Prostate cancer-specific mortality after radical prostatectomy or external beam radiation therapy in men with 1 or more high-risk factors

BACKGROUND: Estimates of prostate cancer-specific mortality (PCSM) were determined after radical prostatectomy (RP) or radiation therapy (RT) in men with >or=1 high-risk factors. METHODS: The study cohort comprised 948 men who underwent RP (N = 660) or RT (N = 288) for localized prostate cancer between 1988 and 2004 and had at least 1 of the following high-risk factors: a prostate-specific antigen (PSA) velocity >2 ng/mL/year during the year before diagnosis, a biopsy Gleason score of >or=7, a PSA level of >or=10 ng/mL, or clinical category T2b or high disease. Grays regression was used to evaluate whether the number and type of high-risk factors were associated with time to PCSM. RESULTS: Multiple determinants of high risk were found to be significantly associated with a shorter time to PCSM after RP (P < .001) or RT (P 2 ng/mL/year was associated with an increased risk of PCSM after RP (hazards ratio [HR] of 7.3; 95% confidence interval [95% CI], 1.0-59 [P = .05]) or RT (HR of 12.1; 95% CI, 1.4-105 [P = .02]) when compared with men with any other single high-risk factor. CONCLUSIONS: Men with a PSA velocity >2 ng/mL/year had a significantly higher risk of PCSM compared with men who had any other single high-risk factor. These men should be considered for randomized trials evaluating the impact on PCSM from adding systemic agents to standards of care for men with high-risk PC.     

Postoperative radiation therapy after radical prostatectomy for prostate carcinoma.

BACKGROUND. The role and benefit of adjuvant radiation therapy after radical prostatectomy is unclear. This role was evaluated in 58 patients who, after undergoing radical prostatectomy for prostate carcinoma, had local extension of disease beyond the prostate or positive surgical margins. Thirty-nine patients treated surgically alone were compared with 19 patients who received adjuvant postoperative radiation therapy. All patients were followed for at least 5 years, and 50 patients had 10-year follow-ups. RESULTS. At 10 years, the actuarial local failure rate was 31% for patients treated with prostatectomy alone versus 6% for the group receiving postoperative radiation therapy (P less than 0.05). The actuarial survival and metastasis-free survival were similar for both groups. When patients with involved lymph nodes were excluded from analysis, the addition of radiation therapy resulted in improved recurrence-free survival (91% versus 46% at 10 years, P = 0.04) and in a trend toward improved metastasis-free survival (91% versus 55%, P = 0.08). Complications occurred in similar frequencies in both groups. CONCLUSIONS. In patients with local disease extension or positive surgical margins after radical prostatectomy, adjuvant radiation therapy improved local control and was administered with acceptable side effects.     

Role of salvage radical prostatectomy for recurrent prostate cancer after radiation therapy.

Patients with isolated local recurrence of prostate cancer after radiation therapy may potentially be cured of their disease by salvage radical prostatectomy (RP). The stage-specific 5-year cancer-control rates of salvage RP resemble those of standard RP. However, the ability to effectively administer salvage treatment to patients with radiorecurrent disease is compromised by the lack of diagnostic tests with sufficient sensitivity and specificity to detect local recurrence at an early stage while it is amenable to local salvage therapy. By the time biochemical recurrence is declared using the current American Society for Therapeutic Radiology and Oncology definition, the majority of patients have advanced local disease, precluding successful local salvage therapy. When salvage RP is performed at prostate-specific antigen levels of 10 ng/mL or less, an estimated 70% of patients are free of disease at 5 years. With better patient selection and technical modifications, the morbidity associated with salvage RP has improved substantially. Rates of urinary incontinence and anastomotic stricture are acceptable, although one third of patients will experience these complications. Salvage cryotherapy is a minimally invasive alternative to salvage RP, but cancer-control rates appear to be inferior and it does not provide a clear advantage over salvage RP in terms of reduced morbidity. Patients with local recurrence after radiation therapy are at increased risk of metastatic progression and cancer-specific mortality. Currently, salvage RP represents the only curative treatment option for these patients. Salvage RP may favorably alter the natural history of biochemical recurrence after radiation therapy, but it must be instituted early in the course of recurrent disease to be effective.     

