Prognostic significance of positive surgical margins in patients with extraprostatic carcinoma after radical prostatectomy

BACKGROUND: A significant number of prostate adenocarcinoma patients undergoing radical prostatectomy are found to have microscopic extraprostatic disease extension. A majority of these patients have focal extraprostatic extension limited to one or both sides of the prostate. In addition, positive surgical margins are a common pathologic finding in this patient subgroup. In the current study, the authors evaluated the impact of positive surgical margins as an independent predictive factor for prostate specific antigen (PSA) progression in patients with pT3a/b N0M0 carcinoma. METHODS: The Mayo Clinic prostate cancer registry list provided 1202 patients with pT3a/b NO prostate carcinoma (no seminal vesicle or regional lymph node involvement) who underwent a radical prostatectomy between 1987-1995. To reduce confounding variables, patients who received preoperative therapy or adjuvant therapy were excluded, resulting in 842 patients who were eligible for analysis. RESULTS: A total of 354 patients (42%) had > or = 1 positive surgical margins whereas 488 patients (58%) demonstrated no margin involvement. The sites of margin positivity were as follows: apex (n = 163), base (n = 47), posterior prostate (n = 227), and anterior prostate (n = 11). A total of 111 patients had > or = 2 positive surgical margins. The 5-year survival free of clinical recurrence and/or biochemical failure (postoperative PSA level > 0.2 ng/mL) for patients with no positive surgical margins was 76% and was 65% for patients with 1 positive surgical margin (P = 0.0001). There was no significant difference in biochemical disease progression between patients with 1 versus those with > or = 2 surgical margins (65% vs. 62%). Multivariate analysis revealed that positive surgical margins were a significant predictor (P = 0.0017) of clinical disease recurrence and biochemical failure (relative risk, 1.55; 95% confidence interval, 1.18-2.04) after controlling for preoperative PSA, Gleason score, and DNA ploidy. CONCLUSIONS: In the current study, positive surgical margins were found to be a significant predictor of disease recurrence in patients with pT3a/b NO prostate carcinoma, a finding that is independent of PSA, Gleason score, and DNA ploidy. The benefit of adjuvant therapy in optimizing recurrence-free survival remains to be tested.     

Temporal trends and predictors of pelvic lymph node dissection in open or minimally invasive radical prostatectomy

BACKGROUND:

Pelvic lymph node dissection (PLND) is an important component of prostate cancer staging and treatment, especially for surgical patients who have high‐risk tumor features. It is not clear how the shift from open radical prostatectomy (ORP) to minimally invasive radical prostatectomy (MIRP) has affected the use of PLND. The objectives of this study were to identify predictors of PLND and to assess the impact of surgical technique in a contemporary, population‐based cohort.

METHODS:

In Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked with Medicare claims, the authors identified men who underwent ORP or MIRP for prostate cancer during 2003 to 2007. The impact of surgical approach on PLND was evaluated, and interactions were examined between surgical procedure, prostate‐specific antigen (PSA), and Gleason score with the analysis controlled for patient and tumor characteristics.

RESULTS:

Of 6608 men who underwent ORP or MIRP, 70% (n = 4600) underwent PLND. The use of PLND declined over time both overall and within subgroups defined by procedure type. PLND was 5 times more likely in men who underwent ORP than in men who underwent MIRP when the analysis was controlled for patient and tumor characteristics. Elevated PSA and biopsy Gleason score, but not clinical stage, were associated with a greater odds of PLND in both the ORP group and the MIRP group. However, the magnitude of the association between these factors and PLND was significantly greater for patients in the ORP group.

CONCLUSIONS:

PLND was less common among men who underwent MIRP, independent of tumor risk factors. A decline in PLND rates was not fully explained by an increase in MIRP. The authors concluded that these trends may signal a surgical approach‐dependent disparity in prostate cancer staging and therapy. Cancer 2011;. © 2011 American Cancer Society.     

Correlation of margin status and extraprostatic extension with progression of prostate carcinoma.

