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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Does local treatment of the prostate in advanced and/or lymph node metastatic disease improve efficacy of androgen-deprivation therapy? A systematic review

PC Verhagen, FH Schroder, L Collette, and CH Bangma.

Review published: 2010.

Link to full article: [Journal publisher]

CRD summary

This review concluded that there may be an interaction between local treatment and androgen-deprivation therapy in prostate cancer. In men at high risk of death from the disease treated with curative intent for their primary tumour, immediate and sustained androgen-deprivation therapy significantly improved survival. Methodological limitations in the review process suggest that these conclusions should be viewed with caution.

Authors' objectives

To clarify a possible interaction between local treatment and androgen-deprivation therapy as immediate versus deferred/adjuvant therapy in patients with prostate cancer.

Searching

MEDLINE and EMBASE were searched (from 1970) for published studies. Search terms were not reported.

Study selection

Randomised studies on immediate versus deferred/adjuvant androgen-deprivation therapy (orchiectomy or luteinising hormone-releasing hormone analogues) in patients with prostate cancer were eligible for inclusion. Studies had to report cancer specific survival and overall survival. Studies of anti-androgens only or oestrogens were excluded.

The included studies compared: immediate versus deferred androgen-deprivation therapy; androgen-deprivation therapy adjuvant to local therapy versus local therapy alone; short-term versus long-term androgen-deprivation therapy adjuvant to radiation therapy; androgen-deprivation therapy neoadjuvant plus concomitant radiation therapy versus radiation therapy alone; and local radiation therapy versus no local therapy combined with androgen-deprivation therapy. When local therapy was administered, it was at 65 to 70Gy, 3D conformal radiation therapy, or a radical prostatectomy. In studies with a delay in treatment control, the delay ranged from 1.8 to seven years (where reported). Prostate cancer stages varied between studies.

The authors did not state how study selection was performed.

Assessment of study quality

The authors did not state that study quality was assessed.

Data extraction

Data were extracted to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs); for one study in which only the total number of events and patients were available, odds ratios (ORs) and 95% confidence intervals were calculated. For the studies of androgen deprivation therapy as adjuvant therapy, the studies were also analysed in radiotherapy and prostatectomy subgroups.

The number of reviewers that performed data extraction was not reported.

Methods of synthesis

Hazard ratios and 95% confidence intervals were pooled in a fixed-effect meta-analysis. Heterogeneity was assessed using Ι² and Χ².

Results of the review

Sixteen RCTs were included in the review (n=11,040 men, range 91 to 1,554; one study provided two treatment arms).

Immediate androgen-deprivation therapy without local treatment was associated with statistically significant improvements in overall survival of 10% (HR 0.90, 95% CI 0.83 to 0.97; five studies, six treatment arms) and improvements in cancer-specific survival of 21% (HR 0.79, 95% CI 0.71 to 0.89; five studies, six treatment arms) compared with delayed (deferred) androgen-deprivation therapy. Heterogeneity (Ι²) was not reported.

Adjuvant androgen-deprivation therapy was associated with a reduction in the risk of death of 31% (HR 0.69, 95% CI, 0.61 to 0.79; five studies; Ι²=10%) and in prostate cancer death of 49% (HR 0.51, 95% CI, 0.41 to 0.63; five studies; Ι²=59%) compared with local treatment alone.

Similar results were shown when restricted to the studies involving radiation as primary treatment.

Authors' conclusions

An interaction between local treatment and androgen-deprivation therapy was suggested in this review. In men with advanced and aggressive disease who were at a high risk of death from prostate cancer and who were treated with curative intent for their primary tumour, immediate and sustained androgen deprivation therapy improved overall survival and cancer-specific survival significantly.

CRD commentary

The research question was supported by inclusion criteria for participants, interventions, comparators, outcomes and study design. However, a wider variety of comparator interventions were included than stated in the inclusion criteria. Search terms were not reported, so the search strategy was not transparent or reproducible. Only two databases were searched for published studies and it was unclear whether language restrictions were applied. The review may be prone to publication bias and it is possible that relevant studies could have been missed. It was not reported whether steps were taken to minimise the risk of error and bias in the review process.

Study quality did not appear to have been assessed, so the reliability of these studies and their results is not known. The authors stated that the primary study populations differed considerably in the analysis of immediate versus deferred androgen deprivation therapy, but statistical heterogeneity was substantial for several other analyses, so the results of these analyses may not be reliable.

Several methodological limitations in the review process suggest that the authors' conclusions should be viewed with considerable caution.

Implications of the review for practice and research

Practice: The authors stated that, although many clinicians hesitated to offer a local treatment to a patient who could not be cured, the current analysis suggested that this was an important component of the optimal therapy that contributed to better survival. Whether the survival advantage of combined treatment was large enough to counterbalance the side effects of prolonged androgen-deprivation therapy and local treatment was an issue that should be settled in discussion with an informed patient.

Research: The authors did not state any implications for research.

Funding

One author was supported by EORTC (European Organisation for Research and Treatment of Cancer) charitable trust.

Bibliographic details

Verhagen PC, Schroder FH, Collette L, Bangma CH. Does local treatment of the prostate in advanced and/or lymph node metastatic disease improve efficacy of androgen-deprivation therapy? A systematic review European Urology 2010; 58(2): 261-269. [PubMed: 20627403]

Indexing Status

Subject indexing assigned by NLM

MeSH

Combined Modality Therapy; Gonadotropin-Releasing Hormone /analogs & derivatives; Humans; Lymphatic Metastasis; Male; Neoplasm Invasiveness; Neoplasm Staging; Orchiectomy; Prostatic Neoplasms /drug therapy /pathology /radiotherapy /surgery; Randomized Controlled Trials as Topic

AccessionNumber

12011000540

Database entry date

23/03/2012

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 20627403

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