Postoperative Prostate-specific Antigen Research Articles

The Association Between Total and Positive Lymph Node Counts, and Disease Progression in Clinically Localized Prostate Cancer

We examined the association between the number of LNs removed, the number of positive LNs and disease progression in patients undergoing pelvic lymph node dissection and radical retropubic prostatectomy for clinically localized prostate cancer. We analyzed 5,038 consecutive patients who underwent radical retropubic prostatectomy between 1983 and 2003. Clinicopathological parameters, including the administration of neoadjuvant hormonal therapy, preoperative prostate specific antigen, specimen Gleason score, surgeon and pathological stage, were collected prospectively in our prostate cancer database. We excluded men treated with radiation or chemotherapy before surgery. BCR was defined as 2 postoperative prostate specific antigen increases greater than 0.2 ng/ml. Cox models were used to determine whether the number of nodes removed or the number of positive nodes predicted freedom from BCR after adjustment for prognostic covariates. The 4,611 eligible patients had a median of 9 LNs (IQR 5 to 13) removed. Positive nodes were found in 175 patients (3.8%). Overall the number of LNs removed did not predict freedom from BCR (HR per additional 10 nodes removed 1.02, 95% CI 0.92 to 1.13, p = 0.7). Results were similar in patients receiving and not receiving neoadjuvant hormonal therapy. Finding any LN involvement was associated with a BCR HR of 5.2 (95% CI 4.2 to 6.4, p <0.0005). However, in men without nodal involvement an increased number of nodes removed correlated significantly with freedom from BCR (p = 0.01). Nodal disease increased the risk of progression. Extensive lymphadenectomy enhances the accuracy of surgical staging. However, we were unable to determine that removing more nodes improves freedom from BCR uniformly. Since the proportion of patients with prostate cancer with positive nodes is low, the value of extensive lymphadenectomy requires a multi-institutional, randomized clinical trial.

Comparison of the effects of on‐pump versus off‐pump coronary artery bypass surgery on serum prostate‐specific antigen levels

To compare the effects of coronary artery bypass operation with or without extracorporeal circulation on serum total prostate-specific antigen levels. Seventy-six men with a mean age of 57.04+/-9.27 years (range 44-77 years), who underwent coronary artery bypass surgery were enrolled to the study. In 50 patients (Group I), coronary revascularization was performed using extracorporeal circulation, and in 26 patients (Group II) coronary bypass grafting was performed on the beating heart without using extracorporeal circulation. All the patients had serum total prostate-specific antigen levels measured preoperatively and twice postoperatively in the first and fifth postoperative days. Differences in mean total prostate-specific antigen levels between the two groups in the postoperative period were analysed. The mean preoperative total prostate-specific antigen levels in Group I and Group II were 1.28+/-1.13 ng/mL and 1.11+/-0.93 ng/mL, respectively, and there was no significant difference in the preoperative total prostate-specific antigen values between the two groups (P=0.519). In Group I, postoperative means were 4.96+/-6.29 ng/mL and 5.86+/-9.09 ng/mL in the first and fifth days, respectively (P=0.0001, P=0.0001). Total prostate-specific antigen means in the same postoperative period for Group II were 2.13+/-2.72 ng/mL and 2.00+/-2.20 ng/mL, respectively (P=0.014, P=0.024). The comparison of total postoperative prostate-specific antigen levels between the groups showed significantly higher elevation in Group I (postoperative day 1: P=0.013; day 5: P=0.05). Coronary revascularization can cause a statistically significant rise in serum total prostate-specific antigen levels. This rise is more marked in patients undergoing conventional coronary revascularization.

94 Postoperative prostate specific antigen (PSA) decline predicts adequacy of adenoma removal with BPH surgical techniques.

