SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Twenty of 391 newly diagnosed cases of prostatic cancer (5%) had a prior prostatectomy for benign disease. Digital rectal examination in 16 of 19 patients (84%) revealed a significant prostatic abnormality. Continued serial digital rectal examination should be performed routinely after prostatectomy for benign disease.
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.
BACKGROUND: Serum prostate specific antigen (PSA) is a sensitive indicator of prostate cancer recurrence after radical prostatectomy. Prostate cancer rarely recurs after radical surgery without PSA elevation. Of the few patients noted in the literature who had a recurrence of cancer without PSA elevation, all had local recurrence alone, except for one, who had bone metastases. METHODS: In the authors' series of 628 patients, PSA was the first indicator of recurrence in all but 2 (2.6%) of 77 patients with clinical T1-T3NxM0 classification prostate cancer. RESULTS: Two of our patients, despite having undetectable PSA levels, had distant recurrence, including one with multiple visceral (lung and brain) metastases. CONCLUSIONS: These two cases demonstrate that although uncommon, prostate cancer can recur and metastasize after radical prostatectomy without an increase in the serum PSA level.
BACKGROUND: This study was performed to evaluate the efficacy of radical prostatectomy for men with clinically localized, poorly differentiated (Gleason score > or = 7) prostate cancer and to characterize further the prognostic significance of traditional pathologic variables. The effectiveness of adjuvant radiotherapy was assessed in a subpopulation of men for whom the pathologic assessment suggested a high risk of persistent disease. METHODS: Two hundred thirty-eight consecutive men, 74 of whom had clinically localized, poorly differentiated carcinoma, were followed for a median of 6.2 and 5.1 years, respectively. The disease specific outcomes were derived from a non-prostate specific antigen (PSA) screened population. RESULTS: The 5-year disease specific survival (DSS) for 52 men with a clinically localized Gleason score of 7 and for 22 men with a Gleason score greater than or equal to 8 carcinoma was 92% and 79%, respectively. The 5-year likelihood of having an undetectable PSA level was 50% for those with a Gleason score of 7 and 38% for those with a Gleason score greater than or equal to 8. Gleason score was the most powerful pathologic predictor of disease progression and survival. Pathologic stage was significantly associated with disease progression for carcinomas with Gleason scores less than 7 but was found to be less predictive of progression for carcinomas with Gleason scores greater than or equal to 7. Adjuvant radiotherapy provided a significantly reduced risk of PSA-detectable progression (P = 0.02, relative risk = 0.56, 95% CI: 0.34, 0.92); however, radiotherapy had no significant impact on DSS. CONCLUSIONS: Long term DSS is possible in a non-PSA screened series of men with poorly differentiated prostate cancer treated by radical prostatectomy. These results compare favorably with alternative treatment strategies, although they do illustrate a continued need to develop more effective adjuvant therapies for men with poorly differentiated prostate cancer.
BACKGROUND: Whether patients who are diagnosed on the basis of a single microscopic focus of prostate carcinoma with a Gleason score </= 7 (micro PC) have potentially life-threatening disease if they are not treated is unknown. METHODS: Pathologic findings and prostate specific antigen (PSA) outcome after radical prostatectomy (RP) for men who were diagnosed with micro PC were determined. Of 917 patients who were managed with RP during 1989-1999 at the Brigham and Women's Hospital, 66 patients (7%) were diagnosed on the basis of micro PC. Pathologic stage, tumor grade, tumor volume, margin status, and PSA outcome were investigated and are reported. Estimates of PSA outcome were calculated using the actuarial method of Kaplan and Meier. Pairwise comparisons were made using the log rank test. RESULTS: The finding of micro PC at biopsy was associated with macroscopic disease (involving at least half of a single lobe) in 92% of the patients in this series. Although these men had favorable pathologic findings (94% had organ confined disease, 89% had negative tumor margins, and 79% had a prostatectomy Gleason score </= 6), approximately 10% of the patients failed biochemically within 5 years after RP. CONCLUSIONS: The finding of micro PC at biopsy should not be used as a surrogate for clinically insignificant disease.
