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.     

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.     

Clinical and pathologic outcome after radical prostatectomy for prostate cancer patients with a preoperative Gleason sum of 8 to 10

BACKGROUND: Men with a biopsy Gleason sum of 8 to 10 are considered high-risk. The current study sought to identify whether there was a subset of men with high biopsy Gleason sums who would have a good pathologic and biochemical outcome with surgical monotherapy. To increase the generalizability of the findings, data were used from patients treated at 2 very different practice settings: a tertiary care referral center (Johns Hopkins Hospital) and multiple equal-access medical centers (Shared Equal Access Regional Cancer Hospital [SEARCH] Database). METHODS: The data were retrospectively reviewed from men with biopsy Gleason sums 8 to 10 treated by radical prostatectomy at the Johns Hopkins Hospital (n = 220, 3.8% of total cohort) and within the SEARCH Database (n = 149, 7.7% of total cohort). The preoperative clinical characteristics predicting unfavorable pathologic disease (nonorgan-confined and/or positive surgical margins) and time to biochemical recurrence were determined using logistic regression and Cox proportional hazards analysis, respectively. RESULTS: Favorable pathologic outcome (organ-confined and negative surgical margins) was observed in 21% of the men in the Johns Hopkins cohort and 41% from the SEARCH cohort. On multivariate analysis, higher serum prostate-specific antigen (PSA) was the only variable that significantly predicted an unfavorable pathologic outcome from both the Johns Hopkins (P = .047) and SEARCH cohorts (P = .002). The 5-year and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 40% (95% confidence interval [CI], 33-48%) and 27% (95% CI, 18-36%), respectively, and 32% (95% CI, 22-42%) and 28% (95% CI, 18-38%) in the SEARCH cohort, respectively. Among men with favorable pathologic findings, the 5- and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 79% (95% CI, 62-89%) and 50% (95% CI, 25-71%), respectively, and 49% (95% CI, 32-65%) and 49% (95% CI, 32-65%) in the SEARCH cohort, respectively. No single preoperative variable significantly predicted the risk of biochemical progression in both the SEARCH or Johns Hopkins cohorts. CONCLUSIONS: The majority of men with a biopsy Gleason sum of >or=8, regardless of where the patient is treated, had unfavorable pathologic disease and experienced a biochemical progression after radical prostatectomy. Even among men with organ-confined disease and negative surgical margins or pathologic Gleason sum <8, at least half of the men experienced a PSA recurrence. Patients with biopsy Gleason sum 8 to 10 cancers are good candidates for multimodal therapy. Whereas multimodal therapy has often meant radiation plus hormonal therapy, newer possibilities for multimodal therapy exist such as surgery with neoadjuvant or adjuvant chemohormonal therapy or surgery with adjuvant radiation.     

Benefit on biochemical control of adjuvant radiation therapy in patients with pathologically involved seminal vesicles after radical prostatectomy

AIMS AND BACKGROUND: To determine whether there is a benefit for biochemical control with adjuvant radiation therapy to the surgical bed following radical prostatectomy in patients with seminal vesicle invasion and pathologically negative pelvic lymph nodes (pT3b-pT4 pN0). METHODS: We retrospectively reviewed the clinical records of radical prostatectomy patients treated between 1995 and 2002. A total of 66 patients with seminal vesicle invasion were identified: 45 of these patients received adjuvant radiation therapy and 21 were observed. Radiation therapy was initiated within 4 months of prostatectomy. Median dose was 66 Gy (range, 60-70 Gy). Median follow-up from the day of surgery was 40.6 months (mean, 41.5; range, 12-99). Biochemical recurrence was defined as the first value > or = 0.2 ng/ml. RESULTS: At two years, the proportion of patients free from biochemical recurrence was 80% in patients who received adjuvant radiation therapy versus 54% for those not given radiation therapy (P = 0.036). Actuarial biochemical recurrence at 5 years was 59% vs 41% for the radiation therapy and no radiation therapy groups, respectively. On univariate Cox regression model, the hazard of biochemical failure was also associated with a detectable (> or = 0.2 ng/ml) postsurgical prostate-specific antigen (P = 0.02) prior to radiation therapy. Pathological T stage (pT3b vs pT4), Gleason score, primary Gleason pattern and positive surgical margins were not significantly associated with biochemical recurrence. The hazard of biochemical failure was around 85% lower in the radiation therapy group than in the observation group (P = 0.002). CONCLUSIONS: Data from the present series suggest that adjuvant radiation therapy for patients with seminal vesicle invasion and undetectable (< or = 0.2 ng/ml) postoperative prostate-specific antigen significantly reduces the likelihood of biochemical failure.     

