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Prostatectomía radical citorreductora comparado a no realizar tratamiento local en pacientes con cáncer de próstata metastásico

Cytoreductive radical prostatectomy versus no local treatment in patients with metastatic prostate cancer

Abstract

Introduction Prostate cancer is one of the most frequent cancers in Chile, with 8157 new cases in 2020. Worldwide, 5 to 10% of men have metastatic disease at diagnosis, and androgen deprivation therapy with or without chemotherapy is the standard of care for these patients. The use of local treatment in this setting has no formal recommendation due to the lack of high- quality evidence. Some retrospective studies have sought to elucidate the benefit of surgery on the primary tumor in the setting of metastatic disease since it has been proven to be an effective local treatment for other metastatic malignant diseases. Despite these efforts, the benefit of cytoreductive radical prostatectomy as local treatment in these patients remains unclear.

Methods We searched Epistemonikos, the largest database of systematic reviews in health, which is main-tained by screening multiple information sources, including MEDLINE, EMBASE, and Cochrane, among others. We extracted data from systematic reviews, reanalyzed data from primary studies, conducted a meta- analysis, and generated a summary results table using the GRADE approach.

Results and conclusions We identified 12 systematic reviews, including seven studies in total, none of which was a trial. Only six of those seven primary studies were used in the results summary. Despite the lack of high- quality evidence, the results summary shows the benefits of performing surgery on the primary tumor in terms of all- cause mortality, cancer- specific mortality, and disease progression. There was also a potential benefit in local complications related to the progression of the prima-ry tumor, supporting the implementation of this intervention in patients with metastatic disease. The absence of formal recommendations highlights the need to evaluate the benefits of surgery on a case- by- case basis, presenting the available evidence to patients for a shared decision- making process and considering future local complications that could be difficult to manage.

Main messages

  • Cytoreductive radical prostatectomy probably reduces the risk of cancer-specific mortality compared to no local treatment in patients with metastatic prostate cancer.
  • All-cause mortality, disease progression, and local complications related to metastatic prostate cancer may be reduced when using cytoreductive radical prostatectomy compared to no local treatment (low certainty of evidence).
  • We are uncertain whether cytoreductive radical prostatectomy reduces the probability of developing castration resistance compared to no local treatment.

Problem

Prostate cancer is the most frequent solid tumor in the Western world. It represents 7.3% of all new cancer cases worldwide, being responsible for 375 304 deaths yearly. In Chile, prostate cancer is the most frequent cancer, with 8157 new cases in 2020, corresponding to 15% of all new cancer cases registered for that year [1,2].

In general, 5 to 10% of men with prostate cancer exhibit metastasic disease at diagnosis[3]. The standard of care for these patients has not changed in recent years, corresponding to a systemic treatment targeting the androgen axis through hormonal deprivation, using drugs, or surgical castration. In recent years, it has been established that androgen deprivation therapy may be administered with chemotherapy using docetaxel or second-generation hormonal therapy [4,5].

Due to the lack of high-quality evidence, there is no formal recommendation to use local treatments for primary tumors (i.e., surgery or radiation therapy) in patients with metastatic prostate cancer. Particularly, several retrospective studies have sought to elucidate the benefit of surgery on the primary tumor in the setting of metastatic disease since there is evidence of its efficacy on other metastatic malignancies, such as ovarian and renal cancer [6,7]. The evidence supporting this idea is based on multiple biological foundations, establishing that the cells in the primary tumor may have the ability to maintain the sowing of metastases to distant organs. Moreover, untreated local tumors could act as a source of remote seeding and for seeding and resistance in the tumor itself [8,9].

This summary aims to review the available literature published on this matter to determine the impact of cytoreductive radical prostatectomy compared to no local treatment in patients with metastatic prostate cancer.

Methods

We searched Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, and Cochrane, among others, to identify systematic reviews and their included primary studies. We extracted data from the identified reviews and reanalyzed data from primary studies included in those reviews. With this information, we generated a structured summary denominated FRISBEE (Friendly Summary of Body of Evidence using Epistemonikos) using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), a meta-analysis of the studies, and when possible, a summary-of-findings table following the GRADE approach and a table of other considerations for decision-making.

The body of evidence for this question

About the body of evidence for this question.
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Summary of findings

Information about the effect of cytoreductive radical prostatectomy on metastatic prostate cancer is based on six observational studies, including 10 731 patients in total.

All studies analyzed in this summary were observational with two different designs, cohort and case-control studies. Given this fact, only studies with the same design were pooled in the analysis of each reported outcome.

Five studies reported the outcome of all-cause mortality [21,22,24,26,27]; however, the data needed for the analysis could not be extracted from one of them [22], and an additional study was excluded since it presented a different design [27]. Three studies reported cancer-specific mortality [22,23,26], but one was also excluded [22]. One study evaluated disease progression [23], and two reported the development of castration resistance [22,27]. Outcomes related to complications were reported in three studies, but only the information available in two could be used in the analysis [22,27].

The summary of findings is as follows:

  1. Cytoreductive radical prostatectomy probably reduces cancer-specific mortality compared to no local treatment.

  2. Local treatment using cytoreductive radical prostatectomy may reduce the risk of all-cause mortality compared to no local treatment.

  3. The treatment with cytoreductive radical prostatectomy may reduce disease progression compared to no local treatment.

  4. Cytoreductive radical prostatectomy may reduce severe local complications compared to no local treatment.

  5. Cytoreductive radical prostatectomy may reduce grade IIIb complications, as measured by the Clavien-Dindo classification, compared to no local treatment.

  6. We are uncertain whether cytoreductive radical prostatectomy reduces the probability of developing castration resistance compared to no local treatment.

iSoF Table.
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About the certainty of the evidence (GRADE)*
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Other considerations for decision-making
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How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and presented it as a matrix of evidence.

Follow the link to access the interactive version: Cytoreductive radical prostatectomy versus no local treatment in patients with metastatic prostate cancer.

Notes

The upper portion of the evidence matrix will display a warning of “new evidence” if new systematic reviews are published after this summary's publication. Even though the project considers the periodic update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence, and the summary should be updated earlier.

After creating an account in Epistemonikos, users can save the matrixes and receive automated notifications whenever new evidence potentially relevant to the question appears. This article is part of the Epistemonikos Evidence Synthesis project. It is elaborated with a pre-established methodology, following rigorous methodological standards and an internal peer review process. Each of these articles corresponds to a summary, denominated FRISBEE (Friendly Summary of Body of Evidence using Epistemonikos), whose main objective is to synthesize the body of evidence for a specific question with a friendly format to clinical professionals.

Its main resources are based on the evidence matrix of Epistemonikos and analysis of results using GRADE methodology. Further details of the methods for developing this FRISBEE are described here: (http://dx.doi.org/10.5867/medwave.2014.06.5997)

Epistemonikos Foundation is a not-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is the Epistemonikos database (www.epistemonikos.org).