Based on our study cohort of 18,841 patients with low-risk PCa from 2010 to 2016 from the SEER database, the main finding of our study was that OS of patients receiving AS/WW treatment was better compared to patients receiving FLA treatment. In a median follow-up of 36.00 months, we found that both OS and CSS showed similar results after model adjustments, PSM, and sensitivity analysis. Using available data, we further examined data of the AS/WW group, which included patients receiving either AS or WW treatment. Although some guidelines and researchers have collectively grouped AS and WW (12, 30–33), and they are treated as a single variable in SEER data, there are important differences between the two approaches. AS is a monitoring strategy for patients with low-risk PCa, allowing patients to delay active treatment without cancer progression. Its purpose is to achieve treatment of progressive diseases without losing the therapeutic window (34). In contrast, WW is a conservative treatment of patients who are considered unsuitable for treatment from the beginning. It requires observation of patients and palliative treatment according to symptoms to maintain quality of life (30). Although we applied many methods to eliminate bias between AS/WW and FLA in our groups, it is still important to consider potential intragroup differences within AS/WW.
Similarly, in our consideration of AS/WW, there are a number of considerations regarding FLA. It is a new protector therapy for PCa, in which thermal ablation using a laser fiber can lead to cell death by raising the temperature above 60 ℃. The intent behind FLA is to reduce complications as well as improve quality of life of patients, albeit having no effect on tumor control (25, 35). To date, a small number of studies with a maximum follow up of one year reported the clinical application of FLA, but they lack long-term evidence (23, 25, 36, 37). Nevertheless, it was determined that FLA provided benefits for patients with low-risk PCa, and furthermore, concluded that FLA was a feasible and safe minimally invasive treatment for patients eligible for AS and radical treatment. However, van Luijtelaar et al. took the position that FLA should not be applied to candidates of AS and patients receiving FLA should be closely followed (38). Therefore, the FLA and AS groups were comparable for clinical use, and the findings match those from our study. OS did differ between patients with low-risk PCa from the AS/WW-treated and FLA-treated groups.
It is not unreasonable to consider that prognostic differences exist for different treatments. A study (39) showed that in a series of men who received AS with selective deferred therapy, many patients who eventually received radical prostatectomy were found to have advanced disease. It was also reported that short-term oncology results of FLA are promising, in which 50% of patients have no evidence of a tumor in the postoperative biopsy and 67% of patients have no tumor in the resection area (40). Such differences may be reflected in the survival and prognosis between these two treatments. As shown in our study, although no statistical differences were observed in CSS, we still found distinguishing characteristics between the AS/WW and FLA groups. Our main results show an obvious and robust difference in OS between the two groups; a finding that suggests the treatment approach of AS/WW is superior to that of FLA. In addition, we conducted a series of sensitivity analyses to evaluate stability and reliability, and found that CSS significantly differed between our groups after PSM. Although this finding was not identical with the main result of our investigation, it is still aligned with the fact that AS/WW improved survival status significantly over FLA. Furthermore, our findings following IPTW analysis confirm this conclusion by identifying differences in OS between groups.
To our knowledge, this investigation is the first comparative study of FLA and AS/WW in prostate cancer. In addition, our study had a number of advantages. First, we were able to recruit a large cohort with over 18,000 patients with low-risk PCa. Second, in contrast to present studies that have focused on short-term tumor control, our cohort had a medium-term follow-up and we also investigated long-term survival. Finally, we used a robust array of statistical analysis methods to eliminate bias. Although the findings from our study warrant further research, there were some limitations. Despite the attempt to randomize our study using statistical methods, a retrospective study cannot have the same level of evidence as a randomized controlled trial. In addition, because of limitations of the SEER database, the baseline data of patients is not comprehensive, and therefore, there may be latent confounders. Although we used PSM to address these limitation, we cannot avoid the possibility of potential bias in the AS/WW group. Further, patients with a long life expectancy would lack long-term AS/WW data.
In conclusion, compared with standard treatment, AS/WW and FLA have the advantage of fewer side effects and the benefit of avoiding overtreatment. The findings from our study show that treatment using AS/WW confers survival benefits to patients with low-risk PCa. We call for further research to investigate the clinical applicability of these treatment modalities toward ensuring that the best treatment is available for patients with low-risk PCa.