Undetectable Postoperative Prostate-specific Antigen Research Articles

Salvage Versus Adjuvant Radiation Therapy Following Radical Prostatectomy in Localised Prostate Cancer: A War Without a Winner

ObjectiveTo review current literature regarding the efficacy of adjuvant radiation therapy (ART) and salvage radiation therapy (SRT) following radical prostatectomy (RP) in patients with undetectable postoperative prostate-specific antigen (PSA) levels and high-risk features of prostate cancer (PCa) recurrence.MethodsSeven randomized controlled trials focused on the use of ART compared with either observation or SRT after RP that had been published in PubMed up to May 2022 were reviewed.ResultsThe use of ART following RP has been the treatment of choice over the past decade. Three RCTs comparing ART with early SRT show that SRT given as soon as biochemical recurrence (BCR) is detected is not inferior to ART while it offers the opportunity to avoid overtreatment and potential RT-related side effects. A meta-analysis summarizing the results from these trials supports these findings.ConclusionsEarly SRT may be suggested as the standard of care for patients with PCa and high-risk features for disease recurrence following RP. Nevertheless, further investigations are needed to identify those patients who will benefit from ART, particularly, in case of lymph node involvement. Moreover, some patients might avoid SRT despite reaching detectable postoperative serum PSA levels.

Blood Prostate-specific Antigen by Volume of Benign, Gleason Pattern 3 and 4 Prostate Tissue

ObjectiveTo evaluate how blood levels of prostate-specific antigen (PSA) relate to prostate volume of benign tissue, Gleason pattern 3 (GP3) and Gleason pattern 4 (GP4) cancer. MethodsThe cohort included 2209 consecutive men undergoing radical prostatectomy at 2 academic institutions with pT2N0, Grade Group 1-4 prostate cancer and an undetectable postoperative PSA. Volume of benign, GP3, and GP4 were estimated. The primary analysis evaluated the association between PSA and volume of each type of tissue using multivariable linear regression. R2, a measure of explained variation, was calculated using a multivariable model. ResultsEstimated contribution to PSA was 0.04/0.06 ng/mL/cc for benign, 0.08/0.14 ng/mL/cc for GP3, and 0.62/0.80 ng/ml/cc for GP4 for the 2 independent cohorts, respectively. GP4 was associated with 6 to 8-fold more PSA per cc compared to GP3 and 15-fold higher compared to benign tissue. We did not observe a difference between PSA per cc for GP3 vs. benign tissue (P = 0.2). R2 decreased only slightly when removing age (0.006/0.018), volume of benign tissue (0.051/0.054) or GP3 (0.014/0.023) from the model. When GP4 was removed, R2 decreased 0.051/0.310. PSA density (PSA divided by prostate volume) was associated with volume of GP4 but not GP3, after adjustment for benign volume. ConclusionGleason pattern 4 cancer contributes considerably more to PSA and PSA density per unit volume compared to GP3 and benign tissue. Contributions from GP3 and benign are similar. Further research should examine the utility of determining clinical management recommendations by absolute volume of GP4 rather than the ratio of GP3 to GP4.

Residual Benign Prostate Glandular Tissue after Radical Prostatectomy is Not Associated with the Development of Detectable Postoperative Serum Prostate Specific Antigen.

To determine if benign glandular tissue at the surgical margin (BGM) is associated with detectable prostate specific antigen (PSA) and/or biochemical recurrence (BCR) after radical prostatectomy (RP). Participants underwent RP for localized prostate cancer between 2004 and 2018. Regression analysis was used to identify demographic, clinical and surgical factors associated with the likelihood of BGM presence on surgical pathology. Oncologic outcomes included detectable PSA (>0.03 ng/ml), BCR (≥0.2 ng/ml) and progression to BCR or salvage treatment after detectable PSA. Life tables and Cox proportional hazards regression models were used to determine the association of BGM and risk of oncologic outcomes. A total of 1,082 men underwent RP for localized prostate cancer with BGM reported on surgical pathology and an undetectable postoperative PSA. BGM was present on 249 (23%) specimens. Younger age, bilateral nerve sparing surgery and robotic approach were associated with presence of BGM while malignancy at the surgical margin (MSM) was not. At 7 years after RP, 29% experienced detectable PSA and 11% had BCR. In the subgroup of men who reached detectable PSA, 79% had progression within 7 years. On multivariate Cox proportional hazards regression, BGM status was not independently associated with detectable PSA, BCR and/or progression from detectable PSA to BCR or salvage treatment. The presence of BGM at RP was not associated with increased risk of MSM, detectable PSA, BCR or progression after detectable PSA.

