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.     

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.     

Caveolin-1 expression is a predictor of recurrence-free survival in pT2N0 prostate carcinoma diagnosed in Japanese patients

BACKGROUND: The authors previously identified elevated caveolin-1 expression in human prostate carcinoma and determined that caveolin-1 levels as detected by immunohistochemistry of radical prostatectomy specimens offered novel prognostic information. A higher incidence of caveolin-1 expression also was reported in African-American men compared with white men in the U.S. To explore these ethnic/racial differences in caveolin-1 expression further, the authors evaluated caveolin-1 expression as a predictive marker in Japanese men with prostate carcinoma. METHODS: Immunohistochemical staining with a caveolin-1 specific antibody was performed on routinely processed paraffin sections from 152 consecutively collected radical prostatectomy specimens. The mean patient age was 64.3 years (range, 49-74 years; median, 64.5 years) and the mean follow-up period was 49.5 months (range, 1.3-103.3 months; median, 48.2 months). Caveolin-1 immunoreactivity was evaluated in association with patient's age; preoperative prostate specific antigen level; clinical stage; and pathologic features including Gleason score, extraprostatic extension, status of surgical margins, seminal vesicle involvement, lymph node involvement, and time to disease progression after surgery. RESULTS: Positive caveolin-1 immunostaining was detected in 46 of the 152 tumors (30.3%) and was found to be associated significantly with a positive surgical margin (P = 0.022). A higher incidence of caveolin-1 expression tended to be found in patients with poorly differentiated tumors (Gleason score > 7, 6-7, and < 6, 35.0% vs. 34.9% vs. 20.4%, respectively) or in patients with extraprostatic extension versus those without extraprostatic extension (35.4% vs. 24.7%) or patients with lymph node involvement compared with those without lymph node involvement (50% vs. 29.5%), although these differences did not reach statistical significance (P = 0.100, P = 0.150, and P = 0.178, respectively, by the Spearman correlation test). Kaplan-Meier analysis revealed that increased caveolin-1 expression was associated with an increased risk of disease progression at 5 years (P = 0.0122 by the log-rank test). In patients with organ-confined (pT2N0) disease, univariate Cox proportional hazards regression analysis revealed that positive caveolin-1 expression was the only significant predictor of disease recurrence after radical prostatectomy (P = 0.011; hazards ratio = 4.75; and 95% confidence interval, 1.43-15.76). CONCLUSIONS: The results of the current study confirm that positive caveolin-1 expression is associated with clinical markers of disease progression and is predictive of poor clinical outcome after surgery in Japanese patients with pT2N0 prostate carcinoma.     

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.     

Risk of positive margins and biochemical recurrence in relation to nerve-sparing radical prostatectomy.

PURPOSE: To assess the effect of nerve-sparing (NS) radical retropubic prostatectomy (RRP) on surgical margins and biochemical recurrence. PATIENTS AND METHODS: Location and incidence of positive surgical margins, recurrence, and time to recurrence were assessed in a consecutive series of 734 men who underwent RRP for localized prostate cancer from 1992 through February 2000. NS procedures were used in 33% (n = 240) of 734 patients studied. RESULTS: Surgical margins were positive for 24% (n = 58) and 31% (n = 152) of NS and non-NS patients, respectively (P =.06). No significant difference between the groups was found in location of positive margins (P =.92). Prostate-specific antigen level greater than 10 ng/mL, extraprostatic extension, tumor volume more than 20%, capsular penetration, Gleason score > or = 7, positive margins, and seminal vesicle invasion were associated with significantly increased risk of recurrence. However, NS patients were not at increased risk of recurrence compared with non-NS patients (hazard ratio, 0.96; 95% confidence interval, 0.53 to 1.72). The cumulative risk of recurrence within 3 and 5 years of surgery in NS patients was 9.7% and 14.4%, respectively, as compared with 17.1% and 21.1% for non-NS patients. CONCLUSION: In patients with localized prostate cancer, neither margin status nor biochemical-free survival within 5 years of surgery were altered by the nerve preservation technique. Given our experience, we recommend preservation of neurovascular bundles in these patients whenever the procedure is technically feasible.     

