Poissonnier et al. 2007; Chaussy and Thuroff 2003; Netsch et al. 2010). In other words, TURP before HIFU is the key point for successful oncological and functional outcomes.

Some limitations of this study should be noted. First, it was a retrospective and non-randomized study. Therefore, the inclusion criteria of the four treatment modalities cannot be defined clearly and the baseline data for the four groups cannot be totally equal. In fact, it is difficult to conduct a randomized controlled trial for surgical devices in the real world. It is a matter of patients’ performance, preference, medical cost and clinicians’ experience. Though the patients’ characteristics have statistically significant differences in each group, we compare the PSA biochemical recurrence rate in D’Amico low, intermediate and high risk group respectively, according to initial PSA, clinical stage and Gleason score. This kind of comparison may be more objective and alleviate the patient selection bias. In addition, the mean follow-up duration of nearly 3 years was relatively shorter for oncological outcomes. However, it may be sufficient for evaluation of the functional outcomes in accordance with previous studies. Finally, postoperative sexual function of patients undergoing RRP should be carefully interpreted due to lack of neurovascular bundle sparing technique in this study.

To the best of our knowledge, it is the first single institutional and comparative study discussing comparison of the oncological and functional outcomes of radical retropubic prostatectomy, high dose rate brachytherapy, cryoablation and high-intensity focused ultrasound for localized prostate cancer. Besides, there is no inter-institutional and inter-operator bias in this study because except for radiation oncologists, almost all patients undergoing these four treatments (radical retropubic prostatectomy, high dose rate brachytherapy, cryoablation and HIFU) had them performed by the same surgeon (Dr. Po Hui Chiang). Moreover, this study will provide useful information and give rise to the interest of urological oncologists. We look forward to further prospective, randomized controlled trials in the treatment of localized prostate cancer in the future.