Adjuvant radiotherapy following radical prostatectomy for pathologic T3 or margin-positive prostate cancer: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Results following radical prostatectomy (RP) are suboptimal in patients found to have cancer extending beyond the prostatic capsule (pT3) or present at the resection margins (R1). The optimal postoperative management of such patients is undefined. Therapeutic alternatives include adjuvant radiotherapy (RT) or active surveillance. METHODS: Randomized controlled trials (RCTs) were eligible for inclusion in this systematic review if they compared adjuvant RT in the immediate period after RP to active surveillance - with therapies held in reserve for salvage - in prostate cancer patients with pT3 or R1 disease or both. The primary outcome of interest was overall survival. RESULTS: Three RCTs representing 1,743 patients satisfied the eligibility criteria. Two trials reported data on overall survival; a meta-analysis of the data showed no significant improvement associated with adjuvant RT (hazard ratio=0.91, 95% CI 0.67-1.22, p=0.52). All trials reported data on biochemical progression-free survival (bPFS). On meta-analysis, adjuvant RT significantly improved bPFS (hazard ratio=0.47, 95% CI 0.40-0.56, p<0.00001). One trial provided comparative graded toxicity data; there were no significant differences between arms in severe (grade 3) gastrointestinal or genitourinary toxicity at five years. CONCLUSIONS: To date, adjuvant RT has not been shown to improve overall survival compared with active surveillance. Longer follow-up from completed RCTs is required to accurately assess this outcome. Adjuvant RT does, however, significantly improve bPFS and is not associated with excess severe late toxicity.

Interferon-alfa in the treatment of patients with inoperable locally advanced or metastatic renal cell carcinoma: a systematic review.

A systematic review was undertaken to determine whether interferon-alfa (IFN-alpha) is an effective treatment for patients with inoperable locally advanced or metastatic renal cell carcinoma (mRCC). MEDLINE, EMBASE, the Cochrane Library, guideline databases and relevant meeting proceedings were searched. Randomized clinical trials (RCTs) or meta-analyses comparing IFN-alpha-containing regimens to placebo or non-immunotherapy controls, and that reported response rate, survival, toxicity or quality of life data were eligible. Two systematic reviews and eight RCTs met the selection criteria. A Cochrane review updated in 2005 reported higher response rates and reduced one-year mortality based on 4 RCTs in patients who received IFN-alpha. Of the eight RCTs, three reporting objective response rate showed significant differences favouring IFN-alpha. Two of five trials reporting survival data showed longer median survival in the IFN-alpha group. Adverse effects of IFN-alpha were consistent across the trials with increased intensity and frequency concordant with increased IFN-alpha dose. Meta-analyses of seven RCTs for objective response and six RCTs for mortality favoured IFN-alpha: odds ratio 6.87 (95% Confidence Interval [CI], 3.29 to 14.35) and hazard ratio 0.79 (95% CI, 0.69 to 0.91), respectively. The effectiveness of IFN-alpha in mRCC has been subject to skepticism. As IFN-alpha has been used as a control arm in RCTs of new targeted therapies, therapies which not all patients may have access to, information about its effectiveness remains relevant. These data confirm genuine, if modest, effectiveness of IFN-alpha in mRCC.

Guideline for optimization of surgical and pathological quality performance for radical prostatectomy in prostate cancer management: evidentiary base.

BACKGROUND: The objective is to provide surgical and pathological guidelines for radical prostatectomy (RP) with or without concurrent pelvic lymph node dissection (PLND) to achieve optimal benefit for patients, with minimal risk of harm. METHODS: For surgical questions, a literature search of MEDLINE, EMBASE and the Cochrane database was performed. A literature search for the pathological questions was not conducted since the protocol for invasive carcinomas of the prostate gland developed by the College of American Pathologists (CAP) was endorsed. Urologists and pathologists were consulted for their assessment of the surgical and pathological recommendations. RESULTS: Limited high-quality evidence from 95 primary studies was available and, therefore, the expert panel developed recommendations on the basis of a consensus of the expert opinion of the working group and through a consultation with urologists and pathologists. In addition to the CAP protocol, some technical recommendations related to the handling and processing of the specimen were made. CONCLUSION: Radical prostatectomy is recommended for the surgical treatment of prostate cancer, depending on a patient's preoperative risk profile. The panel unanimously determined that the goals for RP are to attain a positive margin rate of <25% for pT2 disease, a mortality rate of <1%, rates of rectal injury of <1% and blood transfusion rates of <10% in non-anemic patients. Standard PLND should be mandatory in high-risk patients, should be recommended for intermediate-risk patients and should be optional for low-risk patients. The quality and effectiveness of this treatment and of subsequent patient care depend on good management, effective communication and reporting between surgeons and pathologists working together as part of a multidisciplinary team. The complete guideline document is posted on the Cancer Care Ontario website (www.cancercare.on.ca); search in their Toolbox, Quality Guidelines & Standards, Clinical Program category under "surgery."