DNA ploidy and prostate-specific antigen as prognostic factors in clinically resectable prostate cancer.

Prostate-specific antigen (PSA) and DNA ploidy as measured by flow cytometry were compared with conventional prognostic indicators in 112 patients who underwent radical prostatectomy for clinically resectable prostate cancer. The variables examined included age, race, prostatic acid phosphatase (PAP), Gleason score of the radical prostatectomy specimen, and pathologic stage. No significant relationships were found between DNA ploidy and age, mean PAP value, and absolute PAP value. Of the 112 patients, 65 (58.0%) had disease limited to the prostate (pathologic Stages A and B); 47 (42.0%) had extraprostatic disease (pathologic Stages C and D1). The stage was related to the Gleason score (P less than 0.0001) where extraprostatic disease was associated with a Gleason score of 6 to 10. Nineteen (17.0%) patients had aneuploid tumors, and 93 (83.0%) had diploid tumors. DNA ploidy significantly correlated with pathologic stage (P = 0.04); aneuploidy was identified more frequently in patients with Stages C and D1 tumors. Aneuploid tumors occurred more frequently than diploid tumors in patients with a Gleason score of 6 to 10 (P = 0.034). Mean PSA values were higher in patients with aneuploid tumors (P = 0.078), extraprostatic neoplasms (P = 0.00001), and cancers with a Gleason score of 6 to 10 (P = 0.0004). Furthermore, PSA values greater than 10.0 ng/ml were associated with extraprostatic disease and a Gleason score of 6 to 10 (P less than 0.05 and P less than 0.001, respectively). Significant racial differences were found with respect to DNA ploidy, mean DNA indices, and mean PSA values. The 18 black patients had more DNA aneuploid tumors (P = 0.043), a higher mean DNA index (P = 0.017), and a higher mean PSA value (P = 0.043) than the 94 white patients. Both PSA and DNA ploidy analysis by flow cytometry appear to be valuable indicators in the evaluation of patients with prostatic carcinoma.     

Preliminary results for EORTC trial 22911: radical prostatectomy followed by postoperative radiotherapy in prostate cancers with a high risk of progression]

PURPOSE: Local failure after radiotherapy can arise with cancer extending beyond the capsule and/or involvement of seminal vesicles or positive surgical margins. METHODOLOGY: After undergoing radical prostatectomy 1005 patients were randomly assigned (1999-2001) to a wait and see policy or an immediate postoperative irradiation (60 Gy delivered over 6 weeks); eligible patients had pN0 M0 tumors and one or more pathological risk factors mentioned above. The main end-point was 5-year biochemical progression free survival. RESULTS: After a median follow-up of 5-year biochemical progression free survival was significantly improved in the irradiated group (74%, 98% CI: 68.7-79.3 vs 52.6%, 98% CI: 46.6-58.5; P<0.0001) Clinical progression free survival was also significantly improved (P<0.0009). The cumulative rate of loco-regional failure was also significantly improved (P<0.0009). Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group (P=0.0005), but severe toxicity (grade 3 or higher) were rare with a 5-year rate of 2.6% in the wait-and-see group and 4.2% in the postoperative irradiation group (P=0.07). CONCLUSION: Immediate external irradiation after radical prostatectomy improves biochemical progression free survival and local control in patients with positive surgical margin or pT3 prostate cancer who are at high risk of progression. Further follow-up is needed to assess the impact on overall survival.     

Stronger association between obesity and biochemical progression after radical prostatectomy among men treated in the last 10 years.