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.     

Clinical utility of indium 111-capromab pendetide immunoscintigraphy in the detection of early, recurrent prostate carcinoma after radical prostatectomy

BACKGROUND: Despite the ability of radical prostatectomy to eradicate prostate carcinoma, biochemical evidence of recurrent prostate carcinoma may be seen in approximately 40% of patients 15 years after they undergo surgery. Localization of recurrent disease after radical prostatectomy is difficult and may greatly influence subsequent clinical management. The authors examined the utility of indium 111 ((111)In)-capromab pendetide immunoscintigraphy to detect recurrent prostate carcinoma radiographically in men with early biochemical evidence of failure (serum prostate specific antigen [PSA] < or = 4.0 ng/mL) and assessed the minimum serum PSA level necessary for imaging recurrent disease. METHODS: Between May 1987 and August 1995, 255 hormone-na?ve men with a mean (+/- standard deviation) age of 65 years +/- 7 years who underwent radical prostatectomy for clinically localized prostate carcinoma were followed without adjuvant therapy until early PSA recurrence in this multicenter study. Preoperatively, all patients had negative bone scans and pathologically negative lymph nodes, and they did not undergo hormonal ablation, chemotherapy, or radiation therapy preoperatively or postoperatively until the (111)In-capromab pendetide scan was performed. All men in this study had postoperative serum PSA levels < or = 4.0 ng/mL at the time of radionuclide imaging. All men underwent imaging with the capromab pendetide scan to localize recurrent disease, and charts were reviewed to document clinical evidence of recurrence. RESULTS: Pathologic findings included mean Gleason scores of 6.7 +/- 1.2; pathologic tumors classified as pT2a (18%), pT2b (26%), pT3a (38%), pT3b (16%), and pT4a (2%); a pathologic lymph node status of pN0 (100%); positive surgical margins (44%); and perineural invasion (42%). Capromab pendetide uptake was seen in 72% of 255 men throughout a range of patients' postoperative serum PSA levels (0.1-4.0 ng/mL), with 31% of men having local uptake (prostatic fossa) only. Of 151 men who underwent additional imaging studies, 16 of 139 men (12%) and 15 of 92 men (16%) showed evidence of recurrent disease by bone scintigraphy and computed tomography scans, respectively. Gleason score, pathologic stage, perineural invasion, and margin status were not correlated significantly with the (111)In-capromab pendetide scan. CONCLUSIONS: Capromab pendetide imaging can localize early PSA recurrence and may guide appropriate treatment after patients undergo radical prostatectomy. No minimum serum PSA value was needed to potentially detect radiographic disease after surgery. Further confirmatory studies and long-term follow-up of this cohort documenting response to salvage therapy are needed to validate these imaging findings.     