BACKGROUND: The correlation of surgical margins and extraprostatic extension (EPE) with progression is uncertain with regard to prostate carcinoma patients treated by radical prostatectomy. The objective of this study was to define factors predictive of cancer progression; emphasis was placed on surgical margins and their relation to extraprostatic extension. METHODS: The study group consisted of 377 patients who were treated by radical retropubic prostatectomy and bilateral pelvic lymphadenectomy at the Mayo Clinic between 1986 and 1993. All specimens were totally embedded and whole-mounted. Patients ranged in age from 41 to 79 years (mean, 65 years). Those with seminal vesicle invasion or lymph node metastasis and those treated preoperatively with radiation or androgen deprivation were excluded. Final pathologic T classifications were pT2a (41 patients), pT2b (237), and pT3a (99). Progression was defined as biochemical failure (prostate specific antigen [PSA] >0.2 ng/mL), clinical or biopsy-proven local recurrence, or distant metastasis. The mean follow-up was 5.8 years (range, 0.2-11.4 years). Seventy-nine patients who received adjuvant treatment within 3 months after surgery were excluded from survival analysis. RESULTS: The overall margin positivity rate was 29%. Seventy-two patients (19%) had only positive surgical margins without evidence of EPE ("surgical incision"), 53 (14%) had only EPE, 37 (10%) had both, and 215 (57%) had neither. Positive margins were correlated with the finding of EPE (P = 0.003). Progression free survival rates at 5 and 10 years were 88% and 67%, respectively. In univariate analysis, preoperative PSA concentration, positive surgical margins, Gleason grade, cancer volume, and DNA ploidy were significant in predicting progression (P values, <0.001, <0.001, 0.01, 0.007, and <0.001, respectively). In multivariate analysis, margin status and DNA ploidy were independent predictors of progression (relative risk for margin status, 1.9; 95% confidence interval [CI], 1.1-3.4; P = 0.03; relative risk for DNA ploidy, 5.1; 95% CI, 2.4-10.9; P<0.001). Among patients with positive margins, 5-year progression free survival was 78% for those with negative EPE and 55% for those with positive EPE. CONCLUSIONS: Surgical margin status and DNA ploidy were independent predictors of progression after radical prostatectomy. To improve cancer control, adjuvant therapy may be considered for patients with positive surgical margins or nondiploid cancer.     

Phase 2 study of neoadjuvant docetaxel plus bevacizumab in patients with high-risk localized prostate cancer : A Prostate Cancer Clinical Trials Consortium trial

BACKGROUND:

Treatment of high‐risk localized prostate cancer remains inadequate. The authors performed a phase 2 multicenter trial of neoadjuvant docetaxel plus bevacizumab before radical prostatectomy.

METHODS:

Eligibility included any of the following: prostate‐specific antigen (PSA) >20 ng/mL or PSA velocity >2 ng/mL/y, cT3 disease, any biopsy Gleason score 8 to 10, and Gleason score 7 with T3 disease by endorectal magnetic resonance imaging (MRI) at 1.5 T. Also, those with ≥50% biopsy cores involved and either Gleason score 7, PSA >10, or cT2 disease were eligible. Patients were treated with docetaxel 70 mg/m² every 3 weeks for 6 cycles and bevacizumab 15 mg/m² every 3 weeks for 5 cycles. The primary endpoint was partial response by endorectal MRI.

RESULTS:

Forty‐one patients were treated. Median age was 55 years (range, 40‐66 years). Baseline characteristics included: median PSA, 10.1 ng/mL; cT2, 49%, cT3, 32%; and Gleason score 8 to 10, 73%. Thirty‐eight of 41 (93%) patients completed all 6 cycles. Grade ≥3 adverse events were rare, although 3 of 41 (7%) experienced febrile neutropenia. Twelve patients (29%; 95% confidence interval [CI], 16%‐45%) achieved a >50% reduction in tumor volume, and 9 patients (22%; 95% CI, 11%‐38%) achieved a >50% post‐treatment decline in PSA. Thirty‐seven of the 41 patients underwent radical prostatectomy; there were no complete pathologic responses.

CONCLUSIONS:

Neoadjuvant docetaxel and bevacizumab is safe, and results in reductions in both tumor volume and serum PSA, in men with high‐risk localized prostate cancer. The role of neoadjuvant chemotherapy in prostate cancer, and perioperative antiangiogenic therapy in general, requires further elucidation through ongoing and planned trials. Cancer 2012. © 2012 American Cancer Society.     