Introduction: PSA, in patients with BPH, is correlated with total prostate and transition zone volume. The decline in serum PSA levels may therefore be an important marker of completeness of tissue removal in patients undergoing invasive surgical procedures for BPH (Tinmouth et al 2005). In many techniques no tissue is retrieved therefore PSA decline may be a surrogate for adequacy of surgical treatment.Methods: A Medline search of original articles concerning current endoscopic BPH therapies was undertaken to identify papers in which PSA decline was documented. The amount of tissue retrieved (when relevant) and change in US volume was also recorded.In addition four RCT's performed at this institution involving TURP(two studies) HoLEP(2 studies, HoLRP, Gyrus Enucleation and HoBNI (one study each) were analysed. PSA decline, TRUS and urodynamic data before and after surgery and tissue weight were recorded and correlated.Results: The mean % PSA and %TRUS volume decline noted following various treatments by literature search was as follows: TUNA (0% and 0%), BNI (NA and 0%) CLAP (45% and 15%) PVP (41% and 37%) TURP (73% and 50%) and HoLEP (83% and 76%).Local RCT data ‐ PSA% and TRUS volume decline : HoBNI (36% and 0%), TURP (51% and 46%) HoLRP (56% and 44%), HoLEP (86% and 67%). The following significant correlations were noted on pooled analysis of the four RCT's: PSA % decline and % TRUS volume decline with path. weight and PSA % decline with improvement in urodynamic parameters. Path. weight also correlated with symptom score improvement.Conclusions: BNI, laser ablation and microwave appear to result in less PSA decline and TRUS volume fall than after TURP and by inference less complete removal of adenoma. HoLEP gives larger % falls. A greater fall appears to be associated with better clinical results and may ultimately impact on durability.

Maximal tumor diameter and the risk of PSA failure in men with specimen-confined prostate cancer

Objectives To evaluate whether the maximal tumor diameter (MTD) is significantly associated with the time to postoperative prostate-specific antigen (PSA) failure. Methods Between 1986 and 2002, 781 men with clinical Stage T1c–T2 prostate cancer underwent radical prostatectomy. The MTD was recorded as the maximal dimension of the largest single focus of cancer from all 3-mm step sections. The median follow-up was 5.4 years (range 0.1 to 14.9); 242 men (31%) experienced PSA failure. A Cox regression analysis was used to determine the predictors of time to postoperative PSA failure. Kaplan-Meier estimates of PSA failure-free survival were made, dichotomized about the median MTD value, and compared using a two-sided log-rank test. Results The value of the MTD was significantly associated with the time to PSA failure (adjusted hazard ratio 1.04, 95% confidence interval 1.01 to 1.07, P = 0.004), controlling for preoperative PSA level ( P <0.0001), prostatectomy Gleason score ( P <0.0001), and T stage ( P <0.0001). When margin status was added ( P = 0.0004), the MTD approached statistical significance ( P = 0.07). For patients with a preoperative PSA level of less than 10 ng/mL, prostatectomy Gleason score of 3 + 4 = 7 or less, Stage pT2–T3a, and negative margins, the value of the MTD significantly ( P = 0.05) stratified the time to PSA failure, when dichotomized about the median value (13 mm), with 7-year PSA failure estimates of 17% versus 8%. Conclusions Whether patients with traditionally low-risk but large MTD prostate cancer fare better when treated with adjuvant radiotherapy compared with salvage radiotherapy remains to be answered in the setting of a randomized trial.

Postoperative serum prostate specific antigen levels in patients undergoing surgical treatment for benign prostatic obstruction

Postoperative serum prostate specific antigen levels in patients undergoing surgical treatment for benign prostatic obstruction

Identifying Patients at Risk for Significant Versus Clinically Insignificant Postoperative Prostate-Specific Antigen Failure

We evaluated whether men at risk for significant versus clinically insignificant prostate-specific antigen (PSA) failure after radical prostatectomy could be identified using information available at diagnosis. A prospective prostate cancer screening study that enrolled, diagnosed, and treated 1,011 men with radical prostatectomy at Barnes-Jewish Hospital (St Louis, MO) from January 1, 1989, to June 1, 2002, for localized prostate cancer formed the study cohort. Preoperative predictors of a postoperative PSA doubling time (DT) of less than 3 months and more than 12 months or no PSA failure were identified using logistic regression. A preoperative PSA velocity more than 2.0 ng/mL/yr (P = .001) and biopsy Gleason score 7 (P = .006) or 8 to 10 (P = .003) were significantly associated with having a postoperative PSA DT less than 3 months. A PSA level less than 10 ng/mL (P = .005), a nonpalpable cancer (P = .001) with a Gleason score < or = 6 (P = .0002), and a preoperative PSA increase that did not exceed 0.5 ng/mL/yr (P = .03) were significantly associated with a postoperative PSA DT of at least 12 months or no PSA failure. Most men with these preoperative characteristics and a postoperative PSA DT of 12 months or more had a persistent postoperative PSA level of at least 0.2 ng/mL that did not exceed 0.25 ng/mL after a median follow-up of 3.6 years. A postoperative PSA DT less than 3 months is associated with a preoperative PSA velocity more than 2.0 ng/mL/yr and high-grade disease. Select men with a postoperative PSA DT more than 12 months may not require salvage radiation therapy.