Cancer-specific mortality after radiation therapy with short-course hormonal therapy or radical prostatectomy in men with localized, intermediate-risk to high-risk prostate cancer

BACKGROUND: The presence of multiple determinants of aggressive cancer biology may impact prostate cancer-specific mortality (PCSM) rates compared with fewer factors. The authors estimated PCSM after radiation therapy with short-course androgen suppression therapy (RT+AST) or radical prostatectomy (RP) in men with clinically localized, intermediate-risk to high-risk prostate cancer. METHODS: The study cohort included 3240 men treated from 1981 to 2002 with RT with 6 months of AST (n = 550) or RP (n = 2690) for localized prostate cancer with at least 1 risk factor (prostate-specific antigen [PSA] >10 ng/mL, biopsy Gleason score 7-10, or clinical tumor category T2b or T2c). Competing risks regression analyses were used to determine whether the number of risk factors present was associated with time to PCSM. RESULTS: Men with all 3 risk factors had significantly shorter time to PCSM after RT+AST (adjusted hazards ratio [HR] of 9.3; 95% confidence interval [95% CI], 1.9-44.5 [P(Gray) = .005]) or RP (adjusted HR of 6.3; 95% CI, 3.2-12.2 [P(Gray) < .001]) when compared with men with any 1 or 2 risk factors. The 7-year estimates of PCSM for men having 1, 2, or 3 risk factors were 0.83% (95% CI, 0.27-1.4%), 2.6% (95% CI, 1.0-4.2%), and 12.6% (95% CI, 7.1-18.1%), respectively. CONCLUSIONS: Men with multiple determinants of intermediate-risk to high-risk prostate cancer have significantly increased estimates of PCSM despite aggressive therapy compared with men with only 1 or 2 determinants. These men are appropriate candidates for enrollment onto randomized controlled trials evaluating the benefit of adding systemic therapies such as docetaxel to RT+AST or RP.     

Adjuvant and salvage radiation therapy after radical prostatectomy for adenocarcinoma of the prostate.

PURPOSE: To evaluate the outcome of adjuvant and salvage radiotherapy (RT) after radical prostatectomy (RP) for clinically localized prostate cancer using conventional clinical end-points, and the biochemical relapse-free rate (bRFR). METHODS: Between 1987 and 1994, 113 node negative, hormonally na?ve men received RT 1 month to 12 years after RP. Adjuvant RT was given for positive resection margins and/or pT3 disease. Salvage RT was given for a persistently elevated prostatic specific antigen (PSA), a rising PSA, or palpable recurrence post RP. Clinical and biochemical endpoints determined outcome. Log-rank testing and the Cox proportional hazards model identified factors predictive for biochemical relapse free rate. RESULTS: Median follow-up after RT was 3.7 years (range 0.2-9 years). Five-year clinical local control was 95% for patients with no palpable evidence of disease and 59% for those with palpable recurrence (P < 0.0001). 5-year bRFR was 81% for adjuvant RT, 19% for salvage of biochemical recurrence, 0% for patients with palpable disease (P < 0.0001). Improved bRFR for adjuvant and salvage RT was predicted by a Gleason score < 7 vs. 7 vs. > 7 (hazard ratio 1.53; 95% CI 0.99-2.35) and an undetectable pre-RT PSA vs. PSA < 2.0 ng/ml vs. PSA > 2.0 ng/ml (hazard ratio 3.81; 95% CI 2.47-5.87). Seminal vesicle involvement was not a statistically significant independent predictor of bRFR. CONCLUSIONS: The most favourable bRFR was observed for adjuvant therapy. Salvage was most successful with a pre-RT PSA < 2.0 ng/ml, or Gleason score < 7. Few patients with a pre-RT PSA > 2.0 ng/ml were salvaged, and none with palpable recurrence. These patients require investigation of alternative salvage strategies.     

Pretreatment nomogram for prostate-specific antigen recurrence after radical prostatectomy or external-beam radiation therapy for clinically localized prostate cancer.

PURPOSE: To present nomograms providing estimates of prostate-specific antigen (PSA) failure-free survival after radical prostatectomy (RP) or external-beam radiation therapy (RT) for men diagnosed during the PSA era with clinically localized disease. PATIENTS AND METHODS: A Cox regression multivariable analysis was used to determine the prognostic significance of the pretreatment PSA level, 1992 American Joint Committee on Cancer (AJCC) clinical stage, and biopsy Gleason score in predicting the time to posttherapy PSA failure in 1,654 men with T1c,2 prostate cancer managed with either RP or RT. RESULTS: Pretherapy PSA, AJCC clinical stage, and biopsy Gleason score were independent predictors (P < .0001) of time to posttherapy PSA failure in patients managed with either RP or RT. Two-year PSA failure rates derived from the Cox regression model and bootstrap estimates of the 95% confidence intervals are presented in the format of a nomogram stratified by the pretreatment PSA, AJCC clinical stage, biopsy Gleason score, and local treatment modality. CONCLUSION: Men at high risk (> 50%) for early (< or = 2 years) PSA failure could be identified on the basis of the type of local therapy received and the clinical information obtained as part of the routine work-up for localized prostate cancer. Selection of these men for trials evaluating adjuvant systemic and improved local therapies may be justified.     