Optimizing patient selection for prostate monotherapy

PURPOSE: Patients at low risk for prostate-specific antigen (PSA) failure following definitive local therapy are those with PSA of 10 or less, biopsy Gleason Score of 6 or less, and 1992 American Joint Committee on Cancer (AJCC) clinical Stage T1c or T2a. However, low-risk patients managed with radical prostatectomy and found to have prostatectomy Gleason score > or = 3+4 have a less favorable PSA outcome when compared to patients with prostatectomy Gleason score < or = 3+3. This study was performed to determine whether the percentage of positive prostate biopsy cores could predict upgrading from a biopsy Gleason score of 6 or less to a prostatectomy Gleason score > or = 3+4 in low-risk patients to optimize selection for prostate only radiation therapy. METHODS AND MATERIALS: Concordance testing of the biopsy Gleason score and the primary and secondary prostatectomy Gleason grades was performed in 427 prostate cancer patients treated with radical prostatectomy and at low risk for PSA failure. Logistic regression multivariable analysis was performed to test the ability of the established prognostic factors and the percentage of positive prostate biopsies (<34%, 34-50%, >50%) to predict for upgrading from biopsy Gleason score of 6 or less prostatectomy Gleason score > or = 3+4. PSA failure-free survival was reported using the actuarial method of Kaplan and Meier and comparisons were made using a log-rank test. RESULTS: Twenty-nine percent of the 427 study patients were upgraded from a biopsy Gleason score of 6 or less to a prostatectomy Gleason score > or = 3+4. The presence of greater than 50% positive biopsies was the only significant factor for predicting the upgrading from biopsy Gleason score of 6 or less to prostatectomy Gleason score > or = 3+4 on logistic regression multivariable analysis with the variables treated as continuous and categorical. Specifically, upgrading occurred in 26% vs. 59% of patients with 50% or less vs. greater than 50% positive biopsies, respectively. This translated into a 5-year PSA failure-free survival which was significantly higher (92% vs. 62%, p = 0.00001) for men with 50% or less vs. greater than 50% positive prostate biopsies, respectively. CONCLUSION: The presence of greater than 50% positive biopsies was associated with higher rates of pathologic upgrading which translated into lower 5-year PSA failure-free survival following radical prostatectomy (RP). Therefore, the percentage of positive biopsies may be useful in optimizing the selection of low-risk patients for prostate only radiation therapy such as external beam radiation or implant monotherapy.     

Using PSA,biopsy Gleason score,clinical stage,and the percentage of positive biopsies to identify optimal candidates for prostate-only radiation therapy

PURPOSE: An identification of prostate cancer patients most likely to benefit from prostate-only radiation was made based upon the pretreatment prostate-specific antigen (PSA), biopsy Gleason score, clinical stage, percentage of positive biopsies, and the 5-year postoperative PSA outcome. METHODS: Between 1989 and 2000, 2099 patients underwent radical prostatectomy for clinically localized prostate cancer. The primary end points were pathologic evidence of seminal vesicle invasion 2(SVI), extracapsular extension (ECE) with or without positive surgical margins, and the 5-year postoperative PSA outcome. RESULTS: Pretreatment PSA, biopsy Gleason score, and clinical stage were used to assign patients to low-, intermediate-, and high-risk groups. These risk groups were stratified by the percentage of positive biopsies and the primary pathologic and biochemical outcomes examined. The rates of SVI, ECE with positive margin, and no biochemical evidence of disease (bNED) for low-risk patients with < or =50% positive biopsies were 2%, 7%, and 93%, respectively. Patients with >50% positive biopsies had higher rates of SVI and ECE (5% and 11%, respectively) and 52% bNED (p < 0.0001). For intermediate-risk patients with < or =17% positive biopsies, the rates of SVI, ECE with positive margin, and bNED were 3%, 9%, and 90%, respectively. As the percentage of positive biopsies increased above 17% in intermediate-risk patients, there was a statistically significant increase in SVI and ECE and a significant decrease in bNED. CONCLUSIONS: Low-risk patients with < or =50% positive biopsies and intermediate-risk patients with < or =17% positive biopsies had a very low risk of SVI and ECE with positive surgical margins. Given that the presence of SVI and ECE with positive surgical margins was uncommon (<10%) with a > or =90% PSA failure-free survival after radical prostatectomy, these patients may be optimal candidates for radiation therapy directed at the prostate only (prostate gland + 1.5-cm margin).     

The CAPRA-S score: A straightforward tool for improved prediction of outcomes after radical prostatectomy

BACKGROUND:

The authors previously developed and validated the Cancer of the Prostate Risk Assessment (CAPRA) score to predict prostate cancer recurrence based on pretreatment clinical data. They aimed to develop a similar postsurgical score with improved accuracy via incorporation of pathologic data.

METHODS:

A total of 3837 prostatectomy patients in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE?) national disease registry were analyzed. Cox regression was used to determine the predictive power of preoperative prostate‐specific antigen (PSA), pathologic Gleason score (pGS), surgical margins (SM), extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph node invasion (LNI). Points were assigned based on the relative weights of these variables in predicting recurrence. The new postsurgical score (CAPRA‐S) was tested and compared with a commonly cited nomogram with proportional hazards analysis, concordance (c) index, calibration plots, and decision‐curve analysis.

RESULTS:

Recurrence appeared in 16.8% of the men; actuarial progression‐free probability at 5 years was 78.0%. The CAPRA‐S was determined by adding up to 3 points for PSA, up to 3 points for pGS, 1 point each for ECE and LNI, and 2 points each for SM and SVI. The hazard ratio for each point increase in CAPRA‐S score was 1.54 (95% confidence interval, 1.49‐1.59), indicating a 2.4‐fold increase in risk for each 2‐point increase in score. The CAPRA‐S c‐index was 0.77, substantially higher than 0.66 for the pretreatment CAPRA score and comparable to 0.76 for the nomogram. The CAPRA‐S score performed better in both calibration and decision curve analyses.

