Phase III Postoperative Adjuvant Radiotherapy After Radical Prostatectomy Compared With Radical Prostatectomy Alone in pT3 Prostate Cancer With Postoperative Undetectable Prostate-Specific Antigen: ARO 96-02/AUO AP 09/95

Wiegel, Thomas; Bottke, Dirk; Steiner, U.; Siegmann, Alessandra; Golz, Reinhard; Störkel, Stephan; Willich, N.; Semjonow, Axel; Souchon, Rainer; Stöckle, Michael; Rübe, Christian; Weißbach, L.; Althaus, P; Rebmann, U.; Kälble, T.; Feldmann, Horst Jürgen; Wirth, Manfred P.; Hinke, Axel; Hinkelbein, W.; Miller, Kurt

doi:10.1200/jco.2008.18.9563

Cited by 768 publications

(408 citation statements)

References 19 publications

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“…37 Indeed, we did find here that adjuvant RT was associated with a significant decrease in the risk of the outcome measure receipt of salvage therapy or progression. These data likely reflect the previouslydocumented protective effect of adjuvant RT on BCR, 4,5,36 an outcome measure which has been linked to utilization of secondary cancer treatments. 38 Moreover, additional pathological features, which may have impacted outcome, such as the presence of focal versus extensive positive margins, were not separately analyzed.…”

Section: Discussionsupporting

confidence: 59%

“…As such, decisions to treat with adjuvant and salvage therapies were based on patient preference and physician counseling, and were thereby subject to inherent selection bias. Thus, our findings, in particular, regarding the non-significant association of adjuvant RT with disease progression and mortality must be interpreted in light of this study design, particularly as prospective randomized trials have demonstrated a benefit to adjuvant RT on reducing the risk of BCR 4,5,36 and, in one series, mortality. 37 Indeed, we did find here that adjuvant RT was associated with a significant decrease in the risk of the outcome measure receipt of salvage therapy or progression.…”

Section: Discussionmentioning

confidence: 85%

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Clinicopathological predictors of systemic progression and prostate cancer mortality in patients with a positive surgical margin at radical prostatectomy

Boorjian

Tollefson

Rangel

et al. 2011

Prostate Cancer Prostatic Dis

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BACKGROUND: Although a positive surgical margin (PSM) at radical prostatectomy (RRP) has been consistently linked to an increased risk of biochemical recurrence, the impact of margin status on patient survival continues to be debated. We evaluated long-term outcomes of patients with a PSM at RRP and determined predictors of systemic progression (SP) and mortality in these men. METHODS:We reviewed our institutional registry of 16 749 patients who underwent RRP between 1990 and 2008 to identify 2895 patients with a PSM. Median follow-up was 10.6 years. Postoperative survival was estimated using the Kaplan-Meier method. Cox proportional hazard regression models were used to analyze clinicopathological variables associated with SP and death from prostate cancer. RESULTS:A 15-year SP-free and cancer-specific survival was 90 and 93%, respectively. On multivariate analysis, higher tumor volume, increased pathological Gleason score and advanced pathological tumor stage were associated with significantly increased risks of SP and death from prostate cancer, whereas number and location of PSM did not predict mortality. CONCLUSIONS:The risks of SP and prostate cancer death in patients with a PSM remain low on long-term follow-up. Tumor variables are the primary determinants of cancer death. These results should be considered when evaluating patients with a PSM for adjuvant therapy.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 85%

Clinicopathological predictors of systemic progression and prostate cancer mortality in patients with a positive surgical margin at radical prostatectomy

Boorjian

Tollefson

Rangel

et al. 2011

Prostate Cancer Prostatic Dis

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“…Three randomized multi-centre trials comparing adjuvant radiotherapy versus no adjuvant treatment for post-RP patients who had either EPE, PSM, SVI, or a combination thereof, showed fewer and/or later BCF, metastasis development and longer progression-free survival for those who received adjuvant radiotherapy. 1,2,3,23 The Southwest Oncology Group (SWOG) study by Thompson et al, 2 with longer follow-up, recently also showed an overall survival benefit with adjuvant radiotherapy compared with the 'wait and see' approach. No studies, however, have compared adjuvant therapy with early salvage therapy before PSA failure, an issue which is being addressed with another multi-center randomized controlled trial (the 'RADICALS' study).…”

Section: Discussionmentioning

confidence: 99%

“…For example, although some studies [1][2][3][4] have found that immediate adjuvant treatment decreased the risk of biochemical failure (BCF) in patients with PSM and extracapsular tumor extension, it is not entirely clear what its effects are on distant metastasis and survival, in spite of one recent report (SWOG 8794 study) indicating a statistical advantage for early adjuvant radiotherapy. The SWOG study stated that adjuvant radiotherapy resulted in significantly reducing the risk of PSA relapse and disease recurrence compared to the 'wait and see' approach (median PSA relapse-free survival was 10.3 years for adjuvant therapy vs 3.1 years for observation and median recurrence-free was 13.8 years for adjuvant therapy vs 9.9 years for observation).…”

Section: Introductionmentioning

confidence: 99%

The clinical significance of in-depth pathological assessment of extraprostatic extension and margin status in radical prostatectomies for prostate cancer