Extent of positive surgical margins following radical prostatectomy: impact on biochemical recurrence with long-term follow-up

BackgroundTo assess the prognostic value of the extent of positive surgical margins (PSM) following radical prostatectomy (RP) on biochemical recurrence (BR) with long-term follow-up.MethodsThis retrospective study analyzed 1275 RPs performed between January 1992 and December 2013 in two university centers in Marseille (France). The inclusion criteria were: follow-up > 24 months, undetectable postoperative prostate-specific antigen (PSA), no seminal vesicle (SV) invasion, no lymph node invasion confirmed by surgery (pN0) or imaging (pNx), and no neoadjuvant or adjuvant treatment. BR was defined by PSA level ≥ 0.2 ng/mL on two successive samples. We included 189 patients, divided into two groups:- Focal PSM (fPSM): single PSM (sPSM) ≤3 mm;- Extensive PSM (ePSM): sPSM with linear length > 3 mm or several margins regardless of the length.ResultsThe median follow-up was 101 months (18–283) and the median age was 63 years (46–76). BR occurred in only 12.1% (14/115) of cases involving fPSM and in 54.1% (40/74) of cases involving ePSM. In the multivariate model, ePSM patients were significantly associated with increased BR compared to fPSM (hazard ratio [HR] = 6.11; 95% confidence interval [CI] = 3.25–11.49). The ePSM significantly decreased BR-free survival (p < 0.001) for every patient and every subgroup (pT2, pT3a, pG ≤6, and pG ≥7). The median BR time following RP was significantly shorter for ePSM patients than fPSM (57.2 vs. 89.2 months p < 0.001).ConclusionWith a median 8-year follow-up, ePSM was strongly associated with BR compared to fPSM. Therefore, it seems legitimate to monitor patients with fPSM. In cases of ePSM, adjuvant treatment appears effective.

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

The 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. Between 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. Of 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. The 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.

Assessing the Optimal Timing for Early Salvage Radiation Therapy in Patients with Prostate-specific Antigen Rise After Radical Prostatectomy

BackgroundEarly salvage radiation therapy (eSRT) represents a treatment option for patients who experience a prostate-specific antigen (PSA) rise after radical prostatectomy (RP); however, the optimal PSA level for eSRT administration is still unclear. ObjectiveTo test the impact of PSA level on cancer control after eSRT according to pathologic tumour characteristics. Design, setting, and participantsThe study included 716 node-negative patients with undetectable postoperative PSA who experienced a PSA rise after RP. All patients received eSRT, defined as local radiation to the prostate and seminal vesicle bed, delivered at PSA ≤0.5 ng/ml. Biochemical recurrence (BCR) after eSRT was defined as two consecutive PSA values ≥0.2 ng/ml. Outcome measurements and statistical analysisMultivariable Cox regression analysis tested the association between pre-eSRT PSA level and BCR after eSRT. Covariates consisted of pathologic stage (pT2 vs pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), and surgical margin status (negative vs positive). We tested an interaction with PSA level and baseline pathologic risk for the hypothesis that BCR-free survival differed by pre-eSRT PSA level. Three pathologic risk factors were identified: pathologic stage pT3b or higher, pathologic Gleason score ≥8, and negative surgical margins. Results and limitationsMedian follow-up among patients who did not experience BCR after eSRT was 57 mo (interquartile range: 27–105). At 5 yr after eSRT, BCR-free survival rate was 82% (95% confidence interval [CI], 78–85). At multivariable Cox regression analysis, pre-eSRT PSA level was significantly associated with BCR after eSRT (hazard ratio: 4.89; 95% CI, 1.40–22.9; p<0.0001). When patients were stratified according to the number of risk factors at final pathology, patients with at least two pathologic risk factors showed an increased risk of 5-yr BCR as high as 10% per 0.1 ng/ml of PSA level compared with only 1.5% in patients with one or no pathologic risk factors. ConclusionsIn this retrospective study, cancer control after eSRT greatly depended on pretreatment PSA. The absolute PSA level had a different prognostic value depending on the pathologic characteristics of the tumour. In patients with more adverse pathologic features, eSRT conferred better cancer control when administered at the very first sign of PSA rise. Conversely, the benefit of eSRT was less evident in men with favourable disease at RP. Patient summaryIn this retrospective study, cancer control after early salvage radiation therapy (eSRT) was influenced by pretreatment prostate-specific antigen (PSA) level. This effect was highest in men with at least two of the following pathologic features: pT3b/pT4 disease, pathologic Gleason score ≥8, and negative surgical margins. In these patients, eSRT conferred better cancer control when administered at the very first sign of PSA rise.