Does the Presence of Primary Circulating Prostate Cells Imply the Presence of Agressive Prostate Cancer with Early Biochemical Failure: a Comparison with the Walz Nomogram

Background: To determine the utility of primary circulating prostate cells (CPC) for predicting early biochemical failure after radical prostatectomy for prostate cancer and compare the results with the Walz nomogram. Materials and Methods: A single centre prospective study of men with prostate cancer treated with radical prostatectomy was conducted between 2004 and 2014. Clinicalpathological details were registered, along with total serum PSA presurgery, Gleason score, extracapsular extension, positive surgical margins, infiltration of lymph nodes, seminal vesicles and pathological stage. Primary circulating prostate cells were obtained using differential gel centrifugation and detected using standard immunocytochemistry with antiPSA. Biochemical failure was defined as a PSA >0.2ng/ml, predictive values were calculated using the Walz nomagram and CPC detection. Results: A total of 285 men participated, of whom 103/285 (36.1%) suffered biochemcial failure; 32/103 (31.1%) within two years of radical prostatectomy. Men with higher Gleason scores, higher pathological stage, infiltration of the surgical margin or prostate capsule and infiltration of seminal vesicles were more likely to undergo biochemical failure. There was a significant increase in the frequency of biochemical failure with increasing number of CPCs detected (p     

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.     

Utilizing predictions of early prostate-specific antigen failure to optimize patient selection for adjuvant systemic therapy trials.

PURPOSE: Prostate-specific antigen (PSA) failure within 2 years after radical prostatectomy (RP) has been shown to be a clinically significant predictor of distant failure. This study was performed to estimate 2-year PSA failure rates on the basis of readily available clinical and pathologic factors to identify patients for whom effective adjuvant systemic therapy is needed. PATIENTS AND METHODS: A Cox regression multivariable analysis was used to determine whether the percentage of positive prostate biopsies, PSA level, and the pathologic findings at RP in 1,728 men provided clinically relevant information about PSA outcome after RP. A bootstrapping technique with 2,000 replications was used to provide 95% confidence intervals for the predicted 2-year PSA failure rates, which were determined on the basis of the independent clinical and pathologic predictors of PSA outcome. RESULTS: The independent predictors of time to PSA failure included a percentage of positive prostate biopsies of greater than 34% (P: < or =.009), PSA level greater than 10 ng/mL (P: < or =.01), seminal vesicle invasion (P: =. 02), prostatectomy Gleason score of 8 to 10 (P: =.04), and positive surgical margins (P: =.0001). Predictions of 2-year PSA failure rates and bootstrap estimates of the 95% confidence intervals were arranged in a tabular format, stratified by independent clinical and pathologic predictors of PSA outcome. CONCLUSION: Patients who are most likely to benefit from effective adjuvant systemic therapy after RP can be identified using readily available clinical and pathologic data.     

Predictors of prostate-specific antigen progression among men with seminal vesicle invasion at the time of radical prostatectomy

BACKGROUND: Seminal vesicle (SV) invasion at the time of radical prostatectomy (RP) generally is considered to be indicative of poor outcome. The authors examined whether there was a subset of men with SV invasion who had long-term prostate-specific antigen (PSA) progression-free survival. METHODS: Data were examined from 1687 men who underwent RP between 1988 and 2002 at 5 equal-access medical centers. Patients were grouped based on the presence or absence of SV invasion at the time of RP. Clinical and pathologic variables as well as biochemical outcome data were compared across the groups using rank-sum, chi-square, and log-rank tests. Multivariate Cox proportional hazards analysis was used to determine the significant predictors of time to PSA failure among men with SV invasion. RESULTS: Men with SV invasion had significantly higher PSA values, higher clinical stage, higher grade tumors, and were more likely to have concomitant extracapsular extension or a positive surgical margin. The 5-year PSA progression-free rates for men who had SV invasion was 36%, compared with 70% among men who had no SV invasion. Among men who had SV invasion, using multivariate analysis, only age (P = 0.023), pathologic Gleason score (P = 0.041), and surgical margin status (P = 0.019) were found to be independent predictors of PSA failure. By combining significant prognostic variables, the authors identified a subset of men with SV invasion, low-grade tumors (Gleason score 2-6), and negative surgical margins who had a 5-year PSA progression-free rate of 69%. Men with SV invasion, Gleason scores 2-6 tumors, negative surgical margins, and age > or = 60 years (n = 11; 8%) had a 5-year PSA progression-free rate of 100%. CONCLUSIONS: Although the majority of men with SV invasion have high-grade disease and a short time to biochemical failure, the authors identified a subset of men with low-grade disease, negative surgical margins, and older age who, despite SV invasion, had an extremely favorable clinical course. Thus, SV invasion does not uniformly suggest an unfavorable prognosis. prognosis.     