BACKGROUND: Prior prospective cohort studies found that obesity was associated with increased risk of prostate cancer death. However, in the last 20 years dramatic changes in both the extent of obesity and prostate cancer screening and treatment have occurred. Whether the association between obesity and aggressive disease has changed as a result of these temporal changes is unclear. METHODS: The study population consisted of 2,832 men treated by anatomic radical retropubic prostatectomy between 1985 and 2004 by a single surgeon. We evaluated the associations of obesity (body mass index > or =30 kg/m(2))with tumor stage and grade using logistic regression and with biochemical progression using Cox proportional hazards regression. We examined whether these associations have changed over the last 20 years. RESULTS: On multivariable analysis, the strength of the positive association between obesity and high-grade disease increased over time whereas the strength of the positive association between obesity and positive surgical margins decreased over time. The strength of the positive association between obesity and extraprostatic extension fluctuated over time, although the strongest and only statistically significant association was among men treated since 2000. The association between obesity and biochemical progression was strongest among men treated since 1995 (relative risk, 1.90; 95% confidence interval, 1.09-3.30; P = 0.02). CONCLUSIONS: In the current study, with the exception of positive surgical margins, the positive association between obesity and high-grade disease, advanced stage, and biochemical progression after radical retropubic prostatectomy was in general strongest among men treated in the last 10 years. The reasons for these findings are not clear, although factors possibly related to prostate-specific antigen-based screening and/or other temporal changes in prostate cancer diagnosis and treatment may play a role.     

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.     

Recurrence after radical prostatectomy for organ-confined prostate cancer

BACKGROUND: Some patients from our radical prostatectomy (RPx) series with organ-confined (pT2) prostate cancer and negative surgical margins show a PSA (prostate specific antigen) relapse. Aim of the study was to analyze this cohort of patients that otherwise would have been considered to be cured. PATIENTS AND METHODS: Since the introduction of PSA measurement in the follow-up after RPx, 475 pelvic lymph node dissections with subsequent RPx were performed in our department from 1988 to 1997. Of these, 227 were classified as pT2, 34 (15%) exhibited positive surgical margins, and 4 others were excluded due to an inadequate follow-up. Of the remaining 189 patients (study cohort), 19 (10%) developed a biochemical progression, defined as a minimum of 2 consecutive PSA measurements > or = 0.1 ng/ml. Only in one of them a G3 tumor was present. Median follow-up was 19.1 months. RESULTS: The Kaplan-Meier analysis of biochemical progression showed that after 1, 2 and 5 years, 95% (confidence interval (Cl) 91-99%), 91% (Cl 86-96%), and 77% (Cl 55-89%) of the patients were free of progression, respectively. This means that roughly one fourth of pT2 tumors will become progressive despite negative surgical margins. These 19 patients were subdivided into 4 groups: 1: biopsy-proven local recurrence (n = 2); 2: suspected local recurrence defined as slowly rising PSA < or = 2 ng/ml, but negative biopsies (n = 12); 3: distant metastasis proven by radiologic imaging (n = 1); 4: suspected distant metastasis defined as rapidly rising PSA > 9 ng/ml without direct radiologic evidence (n = 4). Preoperatively all patients from groups 3 + 4 had negative bone scans and 4/5 had preoperative PSA values < 10 ng/ml. In total 7 patients with proven recurrence or with proven metastasis had positive biopsies. CONCLUSION: A pathological diagnosis of organ-confined prostate cancer (pT2) and a meticulous analysis of negative surgical margins do not exclude the occurrence of local relapses in 7% (14/189), and there is evidence for suspect hematogenic spread of PC cells in at least 2% (4/189) of patients.     

Neoadjuvant chemotherapy and hormonal therapy followed by radical prostatectomy: feasibility and preliminary results.