CONCLUSIONS:

The CAPRA‐S offers good discriminatory accuracy, calibration, and ease of calculation for clinical and research settings. Cancer 2011;. © 2011 American Cancer Society.     

Early hypofractionated salvage radiotherapy for postprostatectomy biochemical recurrence

BACKGROUND:

Postprostatectomy adjuvant or salvage radiotherapy, when using standard fractionation, requires 6.5 to 8 weeks of treatment. The authors report on the safety and efficacy of an expedited radiotherapy course for salvage prostate radiotherapy.

METHODS:

A total of 108 consecutive patients were treated with salvage radiation therapy to 65 grays (Gy) in 26 fractions of 2.5 Gy. Median follow‐up was 32.4 months. Median presalvage prostate‐specific antigen (PSA) was 0.44 (range, 0.05‐9.50). Eighteen (17%) patients received androgen deprivation after surgery or concurrently with radiation.

RESULTS:

The actuarial freedom from biochemical failure for the entire group at 4 years was 67% ± 5.3%. An identical 67% control rate was seen at 5 years for the first 50 enrolled patients, whose median follow‐up was longer at 43 months. One acute grade 3 genitourinary toxicity occurred, with no acute grade 3 gastrointestinal and no late grade 3 toxicities observed. On univariate analysis, higher Gleason score (P = .006), PSA doubling time ≤12 months (P = .03), perineural invasion (P = .06), and negative margins (P = .06) showed association with unsuccessful salvage. On multivariate analysis, higher Gleason score (P = .057) and negative margins (P = .088) retained an association with biochemical failure.

CONCLUSIONS:

Hypofractionated radiotherapy (65 Gy in 2.5 Gy fractions in about 5 weeks) reduces the length of treatment by from 1‐½ to 3 weeks relative to other treatment schedules commonly used, produces low rates of toxicity, and demonstrates encouraging efficacy at 4 to 5 years. Hypofractionation may provide a convenient, resource‐efficient, and well‐tolerated salvage approach for the estimated 20,000 to 35,000 US men per year experiencing biochemical recurrence after prostatectomy. Cancer 2011. © 2010 American Cancer Society.     

The combined percentage of Gleason patterns 4 and 5 is the best predictor of cancer progression after radical prostatectomy.

PURPOSE: Clinical outcome is variable in prostate cancer patients treated with radical prostatectomy. The Gleason histologic grade of prostatic adenocarcinoma is one of the strongest predictors of biologic aggressiveness of prostate cancer. We evaluated the significance of the relative proportion of high-grade cancer (Gleason patterns 4 and/or 5) in predicting cancer progression in prostate cancer patients treated with radical prostatectomy. PATIENTS AND METHODS: Radical prostatectomy specimens from 364 consecutive prostate cancer patients were totally embedded and whole mounted. Various clinical and pathologic characteristics were analyzed. All pathologic data, including Gleason grading variables, were collected prospectively. RESULTS: A multiple-factor analysis was performed that included the combined percentage of Gleason patterns 4 and 5, Gleason score, tumor stage, surgical margin status, preoperative prostate-specific antigen (PSA), extraprostatic extension, and total tumor volume. Using Cox regression analysis with bootstrap resampling for predictor selection, we identified the combined percentage of Gleason patterns 4 and 5 (P < .0001) and total tumor volume (P = .009) as significant predictors of PSA recurrence. CONCLUSION: The combined percentage of Gleason patterns 4 and 5 is one of the most powerful predictors of patient outcome, and appears superior to conventional Gleason score in identifying patients at increased risk of disease progression. On the basis of our results, we recommend that the combined percentage of Gleason patterns 4 and 5 be evaluated in radical prostatectomy specimens. The amount of high-grade cancer in a prostatectomy specimen should be taken into account in therapeutic decision making and assessment of patient prognosis.     

