Radical Prostatectomy versus Watchful Waiting in Early Prostate Cancer

Bill‐Axelson, Anna; Holmberg, Lars; Ruutu, Mirja; Häggman, Michael; Andersson, Swen‐Olof; Bratell, Stefan; Spångberg, Anders; Busch, Christer; Nordling, Stig; Garmo, Hans; Palmgren, Juni; Adami, Hans‐Olov; Norlén, Bo Johan; Johansson, Jan‐Erik

doi:10.1056/nejmoa043739

Cited by 1,162 publications

(719 citation statements)

References 13 publications

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“…There are several limitations to our trial, most noteworthy, the use of a surrogate endpoint (treatment failure) rather than death from prostate cancer or metastatic progression. For patients with localized disease, as shown in the Scandinavian trial, 19 cancer-specific death rates are very low in the first 10 years. With a median follow-up of 100 months, we observed only 10 deaths from prostate cancer, including 5 in both treatment groups.…”

Section: Discussionmentioning

confidence: 90%

A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer

Donnelly

Saliken

Brasher

et al. 2009

Cancer

138

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BACKGROUND: Localized prostate cancer can be treated several different ways, but head-to-head comparisons of treatments are infrequent. The authors of this report conducted a randomized, unblinded, noninferiority trial to compare cryoablation with external beam radiotherapy in these patients. METHODS: From December 1997 through February 2003, 244 men with newly diagnosed localized prostate cancer were assigned randomly to receive either cryoablation or radiotherapy (122 men in each arm). All received neoadjuvant antiandrogen therapy. The primary endpoint was disease progression at 36 months based on a trifecta definition: 1) radiologic evidence of metastatic disease, or 2) initiation of further antineoplastic therapy, or 3) biochemical failure. Two definitions of biochemical failure were used: 1) 2 consecutive rises in prostate-specific antigen (PSA) with a final value >1.0 ng/mL, and 2) a rise above PSA nadir þ 2 ng/mL. Secondary endpoints included overall survival, disease-specific survival, and prostate biopsy at 36 months. RESULTS: The median follow-up was 100 months. Disease progression at 36 months was observed in 23.9% (PSA nadir þ 2 ng/mL, 17.1%) of men in the cryoablation arm and in 23.7% (PSA nadir þ 2 ng/mL, 13.2%) of men in the radiotherapy arm. No difference in overall or disease-specific survival were observed. At 36 months, more patients in the radiotherapy arm had a cancer-positive biopsy (28.9%) compared with patients in the cryoablation arm (7.7%). CONCLUSIONS: The observed difference in disease progression at 36 months was small, 0.2%; however, because of the wide confidence interval, from À10.8% to 11.2%, it was not possible to rule out inferiority (defined a priori as a 10% difference). With longer term follow-up, the trend favors cryoablation. Significantly fewer positive biopsies were documented after cryoablation than after radiotherapy. Cancer 2010;116:323-30.

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Section: Discussionmentioning

confidence: 90%

A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer

Donnelly

Saliken

Brasher

et al. 2009

Cancer

138

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“…The Scandinavian Prostate Cancer Group Study No. 4 demonstrated that surgery significantly decreased the risk of death from prostate cancer (Holmberg et al, 2002;Bill-Axelson et al, 2005). However, to prevent one prostate cancer-specific death, 19 men are subjected to treatment and some men died notwithstanding radical surgery.…”

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confidence: 99%

TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort

et al. 2007

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The identification of the TMPRSS2:ERG fusion in prostate cancer suggests that distinct molecular subtypes may define risk for disease progression. In surgical series, TMPRSS2:ERG fusion was identified in 50% of the tumors. Here, we report on a population-based cohort of men with localized prostate cancers followed by expectant (watchful waiting) therapy with 15% (17/111) TMPRSS2:ERG fusion. We identified a statistically significant association between TMPRSS2:ERG fusion and prostate cancer specific death (cumulative incidence ratio ¼ 2.7, Po0.01, 95% confidence interval ¼ 1.3-5.8).Quantitative reverse-transcription-polymerase chain reaction demonstrated high estrogen-regulated gene (ERG) expression to be associated with TMPRSS2:ERG fusion (Po0.005). These data suggest that TMPRSS2:ERG fusion prostate cancers may have a more aggressive phenotype, possibly mediated through increased ERG expression.

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“…As demonstrated most recently by the randomized Scandinavian trial evaluating the benefit of prostatectomy over Watchful Waiting, surgery significantly decreased the risk of death from PCA. 2,3 However, this same study also suggests (albeit with relatively short follow-up) that 19 men need to be treated to benefit one man. Given the high prevalence of the disease, the ease of diagnosis, the aging of the population, and the morbidity of treatment, the ability to distinguish aggressive from indolent forms of PCA is critical.…”

Section: Predicting Risk Of Adverse Outcomementioning

confidence: 86%

Targeted therapy of cancer: new roles for pathologists—prostate cancer

Rubin

2008

Modern Pathology

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The clinical dilemma today in the management of prostate cancer (PCA) is to distinguish men who need definitive treatment from men who have indolent disease. As demonstrated most recently by the randomized Scandinavian trial evaluating the benefit of prostatectomy over Watchful Waiting, surgery significantly decreased the risk of death from PCA. However, this same study also suggests that 19 men need to be treated to benefit one man. Given the high prevalence of the disease, the aging of the population, and the potential morbidity of treatment, the ability to distinguish aggressive from indolent forms of PCA is critical. Treatment for advanced PCA begins with androgen ablation, but eventually hormone-refractory (HR) PCA emerges. Novel therapies are in various stages of clinical trials, including kinase inhibitors, antisense oligonucleotides, and inhibitors of heat-shock proteins. The discovery of novel therapeutic approaches is an active area of clinical research. Eliminating HR PCA before it advances is a high priority in the biomarker field. Therefore, the development of molecular signatures of lethal PCA are critical. In addition, the recent discovery that a significant percentage of PCAs harbor a TMPRSS2-ETS gene fusion suggests that targeting either the ETS transcription factors or the fusion product may offer a novel approach to therapy. However, in 2007, the mainstay of treatment for advanced PCA remains androgen ablation therapy as originally introduced in the early 1940s.

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Radical Prostatectomy versus Watchful Waiting in Early Prostate Cancer

Abstract: Radical prostatectomy reduces disease-specific mortality, overall mortality, and the risks of metastasis and local progression. The absolute reduction in the risk of death after 10 years is small, but the reductions in the risks of metastasis and local tumor progression are substantial.

Cited by 1,162 publications

References 13 publications

A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer

A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer

TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort

Targeted therapy of cancer: new roles for pathologists—prostate cancer

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