Chan

Garcı́a

Chin

et al. 2011

Prostate Cancer Prostatic Dis

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Despite recent Level 1 evidence on the benefits of adjuvant radiotherapy for locally advanced prostate cancer (PCa), the timing and decision to administer adjuvant radiotherapy post-radical prostatectomy (post-RP) remains debatable, particularly for patients with focal extraprostatic extension (EPE) and/or focal positive surgical margins (PSMs). In this study, we assess the utility of detailed pathological assessment of EPE and PSM, as this may influence the criteria for instituting adjuvant radiotherapy. A total of 148 RP cases (1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001) were identified retrospectively as having EPE and/or PSM. All slides were re-reviewed, incorporating recent proposals by the Collage of American Pathologists (CAP) for the reporting of EPE and PSM, and correlated with clinical data. Both EPE and PSM were found to be independent predictors of biochemical failure (BCF); however, only EPE was associated with metastasis and death. BCF was also more likely to be associated with cases that had non-focal EPE than focal EPE. Similarly, non-focal PSM cases had a significantly higher risk of BCF than focal cases. Our study confirms the value of detailed pathological assessment of EPE and PSM post-RP. The results support the concept of selective adjuvant radiotherapy in patients with EPE and PSM, based on focality and extent.

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“…In the Wiegel trial, 1% and 0% of patients had grade 3 bladder and bowel problems. 3 This is despite patients receiving 2-dimensional RT; RT has improved greatly in target localization with image-guided techniques and my experience is that modern RT has even fewer side effects.…”

mentioning

confidence: 99%

Opportunity lost and found: Any easy way to improve outcomes for prostate cancer patients in the postoperative setting?

Loblaw¹

2013

CUAJ

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E vidence-based medicine is a paradigm shift and is a key component in the provision of high-quality care. The highest quality evidence is clinical practice guidelines based on systematic reviews of the randomized controlled trial (RCT) literature. There are many challenges to successfully complete RCTs and it is problematic to synthesize recommendations when the RCTs have conflicting results.However, in the case of the utility of adjuvant postoperative radiotherapy (ART), this is not the case. There are three RCTs showing improvements in local and biochemical control; 1-3 the study with the longest follow-up (SWOG 8794) also demonstrates improvements in distant metastatic disease-free survival and overall survival. 2 Cancer Care Ontario (CCO) published a systematic review of the literature and clinical practice guideline on the topic showing that all subgroups benefitted in biochemical control and overall survival from ART (and those with seminal vesicle involvement seemed to benefit more not less). 4 It is very interesting to see how this evidence is applied in the pragmatic setting. In this issue of CUAJ, Tyldesley and colleagues have published a population-based analysis of postoperative radiotherapy in British Columbia from 2007 to 2009. 5 Many interesting facts are reported. Over the 3-year observation period, 9223 patients were identified from the tumour registry and linked to centralized radiotherapy records. Of these patients, initial therapy was radical prostatectomy in 24%. Postoperatively, 47% had one or more highrisk features (positive surgical margin: 36%; extracapsular spread: 22%; seminal vesicle involvement: 4%). 5 Of the 47% with one or more high-risk features, 23% with any adverse features were seen by a radiation oncologist within 6 months of surgery. Only 10% of these patients received adjuvant ART (i.e., 2% of patients with any highrisk features). Of equal interest, 40% of those with adverse features who were seen were advised against ART.Why are the rates of referral (23%) and recommendation (60%) and use of ART (2%) so low for these patients?The first argument is a lack of knowledge. The EORTC and SWOG studies were published in 2005 and 2006, respectively (and all were presented in abstract before the observation period). Despite this, we know that evidence takes a while to diffuse into practice, particularly community practice. How long is too long when we have a treatment with a solid evidence base that improves not just biochemical, but distant metastatic disease and overall survival rates? Is there anything we could have done differently to accelerate this knowledge dissemination?The second argument is that the treatment is too toxic. It is easy to attribute really bad side effects (such as severe hemorrhagic cystitis) to all patients who might get radiation. However, when prospectively collected, the data demonstrate that the risk of serious RT toxicity was low. In the Wiegel trial, 1% and 0% of patients had grade 3 bladder and bowel problems. 3 This is despite patients receiving 2-d...

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Phase III Postoperative Adjuvant Radiotherapy After Radical Prostatectomy Compared With Radical Prostatectomy Alone in pT3 Prostate Cancer With Postoperative Undetectable Prostate-Specific Antigen: ARO 96-02/AUO AP 09/95

Abstract: Adjuvant RT for pT3 prostate cancer with postoperatively undetectable PSA significantly reduces the risk of biochemical progression. Further follow-up is needed to assess the effect on metastases-free and overall survival.

Cited by 768 publications

References 19 publications

Clinicopathological predictors of systemic progression and prostate cancer mortality in patients with a positive surgical margin at radical prostatectomy

Clinicopathological predictors of systemic progression and prostate cancer mortality in patients with a positive surgical margin at radical prostatectomy

The clinical significance of in-depth pathological assessment of extraprostatic extension and margin status in radical prostatectomies for prostate cancer

Opportunity lost and found: Any easy way to improve outcomes for prostate cancer patients in the postoperative setting?

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