Positive surgical margins after radical prostatectomy: What should we care about?

Positive surgical margins (PSMs) after radical prostatectomy (RP) are a known factor associated with biochemical recurrence (BCR) and raise the issue of adjuvant treatment by radiotherapy versus salvage treatment at recurrence. To help this choice, our study aimed to analyze BCR-free survival and factors associated with BCR in patients with PSM and undetectable postoperative prostate-specific antigen (PSA). Between 2005 and 2008, 630 patients had RP for localized prostate cancer in our center. We included patients with PSM, uninvaded nods, undetectable postoperative PSA and no adjuvant treatment. The 5-year BCR-free survival was calculated using Kaplan-Meier method. Logistic regression models were used to determine the factors associated with BCR in univariate and multivariate analyses (Cox model). The PSM rate was 32.7 % (n = 206 patients), and 110 patients corresponded to the inclusion criteria. The median follow-up was 72 months. The BCR rate was 30 % with a 5-year BCR-free survival of 83.9 %. The factors significantly associated with BCR were preoperative PSA, predominance and percentage of Gleason 4, tumor volume, PSM length and predominance of Gleason 4 at the margin. In the multivariate analysis, the remaining two significant factors were PSM length [OR 4.35, 95 % CI (1.011-1.421), p = 0.037] and tumor volume [OR 4.29, 95 % CI (1.011-1.483), p = 0.038]. Over a 5-year follow-up, only one-third of patients experienced BCR. It might be reasonable to postpone adjuvant radiotherapy for patients with PSM and undetectable PSA after RP. Tumor volume and PSM length were associated with BCR and should be taken into account in the postoperative treatment management.

Need for High Radiation Dose (≥70 Gy) in Early Postoperative Irradiation After Radical Prostatectomy: A Single-Institution Analysis of 334 High-Risk, Node-Negative Patients

To determine the clinical benefit of high-dose early adjuvant radiotherapy (EART) in high-risk prostate cancer (hrCaP) patients submitted to radical retropubic prostatectomy plus pelvic lymphadenectomy. The clinical outcome of 334 hrCaP (pT3-4 and/or positive resection margins) node-negative patients submitted to radical retropubic prostatectomy plus pelvic lymphadenectomy before 2004 was analyzed according to the EART dose delivered to the prostatic bed, <70.2 Gy (lower dose, median 66.6 Gy, n = 153) or >or=70.2 Gy (median 70.2 Gy, n = 181). The two groups were comparable except for a significant difference in terms of median follow-up (10 vs. 7 years, respectively) owing to the gradual increase of EART doses over time. Nevertheless, median time to prostate-specific antigen (PSA) failure was almost identical, 38 and 36 months, respectively. At univariate analysis, both 5-year biochemical relapse-free survival (bRFS) and disease-free survival (DFS) were significantly higher (83% vs. 71% [p = 0.001] and 94% vs. 88% [p = 0.005], respectively) in the HD group. Multivariate analysis confirmed EART dose >or=70 Gy to be independently related to both bRFS (hazard ratio 2.5, p = 0.04) and DFS (hazard ratio 3.6, p = 0.004). Similar results were obtained after the exclusion of patients receiving any androgen deprivation. After grouping the hormone-naïve patients by postoperative PSA level the statistically significant impact of high-dose EART on both 5-year bRFS and DFS was maintained only for those with undetectable values, possibly owing to micrometastatic disease outside the irradiated area in case of detectable postoperative PSA values. This series provides strong support for the use of EART doses >or=70 Gy after radical retropubic prostatectomy in hrCaP patients with undetectable postoperative PSA levels.