The presence of benign prostatic glandular tissue at surgical margins does not predict PSA recurrence

Background: Serum prostate specific antigen (PSA) increases after radical prostatectomy are thought to indicate recurrent disease, although some suggest they result from benign prostatic epithelial tissue left at surgical margins....

TESTOSTERONE AS A PREDICTOR OF PATHOLOGICAL STAGE IN CLINICALLY LOCALIZED PROSTATE CANCER

Substantial controversy exists in the literature regarding the association between pretreatment testosterone and disease outcome in patients with prostate cancer. We explored the relationship between preoperative total testosterone, and pathological stage and progression in patients with clinically localized prostate cancer treated with radical prostatectomy. We retrospectively reviewed the records of consecutive patients with clinically localized prostate cancer treated with radical prostatectomy between January 1990 and June 2003. A total of 326 patients with pretreatment testosterone levels available were eligible for this analysis. Biochemical progression (BCR) was defined by postoperative prostate specific antigen (PSA) greater than 0.4 ng/ml with a confirmatory increase and it occurred in 41 men. No men received adjuvant therapy. Univariate and multivariate logistic regression analyses were done to examine whether pretreatment testosterone was associated with pathological stage. Cox regression was used to assess the association of testosterone and BCR. Median PSA was 6.01 ng/ml (range 0.13 to 86), testosterone was 385 ng/dl (range 133 to 998) and followup was 36 months (range 4 to 136). In 245 patients (75%) disease was organ confined. Lower testosterone correlated with adverse pathological stage on multivariate analysis (p = 0.01), as did clinical stage, biopsy grade and PSA. However, we found no relationship between testosterone and BCR after adjusting for covariates. Furthermore, we found no evidence of an interaction between PSA and testosterone (p = 0.4). On multivariate analysis low preoperative total testosterone was associated with advanced pathological stage but not with BCR. Future studies are warranted with data on more patients who have progressed.

Does Ischemia-Induced Prostate Damage during Cardiac Surgery Involving Cardiopulmonary Bypass Cause Bladder Outlet Obstruction?

Objective: This study sought to investigate whether ischemia-induced prostate damage during cardiac surgery involving cardiopulmonary bypass causes bladder outlet obstruction. Materials and Methods: The study involved 37 men who underwent elective cardiac surgery involving cardiopulmonary bypass. Prostate-specific antigen (PSA) levels were determined preoperatively (baseline) and on postoperative days 1, 5, and 30. In 4 cases, the PSA level after the operation was unchanged from the preoperative level, so these 4 men were excluded from the study. In the remaining 33 patients, symptoms of bladder outlet obstruction were assessed using the International Prostate Symptom Score. Each subject completed this test preoperatively and 3, 6 and 9 months postoperatively, and the means scores at these time points were compared. The effects of patient age, operative time, CPB time, and aortic clamping time on postoperative increases in PSA levels were investigated. Results: Thirty-three (89.2%) of the 37 men exhibited increased postoperative PSA levels compared to baseline. The mean PSA level for the 33 cases on day 5 was significantly higher than the baseline mean, but the mean levels on postoperative days 1 and 30 were comparable to baseline. Nine (24.3%) of the 33 men had postoperative PSA levels greater than 4.0 ng/dl (the upper normal limit). There was no significant difference between preoperative and postoperative International Prostate Symptom Scores. Conclusion: The study indicates that men’s PSA levels are, indeed, increased after cardiac surgery with cardiopulmonary bypass. However, in 9 months of follow-up, there was no association between this PSA rise and development of BOO, according to International Prostate Symptom Scores.

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.