The impact of the biopsy Gleason score on PSA outcome for prostate cancer patients with PSA < or = 10 ng/ml and T1c,2a: implications for patient selection for prostate-only therapy

PURPOSE: This study was performed to determine the ability of the biopsy Gleason score, prostate-specific antigen (PSA) level, and the 1992 American Joint Commission on Cancer (AJCC) clinical T-stage for predicting time to postoperative PSA failure for patients with a PSA < or =10 ng/ml and T1c or T2a disease. Specific attention is given to the patient subgroup with biopsy Gleason 3 + 4 vs. 4 + 3. METHODS AND MATERIALS: A concordance map of the biopsy and prostatectomy Gleason grades and a clinical-pathologic correlation of the PSA, biopsy Gleason score, and 1992 AJCC T-stage and pathologic stage were performed. A Cox regression multivariable analysis was used to evaluate the ability of the biopsy Gleason score, PSA, and 1992 AJCC T-stage to predict time to PSA failure for 457 men managed with a radical prostatectomy (RP). RESULTS: The absence of prostatectomy Gleason grade 4 or 5 disease was noted in 71%, 50%, and 11% of patients with biopsy Gleason score 2-6, 3 + 4, and > or =4 + 3 disease respectively while pathologic evidence of seminal vesicle invasion was noted in 2%, 4%, and 17% of these patients respectively. Estimates of 5-year PSA failure-free survival rates were not statistically different for patients with biopsy Gleason score 2-6 vs. 3 + 4 (79% vs. 81%; p = 0.93), but were significantly different for patients having biopsy Gleason score 2-6 vs. 4 + 3 (79% vs. 62%; p = 0.04) or 2-6 vs. 8-10 (79% vs. 18%; p = 0.0001) prostate cancer. CONCLUSION: Based on the pathologic stage and PSA control data following RP, patients with biopsy Gleason 3 + 4 disease and PSA < or =10 ng/ml and 1992 AJCC T1c or T2a disease may be suitable candidates for radiation therapy directed at the prostate only.     

Preoperative prediction of surgical margin status in patients with prostate cancer treated by radical prostatectomy.

PURPOSE: We sought to determine the preoperative factors associated with surgical margin status in patients who underwent radical prostatectomy for prostate cancer. PATIENTS AND METHODS: The study group consisted of 339 patients who were treated by radical retropubic prostatectomy and bilateral pelvic lymphadenectomy at the Mayo Clinic. None received preoperative adjuvant therapy. The mean age at the time of surgery was 66 years (range, 45 to 79 years). All specimens were totally embedded and whole-mounted. Positive surgical margin was defined as the presence of cancer cells at the inked margins. Numerous pathologic characteristics in needle biopsies and preoperative clinical findings were analyzed. RESULTS: The overall margin positivity rate was 24%. In univariate analysis, preoperative serum prostate-specific antigen (PSA) level, Gleason score, perineural invasion, percentage of cancer in the biopsy specimens, and number and percentage of biopsy cores involved by cancer were all associated with positive surgical margins. In multivariate analysis, preoperative serum PSA level (odds ratio for a doubling of PSA levels, 1.9; 95% confidence interval, 1.5 to 2.4; P <.001) and percentage of cancer in the biopsy specimens (odds ratio for a 10% increase, 1.3; 95% confidence interval, 1.2 to 1.4; P <.001) were predictive of margin status in radical prostatectomy. With use of preoperative serum PSA level and percentage of cancer in the biopsy as predictors of surgical margins, the overall accuracy as measured by the area under the receiver operating characteristic curve was 0.74. CONCLUSION: Preoperative serum PSA level and percentage of cancer in the biopsy specimens were independently associated with surgical margin status in patients who underwent radical prostatectomy for prostate cancer. The combination of these two factors provides a high level of predictive accuracy for margin status.     

Importance of margin extent as a predictor of outcome after adjuvant radiotherapy for Gleason score 7 pT3N0 prostate cancer

PURPOSE: To evaluate, in Gleason score 7, pT3N0 prostate cancer patients with positive surgical margins, the predictors of progression-free survival and to identify a patient subgroup that would benefit from immediate adjuvant postoperative radiotherapy (ART). METHODS AND MATERIALS: Between November 1989 and August 1998, 76 men underwent radical prostatectomy and were found to have capsular penetration (pT3N0), surgical Gleason score 7, tumor present at the resection margin, and an undetectable postoperative prostate-specific antigen (PSA) level. All surgical specimens underwent whole-mount serial sectioning to determine the degree of margin positivity (focal vs. extensive). Of the 76 men, 45 underwent early ART (within 6 months with a median dose of 64.8 Gy), and 31 had no immediate treatment. We defined freedom from PSA failure (bNED) as the absence of two consecutive PSA rises >0.2 ng/mL. RESULTS: The median follow-up time was 5.1 years (range, 2-10 years). The ART and non-ART patients were similar with respect to preoperative PSA level, Gleason score (4 + 3 vs. 3 + 4), presence of seminal vesicle invasion, and margin extent. On univariate analysis, margin extent was predictive for improved bNED (5-year bNED rate of 92% vs. 58%, p = 0.010, for men with focal and extensive margins, respectively). Gleason score (4 + 3 vs. 3 + 4), seminal vesicle invasion, and ART were not statistically significant predictors. On multivariate analysis, the preoperative PSA level, margin extent, and ART were independent significant factors. In the group with extensive surgical margins, men receiving ART had a significantly greater 5-year bNED survival rate compared with the non-ART patients (73% vs. 31%, p = 0.004). CONCLUSION: These data suggest that the amount of microscopic residual tumor significantly affects bNED after radical prostatectomy for Gleason score 7, pT3N0 prostate cancer. In addition, men with pathologic evidence of microscopic local disease appear to benefit from early ART compared with untreated controls.     