Robotic radical prostatectomy in Greece: the learning curve and beyond. The initial 40 cases.

Radical prostatectomy is the treatment of choice for management of organ-confined prostate cancer. Minimally invasive treatments, as an alternative, have refined been recently by the introduction of da Vinci robotic technology which has the potential to improve surgical outcomes and reduce the steep learning curve associated with conventional laparoscopic radical prostatectomy. We report on our experience with robotic radical prostatectomy using the first da Vinci robotic system in our country. During 8months, 40 robotic radical prostatectomies were performed by a single surgical team at Athens Medical Centre (Marousi, Greece). Preoperative data collection included basic demographics, prostate-specific antigen (PSA), clinical stage, and Gleason score. Operative outcomes included operative time, estimated blood loss, and complications. Postoperative outcomes included hospital stay, pain, catheter time, pathology, PSA, return of continence, and potency. Average operative time was 186.25min with an estimated mean blood loss of 135ml. There were no intra-operative complications. Ninety per cent of the patients were discharged home on postoperative day 1 with mean haematocrit 36.7 (range 29-43). All patients reported minimal postoperative pain and resumed regular diet on the first postoperative day. Average catheter time was 6.6days (range 5-10). Early continence was observed in 47.5% of the patients, seven days after catheter removal. Continence at 1, 3, and 6months was 75, 82.5 and 95%, respectively. The overall positive margin rate was 17.5%. Ninety-five per cent of the patients had undetectable postoperative PSA levels (less than 0.1ng/ml) at a median follow-up of 6months. Our initial experience with robotic radical prostatectomy is very promising. The learning curve was approximately 10-12 cases. With a methodical approach we were able to implement the method safely and effectively in our practice, combining minimal morbidity with good oncological and functional outcomes.

Prostate-Specific Antigen Control with Low-Dose Adjuvant Radiotherapy for High-Risk Prostate Cancer

To analyze the prostate-specific antigen (PSA) outcome after low-dose adjuvant RT at a single institution, because the role and optimal dose of external beam radiotherapy (RT) after radical prostatectomy for prostate cancer remain controversial. We retrospectively identified 65 men who had received low-dose adjuvant RT (median 50 Gy) for microscopically positive margins with an undetectable postoperative PSA from 1990 to 2004. Biochemical failure-free survival was the primary endpoint. Biochemical failure was defined as two consecutive PSA increases to greater than 0.2 ng/mL. At a median follow-up of 5 years, 2 men had developed distant metastasis, 2 had local recurrence, and 2 had died (neither attributable to prostate cancer). Biochemical failure had occurred in 7 men (11%). The 5 and 8-year rate of biochemical failure-free survival was 87%. A greater Gleason score (P = 0.04) and seminal vesicle invasion (P = 0.04) predicted significantly for increased biochemical failure on univariate analysis. No single factor was significant on multivariate analysis. Men with a Gleason score of 7 or less had a 5-year biochemical failure-free survival rate of more than 90%. In contrast, those with a Gleason score of 8 or more had a 50% risk of biochemical failure at 5 years. Acute bowel or bladder toxicity (all grade 2 or less) developed in 25%. Two men developed chronic urethral stricture requiring dilation, and 34 (51%) developed surgery-related toxicity that persisted throughout and after RT. Low-dose RT is well tolerated and can potentially provide PSA control in men with Gleason score 7 or less disease with positive surgical margins after radical prostatectomy.