PURPOSE: We assessed the feasibility and efficacy of integrating chemotherapy and androgen ablation with radical prostatectomy in patients with locally advanced prostate cancer. The neoadjuvant approach was adopted because it allows an in situ assessment of antitumoral activity. PATIENTS AND METHODS: Thirty-three patients were enrolled who met the clinical criteria of stage T1-2, Gleason score of >/= 8 or T2b-T2c, Gleason score of 7 and prostate-specific antigen (PSA) level greater than 10 ng/mL (n = 15), or clinical stage T3 (n = 18). Therapy consisted of 12 weeks of ketoconazole and doxorubicin alternating with vinblastine, estramustine, and androgen ablation followed by prostatectomy. The ability of neoadjuvant chemotherapy and hormonal therapy to induce a 20% rate of pT0 in the prostatectomy specimen as well as surgical feasibility were assessed. RESULTS: Chemotherapy complications were comparable to those reported with this regimen previously. No major intraoperative complications occurred. Postoperative complications occurred in 10 (33%) of 30 patients. One patient died at home after discharge (postoperative day 17; no autopsy was performed). Ten (33%) of the 30 patients had organ-confined disease, and 20 (70%) of 30 had extraprostatic extension; 11 (37%) of the 30 had positive lymph nodes. Only five (17%) of 30 exhibited positive surgical margins. All patients achieved an undetectable PSA level postoperatively, and 20 of the surviving 29 patients remain without disease recurrence with a median follow-up of 13 months (range, 9 to 18 months). CONCLUSION: Chemotherapy and androgen ablation followed by radical prostatectomy was feasible in patients with locally advanced prostate cancer. Although the goal of achieving a 20% rate for pT0 status was not achieved, we believe this type of integrated therapeutic strategy should be investigated further for its ability to alter the course of regionally advanced prostate cancer.     

Risk of prostate carcinoma death in patients with lymph node metastasis

BACKGROUND: The presence of lymph node metastasis is a poor prognostic sign for patients with prostate carcinoma. Results of published reports on survival among patients with lymph node metastasis are difficult to assess because of treatment selections. The extent to which lymph node status will have an impact on a patient's survival is uncertain. METHODS: The authors analyzed 3463 consecutive Mayo Clinic patients who underwent radical prostatectomy and bilateral pelvic lymphadenectomy for prostate carcinoma between 1987 and 1993. Of these patients, 322 had lymph node metastasis at the time of surgery, and 297 lymph node positive patients also received adjuvant hormonal therapy within 90 days of surgery. The progression free rate and the cancer specific survival rate were used as outcome endpoints in univariate and multivariate Cox proportional hazards models. The median follow-up was 6.3 years. Progression was defined by elevation of serum prostate specific antigen (PSA) > or = 0.4 ng/mL after surgery, development of local recurrence, or distant metastasis documented by biopsy or radiographic examination. RESULTS: The 5-year and 10-year progression free survival rates (+/- standard error [SE]) for patients with lymph node metastasis were 74% +/- 2% and 64% +/- 3%, respectively, compared with 77% +/- 1% and 59% +/- 2%, respectively, for patients without lymph node metastasis. The 5-year and 10-year cancer specific survival rates were 94% +/- 1% and 83% +/- 4%, respectively, compared with 99% +/- 0.1% and 97% +/- 0.5%, respectively, for patients without lymph node metastasis. Among patients with a single lymph node metastasis, the 5-year and 10-year cancer specific survival rates were 99% +/- 1% and 94% +/- 3%, respectively. After adjustment for extraprostatic extension, seminal vesicle invasion, Gleason grade, surgical margins, DNA ploidy, preoperative serum PSA concentration, and adjuvant therapy, the hazard ratio for death from prostate carcinoma among patients with a single lymph node metastasis compared with patients who were without lymph node metastasis was 1.5 (95% confidence interval, 0.5-5.0; P = 0.478), whereas the hazard ratio for death from prostate carcinoma was 6.1 (95% confidence interval, 1.9-19.6; P = 0.002) for those with two positive lymph nodes and 4.3 (95% confidence interval, 1.4-13.0; P = 0.009) for those with three or more positive lymph nodes. There was no significant difference in the progression free survival rate among patients with or without lymph node metastasis in multivariate analysis after controlling for all relevant variables, including treatments (hazard ratio,1.0; 95% CI, 0.7-1.3; P = 0.90). CONCLUSIONS: Patients with prostate carcinoma who have multiple regional lymph node metastases had increased risk of death from disease, whereas patients with single lymph node involvement appeared to have a more favorable prognosis after radical prostatectomy and immediate adjuvant hormonal therapy. Excellent local disease control was achieved by using combined surgery and adjuvant hormonal therapy in patients with positive lymph nodes.     