1135: Who Dies from Prostate Cancer after Radical Prostatectomy? Influence of Post-Operative Prostate Specific Antigen Doubling Time, Pathological Gleason Sum, and Time from Surgery to Biochemical Recurrence

1135: Who Dies from Prostate Cancer after Radical Prostatectomy? Influence of Post-Operative Prostate Specific Antigen Doubling Time, Pathological Gleason Sum, and Time from Surgery to Biochemical Recurrence

Predictors of short postoperative prostate-specific antigen doubling time for patients diagnosed during PSA era

Objectives To determine the preoperative and postoperative predictors of a short prostate-specific antigen (PSA) doubling time (PSADT) after radical prostatectomy for patients diagnosed during the PSA era. Methods Between 1989 and 2003, 1785 men underwent radical prostatectomy for 2002 American Joint Committee on Cancer (AJCC) Stage T1c or T2 prostate cancer. Of these men, 205 had documented PSA failure. The PSADT was calculated by assuming first-order kinetics and using a minimum of two detectable postoperative PSA measurements after a previous undetectable level. Multivariable logistic regression analyses were performed to determine the significant preoperative and postoperative predictors of a PSADT of less than 6 months. Results Patients with a greater biopsy Gleason score ( P = 0.006), greater preoperative risk group ( P = 0.002), greater prostatectomy Gleason score ( P = 0.0006), greater 2002 AJCC pathologic stage ( P = 0.01), or shorter time to postoperative PSA failure ( P = 0.04) were more likely to have a shorter PSADT. Using multivariable analysis, high-risk disease ( P = 0.0001) was the only preoperative factor that remained an independent significant predictor of a PSADT of less than 6 months. Of the postoperative factors, a prostatectomy Gleason score of 8 to 10 ( P = 0.002), 2002 AJCC pathologic Stage T3b ( P = 0.03), and time to PSA failure of less than 2 years ( P = 0.05) remained significant independent predictors of a PSADT of less than 6 months. Conclusions High-risk disease preoperatively and a prostatectomy Gleason score of 8 to 10, seminal vesicle invasion, or a time to PSA failure of less than 2 years postoperatively were significant independent indicators of developing a postoperative PSADT of less than 6 months. For these men, trials studying systemic therapy in addition to radical prostatectomy are needed.

Improved biochemical outcome with adjuvant radiotherapy after radical prostatectomy for prostate cancer with poor pathologic features

The indications for adjuvant external beam radiotherapy (EBRT) after radical prostatectomy (RP) are poorly defined. We performed a retrospective comparison of our institution's experience treating prostate cancer with RP vs. RP followed by adjuvant EBRT. Between 1987 and 1998, 617 patients with clinical Stage T1-T2N0M0 prostate cancer underwent RP. Patients who underwent preoperative androgen deprivation and those with positive lymph nodes were excluded. Of the 617 patients, 34 (5.5%) with an undetectable postoperative prostate-specific antigen (PSA) level underwent adjuvant prostatic fossa RT at a median of 0.25 year (range, 0.1-0.6) postoperatively because of poor pathologic features. The median total dose was 59.4 Gy (range, 50.4-66.6 Gy) in 1.8-2.0-Gy fractions. These 34 RP+RT patients were compared with the remaining 583 RP patients. Biochemical failure was defined as any postoperative PSA level > or =0.1 ng/mL and any postoperative PSA level > or =0.3 ng/mL (at least 30 days after surgery). Administration of androgen deprivation was also scored as biochemical failure when applying either definition. The median clinical follow-up was 8.2 years (range, 0.1-11.2 years) for RP and 8.4 years (range, 0.3-13.8 years) for RP+RT. Radical prostatectomy + radiation therapy patients had a greater pathologic Gleason score (mean, 7.3 vs. 6.5; p < 0.01) and pathologic T stage (median, T3a vs. T2c; p < 0.01). Age (median, 65.7 years) and pretreatment PSA level (median, 7.9 ng/mL) were similar between the treatment groups. Extracapsular extension was present in 72% of RP+RT patients vs. 27% of RP patients (p < 0.01). The RP+RT patients were more likely to have seminal vesicle invasion (29% vs. 9%, p < 0.01) and positive margins (73% vs. 36%, p < 0.01). Despite these poor pathologic features, the 5-year biochemical control (BC) rate (PSA <0.1 ng/mL) was 57% for RP+RT and 47% for RP (p = 0.28). For patients with extracapsular extension, the 5-year BC rate was 52% for RP+RT vs. 30% for RP (p < 0.01). The 5-year BC rate for patients with seminal vesicle invasion was 60% for RP+RT vs. 18% for RP (p < 0.01). For those with positive margins, the 5-year BC rate was 64% for RP+RT vs. 27% for RP (p < 0.01). The use of adjuvant RT remained statistically significant on multivariate analysis when applying either biochemical failure definition. Adjuvant RT also remained statistically significant when including the postoperative PSA level (>30 days after surgery) in the multivariate analyses. In addition, 99 (17%) of the 583 RP patients required salvage prostatic fossa RT (median dose, 59.4 Gy) at a median interval of 1.3 years after surgery (range, 0.1-8.4) for a palpable recurrence (n = 10) or a detectable/rising postoperative PSA level (n = 89). The median PSA level before salvage RT was 0.8 ng/mL (mean, 3.2 ng/mL). The 5-year and 8-year BC rate, using the PSA <0.1 ng/mL definition, from the date of salvage RT was 41% and 35%, respectively. The 5-year and 8-year BC rate, using the PSA <0.3 ng/mL definition, was 46% and 36%, respectively. The 8-year local recurrence rate after salvage RT was 4%. Adjuvant RT demonstrated improved efficacy against prostate cancer. For patients with poor pathologic features (extracapsular extension, seminal vesicle invasion, positive margins), adjuvant RT improved the biochemical outcome independent of other prognostic factors.

