Ki-67 Staining Is a Strong Predictor of Distant Metastasis and Mortality for Men With Prostate Cancer Treated With Radiotherapy Plus Androgen Deprivation: Radiation Therapy Oncology Group Trial 92–02

Pollack, Alan; DeSilvio, Michelle; Khor, Li Yan; Li, R.; Al‐Saleem, Tahseen; Hammond, Margaret E.; Venkatesan, Varagur; Lawton, Colleen A.; Roach, Mack; Shipley, William U.; Hanks, Gerald E.; Sandler, Howard M.

doi:10.1200/jco.2004.09.150

Cited by 140 publications

(108 citation statements)

References 22 publications

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“…A significant association of Ki-67 LI with outcome of radical treatment has been Biopsy TMA technique S Jhavar et al demonstrated in several studies. 14,17,18,21 In addition, two studies have examined the prognostic utility of Ki-67 LI in prostate cancer patients managed conservatively. 20,22 Both demonstrated a significant association between Ki-67 LI and prostate cancer disease-free survival.…”

Section: Discussionmentioning

confidence: 99%

“…9,10 Evidence for the predictive role of Ki-67 LI in determining prostate cancer outcomes has been established for men that are treated radically. [11][12][13][14][15][16][17][18] In most studies, Ki-67 LI has been evaluated on cancer tissue obtained from transurethral resection (TURP) or radical prostatectomy specimens, although two of the studies used pre-treatment needle biopsies taken from patients who subsequently received radiotherapy. 14,18 The prognostic role of Ki-67 LI has also been established for prostate cancer-specific survival in patients managed by watchful waiting.…”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13][14][15][16][17][18] In most studies, Ki-67 LI has been evaluated on cancer tissue obtained from transurethral resection (TURP) or radical prostatectomy specimens, although two of the studies used pre-treatment needle biopsies taken from patients who subsequently received radiotherapy. 14,18 The prognostic role of Ki-67 LI has also been established for prostate cancer-specific survival in patients managed by watchful waiting. 19,20 Importantly however, none of these studies were targeted at men with low-risk localized disease who are suitable for management by active surveillance.…”

Section: Introductionmentioning

confidence: 99%

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Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance

Jhavar

Bartlett

Kovács

et al. 2008

Prostate Cancer Prostatic Dis

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Active surveillance provides a unique opportunity to study biomarkers of prostate cancer behaviour, although only small volumes of tumor tissue are typically available. We have evaluated a technique for constructing tissue microarrays (TMAs) from needle biopsies for assessing immunohistochemical markers in localized prostate cancer managed by active surveillance. TMAs were constructed from diagnostic prostate biopsies for 60 patients with localized prostatic adenocarcinoma in a prospective cohort study of active surveillance. Radical treatment was recommended for a prostate-specific antigen (PSA) velocity greater than 1 ng ml À1 per year or adverse histology in repeat biopsies, defined as Gleason score X4 þ 3 or 450% of cores involved. Sections from the TMAs were stained with H&E, P63/AMACR and Ki-67. Time to radical treatment was analysed with respect to clinical characteristics and Ki-67 LI. At a median follow up of 36 months, 25/60 (42%) patients had received radical treatment. On univariate analysis, PSA density (P ¼ 0.001), Gleason score (P ¼ 0.001), clinical T stage (P ¼ 0.01), Ki-67 LI (P ¼ 0.02) and initial PSA (P ¼ 0.04) were associated with time to radical treatment. On multivariate analysis, PSA density (P ¼ 0.01), Ki-67 LI (P ¼ 0.03) and Gleason score (P ¼ 0.04) were independent determinants of progression to radical treatment. TMAs constructed from prostate needle biopsies can be used to assess immunohistochemical markers in localized prostate cancer managed by active surveillance. Ki-67 LI merits further study as a possible biomarker of early prostate cancer behaviour.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance

Jhavar

Bartlett

Kovács

et al. 2008

Prostate Cancer Prostatic Dis

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“…21,22 Briefly, the RTOG 92-02 trial was a randomised trial studying long-term neoadjuvant concurrent and adjuvant androgen deprivation (28 months goserelin) versus short-term neoadjuvant and concurrent androgen deprivation (4 months goserelin and flutamide) with external-beam radiotherapy (65-70 Gy to the prostate and 44-50 Gy to the pelvic lymph nodes) in patients with locally advanced prostate cancer (T2c-T4). The findings of the RTOG 92-02 trial supported the use of LTAD with radiotherapy rather than STAD with radiotherapy for patients with T2c-T4 stage cancer.…”

Section: Patients and Proceduresmentioning

confidence: 99%

COX-2 expression predicts prostate-cancer outcome: analysis of data from the RTOG 92-02 trial

Khor

Bae

Pollack

et al. 2007

The Lancet Oncology

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SummaryBackground-COX-2 is overexpressed in some cancers, including prostate cancer; however, little is known about the effect of COX-2 overexpression on outcome in radiation-treated patients with prostate cancer. We aimed to study COX-2 overexpression and outcome in a well-defined cohort of men who received treatment with short-term androgen deprivation (STAD) plus radiotherapy or longterm androgen deprivation (LTAD) plus radiotherapy.

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“…The methods used are the same as those we have been applying to archival diagnostic clinical samples (52). Image analysis was used to quantify the expression of these proteins in terms of the proportion of cells showing nuclear accumulation.…”

Section: Discussionmentioning

confidence: 99%

Antisense-MDM2 Sensitizes LNCaP Prostate Cancer Cells to Androgen Deprivation, Radiation, and the Combination In Vivo

Stoyanova

Hachem

Hensley

et al. 2007

International Journal of Radiation Oncology*Biology*Physics

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Purpose-To test the effects of antisense (AS)-MDM2 alone and with androgen deprivation (AD), radiotherapy (RT), and AD + RT on wild-type LNCaP cells in an orthotopic in vivo model. Methods-Androgen-sensitiveLNCaP cells were grown in the prostates of nude mice. Magnetic resonance imaging-based tumor volume and serum prostate-specific antigen (PSA) measurements were used to assess effects on tumor response. Tumor response was measured by biochemical and tumor volume failure definitions and doubling time estimates from fitted PSA and tumor volume growth curves. Expression of MDM2, p53, p21, and Ki-67 was quantified using immunohistochemical staining and image analysis of formalin-fixed tissue, analogous to methods used clinically.Results-Antisense-MDM2 significantly inhibited the growth of LNCaP tumors over the mismatch controls. The most significant increase in tumor growth delay and tumor doubling time was from AS-MDM2 + AD + RT, although the effect of AS-MDM2 + AD was substantial. Expression of MDM2 was significantly reduced by AS-MDM2 in the setting of RT.Conclusions-This is the first in vivo investigation of the effects of AS-MDM2 in an orthotopic model and the first to demonstrate incremental sensitization when added to AD and AD + RT. The results with AD underscore the potential to affect micrometastatic disease, which is probably responsible for treatment failure in 30-40% of men with high-risk disease.

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Ki-67 Staining Is a Strong Predictor of Distant Metastasis and Mortality for Men With Prostate Cancer Treated With Radiotherapy Plus Androgen Deprivation: Radiation Therapy Oncology Group Trial 92–02

Abstract: Ki67-SI was the most significant determinant of DM and CSD and was also associated with OD. The Ki67-SI should be considered for the stratification of patients in future trials.

Cited by 140 publications

References 22 publications

Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance

Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance

COX-2 expression predicts prostate-cancer outcome: analysis of data from the RTOG 92-02 trial

Antisense-MDM2 Sensitizes LNCaP Prostate Cancer Cells to Androgen Deprivation, Radiation, and the Combination In Vivo

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