Analysis of clinicopathologic factors predicting outcome after radical prostatectomy

BACKGROUND: A variable biochemical failure rate has been reported for patients undergoing radical prostatectomy. The authors analyzed their 1987-1993 prostatectomy experience retrospectively to stratify the risk of failure in order to appropriately select patients who potentially may benefit from adjuvant therapy. METHODS: A stepwise logistic regression was used to identify variables associated with biochemical failure in 265 patients who underwent radical prostatectomy only. Prostate tumors were examined by one pathologist using 4-mm step sections. Numerous clinicopathologic variables were evaluated, and the neoplasms were subclassified into five pathologic categories based on tumor extent and margin status. Actuarial projections of biochemical failure were created using the Kaplan-Meier method. RESULTS: Pathologically, 56.2% of the tumors were organ-confined with negative margins, 12.8% had a positive surgical margin without evidence of extraprostatic extension (EPE), 24.2% had EPE (17% with negative margins and 7.2% with positive margins), and 6.8% had seminal vesicle involvement. The Gleason score was > or = 7 in 86.4% of the total population. Values for the preoperative prostate specific antigen assay were < or = 4.0 ng/mL in 23.4% of the men and > 10 ng/mL in 27.7%. The overall observed biochemical failure rate in this patient group with a minimum 48 months of follow-up was 15.5%. Overall, stepwise logistic regression analysis revealed that pathologic category was the variable most strongly associated with biochemical failure and that vascular invasion was the only other examined variable associated with failure. CONCLUSIONS: The combination of pathologic category and the prostatectomy Gleason score can stratify a patient's probability of biochemical failure into three distinct groups and can identify the appropriate patients who may benefit from novel adjuvant therapeutic strategies.     

Phase II trial of neoadjuvant docetaxel and gefitinib followed by radical prostatectomy in patients with high‐risk,locally advanced prostate cancer

BACKGROUND:

Prostate cancer trials investigating neoadjuvant hormonal therapy, followed by surgery, have demonstrated that elimination of all tumor cells from the primary site is rare. The authors report a phase 2 trial assessing the efficacy and toxicity of docetaxel and gefitinib in patients with high‐risk localized prostate cancer as neoadjuvant therapy before radical prostatectomy (RP).

METHODS:

Thirty‐one patients with high‐risk prostate cancer were treated with docetaxel and gefitinib for 2 months before RP. All patients met the criteria of clinical stage T2b‐3 or serum prostate‐specific antigen (PSA) level >20 ng/mL, or Gleason score of 8 to 10. The primary endpoint was pathologic complete response. Secondary objectives included clinical response. When available, endorectal coil magnetic resonance imaging (eMRI) was performed as part of clinical response evaluation. Immunohistochemical staining of epidermal growth factor receptor and HER‐2/neu was performed on prechemotherapy and postchemotherapy prostate tissue.

RESULTS:

The median age of the patients was 60 years, the median pretreatment PSA level was 7.43 ng/mL, and the median Gleason score was 8. Clinical staging prior to treatment consisted of: T1 in 4 patients, T2 in 17 patients, and T3 in 10 patients. One patient with enlarged pelvic adenopathy and T4 disease did not undergo RP. Thirty patients received all scheduled therapies including RP. Grade 3 toxicities included asymptomatic liver function test elevation in 4 (13%) patients, diarrhea in 1 (3%) patient, and fatigue in 1 (3%) patient. One patient experienced grade 4 toxicity with elevated alanine aminotransferase. RP specimen pathology demonstrated residual carcinoma in all cases. Twenty‐nine (94%) patients achieved a clinical partial response, including 35% of patients who demonstrated radiographic improvement on eMRI.

CONCLUSIONS:

No pathologic complete response was noted in 31 patients treated with docetaxel and gefitinib. This combination was well tolerated, and did not result in increased surgical morbidity. Cancer 2009. © 2009 American Cancer Society.     

Dose‐escalated radiation therapy for intermediate‐risk prostate cancer

BACKGROUND:

Randomized trials supported the use of androgen deprivation therapy (ADT) with radiation therapy (RT) for intermediate‐risk prostate cancer. However, the value of concurrent ADT was less certain with dose‐escalated RT. Better methods of stratifying patients in this risk group may help select patients who are most likely to benefit.