Prediction of response to salvage radiation therapy in patients with prostate cancer recurrence after radical prostatectomy.

PURPOSE: To identify factors predictive of local recurrence as defined by a complete response to salvage radiation therapy in patients whose disease recurs after radical prostatectomy. PATIENTS AND METHODS: Ninety-five patients with recurrence after radical prostatectomy who were evaluated by prostatic fossa biopsies, and a subset of 49 of these patients treated with radiation for control of presumed or biopsy-proven local recurrence, were studied. RESULTS: Biopsies were positive in 40 (42%) of the 95 biopsied patients. Multivariate analysis revealed that prebiopsy prostate-specific antigen (PSA) level, postrecurrence PSA doubling time, and positive digital rectal examination (DRE) of the prostatic fossa were all statistically significant predictors of a positive biopsy. For the 49 patients subsequently treated with salvage radiation therapy, the overall actuarial 3- and 5-year PSA relapse-free probabilities were 43% and 24%, respectively. Univariate analysis showed no differences in the PSA relapse-free probabilities associated with any pathologic features of the radical prostatectomy specimen, biopsy confirmation of local recurrence, or DRE of the prostatic fossa. In multivariate analysis, controlling for all other variables, preradiation PSA and postrecurrence PSA doubling time measured before radiation were the only statistically significant predictors of outcome. CONCLUSION: DRE of the prostatic fossa, prebiopsy PSA, and postrecurrence PSA doubling time predict which patients will have biopsy-proven local recurrence. However, response to salvage radiation therapy is associated with postrecurrence PSA doubling time and with preradiation PSA level only. DRE of the prostatic fossa and biopsy confirmation of local recurrence are not associated with salvage radiation outcome.     

Determinants of prostate cancer-specific survival after radiation therapy for patients with clinically localized prostate cancer.

PURPOSE: Identifying pretreatment and posttreatment predictors of time to prostate cancer-specific death (PCSD) after external-beam radiation therapy (RT) was the subject of this study. PATIENTS AND METHODS: A Cox regression analysis was used to evaluate the ability of the pretreatment risk group to predict time to PCSD for 381 patients who underwent RT for clinically localized prostate cancer. Posttreatment factors analyzed for the 94 patients who experienced prostate-specific antigen (PSA) failure included the time to PSA failure, the posttreatment PSA doubling time (DT), and the timing of salvage hormonal therapy. RESULTS: Despite the median age of 73 years at diagnosis, 45% of patients with high-risk disease were estimated to die from prostate cancer within 10 years after RT compared with 0% (P =.004) and 6% (P =.05) for patients with low- or intermediate-risk disease, respectively. Predictors of time to PCSD after PSA failure included PSA DT (P =.01) and delayed use of hormonal therapy (P 相似文献   

Predictors of biochemical outcome with salvage conformal radiotherapy after radical prostatectomy for prostate cancer.

PURPOSE: To identify predictors of biochemical outcome following radiotherapy in patients with a rising prostate-specific antigen (PSA) after radical prostatectomy for prostate cancer. PATIENTS AND METHODS: One hundred fifteen patients with a rising PSA after radical prostatectomy received salvage three-dimensional conformal radiotherapy (3D-CRT) alone or with neoadjuvant androgen deprivation. Tumor-related and treatment-related factors were evaluated to identify predictors of subsequent PSA failure. RESULTS: The median follow-up time after 3D-CRT was 42 months. The 4-year actuarial PSA relapse-free survival, distant metastasis-free survival, and overall survival rates were 46%, 83%, and 95%, respectively. Multivariate analysis, which was limited to 70 patients receiving radiation without androgen deprivation therapy, showed that negative/close margins (P =.03), absence of extracapsular extension (P <.01), and presence of seminal vesicle invasion (P <.01) were independent predictors of PSA relapse after radiotherapy. Neoadjuvant androgen deprivation did not improve the 4-year PSA relapse-free survival in patients with positive margins, extracapsular extension, and no seminal vesicle invasion (P =.24). However, neoadjuvant androgen deprivation did improve PSA relapse-free survival when one or more of these variables were absent (P =.03). CONCLUSIONS: Salvage 3D-CRT can provide biochemical control in selected patients with a rising PSA after radical prostatectomy. Among patients with positive margins and no poor prognostic features, 77% achieved PSA control after salvage 3D-CRT. Salvage neoadjuvant androgen deprivation therapy may improve short-term biochemical control, but it requires further study.     