Third Prize: Laparoscopic Radical Prostatectomy: Is Intact Organ Removal Attainable? Study of Margin Status

To determine the initial oncologic results (pathology) of specimens removed by laparoscopic radical prostatectomy (LRP) by examining the surgical margins. The 70 consecutive LRP procedures performed for clinically localized prostate cancer at Eastern Virginia Medical School from April 2001 to November 2002 were reviewed for preoperative and important intraoperative variables. The initial histopathology report and a prospective review by a single genitourinary pathologist for margin status as well parenchymal exposure of benign glands were assessed. Postoperative prostate specific antigen (PSA) levels were noted. The clinical stage distribution was as follows: T1c = 59, T2a = 10, and T2b = 1. The preoperative median PSA value was 6.96 ng/mL. The mean operative time was 307 minutes. The mean estimated blood loss was 298 mL. The prospective pathologic review results were as follows: 1 pT0 (1.4%), 60 pT2 (85.7%), and 9 pT3 (12.8%). The overall positive surgical-margin rate was 15.7%. Of those patients with pT2 disease; 8 specimens (13.3%) had a positive margin, whereas 33% of patients with pT3 disease had a positive surgical margin. Parenchymal exposure of benign glands on the inked surface was recognized in 8 patients (13.3%). Data from PSA assays 1 month postoperatively were available in 69 patients. Serum PSA was undetectable (< or =0.1 ng/mL) in 67 men (97%). An LRP can offer surgical margins comparable to those of open procedures series reported in the literature. Long-term progression and survival outcome data are necessary before this procedure should be offered as a replacement for open prostatectomy.

Long-term outcome of patients with prostate cancer and pathologic seminal vesicle invasion (pT3b): effect of adjuvant radiotherapy