Prognostic value of surgical margin status for biochemical recurrence following radical prostatectomy

OBJECTIVE: We evaluated the preoperative parameters to predict a positive surgical margin (SM) at radical prostatectomy for patients with prostate cancer. In addition, the prognostic factors for biochemical recurrence were determined in patients with positive SMs. METHODS: We retrospectively analysed 238 patients with prostate cancer who underwent retropubic radical prostatectomy and bilateral pelvic lymph node dissection from May 1985 to July 2005 in our hospital. Biochemical recurrence was defined as an increase of undetectable prostate-specific antigen (PSA) to 0.2 ng/ml or greater. RESULTS: Of the 238, 82 patients (34.4%) had positive SMs. On multivariate analysis, preoperative PSA (>/=10 ng/ml), clinical T stage (>/=T2a) and the positive core rate (>/=35%) were parameters that could predict a positive SM. During the median follow-up of 31.2 months, 48 patients (20.2%) developed biochemical recurrence. The 5-year biochemical progression-free survival rates were 81.7% and 62.6% in patients with negative and positive SMs, respectively (P < 0.001). In the Cox proportional hazards model, preoperative PSA of >/=20 ng/ml and a pathological T stage of pT3a/pT3b were significant risk factors for biochemical recurrence in patients with positive SMs. CONCLUSIONS: SM status at radical prostatectomy depends on preoperative PSA, clinical stage and the positive core rate. Patients with a positive SM had a higher risk for biochemical recurrence than those with a negative one. Patients with a positive margin had a higher risk for biochemical recurrence if they exhibited preoperative PSA of >/=20 ng/ml and/or pathological T stage of pT3a/pT3b.     

Caveolin-1 expression in clinically confined human prostate cancer: a novel prognostic marker

We demonstrated previously elevated caveolin-1 expression in metastatic mouse and human prostate cancer cells both in vitro and in vivo. In this study, we analyzed its prognostic value for progression of clinically confined human prostate cancer. Immunohistochemical staining with a caveolin-1-specific antibody was performed on routinely processed paraffin sections from 189 radical prostatectomy specimens. Caveolin-1 immunoreactivity was evaluated in association with patients' age, race, preoperative prostate-specific antigen, clinical stage, and pathological features including Gleason score, extraprostatic extension, status of surgical margins, and time to disease progression after surgery. Positive caveolin-1 immunostaining was detected in 47 of the 189 cancers (25%) and correlated positively with Gleason score, positive surgical margin, as well as lymph node involvement (P = 0.0071, 0.0267, and 0.0399, respectively). In lymph node-negative cancers (n = 162), caveolin-1 immunoreactivity predicts a shorter time to disease progression after surgery (P = 0.0033, univariate analysis). Multivariate analyses that included caveolin-1 and other prognostic pathological markers identified positive caveolin-1 immunostaining as an independent predictor for time to disease progression (P = 0.0186). Thus, our study establishes caveolin-1 as a novel prognostic marker for clinically confined human prostate cancer.     

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).     

胃癌根治术后切缘阳性患者的临床病理特征和预后分析

  目的  探讨胃癌根治术后切缘阳性患者的临床病理特征及其对预后影响。  方法  回顾性分析河北医科大学第四医院2011年1月至2016年1月收治的胃癌根治术后切缘阳性患者的临床病理资料。按1∶2随机数法选取同期收治的切缘阴性患者,比较阳性和阴性切缘患者的一般临床病理学特征及预后情况。  结果  共纳入73例切缘阳性患者,与同期纳入的146例切缘阴性病例比较,阳性组的肿瘤直径更大、更多位于贲门或全胃,组织学类型更差、Lauren分型趋于弥漫型、Borrmann分型多为Ⅲ～Ⅳ型、肿瘤浸润深度以T4a～4b为主、pTNM分期更晚,脉管浸润率及淋巴结转移率也更高,同时术者经验、手术方式的差异也与阳性切缘发生有关（均P<0.05）。全组共有205例患者获得完整随访,两组患者5年总生存（overall survival,OS）率及无进展生存（progression-free survival,PFS）率均有显著性差异（23.19% vs. 58.82%,15.94% vs. 47.06%,均P<0.001）。Cox多因素分析显示,切缘状态（P=0.012）、pTNM分期（P=0.023）及术后综合治疗（化疗/化疗联合放疗）（P<0.001）是影响胃癌预后的独立因素。  结论  胃癌根治术后切缘状态与多种临床病理特征相关,切缘阳性患者预后较差。      