Detectable Prostate Specific Antigen Between 60 and 120 Days Following Radical Prostatectomy for Prostate Cancer: Natural History and Prognostic Significance

Following radical retropubic prostatectomy for prostate cancer, if the serum prostate specific antigen fails to become undetectable, occult micrometastatic disease is suspected. We assessed the natural history of disease progression, and predictors of recurrence and survival in this group of patients. We identified 303 men treated with radical retropubic prostatectomy for prostate cancer between 1990 and 1999, who had a detectable prostate specific antigen between 60 and 120 days postoperatively. Systemic recurrence-free and cancer specific survival were estimated using the Kaplan-Meier method, and analyzed using Cox proportional hazards models. Clinical and pathological features were more adverse among men whose postoperative prostate specific antigen was detectable. These men had poorer systemic recurrence-free survival and cancer specific survival compared to men with an undetectable postoperative prostate specific antigen, and even men whose prostate specific antigen subsequently became detectable. These differences persisted after multivariate adjustment for preoperative prostate specific antigen, specimen Gleason score, seminal vesicle and margin status. With a median followup of 8.5 years, 50 systemic recurrences and 26 deaths from cancer were observed. Gleason score and the prostate specific antigen doubling time were multivariate predictors of systemic recurrence, while Gleason score, margin status and seminal vesicle invasion were predictors of death from cancer. A detectable prostate specific antigen immediately following radical retropubic prostatectomy confers an increased risk of progression and death, but only in a subset of patients, who may be identified on the basis of pathological features and prostate specific antigen doubling time. In future such patients may be suitable for trials of systemic therapy.

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.

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.

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.

Radiotherapy after prostatectomy.

The role of radiotherapy after prostatectomy is controversial. This paper tries to give some guidelines for everyday practice through an analysis of literature data. The potential role of radiotherapy in the adjuvant and salvage setting is discussed. We also report and interpret available literature data for both settings. As regards an increase in or detectable prostate-specific antigen (PSA) after radical prostatectomy, about 40-50% of patients are rendered bNED with local salvage radiotherapy, but only 10-50% are long-term (5 years) biochemically controlled. A timely salvage treatment is crucial to optimize control probability. As regards adjuvant radiotherapy for undetectable postoperative PSA in patients at high risk of failure as judged on pathology, results are more encouraging. Recent data report bNED rates > 70% at 5 years. Although results are far from satisfactory, salvage radiotherapy should be considered for every patient with an increased or detectable PSA after surgery. Adjuvant radiotherapy seems preferable to salvage radiotherapy for patients at high (> 30%) risk of failure.

Positive resection margin and/or pathologic T3 adenocarcinoma of prostate with undetectable postoperative prostate-specific antigen after radical prostatectomy: to irradiate or not?

Purpose : To evaluate the efficacy of postoperative adjuvant radiotherapy (RT) for positive resection margin and/or pathologic T3 (pT3) adenocarcinoma of the prostate with undetectable postoperative prostate-specific antigen (PSA) levels. Methods and materials : We retrospectively analyzed 125 patients with a positive resection margin and/or pT3 adenocarcinoma of the prostate who had undetectable postoperative serum PSA levels after radical prostatectomy. Seventy-three patients received postoperative adjuvant RT and 52 did not. Follow-up ranged from 1.5 to 12.0 years (median 4.2 for the irradiated group and 4.9 for the nonirradiated group). PSA outcome was available for all patients. Freedom from failure was defined as the maintenance of a serum PSA level of ≤0.2 ng/mL, as well as the absence of clinical local recurrence and distant metastasis. Results : No difference was found in the 5-year actuarial overall survival between the irradiated and nonirradiated group (94% vs. 95%). However, patients receiving adjuvant RT had a statistically superior 5-year actuarial relapse-free rate, including freedom from PSA failure, compared with those treated with surgery alone (88% vs. 65%, p = 0.0013). In the irradiated group, 8 patients had relapse with PSA failure alone. None had local or distant recurrence. In the nonirradiated group, 15, 1, and 2 had PSA failure, local recurrence, and distant metastasis, respectively. On Cox regression analysis, pre-radical prostatectomy PSA level and adjuvant RT were statistically significant predictive factors for relapse, and Gleason score, extracapsular invasion, and resection margin status were not. There was a suggestion that seminal vesicle invasion was associated with an increased risk of relapse. The morbidity of postoperative adjuvant RT was acceptable, with only 2 patients developing Radiation Therapy Oncology Group Grade 3 genitourinary complications. Adjuvant RT had a minimal adverse effect on urinary continence and did not cause serious gastrointestinal toxicity. Conclusion : Postoperative adjuvant RT was associated with a lower risk of relapse, including freedom from PSA failure, compared with observation alone for pT3 and/or margin-positive disease with undetectable postoperative PSA levels. This was accomplished with a minimal risk of serious RT morbidity.