Biochemical outcome after radical prostatectomy or external beam radiation therapy for patients with clinically localized prostate carcinoma in the prostate specific antigen era

BACKGROUND: To the authors' knowledge, consensus is lacking regarding the relative long-term efficacy of radical prostatectomy (RP) versus conventional-dose external beam radiation therapy (RT) in the treatment of patients with clinically localized prostate carcinoma. METHODS: A retrospective cohort study of 2635 men treated with RP (n = 2254) or conventional-dose RT (n = 381) between 1988-2000 was performed. The primary endpoint was prostate specific antigen (PSA) survival stratified by treatment received and high-risk, intermediate-risk, or low-risk group based on the serum PSA level, biopsy Gleason score, 1992 American Joint Commission on Cancer clinical tumor category, and percent positive prostate biopsies. RESULTS: Estimates of 8-year PSA survival (95% confidence interval [95% CI]) for low-risk patients (T1c,T2a, a PSA level < or = 10 ng/mL, and a Gleason score < or = 6) were 88% (95% CI, 85, 90) versus 78% (95% CI, 72, 83) for RP versus patients treated with RT, respectively. Eight-year estimates of PSA survival also favored RP for intermediate-risk patients (T2b or Gleason score 7 or a PSA level > 10 and < or = 20 ng/mL) with < 34% positive prostate biopsies, being 79% (95% CI, 73, 85) versus 65% (95% CI, 58, 72), respectively. Estimates of PSA survival in high-risk (T2c or PSA level > 20 ng/mL or Gleason score > or = 8) and intermediate-risk patients with at least 34% positive prostate biopsies initially favored RT, but were not significantly different after 8 years. CONCLUSIONS: Intermediate-risk and low-risk patients with a low biopsy tumor volume who were treated with RP appeared to fare significantly better compared with patients who were treated using conventional-dose RT. Intermediate-risk and high-risk patients with a high biopsy tumor volume who were treated with RP or RT had long-term estimates of PSA survival that were not found to be significantly different.     

Phase I-II study of intraoperative radiation therapy (IORT) after radical prostatectomy for prostate cancer

PURPOSE: Recent studies have suggested an alpha/beta ratio in prostate cancer of 1.5-3 Gy, which is lower than that assumed for late-responsive normal tissues. Therefore the administration of a single, intraoperative dose of irradiation should represent a convenient irradiation modality in prostate cancer. MATERIALS AND METHODS: Between February 2002 and June 2004, 34 patients with localized prostate cancer with only one risk factor (Gleason score > or =7, Clinical Stage [cT] > or =2c, or prostate-specific antigen [PSA] of 11-20 ng/mL) and without clinical evidence of lymph node metastases were treated with radical prostatectomy (RP) and intraoperative radiotherapy on the tumor bed. A dose-finding procedure based on the Fibonacci method was employed. Dose levels of 16, 18, and 20 Gy were selected, which are biologically equivalent to total doses of about 60-80 Gy administered with conventional fractionation, using an alpha/beta ratio value of 3. RESULTS: At a median follow-up of 41 months, 24 (71%) patients were alive with an undetectable PSA value. No patients died from disease, whereas 2 patients died from other malignancies. Locoregional failures were detected in 3 (9%) patients, 2 in the prostate bed and 1 in the common iliac node chain outside the radiation field. A PSA rise without local or distant disease was observed in 7 (21%) cases. The overall 3-year biochemical progression-free survival rate was 77.3%. CONCLUSIONS: Our dose-finding study demonstrated the feasibility of intraoperative radiotherapy in prostate cancer also at the highest administered dose.     

Radiation therapy after radical prostatectomy is associated with higher other-cause mortality

Cancer Causes & Control - To test the association between external beam radiotherapy (EBRT) after radical prostatectomy (RP) vs RP only on rates of other-cause mortality (OCM) in men with...     

Defining prostate cancer risk after radical prostatectomy

Prostate cancer encompasses a wide spectrum of tumor phenotypes with differing prognoses and a part of these patients are at risk of experiencing tumor recurrence after initial treatment. This review discusses the parameters that determine PCa risk for failure after radical prostatectomy and also focuses on the ability of currently available post-treatment nomograms to predict treatment outcomes, and probability of treatment failure. The use of predictive nomograms may be therefore helpful in the complex decision making process.     