METHODS:

A total of 238 men with intermediate‐risk (prostate specific antigen [PSA] 10‐20, Gleason 7, or stage T2b‐c) adenocarcinoma of the prostate were treated with external beam RT between 1989 and 2006. Patients had Gleason≤6 (39%) or 7 (61%) tumors; median PSA was 10.5 ng/mL. A median of 37.5% of biopsy cores were positive from a median of 9 biopsy cores sampled. The median RT dose was 74 Gy to the prostate. A total of 112 patients (47%) received neoadjuvant and concurrent ADT (median, 4 months). Median follow‐up period was 49 months.

RESULTS:

The freedom from biochemical failure (FFBF, nadir + 2 definition) was 93% at 3 years, 86% at 4 years, and 80% at 5 years. On univariate analysis, the only factor associated with FFBF was percentage of positive cores (PPC, P = .0340). The prognostic value of PPC≥50 was not evident in patients receiving ADT (FFBF at 4 years 90% vs 91%, P = .3015). For patients not receiving ADT, the impact of PPC≥50 (FFBF at 4 years 76% vs 93%, P = .0844) was more pronounced. On multivariate analysis, PPC (P = .0388) was significantly associated with FFBF, whereas Gleason sum, ADT, RT dose, PSA, and T‐stage were not.

CONCLUSIONS:

After dose‐escalated external beam RT, intermediate‐risk prostate cancer patients with PPC≥50 had the highest risk for biochemical failure and may be most likely to derive a benefit from ADT. Cancer 2009. © 2009 American Cancer Society.     

The efficacy of early adjuvant radiation therapy for pT3N0 prostate cancer: a matched-pair analysis.

PURPOSE: This study examines the effect of adjuvant radiation therapy (RT) on outcome in patients with pT3N0 prostate cancer and makes comparisons to a matched control group. METHODS AND MATERIALS: At our center, 149 patients undergoing radical prostatectomy were found to have pT3N0 prostate cancer, had an undetectable postoperative prostate-specific antigen (PSA) level, and had no immediate hormonal therapy. Fifty-two patients received adjuvant RT within 3 to 6 months of surgery. Ninety-seven underwent radical prostatectomy alone and were observed until PSA failure. From these two cohorts, we matched patients 1:1 according to preoperative PSA (<10 ng/ml vs. >10 ng/ml), Gleason score (<7 vs. > or =7), seminal vesicle invasion, and surgical margin status. Seventy-two patients (36 pairs) were included in the analysis. Median follow-up time was 41 months. We calculated a matched-pairs risk ratio for cumulative risk of PSA relapse (a rise above 0.2 ng/ml). RESULTS: After controlling for the prognostic factors by matching, there was an 88% reduction (95% confidence interval [CI]: 78-93%) in the risk of PSA relapse associated with adjuvant RT. The 5-year freedom from PSA relapse rate was 89% (95% CI: 76-100%) for patients receiving adjuvant RT as compared to 55% (95% CI: 34-79%) for those undergoing radical prostatectomy alone. CONCLUSIONS: These data suggest that adjuvant RT for pT3N0 prostate cancer may significantly reduce the risk of PSA failure as compared to radical prostatectomy alone. Its effect on clinical outcome awaits further follow-up.     

Prostate specific antigen outcome based on the extent of extracapsular extension and margin status in patients with seminal vesicle negative prostate carcinoma of Gleason score < or = 7

BACKGROUND: Early (< or = 2 years) prostate specific antigen (PSA) failure after radical prostatectomy (RP) has been shown to predict for distant failure. After excluding patients with the pathologic predictors of early PSA failure, an analysis of PSA failure free (bNED) survival was performed to identify patients who may benefit from the use of postprostatectomy radiation therapy (RT). METHODS: Of 1,028 patients treated with RP for clinically localized prostate carcinoma between 1989 and 1999, 862 (84%) had either organ confined (OC), specimen confined (SC), or margin positive disease with negative seminal vesicles (SV) and a prostatectomy Gleason score < or = 7. A Cox regression multivariate analysis was performed in these patients evaluating the ability of the extent of extracapsular extension (ECE) (into but not through the capsule, SC focal ECE, SC established ECE, margin positive) and prostatectomy Gleason score (2-6 vs. 7) to predict time to postoperative PSA failure. RESULTS: SC focal ECE (P = 0.0017), SC established ECE (P < 0.0001), and margin positive disease (P < 0.0001) were significant predictors of time to postoperative PSA failure, whereas prostatectomy Gleason score and disease extending into but not through the capsule were not. Five-year bNED rates were 90%, 88%, 69%, 45%, and 33% for patients with OC, into but not through capsule, SC focal ECE, SC established ECE, and margin positive prostate carcinoma, respectively. CONCLUSIONS: Patients with SC ECE or margin positive prostate carcinoma and a prostatectomy Gleason score < or = 7 with no evidence of SV invasion may benefit from adjuvant postoperative RT.     

