ABSTRACT
OBJECTIVES: To determine the biochemical disease-free survival rates in patients 60 years old or younger who were treated with surgery for localized prostate cancer. METHODS: We reviewed the medical records of 291 patients 60 years old or younger who had undergone radical prostatectomy as the sole primary treatment for prostate cancer. Follow-up prostate-specific antigen (PSA) levels were measured 6 to 8 weeks after surgery and 4 to 6 months thereafter. Biochemical failure was defined as a detectable PSA level (greater than 0.01 ng/mL). The median follow-up of the entire study group was 50 months. RESULTS: Eighty-one percent of the patients presented with a serum PSA level of 10 ng/mL or less, and 52% had a Gleason score of less than 7 on prostate biopsy. The radical prostatectomy specimens showed organ-confined disease in 72% of patients, and 83% of tumors had a Gleason score of 7. The 1, 5, and 7-year biochemical disease-free survival rate was 99%, 91%, and 91%, respectively. The fitted multivariate Cox proportional hazards model showed that having a prostatectomy specimen Gleason score greater than 7 or seminal vesicle invasion or nodal disease significantly increased the risk of biochemical failure. CONCLUSIONS: In the PSA era, men with prostate cancer who are 60 years old or younger and treated with surgery have an excellent biochemical disease-free outcome.
Subject(s)
Prostate-Specific Antigen/blood , Prostatectomy , Prostatic Neoplasms/blood , Prostatic Neoplasms/surgery , Age Factors , Disease-Free Survival , Humans , Male , Middle Aged , PrognosisABSTRACT
Bcl-2 is associated with resistance to radiotherapy in prostate cancer. It was recently demonstrated that transduction of LNCaP prostate cells with the PTEN gene resulted in Bcl-2 downregulation. We hypothesized that forced expression of PTEN in prostate cancer cells would sensitize cells to radiation, downregulate Bcl-2 expression, and potentiate the G2M block induced by radiation. Four cell lines - PC-3-Bcl-2 (Bcl-2 overexpression, deleted PTEN), PC-3-Neo (wild-type Bcl-2, deleted PTEN), LNCaP (Bcl-2 overexpression, deleted PTEN), and DU-145 (wild-type Bcl-2 and PTEN) - were transduced with a recombinant adenovirus-5 vector expressing the human wild-type PTEN cDNA under the control of a human cytomegalovirus promoter (Ad-MMAC). After correction for the effect of Ad-MMAC on plating efficiency, Ad-MMAC treatment reduced the surviving fractions after 2 Gy as follows: PC-3-Bcl-2, from 60.5 to 3.6%; PC-3-Neo, no reduction; LNCaP, from 29.6 to 16.3%; and DU-145, from 32.7 to 25.7%. PTEN expression was associated with the downregulation of Bcl-2 expression in PC-3-Bcl-2 and LNCaP cell lines. Ad-MMAC plus radiotherapy potentiated the G2M block seen with radiotherapy alone only in PC-3-Bcl-2 cells. These findings suggest that overexpression of Bcl-2 result in radioresistance and inability of radiation to cause its typical G2M cell-cycle arrest.
Subject(s)
Adenoviridae/genetics , Phosphoric Monoester Hydrolases/genetics , Prostatic Neoplasms/radiotherapy , Proto-Oncogene Proteins c-bcl-2/metabolism , Tumor Suppressor Proteins/genetics , Cell Cycle/genetics , Cell Line, Tumor , Combined Modality Therapy , Down-Regulation/genetics , Flow Cytometry , Gene Expression Regulation, Neoplastic , Genetic Therapy/methods , Genetic Vectors/genetics , Humans , Immunochemistry , Male , PTEN Phosphohydrolase , Phosphoric Monoester Hydrolases/metabolism , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/therapy , Radiation Tolerance , Transfection , Transgenes/genetics , Tumor Suppressor Proteins/metabolismABSTRACT
PURPOSE: We set out to determine whether patients who underwent prostatectomy for recurrence after external-beam radiotherapy for prostate cancer had a higher incidence of alterations in the apoptotic pathway than did patients who underwent surgery as initial treatment. MATERIALS AND METHODS: Twenty patients who underwent unsuccessful full-dose external-beam radiotherapy for prostate cancer and subsequently underwent salvage radical surgery (radio-recurrent group), and 20 patients matched for various clinical parameters who underwent only radical prostatectomy for localized or locally advanced prostate cancer (radio-naive group), were studied. Tissue samples were examined for immunoreactivity for p53, p21, Bcl-2, and Ki-67 proteins. Statistically, the two groups were compared using exact logistic regression. RESULTS: Fifty-five percent of the tumors from patients initially treated with radiotherapy were noted to overexpress Bcl-2; whereas, in the radio-naive group, no patient had Bcl-2 overexpression (p = 0.0004). More patients who underwent salvage radical surgery were found to have a higher mean proliferative index (Ki-67 staining) (39.6%), compared with patients undergoing prostatectomy alone (22.1%), p = 0.0800. No significant difference was noted in immunohistochemical expression of p53 and p21 between the two groups. CONCLUSIONS: Patients undergoing radical prostatectomy after radiotherapy had a significantly higher rate of Bcl-2 overexpression than did patients who underwent surgery as the initial treatment. Alterations in the apoptotic pathway may be important in the development of local recurrence after radiation therapy.
