Some prior reports have indicated that cytoreductive surgical treatment of primary tumors can afford benefits to the survival and quality of life of patients with certain cancer types, leading some researchers to propose a ‘seed and soil’ theory in which primary tumor cells can be regarded as circulating tumor cells that can seed both local and distal metastatic tumor growth. As such, prolonged primary tumor survival may increase the odds of further disease metastasis [35–39].
In certain diseases including ovarian cancer, metastatic renal cell carcinoma, and pancreatic neuroendocrine tumors, the benefits of primary tumor cytoreductive surgery have been confirmed. There is also further evidence that tumor reduction can improve the quality of life in oligometastatic prostate cancer patients [40, 41]. Importantly, this surgical intervention is feasible and safe in individuals with metastatic prostate cancer. However, as randomized controlled trials focused on this surgical intervention in oligometastatic prostate cancer patients are lacking, its purported survival benefits remain controversial.
The meta-analysis published by Cheng et al.[42] demonstrated that cytoreductive surgery offered obvious advantages in terms of overall survival, tumor-specific survival, and progression-free survival. In contrast, our included studies were more recent (after 2000), and includedmore comprehensive and updated data. In addition, instead of assessing at OS, CSS, and PFS, we examined 3-year and 5-year OS, CSS, and PFS in patients, which may have led to distinct study findings. Our analysis revealed that cytoreductive surgery can effectively improve the 3-year CSS and 5-year-PFS of patients, it cannot improve the overall survival rate and 5-year CSS of patients in the short- and medium-term. Multiple reports have similarly demonstrated the benefits of cytoreductive surgery in metastatic prostate cancer, as in a study performed by Cul et al. [43] assessing 8185 patients with IV (M1a–c) PCa (NSR (n = 7811), RP (n = 245)), which found debulking surgery to significantly improve both 5-year OS (67.4% vs 22.5%) and 5-year CSS (75.8% vs 48.7%) in these patients (p < 0.01). Gratzke et al. [44] also recently analyzed the Munich Cancer Registry dataset and found that of the 1538 newly diagnosed prostate cancer patients, 74 who had undergone RP exhibited significantly higher 5-year survival outcomes as compared to patients that did not (55% vs. 21%) (p < 0.01). Heidenreich et al. [45]further analyzed 113 metastatic prostate cancer patients from 4 institutions who had undergone surgical treatment, and observed respective 3- and 5-year OS rates of 87.6%, and 79.6%, with 3- and 5-year CSS rates of 89.3% and 80.5%, respectively. As such, cytoreductive debulking therapy offers benefits to the CSS and OS of metastatic prostate cancer patients. However, whether cytoreductive surgery also has an overall benefit for oligometastatic prostate cancer remains to be confirmed. Using prospective institutional data, Steuber et al. [46]compared 43 patients with oligometastatic prostate cancer treated with CRP and 40 patients with optimal systemic therapy and found that at a median follow-up of 82.2 months, there were no significant differences in CSS (p = 0.92) or OS (p = 0.25). The findings of this study are consistent with our results suggesting that debulking surgery did not improve the overall survival rate of patients.
In one single-institution long-term analysis of 11 oligometastatic prostate cancer patients, Gandaglia et al. [47] reported 7-year clinical progression and cancer-specific mortality (CSM)-free survival rates of 45% (95% CI, 30–85%) and 82% (95% CI, 62–99%), respectively, with long-term rates of CSM-free survival being higher than those for ADT only (48%-55%) [43, 47]. This is inconsistent with the results of our analysis, which may also be due to the short follow-up time of the included studies. However, Battaglia et al. [48] further conducted metastatic surgical treatment in 17 oligometastatic prostate cancer patients, and observed a 4-year OS of 66%, with three patients dying of prostate cancer. These results and those of our analysis suggest that cytoreductive surgery can significantly improve short-term oligometastatic prostate cancer patient CSS.
Overall, the results of this meta-analysis suggest that cytoreductive surgery does not improve the OS of prostate cancer patients. This may be attributable to the limited number of included studies and limited overall sample size, or may suggest that the side effects associated with cytoreductive surgery may contribute to a lack of overall benefit to patient OS.
There are several limitations to this analysis. For one, as randomized clinical trials on this therapeutic approach are lacking, the majority of included studies were retrospective in nature and of varying quality levels. There were also inconsistencies among studies with respect to the standards used for patient inclusion, and parameters such as PSA levels or age cannot be controlled for in our pooled analyses. Moreover, our results are inevitably affected by the short follow-up period and limited number of included patients. There was also substantial heterogeneity among the stage of metastatic prostate cancer patients included in the analyzed studies, further complicating the interpretation of these results and underscoring directions for further study.