BACKGROUND: The objective was to compare the changes in pathologic and clinical data over time for African-American (AA) and white men with prostate carcinoma undergoing radical prostatectomy in an attempt to determine the early impact of prostate specific antigen (PSA). METHODS: Data from 195 AA and 587 white men who underwent radical prostatectomy from 1988 to 1999 in an equal access, tertiary, military medical facility were collected. Statistical analysis was used to determine the significance of the changes in the rates of extracapsular extension (ECE), positive margins, pretreatment PSA levels, and age at the time of surgery for each race over time. RESULTS: Comparing 1988-99 results, the authors found that the percentage of AA men with ECE decreased from 100% to 34.8% (P = 0.007), and for white men from 56.9% to 43.2% (P = 0.269). The percentage of AA men with positive margins decreased from 100% to 26.1% (P < 0.0001), and for white men from 41.2% to 27.0% (P = 0.021). Mean age at surgery decreased from 66.6 to 59.9 years for AA men (P < 0.001) and from 65.9 to 61.1 years for white men (P < 0.001). Also, PSA levels decreased from 10.1 to 6.6 ng/dL for white men (P < 0.001) and from 16.5 to 6.5 ng/dL for AA men (P < 0.001). CONCLUSIONS: The authors believe that the decrease in ECE and positive margins in AA men is primarily because of PSA testing, coupled with improved public awareness and equal access to care. It appears reasonable to recommend PSA testing in AA men, who have historically experienced poor outcomes from prostate carcinoma.
A comparison of the results of prostatectomy in the same hospital after a 15-year interval has shown that there has been a significant reduction in the mortality (2-3 per cent versus 6-7 per cent). However, on reviewing the results of prostatectomy over the past 30 years it is evident that in spite of improved pre- and postoperative care the mortality and morbidity for high risk patients have remained constant. If the safety for this operation is to improve, it would seem that more care in patient selection is necessary and that other means of achieving urinary drainage will need consideration and evaluation in elderly men with significant cardiovascular and respiratory disease.
Eighty-three patients with post-prostatectomy urinary incontinence were treated by silicone gel prostheses implanted over the bulbous urethra. The prosthesis provides continence by passively increasing the urethral resistance. Successful results were achieved in 72% of patients. The mechanism of post-prostatectomy incontinence and the development of anti-incontinence surgery is briefly reviewed.
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.
BACKGROUND: Predicting outcome for men with clinically localized prostate carcinoma treated with curative intent remains imprecise and further evaluation of accepted and potential predictive factors is needed. METHODS: The authors studied 696 men with localized prostate carcinoma diagnosed on transrectal biopsy and treated with radical prostatectomy at one institution between 1986 and 1999 to determine the relation between putative pretreatment prognostic factors and disease-free survival. Clinical stage, Gleason score, perineural invasion, number of biopsies containing tumor, and serum prostate specific antigen (PSA) were evaluated as predictors of extracapsular extension, seminal vesicle involvement, lymph node metastases, and surgical margin involvement as well as outcome after surgery. Kaplan-Meier method and Cox regression analyses were used to evaluate the contribution of different factors to adverse pathologic features and relapse. RESULTS: At mean follow-up of 56.9 months (range, 1.0-177.9 months; median, 54.9 months), 26.1% (182 of 696 patients) of patients had developed a disease recurrence. Pretreatment serum PSA concentration, biopsy Gleason score, and clinical stage as well as number of biopsies involved with tumor as a percentage of the total number obtained were found to be independent predictors of outcome. In patients with PSA > 10 ng/mL, biopsy perineural invasion and percentage of biopsies containing tumor were found to independently predicted disease recurrent. Increased number of biopsies involved with tumor independently predicted extracapsular extension, margin involvement, seminal vesicle, and lymph node involvement. CONCLUSIONS: This study demonstrated that the proportion of prostate biopsy cores containing tumor is an independent predictor of outcome after subsequent radical prostatectomy and suggested that perineural invasion has a predictive role in patients with a preoperative PSA > 10 ng/ml.