The efficacy of early adjuvant radiation therapy for pt3n0 prostate cancer: a matched-pair analysis

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

Durable efficacy of early postoperative radiation therapy for high-risk pT3N0 prostate cancer: the importance of radiation dose

Objectives. To determine the durable efficacy of early postoperative radiation therapy (RT) in patients with pT3N0 prostate cancer who were at an increased risk of biochemical failure. We also evaluated the long-term benefit derived from using higher RT doses. Methods. Seventy-nine patients with pathologic Stage T3N0 prostate cancer and high-risk postoperative features underwent RT within 6 months after surgery. No patient received prior hormonal therapy. Fifty-nine patients had positive surgical margin, 29 had pathologic seminal vesicle invasion, and 27 had persistently elevated postoperative prostate-specific antigen (PSA) levels. Freedom from biochemical relapse (bNED) was defined as an undetectable (less than 0.2 ng/mL) PSA level. Median follow-up time was 39 months, and the median radiation dose was 64.8 Gy. All patients were followed for at least 2 years to be considered biochemically controlled. Results. Patients receiving adjuvant RT for an undetectable pre-RT PSA level had a 3-year bNED rate of 90%, compared with 44% for those receiving salvage RT for a detectable level ( P < 0.0001). In the group of adjuvant patients, RT doses more than 61.2 Gy resulted in a 3-year bNED rate of 90% compared with 64% for those receiving a lower dose ( P = 0.015). The salvage patients irradiated with a dose of 64.8 Gy or greater had a 3-year bNED rate of 52% compared with 18% for those irradiated with lower doses ( P = 0.048). Severe late RT-related complications were infrequent and did not correlate with dose. Conclusions. In patients with high-risk pT3N0 prostate cancer, an RT dose response may exist. Although some studies suggest limited durable efficacy for early postoperative RT, our data suggest that RT doses of 64.8 Gy or more appear superior to prevent future biochemical failures. A prospective randomized study evaluating a postoperative RT dose response is warranted.

Postoperative prostate-specific antigen as a prognostic indicator in patients with margin-positive prostate cancer, undergoing adjuvant radiotherapy after radical prostatectomy

Objectives To identify a population of patients within the group with positive surgical margins after radical prostatectomy who would benefit in terms of improved local control of disease by the administration of adju- vant radiation therapy to the prostate bed. Methods Postoperative prostate-specific antigen (PSA) values were evaluated in 45 patients with margin-pos- itive (MP) disease who underwent adjuvant radiotherapy within 6 months of surgery. All patients were clini- cally T1 -2 MO, and pNO. A cutoff of 0.5 ng/mL or less was used as the level below which PSA was considered undetectable. The mean follow-up time from date of radiation was 33 months. Results In 30 of 45 (67%) patients, PSA levels did drop to undetectable levels postoperatively. In 15 of 45 (33%) patients postoperative PSA levels did not drop to undetectable levels. In the group with detectable post- operative PSA, 12 of 15 (80%) failed adjuvant radiotherapy as determined by a progressive increase in PSA levels in a mean time of 0.95 years (range, 4 months to 2.02 years; median, 0.92 years). When postoperative PSA reached undetectable levels, only 10 of 30 (33%) failed treatment, with a mean time to failure of 2.1 years (range, 4 months to 7.8 years; median, 3.31 years). Conclusions The data would suggest that patients who are MP, but attain an undetectable PSA level post-operatively accompanied by a progressive delayed increase in PSA, probably represent a group with local disease recurrence in the prostate fossa, whereas patients whose PSA levels are detectable postoperatively may represent a group with microscopic metastatic disease or a combination of local recurrence and distant disease or large volume local persistent disease. It is in the group of patients in whom the postoperative PSA decreased to undetectable levels that adjuvant radiotherapy may be effective in controlling local progression of prostate cancer through improved local control, as indicated by a durable decrease in PSA values to undetectable levels in roughly two thirds of these patients. Longer follow-up of these patients will be required to determine whether this improved local control will translate into improved survival.