Recursive partitioning for prognostic grouping of patients with clinically localized prostate carcinoma

BACKGROUND: Patients treated with radical prostatectomy for clinically localized prostate carcinoma present considerable heterogeneity in terms of disease free survival outcome. Multiple studies have attempted to create prognostic groupings of these patients in the perioperative phase, using information available regarding several clinicopathologic variables. Such groupings allow physicians to make early yet prudent decisions regarding adjuvant combination therapies. The current study presents results from a statistical analysis that enables the natural identification of such prognostic groups. METHODS: Examination of consecutive radical prostatectomy specimens was performed between January 1991 and December 1995 at Wayne State University, Harper Hospital, Detroit, Michigan. Disease free survival in a cohort of 485 of these men was analyzed using recursive partitioning and amalgamation technique. Clinicopathologic parameters evaluated included age, race, preoperative prostate specific antigen (PSA) level, clinical and pathologic stage, and Gleason grade of the fine-needle biopsy as well as the radical prostatectomy specimen. RESULTS: A binary decision tree representation was generated for classifying patients based on the clinicopathologic variables mentioned earlier. The worst prognosis was for patients with either advanced stage and a PSA level > 24.1 ng/mL or advanced stage, a PSA level 相似文献   

Long-term survival after radical prostatectomy versus external-beam radiotherapy for patients with high-risk prostate cancer

BACKGROUND:

The long‐term survival of patients with high‐risk prostate cancer was compared after radical prostatectomy (RRP) and after external beam radiation therapy (EBRT) with or without adjuvant androgen‐deprivation therapy (ADT).

METHODS:

In total, 1238 patients underwent RRP, and 609 patients received with EBRT (344 received EBRT plus ADT, and 265 received EBRT alone) between 1988 and 2004 who had a pretreatment prostate‐specific antigen (PSA) level ≥ 20 ng/mL, a biopsy Gleason score between 8 and 10, or clinical tumor classification ≥ T3. The median follow‐up was 10.2 years, 6.0 years, and 7.2 years after RRP, EBRT plus ADT, and EBRT alone, respectively. The impact of treatment modality on systemic progression, cancer‐specific survival, and overall survival was evaluated using multivariate Cox proportional hazard regression analysis and a competing risk‐regression model.

RESULTS:

The 10‐year cancer‐specific survival rate was 92%, 92%, and 88% after RRP, EBRT plus ADT, and EBRT alone, respectively (P = .06). After adjustment for case mix, no significant differences in the risks of systemic progression (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.51‐1.18; P = .23) or prostate cancer death (HR, 1.14; 95% CI, 0.68‐1.91; P = .61) were observed between patients who received EBRT plus ADT and patients who underwent RRP. The risk of all‐cause mortality, however, was greater after EBRT plus ADT than after RRP (HR, 1.60; 95% CI, 1.25‐2.05; P = .0002).

CONCLUSIONS:

RRP alone and EBRT plus ADT provided similar long‐term cancer control for patients with high‐risk prostate cancer. The authors concluded that continued investigation into the differing impact of treatments on quality‐of‐life and noncancer mortality will be necessary to determine the optimal management approach for these patients. Cancer 2011. © 2011 American Cancer Society.     

Percentage of Gleason pattern 4 and 5 predicts survival after radical prostatectomy

BACKGROUND: Morphologic and clinical heterogeneity within tumor grades is well recognized in prostate cancer. The objective of the current study was to determine whether the combined percentage of Gleason patterns 4 and 5 in radical prostatectomy specimens is an independent predictor of cancer-specific survival in prostate cancer patients. METHODS: The radical prostatectomy specimens were analyzed from 504 consecutive prostate cancer patients who were treated at Indiana University Medical Center between 1990 and 1998. Various clinical and pathologic characteristics were analyzed. RESULTS: A higher combined percentage of Gleason patterns 4 and 5 was associated with older age, higher preoperative serum prostate-specific antigen level, higher pathologic stage, positive surgical margins, extraprostatic extension of tumor, higher Gleason score, perineural invasion, and lymph node metastasis. In the multivariate Cox regression model, the combined percentage of Gleason patterns 4 and 5 was found to be an independent predictor of cancer-specific survival (P = .04). CONCLUSIONS: The combined percentage of Gleason patterns 4 and 5 is a powerful predictor of prostate cancer-specific survival. Assessment of high-grade cancer amounts may allow for better stratification of patients into appropriate prognostic groups and treatment protocols.