PMID- 17634487
OWN - NLM
STAT- MEDLINE
DCOM- 20070822
LR  - 20220330
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 25
IP  - 21
DP  - 2007 Jul 20
TI  - Prognostic value of p16 in locally advanced prostate cancer: a study based on 
      Radiation Therapy Oncology Group Protocol 9202.
PG  - 3082-9
AB  - PURPOSE: Deregulation of the retinoblastoma (RB) pathway is commonly found in 
      virtually all known human tumors. p16, the upstream regulator of RB, is among the 
      most commonly affected member of this pathway. In the present study, we examined 
      the prognostic value of p16 expression in men with locally advanced prostate 
      cancer who were enrolled on Radiation Therapy Oncology Group protocol 9202. 
      PATIENTS AND METHODS: RTOG 9202 was a phase III randomized study comparing 
      long-term (LT) versus short-term (ST) androgen-deprivation therapy (AD). Of the 
      1,514 eligible cases, 612 patients had adequate tumor material for p16 analysis. 
      Expression levels of p16 were determined by immunohistochemistry (IHC). IHC 
      staining was scored quantitatively using an image analysis system. RESULTS: On 
      multivariate analysis, intact p16 expression was significantly associated with 
      decreased rate of distant metastases (P = .0332) when both STAD and LTAD 
      treatment arms were considered together. For patients with intact (high levels of 
      immunostaining) p16 (mean p16 index > 81.3%), LTAD plus radiotherapy (RT) 
      significantly improved prostate cancer survival (PCS) compared with STAD plus RT 
      (P = .0008) and reduced the frequency of distant metastasis (P = .0069) compared 
      with STAD plus RT. In contrast, for patients with tumors demonstrating p16 loss 
      (low levels of immunostaining, mean p16 index < or = 81.3%), LTAD plus RT 
      significantly improved biochemical no evidence of disease survival over STAD (P < 
      .0001) primarily by decreasing the frequency of local progression (P = .02), as 
      opposed to distant metastasis, which was the case in the high-p16 cohort. 
      CONCLUSION: Low levels of p16 on image analysis appear to be associated with a 
      significantly higher risk of distant metastases among all study patients. p16 
      expression levels also appear to identify patients with locally advanced prostate 
      cancer with distinct patterns of failure after LTAD.
FAU - Chakravarti, Arnab
AU  - Chakravarti A
AD  - Massachusetts General Hospital/Harvard Medical School, Department of Radiation 
      Oncology, Boston, MA 02114, USA. achakravarti@partners.org
FAU - DeSilvio, Michelle
AU  - DeSilvio M
FAU - Zhang, Min
AU  - Zhang M
FAU - Grignon, David
AU  - Grignon D
FAU - Rosenthal, Seth
AU  - Rosenthal S
FAU - Asbell, Sucha O
AU  - Asbell SO
FAU - Hanks, Gerald
AU  - Hanks G
FAU - Sandler, Howard M
AU  - Sandler HM
FAU - Khor, Li-Yan
AU  - Khor LY
FAU - Pollack, Alan
AU  - Pollack A
FAU - Shipley, William
AU  - Shipley W
CN  - Radiation Therapy Oncology Group
LA  - eng
GR  - U10CA37422/CA/NCI NIH HHS/United States
GR  - R01 CA101984-05/CA/NCI NIH HHS/United States
GR  - U10 CA037422/CA/NCI NIH HHS/United States
GR  - R01 CA101984/CA/NCI NIH HHS/United States
GR  - U10 CA021661/CA/NCI NIH HHS/United States
GR  - R01 CA101984-01/CA/NCI NIH HHS/United States
GR  - U10CA21661/CA/NCI NIH HHS/United States
GR  - U10CA32115/CA/NCI NIH HHS/United States
GR  - U10 CA032115/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Androgen Antagonists)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
SB  - IM
MH  - Aged
MH  - Androgen Antagonists/*therapeutic use
MH  - Biomarkers, Tumor/*blood
MH  - Biopsy, Needle
MH  - Combined Modality Therapy
MH  - Cyclin-Dependent Kinase Inhibitor p16/*metabolism
MH  - Disease-Free Survival
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Probability
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Prostate-Specific Antigen/blood
MH  - Prostatic Neoplasms/*mortality/pathology/*therapy
MH  - Radiotherapy, Conformal/*methods
MH  - Reference Values
MH  - Risk Assessment
MH  - Survival Analysis
MH  - Treatment Outcome
PMC - PMC2777649
MID - NIHMS150065
COIS- AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated 
      no potential conflicts of interest.
EDAT- 2007/07/20 09:00
MHDA- 2007/08/23 09:00
PMCR- 2009/11/16
CRDT- 2007/07/20 09:00
PHST- 2007/07/20 09:00 [pubmed]
PHST- 2007/08/23 09:00 [medline]
PHST- 2007/07/20 09:00 [entrez]
PHST- 2009/11/16 00:00 [pmc-release]
AID - 25/21/3082 [pii]
AID - 10.1200/JCO.2006.08.4152 [doi]
PST - ppublish
SO  - J Clin Oncol. 2007 Jul 20;25(21):3082-9. doi: 10.1200/JCO.2006.08.4152.