Biochemical disease-free survival following adjuvant and salvage irradiation after radical prostatectomy

PURPOSE: To present the biochemical cure rates (biochemically no evidence of disease) after external irradiation (RT) in patients with high-risk prostate cancer after radical prostatectomy. METHODS AND MATERIALS: Seventy-six patients who underwent radical prostatectomy and subsequent RT were included in this analysis. No patient received hormonal therapy. Adjuvant RT was administered in 35 patients (46%), and 41 patients (54%) underwent salvage RT. After prostatectomy, the Gleason score was <7 in 87%, and 24% had seminal vesicle invasion. The median RT dose in the adjuvant RT and salvage RT groups was 60 Gy and 65 Gy, respectively. The biochemical cure rate was defined as a serum prostate-specific antigen of < or =0.2 ng/mL. RESULTS: The overall 5-year Kaplan-Meier biochemical control rate from the end of RT was 70%. The 5-year biochemical cure rate for adjuvant RT was significantly superior to that after salvage RT (86% vs. 57%). The significant predictors of biochemical failure were seminal vesicle invasion in the adjuvant RT group and the presence of Gleason grade 4 or 5 in the salvage RT group. The clinical local control rate in the prostate bed was 100%. CONCLUSION: This report demonstrates the efficacy of RT in achieving high biochemical cure rates after radical prostatectomy. Additional clinical studies are required to determine the optimal treatment of patients at high risk of biochemical failure after postprostatectomy RT.     

Analysis of pathologic extent of disease for clinically localized prostate cancer after radical prostatectomy and subsequent use of adjuvant radiation in a national cohort

BACKGROUND:

The Surveillance, Epidemiology, and End Results database was analyzed to explore the pathologic extent of disease for clinically localized prostate cancer after radical prostatectomy as well as the use of adjuvant radiation in this population.

METHODS:

Identified were patients from 2004 to 2006 with clinically staged T1c‐2cNx‐0M0 prostate adenocarcinoma who underwent radical prostatectomy. All patients had complete clinical and pathologic data. The use of postoperative radiation was recorded. Logistic regression analysis was performed to identify unadjusted and adjusted predictors for extraprostatic disease or positive surgical margins and for adjuvant radiation use.

RESULTS:

A total of 35,642 patients were identified. For those patients with Gleason 7 (4 + 3) and a prostate‐specific antigen (PSA) level of ≥10.1 ng/mL or Gleason 8 to 10 with any PSA level, the rate of organ‐confined disease with negative surgical margins was found to be <50%. Of those with indications for adjuvant radiation, 11.1% received the treatment.

CONCLUSIONS:

This large population‐based study detailed the risk of extraprostatic extension and positive surgical margins in a broad setting across multiple regions and communities, as well as the use of adjuvant radiation for these patients. As of 2006, 11.1% of patients who had indications for adjuvant radiation received this treatment, providing a useful baseline for future patterns of care studies. Cancer 2010. © 2010 American Cancer Society.     

Role of postoperative radiotherapy after pelvic lymphadenectomy and radical retropubic prostatectomy: a single institute experience of 415 patients