Objectives To evaluate the long-term outcome of patients with prostate cancer who have pathologic seminal vesicle invasion without lymph node metastasis (pT3bN0M0) and compare management strategies. Methods From October 1987 to August of 1997, 43 men underwent radical prostatectomy at Thomas Jefferson University Hospital, had pT3bN0M0 disease, complete preoperative and postoperative prostate-specific antigen (PSA) data, and a minimum of 2 years of follow-up. Eighteen patients with undetectable postoperative PSA levels received adjuvant radiotherapy (RT) within 6 months of surgery. Twelve patients with undetectable PSA levels postoperatively were considered for salvage treatment at biochemical progression. Thirteen patients with persistently elevated PSA levels postoperatively underwent immediate salvage RT. We evaluated the prognostic factors for freedom from biochemical failure (bNED), distant metastasis (DM), disease-specific survival, and overall survival. Results The median follow-up time was 5.9 years (range 2 to 10). Patients who received adjuvant RT had significantly greater 5-year bNED survival than patients who did not (80% versus 8%, P <0.001) and increased freedom from DM that was of borderline significance ( P = 0.05). The 5-year survival estimates for DM were 0% for the adjuvant RT versus 17% for the observed patient group. In patients with undetectable postoperative PSA levels, the preoperative PSA level was an independent prognostic factor for later disease progression. Patients with a preoperative PSA level of less than 20 ng/mL showed significantly greater 5-year bNED survival than those with a preoperative PSA level of 20 ng/mL or greater (56% versus 32%, P <0.05). The survival curves for risk of DM and death from prostate cancer for those two patient groups were not significantly different statistically. Conclusions Although pathologic seminal vesicle invasion has been associated with poor prognosis and high DM risk, adjuvant RT may result in improved bNED survival in patients with undetectable PSA levels after radical prostatectomy. The effect on clinical outcome awaits additional follow-up.

PREDICTORS OF METASTATIC DISEASE IN MEN WITH BIOCHEMICAL FAILURE FOLLOWING RADICAL PROSTATECTOMY

We determined clinical and pathological predictors of positive bone scans and computerized tomography (CT) in patients with biochemical recurrence after radical prostatectomy (RP). A retrospective analysis of patients treated with RP at West Los Angeles Veterans Affairs Medical Center and University of California-Los Angeles Medical Center was performed to identify men with biochemical recurrence. All postoperative bone scans and pelvic CT following recurrence and prior to the initiation of hormone ablation therapy were reviewed. Preoperative clinical variables, pathological findings, serum prostate specific antigen (PSA) at postoperative imaging and postoperative PSA doubling time were compared between patients with positive and negative imaging study results. A total of 128 patients with biochemical recurrence after RP who had postoperative pelvic CT or bone scans available were identified. A total of 97 bone scans were obtained, of which 11 (11%) were positive, and 71 CT scans were obtained, of which 5 (7%) were positive. Men with PSA doubling time less than 6 months were at increased risk of a positive bone scan (26% vs 3%) or positive CT (24% vs 0%) relative to men with longer PSA doubling time. In men with PSA doubling time less than 6 months the risk of a positive study highly depended on PSA at the time of imaging. In men with PSA less than 10 ng/ml the incidence of a positive study was 0% for pelvic CT and 11% for bone scan. In men with PSA greater than 10 ng/ml the risk of a positive study was 57% for pelvic CT and 46% for bone scan. In men with PSA doubling time greater than 6 months no clear relationship to PSA was seen, although the number of patients with a positive study was extremely low (positive bone scans 3% and positive CT 0%). However, none of the 6 imaging studies performed in men with PSA doubling times greater than 6 months and a markedly elevated PSA of 20 to 90 ng/ml was positive. The risk of detecting metastatic disease by bone scan or pelvic CT in men with biochemical recurrence following RP with PSA doubling time greater than 6 months is low despite marked PSA increases up to 90 ng/ml. In men with PSA doubling time less than 6 months the risk of detecting metastatic disease markedly increases when PSA is greater than 10 ng/ml. These results have important implications for the timing of imaging in patients with biochemical recurrence following RP.

Current opinion on adjuvant and salvage treatment after radical prostatectomy.

The role of postoperative radiotherapy and hormone treatment after radical prostatectomy is uncertain, with no good evidence base to guide practice. In particular, it is not known whether a blanket policy of adjuvant therapy offers any advantage over a selective approach using salvage treatment in people who develop biochemical failure. Furthermore the technique for postoperative radiotherapy to the prostate bed has not been well described. We surveyed the opinion of UK clinical oncologists to describe current practice, with a view to informing the design of clinical trials in this setting. A questionnaire was designed to elicit the opinion and clinical practice of UK clinical oncologists on the use of radiotherapy and hormone therapy after radical prostatectomy. The questionnaire was distributed to the delegates at the British Institute of Radiology Conference 'Contemporary issues in Prostate Cancer Radiotherapy' on 9 May 2003. Forty-nine out of 70 (70%) clinical oncologists completed the questionnaire. With an undetectable postoperative prostate-specific antigen (PSA) less than 0.04 ng/ml, opinion was divided on the role of adjuvant therapy. For example, adjuvant radiotherapy was recommended by 51% (25/49) of respondents for cases with pT3 margin positive disease. When recommending adjuvant radiotherapy, 60% (59/99) recommended hormone therapy in addition. In cases with an asymptomatic rising PSA after radical prostatectomy who had not received adjuvant therapy, 93% (43/46) recommended salvage radiotherapy, but the PSA threshold for recommending such treatment varied widely. The two most common dose-fractionation regimens for salvage radiotherapy to the prostate bed were 62-64 Gy in 2 Gy daily fractions (47%), and 50-55 Gy in 20 fractions (30%). Opinion is varied within the UK on the role of radiotherapy and hormone therapy after radical prostatectomy. The results of this survey should inform the design of future clinical trials.