BACKGROUND: The 1997 TNM staging system for prostate carcinoma defines a pT2a disease as a tumor histologically involving one lobe of the prostate and pT2b disease as a tumor histologically involving both prostatic lobes. Whether this distinction provides prognostic significance is unclear. The authors evaluated biochemical outcomes between men with pT2aN0 and pT2bN0 disease. METHODS: The authors identified 1606 men with organ-confined disease (pT2N0) who were treated with radical prostatectomy between 1982 and 2003 by one surgeon. Clinical characteristics were compared between men with pT2a and pT2b tumors using rank-sum analysis, and prostate-specific antigen (PSA) recurrence data were compared using log-rank analysis. The significant independent predictors of PSA recurrence were determined using a multivariate Cox proportional hazards model. RESULTS: There were no significant differences between men with pT2a and pT2b tumors at the time of surgery in terms of clinicopathologic characteristics (biopsy and pathologic Gleason score, serum PSA level, clinical stage, and age). Log-rank analysis revealed no significant differences in time to PSA recurrence between men with pT2a and pT2b tumors (P = 0.755). The 10-year PSA progression-free survival rate was 95% (confidence interval [CI], 92-97%) for men with pT2a tumors and 93% (CI, 90-95%) for men with pT2b tumors. Multivariate analysis showed that the significant predictors of PSA recurrence included serum PSA level, biopsy and pathologic Gleason score, and clinical stage. In the current cohort of men with organ-confined disease, pathologic stage (pT2a vs. pT2b) was not a significant predictor of PSA recurrence on multivariate analysis. CONCLUSIONS: There was no difference in PSA recurrence rates between men with pT2aN0 versus pT2bN0 tumors. In men with organ-confined disease, radical prostatectomy provided excellent 10-year PSA progression-free survival regardless of tumor burden (pT2a vs. pT2b). Consideration should be given to modifying the TNM staging system to eliminate substratification of pT2 tumors.
BACKGROUND: Because the recovery of erectile function and the avoidance of positive surgical margins are important but competing outcomes, the decision to preserve or resect a neurovascular bundle (NVB) during radical prostatectomy (RP) should be based on the most accurate information concerning the location and extent of the tumor. In the current study, the authors determined the incremental value of endorectal magnetic resonance imaging (eMRI) in making this decision. METHODS: eMRI was performed in 135 patients preoperatively. For each NVB, tumor extension to the NVB and the need for NVB resection was judged by a surgeon on a scale from 1 (definite preservation) to 5 (definite resection) before and after reviewing eMRI with a radiologist. Histopathologic findings were used as the standard of reference. The value of eMRI was assessed using binormal receiver operating characteristic (ROC) analysis adjusted for multiple observations per patient, and a mixed effects ordinal regression model was used for risk stratification. RESULTS: Histopathologic examination determined that NVB resection was warranted in 44 of 270 NVBs (16%) because of posterolateral extracapsular extension (n = 29), positive surgical margins (n = 7), or both (n = 8). The areas under the ROC curves (AUC) were 0.741 for pre-MRI and 0.832 for post-MRI surgical planning (P < 0.01). MRI findings suggested altering the surgical plan in 39% of NVBs (106 of 270 NVBs). When the surgeon judged that the NVB resection was definitely not necessary (165 NVBs), MRI confirmed that decision in 138 NVBs (84%); the concordant decision was correct in 96% of the cases (133 of 138 NVBs). In 36 high-risk patients (> or = 75% probability of extracapsular extension), MRI findings changed the surgical plan for 28 NVBs (78%); the change was found to be appropriate in 26 cases (93%). CONCLUSIONS: MRI was found to significantly improve the surgeon's decision to preserve or resect the NVB during radical prostatectomy.
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.
