| To whom this evidence does and does not apply |
| The evidence applies to patients with metastatic prostate cancer that will undergo surgery on the primary tumor. Patients with oligometastatic disease are included in this analysis.The results do not apply to patients in earlier prostate cancer stages undergoing local treatment or patients with metastatic disease treated with a local treatment different from cytoreductive radical prostatectomy. |
| About the outcomes included in this summary |
| The most frequently reported outcomes in the systematic reviews are all-cause mortality, also named overall survival, and cancer-specific mortality, also called cancer-specific survival. The authors of this summary agree that these outcomes are of great importance for the decision-making process of the treatment for metastatic prostate cancer.Other secondary oncological outcomes reported were progression-free survival, referred to as disease progression in this summary, and castration-free survival, named development of castration resistance here, but only in systematic reviews without meta-analysis due to the low frequency in which they are reported. These outcomes provide relevant information about the benefit of the intervention; however, outcomes related to mortality are essential for patients' and doctors’ decision-making.Regarding complications, the outcomes reported in this summary are critical for decision-making since they represent local complications derived from disease progression. Severe local complications represent a more general outcome that may be more understandable to patients, including complications related to disease and surgery. Complications reported using the Clavien-Dindo classification are informative for clinicians because they report complications specifically associated with surgical procedures. Only complications graded IIIb or greater were reported, reflecting the need for further surgeries. No grade IV or V complications were presented in either group; therefore, those results were not reported in the summary.Surgical or percutaneous intervention and urinary tract complications in patients without local treatment and urinary continence in patients undergoing prostatectomy are also important outcomes to declare, as they represent what can be avoided when deciding to use one treatment or the other. However, since these outcomes cannot be reported for both groups, they were excluded from this summary. |
| Balance between benefits and risks and certainty of the evidence |
| Cytoreductive radical prostatectomy was associated with improved cancer-specific mortality, reducing the risk of death because of cancer by 61% compared to no local treatment (HR = 0.39; CI 0.22 to 0.69). The risk of all-cause mortality was reduced by 50% in patients undergoing surgery (HR = 0.50; CI 0.44 to 0.57), but this result is less probable since it was obtained from low-quality evidence.Cytoreductive radical prostatectomy may also reduce disease progression and showed a potential benefit in preventing secondary local complications related to the primary tumor progression.The benefit of cytoreductive radical prostatectomy compared to no local treatment in the development of castration resistance is uncertain because the quality of the evidence reporting this outcome was very low. |
| Resource considerations |
| None of the systematic reviews reported analyses of the cost of surgery in relation to its benefits for patients with metastatic prostate cancer. The nature of available evidence makes it inappropriate for estimating the benefits of the intervention to determine its cost-benefit since it comes from observational studies. Further high-quality studies (i.e., randomized trials) are needed to determine the cost-effectiveness of cytoreductive radical prostatectomy compared to no local treatment.Despite the lack of formal analyses in this matter, it is important to notice that even though the surgery implies more costs for patients than no local treatment, cytoreductive radical prostatectomy may avoid the need for future surgeries related to complications derived from disease progression, reducing future costs.Formal analyses are needed to elucidate the cost-effectiveness of cytoreductive radical prostatectomy compared to no local treatment in metastatic prostate cancer. |
| What would patients and their doctors think about this intervention |
| The management of metastatic prostate cancer considers systemic hormonal deprivation as the main treatment, with no localized therapy on the prostate. This could be a difficult fact for patients to understand, especially for those with de novo metastases, where primary tumor treatment has not been formally recommended. Additionally, a part of the urologist community may reject the idea of performing surgery on these patients because they consider surgery a more complex, high-risk procedure with no proven clinical benefit.The decision to use this surgical treatment must be discussed and evaluated jointly by patients and doctors since cytoreductive prostatectomy is not the standard of care for metastatic prostate cancer. It is important to clarify and explain the procedure's potential risks and benefits, focusing on the possible benefits of disease control regarding mortality, disease progression, time to castration resistance, and complication. The benefit of providing information on the time to castration resistance to patients is still unclear.Additionally, it must be explained to the patients that this intervention aims to prolong survival and improve local control regarding long-term symptoms. Patients value this last point because they are afraid of feeling pain and of the need for additional surgeries, which could be more complex in patients that did not undergo cytoreductive radical prostatectomy as a first treatment.It is very unlikely that the results of this summary influence the recommendations in the clinical guidelines; however, they provide important information that should be shared with patients about oncological and symptomatic management. |
| Differences between this summary and other sources |
| The results of this summary are consistent with those reported in the systematic reviews included in this summary, where cytoreductive radical prostatectomy was associated with a reduction in mortality compared to no local treatment in terms of all-cause mortality and cancer-specific mortality. Disease progression and development of castration resistance were less reported in primary studies and systematic reviews; therefore, no clear conclusions can be reported about these outcomes. Despite these conclusions about survival benefits, all systematic reviews acknowledge the need for randomized trials to elucidate the real benefit of prostatectomy on patients with metastatic prostate cancer.Regarding non-oncological outcomes, the systematic reviews agree that cytoreductive radical prostatectomy is a beneficial intervention for these patients since it reduces local complications compared to no local treatment. Our results are consistent with this conclusion, as severe local complications and grade IIIb complications in the Clavien-Dindo classification were reduced in the group undergoing surgery.Guidelines establish that the standard of care for patients with metastatic disease at presentation is androgen deprivation therapy with or without chemotherapy. The evaluation of the role of cytoreductive radical prostatectomy in these patients has not been described yet, as results of ongoing trials assessing its benefit have not been reported yet [4,5]. |
| Could this evidence change in the future? |
| In general, the results of this summary are likely to change due to the low and very low certainty of the evidence for overall survival, progression-free survival, castration-resistance-free survival, and the outcomes related to complications. Only the result of cancer-specific survival had moderate certainty of evidence; therefore, in the presence of new studies, the effect found may change, but it is less likely.Cohort studies have an inherent selection bias, where patients in the group with cytoreductive radical prostatectomy were normally younger and had fewer comorbidities, lower T-stage, and lower initial level of prostate-specific antigen, among other characteristics. Some of the included studies used a propensity score matching to deal with this issue; however, those results were not included in this summary since, in some cases, their sample size was not reported. This is important to mention since this problem may influence our results, and randomized trials are needed to confirm our findings.We found one prospective cohort study [28] that could be relevant. Still, it was not cited in any of the systematic reviews included in this summary or the clinical guidelines used in our institution.Six ongoing randomized trials evaluating cytoreductive radical prostatectomy versus no local treatment in patients with metastatic prostate cancer were reported in the systematic reviews, and the clinical trials register (clinicaltrials.gov) [29–34]. Additionally, two ongoing systematic reviews were found in the International Prospective Register of Systematic Reviews (PROSPERO) [35,36]. |