Perineural invasion associated with increased cancer-specific mortality after external beam radiation therapy for men with low- and intermediate-risk prostate cancer

PURPOSE: To identify an association between perineural invasion (PNI) and cancer-specific survival in patients with prostate cancer after standard-dose external beam radiation therapy (RT). METHODS AND MATERIALS: A total of 517 consecutive patients who underwent RT (median dose, 70.5 Gy) between 1989 and 2003 for low-risk or intermediate-risk prostate cancer were studied. A genitourinary pathologist (AAR) scored presence or absence of PNI on all prostate needle-biopsy specimens. A Cox regression multivariable analysis was performed to assess whether the presence of PNI was associated with risk of prostate cancer-specific mortality after RT when the recognized risk-group variables were factored into the model. Estimates of cancer-specific mortality were made using a cumulative incidence method. Comparisons of survival were made using a two-tailed log-rank test. RESULTS: At a median follow-up of 4.5 years, 84 patients (16%) have died, 15 of 84 (18%) from prostate cancer. PNI was the only significant predictor of prostate cancer-specific mortality after RT (p=0.012). The estimated prostate cancer-specific mortality was 14% at 8 years for PNI+ patients vs. 5% for PNI- patients (p=0.0008). CONCLUSIONS: Patients with low- or intermediate-risk prostate cancer who have PNI on prostate needle biopsy have a significantly higher rate of prostate cancer-specific mortality after standard-dose radiation therapy than patients without PNI. Although this analysis is retrospective, this association argues for consideration of the use of more aggressive therapy, such as hormonal therapy with RT or dose escalation, in these select patients.     

pT0 prostate cancer after radical prostatectomy

The purpose of our study was to perform a literature review of current data to determine the frequency and correlates of pT0 prostate cancer after radical prostatectomy alone. A comprehensive search was made of MEDLINE and PUBMED. Seven studies were identified involving 18,135 patients with 74 reported pT0 cases. The most frequent correlates from our pooled data of patients with pT0 specimens include preoperative PSA <10 ng/ml, only one positive core biopsy, and Gleason score <7. J. Surg. Oncol. 2010;102:331–333. © 2010 Wiley‐Liss, Inc.     

Rosiglitazone versus placebo for men with prostate carcinoma and a rising serum prostate-specific antigen level after radical prostatectomy and/or radiation therapy

BACKGROUND: The objective of this study was to assess the biologic activity of rosiglitazone, a peroxisome proliferator-activated receptor gamma agonist that has been approved to treat type 2 diabetes, in men with recurrent prostate carcinoma using change in prostate specific antigen (PSA) doubling time (PSADT) as the primary outcome variable. METHODS: Men with histologically confirmed prostate carcinoma, no recent hormone therapy, a rising serum PSA level after radical prostatectomy and/or radiation therapy, and no radiographic evidence of metastases were assigned randomly to receive either oral rosiglitazone (4 mg twice daily) or placebo. The treatment was continued until the men developed disease progression or adverse effects. A positive outcome was defined as a posttreatment PSADT > 150% the baseline PSADT and no new metastases. RESULTS: One hundred six men were enrolled. The median treatment duration was 315 days for men in the placebo group and 338 days for men in the rosiglitazone group (P = 0.28). Forty percent of men in the in the placebo group and 38% of men in the rosiglitazone group had a posttreatment PSADT > 150% of the baseline PSADT and no new metastases (P = 1.00). In exploratory analyses, the rate of a positive outcome remained higher than expected in the placebo group, even when a positive outcome was redefined using more stringent criteria. The time to disease progression was similar between the groups. CONCLUSIONS: Rosiglitazone did not increase PSADT or prolong the time to disease progression more than placebo in men with a rising PSA level after radical prostatectomy and/or radiation therapy. The unexpected discordance between baseline and posttreatment PSADT in the placebo group reinforced the importance of randomized controlled trials in this setting.     

The role of external beam radiation therapy after prostatectomy for prostate cancer

The role of radiation therapy as an adjuvant to prostatectomy is evaluated in 21 patients. Eleven were treated prior to clinical recurrence with 100% local control, no serious complications, and 86% long-term survival. Ten were treated after local recurrence with 80% local control, no serious complications, and 71% long-term survival. These data and the available literature indicate that the patient found to have capsular penetration, seminal vesicle involvement, or positive surgical margins at prostatectomy can be salvaged by postsurgical radiation therapy. When this is done after recovery from surgery, rather than waiting for clinical recurrence, a lower radiation dose can be used (6000 rad vs. 7000 rad), improved local control is obtained (94% vs. 79%), and fewer serious complications are observed.