BACKGROUND: The authors examined the impact of the number of CAG repeats in exon 1 of the androgen receptor on disease progression among men with prostate carcinoma after prostatectomy. This polymorphism has been associated with alterations in activity of the androgen receptor in in vitro systems and with the risk of clinically diagnosed prostate carcinoma in some epidemiologic studies. An earlier series found that, among men at low risk of progressive disease, a small number of CAG repeats predicted a high risk of recurrence, and the impact of CAG repeats varied among men with different risks of progressive disease. METHODS: The authors analyzed specimens from a large clinical series of fixed tissue specimens from men who underwent prostatectomy at a single institution, including 413 American white men (WM) and 298 African-American men (AAM), with 5-10 years of available clinical follow-up. RESULTS: There was little association between the number of CAG repeats and extent of disease, Gleason score, and preoperative PSA level at diagnosis. Overall, patients who had > 18 CAG repeats had a greater risk of recurrence compared with patients who had </= 18 CAG repeats (hazard ratio [HR] = 1.52; P = 0.03). Excess risk was not found among men who were at low risk of recurrence (HR = 0.93; P = 0.96); however, among men who were at high risk of recurrence, the risk elevated for WM (HR = 1.75; P = 0.28), AAM (HR = 1.49; P = 0.06), and both races combined (HR = 1.53; P = 0.03). CONCLUSIONS: Overall, men with prostate carcinoma who had > 18 CAG repeats had an estimated 52% increased risk of disease recurrence. The increased risk could be attributed to men who were at high risk of recurrence.
BACKGROUND: Several studies have recently suggested an association between body mass index (BMI) and disease progression after radical prostatectomy. In the current study, the authors examined this association and that between the reciprocal of BMI (INVBMI, 1/BMI) and progression-free probability in men treated with radical retropubic prostatectomy (RRP) for clinically localized prostate carcinoma. METHODS: The authors retrospectively studied 2210 patients who underwent RRP at Memorial Sloan-Kettering Cancer Center between September 1986 and May 2003. Clinicopathologic variables analyzed included BMI (kg/m2), preoperative serum prostate-specific antigen level (ng/mL), clinical T classification, year of surgery, race, biopsy-derived primary and secondary Gleason grades, and INVBMI, known to better correlate with percent body fat than BMI. Cox regression analysis was used to examine the possible association between BMI or its reciprocal with disease progression after controlling for the effects of common prognostic factors. The areas under the receiver operating curve (AUC) for models with and without INVBMI were calculated. RESULTS: Of the 2210 patients analyzed, 251 experienced disease progression in a median follow-up time of 25.9 months (range, 0-143 months). After adjusting for all clinical variables, both BMI (P = 0.071; hazards ratio [HR] = 1.027) and INVBMI (P = 0.041; HR < 0.001) were associated with disease progression. However, the areas under AUC for models with and without INVBMI were similar (range, 0.794-0.798). CONCLUSIONS: Although conflicting evidence has been reported regarding the link between obesity and an increased risk of developing prostate carcinoma, as well as an increased risk of developing aggressive disease and prostate carcinoma-related mortality, the authors found weak associations with disease progression for both BMI and INVBMI. These variables were of negligible prognostic value in men who received surgery. Studies with longer follow-up, that examine alternative end points, and that follow treatment(s) besides surgery are needed.
BACKGROUND: Gene expression profiling of prostate carcinoma offers an alternative means to distinguish aggressive tumor biology and may improve the accuracy of outcome prediction for patients with prostate carcinoma treated by radical prostatectomy. METHODS: Gene expression differences between 37 recurrent and 42 nonrecurrent primary prostate tumor specimens were analyzed by oligonucleotide microarrays. Two logistic regression modeling approaches were used to predict prostate carcinoma recurrence after radical prostatectomy. One approach was based exclusively on gene expression differences between the two classes. The second approach integrated prognostic gene variables with a validated postoperative predictive model based on standard variables (nomogram). The predictive accuracy of these modeling approaches was evaluated by leave-one-out cross-validation (LOOCV) and compared with the nomogram. RESULTS: The modeling approach using gene variables alone accurately classified 59 (75%) tissue samples in LOOCV, a classification rate substantially higher than expected by chance. However, this predictive accuracy was inferior to the nomogram (concordance index, 0.75 vs. 0.84, P = 0.01). Models combining clinical and gene variables accurately classified 70 (89%) tissue samples and the predictive accuracy using this approach (concordance index, 0.89) was superior to the nomogram (P = 0.009) and models based on gene variables alone (P < 0.001). Importantly, the combined approach provided a marked improvement for patients whose nomogram-predicted likelihood of disease recurrence was in the indeterminate range (7-year disease progression-free probability, 30-70%; concordance index, 0.83 vs. 0.59, P = 0.01). CONCLUSIONS: Integration of gene expression signatures and clinical variables produced predictive models for prostate carcinoma recurrence that perform significantly better than those based on either clinical variables or gene expression information alone.