Factors that influence the incidence of microscopic carcinoma in frozen and preserved specimens from patients with breast carcinoma after breast-conserving surgery

Because a positive margin is an important risk factor for decreased survival of patients with breast cancer after breast-conserving surgery (BCS), we examined the rate of positive surgical margins after BCS, determined from intraoperative frozen and preserved sections, and we assessed factors that influence the incidence of positive margins in surgical specimens. The cases of 172 patients who underwent BCS between June 1989 and March 2001 were studied. The pathologic features and positive margins were evaluated by microscopic examination of frozen and preserved sections. The grade of each positive margin was arbitrarily classified into one of four groups: i) cancer involved; ii) closed margin (<2 mm); iii) partially closed margin (>3 mm and <5 mm) and iv) free margin (>5 mm). Biomarkers were estimated by immunohistochemistry and DNA ploidy, and the relationship of clinical parameters was statistically analyzed using the chi(2) test. In 59 of 172 cases (34.3%), the surgical margin was positive: horizontal in 47 cases (27.3%) and vertical in 12 cases (6.9%). The free margin was significantly correlated with positive status of estrogen and progesterone receptors and middle age (35-50 years) in the patients, while clinicopathologic factors were not correlated with positive margins in surgical specimens. Although 17 cases of cancer were found in 9 frozen specimens and 8 preserved sections, the mammographic findings showed spiculated masses in 7 of the 9 frozen specimens (77.7%) and 4 of the 8 preserved sections (50%), and microcalcification in 2 frozen specimens (22.2%) and 4 preserved sections (50%). The overexpression (2+ or 3+) of the HER-2 protein was found in 8 of the 9 frozen specimens (87.5%) and in 7 of the 8 preserved sections (88.8%). In the 11 cases with spiculated masses, extensive intraductal components (EICs) of various grades were found; the presence of EICs in a spiculated lesion was observed in 5 of the 7 frozen specimens and in all 4 of the preserved sections. The local extension of breast carcinoma cells in BCS is associated in part with the findings of spiculation and microcalcification, which are associated with EICs. The overexpression of HER-2 protein appears to play a role in EICs in positive margins, and needs to be considered for avoiding positive margins in BCS on patients with breast carcinoma.     

Prediction by quantitative histology of pathological stage in prostate cancer.

AIMS: To find a predictor of extraprostatic extension in clinically localized prostate cancer (PCa), pre-operative ultrasound-guided prostate needle biopsies and clinico-pathological data were reviewed. METHODS: One hundred and eighty-three consecutive patients who underwent radical retropubic prostatectomy for clinical T1-T2 PCa and serum PSA <10 ng/ml were reviewed. Pre-operative biopsy was performed according to an extended protocol and whole-mount prostatectomy specimens were processed. The following biopsy variables were categorized to this analysis: Gleason score (< or =6, >6), TPC (< or =20%; >20%), GPC (< or =50%; >50%), cancer-positive cores (< or =2; >2), cancer-positive cores in both lateral portions (yes; no), PCa (monolateral; bilateral). RESULTS: Only 60/183 specimens showed an organ-confined PCa; the remaining ones showed pT3a in 57 cases, pT3b in 11 and pT3 with positive surgical margins in 55. A locally advanced PCa was found in 60.2 and 76.8% of T1c and T2 clinical stage, respectively. The positive predictive value and negative predictive value of biopsy findings to predict a locally advanced PCa was 89.9 and 75%, respectively. All biopsy variables associations were statistically significant; however, among these variables (non-categorized), in multivariate logistic regression analysis, only GPC was significantly associated with pathologic stage (odds ratio estimate was 1.075, 95% CI: 1.053-1.098). CONCLUSIONS: Quantitative histology, especially GPC, seems to be helpful for pre-operative staging of PCa in patients with T1c-T2 clinical stage and PSA < 10 ng/ml.     