PURPOSE: To evaluate the clinical benefit deriving from early (within 6 months) radiotherapy (ERT) after pelvic lymphadenectomy and radical retropubic prostatectomy for localized/locally advanced adenocarcinoma of the prostate in a single-institution series. METHODS AND MATERIALS: We retrospectively analyzed 415 patients who underwent pelvic lymphadenectomy and radical retropubic prostatectomy between 1986 and 1998 for pT2b-pT4, pN0-pN1 prostate carcinoma. Of the 415 patients, 237 underwent ERT for adverse pathologic findings and 178 patients did not receive RT or underwent salvage RT < or =6 months (salvage or no RT [SNRT]). RESULTS: After a median follow-up of 62 months, the 8-year actuarial freedom from biochemical, local and systemic failure, and cause-specific survival rate was 69% vs. 31% (p <0.0001, log-rank), 93% vs. 63% (p <0.0001), 88% vs. 75% (p = 0.04), and 93% vs. 80% (p = 0.02) in the ERT and SNRT group, respectively. A subgroup analysis indicated that an improvement in 8-year actuarial cause-specific survival was associated with ERT in patients with positive resection margins (91% vs. 67%, p = 0.007), extracapsular extension (92% vs. 75%, p = 0.002), Gleason score > or =7 (88% vs. 72%, p = 0.02), and lymph node metastases (88% vs. 68%, p = 0.04). This strong association between ERT and cause-specific survival persisted at multivariate analysis in the whole group of patients examined (hazard ratio, 4.3) and in the subgroups of patients with extracapsular extension (hazard ratio, 4.9), positive resection margins (hazard ratio, 4.7), Gleason score > or =7 (hazard ratio, 4.4), and lymph node metastases (hazard ratio, 7.4). CONCLUSION: The results of this retrospective analysis indicate that ERT after pelvic lymphadenectomy and radical retropubic prostatectomy improved the 5-year and actuarial 8-year cause-specific survival of patients with adverse pathologic findings such as extracapsular extension, positive resection margins, Gleason score > or =7, and/or positive lymph nodes.     

Prostate biopsy volume indices do not predict for significant Gleason upgrading

Significant discordance exists between biopsy and matched prostatectomy grades. This study tests the hypothesis that surrogate tumor volume indices available from biopsies could yield an improved prediction of the underlying pathologic Gleason grade. Records of 124 patients who underwent radical prostatectomy were reviewed. Biopsies were characterized by primary and secondary Gleason grade, number of positive cores, and linear tumor length. Surgical specimens were characterized by primary and secondary Gleason grade, organ-confined disease, seminal vesicle invasion, and margins. Biochemical failure (BF) was defined by a postoperative prostate-specific antigen >0.05 ng/mL. There were 28 patients (24%) who experienced biochemical failure. On multivariate analysis, only the pathologic Gleason sum (P = 0.012) and the cumulative tumor length (P = 0.050) were independently associated with BF, and only the cumulative tumor length was associated with nonorgan-confined disease (P = 0.034). For patients with a cumulative tumor length >10 mm, 49% (18 of 37) had nonorgan-confined disease and 37% (13 of 35) had BF compared with 29% (25 of 87) and 19% (15 of 80), respectively, if they had cumulative tumor length < or =10 mm (P <0.034). Overall, an exact match was seen in 39% of biopsy Gleason grades, whereas 21% were downgraded by 1 or more points, and 41% were upgraded by 1 or more points. On univariate or multivariate analysis, none of the biopsy surrogate volume indices examined achieved significance or suggested a trend in predicting for a clinically meaningful grade change. Although indices of tumor volume from prostate needle biopsies independently predict for organ-confined disease and BF after prostatectomy, none predicted for a clinically significant upgrading or downgrading of biopsies. This suggests that the correlation that exists between such volume surrogates and outcomes after surgery reflect tumor volume effects only, independently of any possible association between tumor volume and Gleason grade.     