BACKGROUND: The objective of this study was to compare the ability of the 1992 American Joint Committee on Cancer (AJCC) TNM staging system for nonorgan-confined prostate carcinoma (PCa) (pathologic T3 [pT3a], pT3b,and pT3c) to predict biochemical recurrence (BCR) after radical prostatectomy with its revision from 1997/2002 (pT3a and pT3b). METHODS: The authors analyzed prospectively collected data from 971 consecutive patients with pT3 tumors who underwent radical prostatectomy alone at a single institution. According to the 1992 AJCC substages, 494 patients had pT3a PCa (51%), 85 patients had pT3b PCa (9%), 302 patients had pT3c PCa (31%) and 91 patients had pT3 PCa (9%) with metastatic lymph node invasion (LNI). Kaplan-Meier and Cox proportional hazards regression analyses were employed to assess the BCR rate using the preoperative prostate-specific antigen (PSA) level, surgical margin (SM) status, pathologic Gleason score, and LNI. The predictive accuracy of this "base" model was compared with models that added either the AJCC 1992 or the AJCC 1997/2002 staging definitions. RESULTS: BCR was observed in 345 patients (36%). The actuarial 5-year recurrence-free probability for patients with AJCC 1992 pT3a, pT3b, and pT3c PCa was 69%, 42%, and 33%, respectively, and differed significantly between men with pT3a tumors and men with pT3b tumors (log-rank test; P < 0.0005). In Cox regression analyses, the 1992 substages were associated significantly with BCR after controlling for PSA, SM status, Gleason grade, and LNI (P < 0.0005). The predictive accuracy of the base model (bootstrap-corrected concordance index, 0.739) was improved after addition of the 1992 TNM staging criteria (concordance index, 0.747). However, predictive accuracy was similar for the model that included the 1997/2002 substages (concordance index, 0.746). CONCLUSIONS: Substaging of pT3 tumors according to the less complex 1997/2002 pT3 classification improved the predictive accuracy of the BCR rate virtually to the same extent as the more detailed 1992 classification. Therefore, the current data favor the use of the 1997/2002 pT3 substaging system.
BACKGROUND: Occasionally, patients with clinical T4 (cT4) prostate cancer undergo surgery. Published data on outcomes after radical prostatectomy (RP) in patients with such advanced stage disease and on the impact of adjuvant radiation therapy (RT) and hormone therapy (HT) are nonexistent. METHODS: Data from the Surveillance Epidemiology and End Results (SEER) data base were reviewed for the 7-year period from 1995 to 2001. Specifically, data were analyzed for 1093 patients with cT4, lymph node-negative or lymph node-positive, M0 prostate cancer without distant lymph node involvement or a history of other cancer. Using follow-up data through 2002, postdiagnosis survival was examined in 5 treatment groups: radical prostatectomy (RP) either alone or in combination with other therapy, radiation therapy (RT) alone, hormone therapy (HT) alone, RT plus HT, and no treatment (NT). All results were expressed as 1-year, 3-year, and 5-year observed survival and corresponding relative survival. Mortality across treatment categories was compared by using a Cox proportionate hazards model controlling for age, year of diagnosis, race, tumor grade, regional lymph node involvement, clinical tumor extension, and SEER registry. RESULTS: Observed and relative survival rates were lowest among patients who received NT and highest among patients who underwent RP. Adding adjuvant RT or HT to RP conferred no survival benefit. Multivariate survival analyses revealed a significant increase in mortality among HT-only patients and among patients who received NT compared with patients who underwent RP. The differences in survival among treatment types were most pronounced in a relatively small group of patients who had positive regional lymph node extension. In all other patients, the results suggested a modest (but not significant) improvement in survival after RT plus HT. CONCLUSIONS: SEER data revealed that patients who underwent RP for cT4 prostate cancer had increased survival compared with patients who received RT alone or HT alone and had a survival comparable to that of patients who received RT plus HT. The benefit of RP appears to be limited to a relatively small subset of patients who have regional lymph node extension.