Adjuvant radiotherapy after radical prostatectomy

Background:Within 5 years following radical prostatectomy, between 15 and 60% of patients with pT3 prostate carcinomas show an increasing prostate specific antigen (PSA)as a sign of local and/or systemic tumour progression. Adjuvant radiotherapy (RT)for positive margins (R1)aims to reduce residual tumour cells in the prostatic bed, thus possibly reducing the biochemical progression rate. Apart from a large number of retrospective investigations, available results are presented from three randomised studies which have either been published completely (or in abstract form).Results:For pT3 prostate carcinomas, agreeing data are presented from three randomised studies, which show around a 20% reduced biochemical progression rate (bNED)after 4 to 5 years. With these data the results of numerous retrospective studies were conformed. The majority of the authors used total doses of 60 Gy. From one randomised study an increased local control rate was demonstrated as basis for the extended freedom of biochemical progression. The rate of acute and late side effects after three dimensional (3-D)planned radiotherapy with 60 Gy is very small and the rate of severe side effects is below 2%. The data situation for pT2 prostate carcinomas with positive margins is worse. Here, controversial data are presented, which require further investigation. Only retrospective data demonstrated a 25% advantage for adjuvant RT. Therefore, adjuvant radiotherapy also seems reasonable for pT-2 carcinomas with positive margins.Conclusions:The effectiveness of adjuvant radiotherapy for patients with pT-3 tumours with positive margins with and without undetectable PSA levels with 60 Gy total dose has been demonstrated. A survival advantage has not been shown until now. 3-D treatment planning remains the standard technique for these patients.For patients with positive margins in organ-limited prostate carcinomas (pT2 R 1)randomised studies are recommended.It remains unclear whether the adjuvant RT is superior to the radiotherapy for rising PSA levels out of the undetectable range after radical prostatectomy.     

Racial differences in prognostic value of adult height for biochemical progression following radical prostatectomy.

PURPOSE: Adult height, as a surrogate of childhood and adolescent hormone activity and diet, has been associated with the risk for development and death from prostate cancer in predominantly White populations. However, hormonal activity and diets vary between races. We examined whether height was significantly associated with biochemical progression following radical prostatectomy and whether there was an interaction between height and race. EXPERIMENTAL DESIGN: Multivariate Cox proportional hazards analysis was used to determine if height significantly predicted biochemical progression among 1,503 men (450 Black and 1,053 White) treated with radical prostatectomy between 1988 and 2003. We examined for possible interactions between height and race. RESULTS: Taller men (>175.3 cm) were significantly younger (P = 0.001), treated in more recent years (P = 0.02), had more clinical stage T(1) disease (P = 0.001), and were less likely to have extraprostatic extension (P = 0.02) than shorter men (< or =175.3 cm). Height was not significantly related to race, preoperative serum prostate-specific antigen concentrations, biopsy or pathologic Gleason sum, positive surgical margins, seminal vesicle invasion, or lymph node metastasis. Height was significantly associated with progression among Black men [relative risk (RR), 1.67; 95% confidence interval (95% CI), 1.00-2.79] but not among White men (RR, 1.03; 95% CI, 0.77-1.38). The interaction between race and height for predicting biochemical progression was statistically significant (P(interaction) = 0.05). CONCLUSIONS: There was an interaction between height and race in that height predicted progression for Black men but not for White men. The explanation for these findings is unclear, although lower insulin-like growth factor-binding protein-3 concentrations among Black men may be involved.