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.

Invasion of seminal vesicles by adenocarcinoma of the prostate: PSA outcome determined by preoperative and postoperative factors

Objectives To determine which preoperative and postoperative factors were predictive of the time to prostate-specific antigen (PSA) failure after radical retropubic prostatectomy (RRP) for patients with seminal vesicle invasion (SVI). SVI by prostate cancer is associated with high PSA failure rates after RRP and subsequent distant metastases. Methods Between 1988 and 2002, 1697 patients with prostate cancer underwent RRP at Brigham and Women's Hospital, of whom 103 (6%) had SVI. Cox regression multivariable analysis was used to determine whether the preoperative PSA level, prostatectomy Gleason score, margin status, or presence of extraprostatic extension was predictive of the time to postoperative PSA failure. Estimates of PSA outcome were made using the actuarial method of Kaplan and Meier for patients who had none, all, or at least one of the factors that predicted for the time to postoperative PSA failure. Results The statistically significant categorical predictors of the time to PSA failure after RRP in patients with SVI included prostatectomy Gleason score of 4+3 or greater ( P = 0.009), preoperative PSA level greater than 20 ng/dL when evaluated as a categorical or as a continuous variable ( P = 0.002 and P = 0.001, respectively), and margin positivity ( P = 0.075) which was of borderline significance. The 3-year estimate of PSA control was 52% to 100%, 28%, and 0% for patients with negative margins, preoperative PSA less than 20 ng/dL, and prostatectomy Gleason score of 3+4 or less versus having one to two or all three predictors of the time to postoperative PSA failure. Conclusions The PSA outcome after RRP for patients with SVI varies depending on the preoperative PSA level, prostatectomy Gleason score, and margin status.

Radical prostatectomy for prostate cancer patients with prostate-specific antigen >20 ng/ml.

Prostate cancer patients with prostate-specific antigen (PSA) >20 ng/ml are at high risk of progression after radical prostatectomy. Comparison has seldom been made between the outcomes of patients with PSA 20.1-50 ng/ml and those with PSA >50 ng/ml after radical prostatectomy. We retrospectively analyzed the outcomes of these two groups. From 1993 to 2002, 60 prostate cancer patients receiving radical prostatectomy were enrolled in this study. Thirty-seven patients with PSA 20.1-50 ng/ml were assigned to Group I. Twenty-three patients with PSA >50 ng/ml were assigned to Group II. Preoperatively, Group II had greater PSA and PSA density than Group I (P < 0.0001). Group II had higher biopsy Gleason score and clinical stage than Group I (P < 0.05). Pathological categories and outcomes of both groups were compared. Group II had higher Gleason score and tumor volume than Group I (P < 0.05). The incidence of organ-confined diseases was 29.7% in Group I and 0% in Group II (P < 0.05). Group II had higher incidence of extracapsular tumor extension, positive surgical margin and lymph node involvement than Group I (P < 0.05). The incidence of postoperative PSA >0.01 ng/ml and PSA failure were higher in Group II than Group I (P < 0.05). Need for adjuvant treatment and death from prostate cancer was similar in both groups. Patients with PSA >50 ng/ml had a poorer prognosis than patients with PSA 20.1-50 ng/ml. Those with PSA >50 ng/ml had shorter freedom from PSA failure survivals than those with PSA 20.1-50 ng/ml (P = 0.004). Classification of high-risk prostate patients into two sub-groups with PSA 20.1-50 ng/ml and PSA >50 ng/ml should be considered.