Accuracy of CAPRA-S Score for Predicting Long-Term Biochemical Progression After Radical Prostatectomy

BackgroundThe Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score is a tool to stratify patients into groups according to their risk for biochemical recurrence after radical prostatectomy. The aim of this study was to assess the accuracy of the CAPRA-S score for predicting biochemical progression at 5 and 10 years in our cohort of patients after radical prostatectomy.Patients and MethodsBetween June 2004 and December 2015, radical prostatectomy was performed as the main treatment option for patients with localized prostate cancer. Patients who had received adjuvant or neoadjuvant treatment were excluded from this study. Biochemical progression after radical prostatectomy was considered in patients by prostate-specific antigen (PSA) > 0.1 ng/mL after surgery (biochemical persistence) and by at least 2 determinations of PSA > 0.2 ng/mL in those patients with initial undetectable postoperative PSA any time during their follow-up (biochemical failure). Cox proportional hazard model and Kaplan-Meier analysis were used for the statistical analysis.ResultsOf 531 patients who underwent radical prostatectomy, 479 met the inclusion criteria. Mean follow-up was 85 months (min-max, 13-153 months). The rate of biochemical progression–free survival at 10 years was 84.2%, 55.1%, and 32.8%, respectively, for high-, intermediate-, and low-risk patients according to the CAPRA-S score. The concordance index for CAPRA-S predicting biochemical progression at 5 years was 0.71 and at 10 years was 0.70.ConclusionThe CAPRA-S score is a useful and easy-to-use tool in patients after radical prostatectomy to classify their risk for biochemical progression, thus helping decide if adjuvant treatment should be required.     

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).     

Population-Based Referrals for Adjuvant Radiotherapy After Radical Prostatectomy in Men With Prostate Cancer: Impact of Randomized Trials

IntroductionTo examine the impact of published randomized controlled trial (RCT) data on referrals for adjuvant radiotherapy (RT) in patients who had high-risk pathologic features after radical prostatectomy (RP).MethodsIn this population-based, retrospective Canadian study, all patients who received a diagnosis of prostate adenocarcinoma and underwent RP from 2003-2008 were identified through the Manitoba Cancer Registry. Manual review of pathology reports was performed, and patients who had high-risk pathologic features of extracapsular extension, seminal vesicle invasion, or positive surgical margins were included. Referrals for adjuvant RT were examined before and after publication of RCT data to determine their influence on practice. Multivariable logistic regression was used to identify factors related to referral.ResultsOf the 1080 identified patients, 546 (50.6%) had ≥ 1 high-risk pathologic feature. Only 78 (14.3%) of the 546 patients were referred for adjuvant RT within 6 months of RP. Year of diagnosis, in relation to the publication of the RCT, was not significantly associated with referral (P = .60). Higher pT stage (P < .0001), Gleason score (P = .035), and increased distance from cancer center (P = .004) were associated with referral.ConclusionIn patients who had high-risk pathologic features after RP, referral rates for adjuvant RT were low and did not increase after presentation of RCT. Men who had higher pT stage, Gleason score, and rural residence were more likely to be referred.     

Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence.

PURPOSE: To examine the relationship between pathologic margin status and outcome at 8 years after breast-conserving surgery and radiation therapy. PATIENTS AND METHODS: The study population comprised 533 patients with International Union Against Cancer/American Joint Committee on Cancer clinical stage I or II breast cancer who had assessable margins, who received at least 60 Gy to the primary tumor bed, and who had more than 8 years of potential follow-up. Each margin was scored (according to the presence of invasive or in situ disease that touched the inked surgical margin) as one of the following: negative, close, focally positive, or extensively positive. Outcome at 8 years was calculated using crude rates of first site of failure. A polychotomous logistic regression analysis was performed. Median follow-up time was 127 months. RESULTS: At 8 years, patients with close margins and those with negative margins both had a rate of local recurrence (LR) of 7%. Patients with extensively positive margins had an LR rate of 27%, whereas patients with focally positive margins had an intermediate rate of LR of 14%. In the polychotomous logistic regression model, margin status and the use of systemic therapy were the only two variables that had significant effects on the risk ratio of LR to remaining alive and free of disease. Among the 45 patients with focally positive margins who received systemic therapy, the crude LR rate was 7% at 8 years (95% confidence interval, 1% to 20%). CONCLUSION: Pathologic margin status and the use of adjuvant systemic therapy are the most important factors associated with LR among patients treated with breast-conserving surgery and radiation therapy.