Detectable 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.

Effect of 3-Dimensional, Virtual Reality Models for Surgical Planning of Robotic Prostatectomy on Trifecta Outcomes: A Randomized Clinical Trial.

Planning complex operations such as robotic-assisted radical prostatectomy requires surgeons to review 2-dimensional magnetic resonance imaging (MRI) cross-sectional images to understand 3-dimensional (3D), patient-specific anatomy. We sought to determine surgical outcomes for robotic-assisted radical prostatectomy when surgeons reviewed 3D, virtual reality (VR) models for operative planning. A multicenter, randomized, single-blind clinical trial was conducted from January 2019 to December 2020. Patients undergoing robotic-assisted laparoscopic radical prostatectomy were prospectively enrolled and randomized to either a control group undergoing usual preoperative planning with prostate biopsy results and MRI only or to an intervention group where MRI and biopsy results were supplemented with a 3D VR model. The primary outcome measure was margin status, and secondary outcomes were oncologic control, sexual function and urinary function. Ninety-two patients were analyzed, with trends toward lower positive margin rates (33% vs 25%) in the intervention group, no significant difference in functional outcomes and no difference in traditional operative metrics (p >0.05). Detectable postoperative prostate specific antigen was significantly lower in the intervention group (31% vs 9%, p=0.036). In 32% of intervention cases, the surgeons modified their operative plan based on the model. When this subset was compared to the control group, there was a strong trend toward increased bilateral nerve sparing (78% vs 92%), and a significantly lower rate of postoperative detectable prostate specific antigen in the intervention subset (31% vs 0%, p=0.038). This randomized clinical trial demonstrated patients whose surgical planning involved 3D VR models have better oncologic outcomes while maintaining functional outcomes.

Tailored postoperative treatment of prostate cancer: final results of a phase I/II trial

BackgroudThe European Organization for Research and Treatment of Cancer (EORTC) trial 22,911 reported 74% 5-year biochemical disease-free survival (bDFS) in patients with prostate carcinoma treated with radical prostatectomy (RP) followed by postoperative radiotherapy (RT). This study aimed to improve these outcomes by using a combined-intensified-modulated-adjuvant treatment, including RT and hormone therapy (HT) after RP.Materials and methodsThis phase I/II trial treatment was designed to improve 5-year bDFS from ~ 75 to 90%. Patients were consecutively enrolled using the following inclusion criteria: age < 80 years, histological diagnosis of prostate adenocarcinoma without known metastases, stage pT2-4N0-1, and Eastern Cooperative Oncology Group performance status of 0–2. All patients had at least one of these pathologic features: capsular perforation, positive surgical margins, seminal vesicle invasion, and pelvic lymph nodes involvement. A minimum dose of 64.8 Gy to the tumor bed was delivered in all patients. Depending on tumor characteristics at diagnosis, patients received a higher dose (70.2 Gy; 85.4%) and/or prophylactic pelvic lymph nodes irradiation (57.7%) and/or HT (69.1%). Biochemical relapse was defined as two consecutive rising prostate-specific antigen (PSA) values > 0.2 ng/ml.ResultsA total of 123 patients were enrolled in the study and completed the scheduled treatment. Median preoperative and postoperative PSA were: 8.8 and 0.06 ng/mL, respectively. The percentages of patients with pathologically involved nodes and positive resection margins were: 14.6% and 58.5%, respectively. With a median follow-up of 67 months (range: 37–120 months), the actuarial 5-year bDFS, local control, metastasis-free survival, and overall survival (OS) were: 92.9%, 98.7%, 96.1%, and 95.1%, respectively.ConclusionA higher 5-year bDFS (92.9%) was recorded compared to studies based on standard adjuvant RT, even though patients with nodal disease and detectable postoperative PSA were enrolled. Clinical end points, as long-term disease-free survival and OS, will require further assessments. (ClinicalTrials.gov: NCT03169933)

Novel Clinical Tools to Guide Management of Prostate Cancer: Preoperative Predictive Models to Identify Patients at Risk for Needing Adjuvant Radiation (T3 or +margin) or Having Detectable Postoperative PSA

Several valuable models use preoperative data to predict organ- confined disease at the time of radical prostatectomy. However, there are no similar tools to predict which patients will qualify for adjuvant radiation therapy (ART), or have a detectable postoperative prostate specific antigen (PSA). We developed logistic regression models to predict risk for extracapsular extension (ECE) and seminal vesicle invasion (SVI) and compared them to others (Roach, CAPRA, Memorial Sloan Kettering, and Partin models). We then created two novel formulas to predict risk for ART (either T3 or +margin) or detectable postoperative PSA. We conducted a retrospective multi-institutional review of patients with clinically localized prostate adenocarcinoma who had radical prostatectomy from 2001-2015 (N=1,676) at Kaiser Permanente in Southern California. Patients treated with preoperative leuprolide or missing data were excluded. Three multivariate models were developed to predict ECE, SVI, and either ECE or SVI. A fourth model was developed to predict ECE/SVI/+margin. A fifth model was developed to predict detectable postoperative PSA (≥0.1). The area under the receiver curve (AUC) was calculated and corrected using bootstrap resampling with 2000 samples. Statistical analysis was performed with R version 3.3.1. Statistically significant factors on multivariate analysis included percent positive biopsy cores, biopsy Gleason score, PSA, and clinical T-stage. Age and year of surgery were not statistically significant. The ECE, SVI, and ECE/SVI models (AUC 0.69-0.81) performed favorably compared to other tools (AUC 0.72-0.79) [Table 1]. Our T3/+margin model performs at corrected AUC 0.75. Our detectable postoperative PSA model performs at corrected AUC 0.81 [Table 1]. We developed three models predicting risk of extraprostatic disease, which compared favorably over other widely used models. We created two novel clinical formulas to predict preoperatively whether patients may require ART or have a detectable postoperative PSA. These tools may help guide the selection of surgery or radiation upfront, and could potentially reduce dual modality treatment. While our novel clinical prediction models performed well in our data set, no known tools exist for comparison, and external validation is needed.Abstract 2630; Table 1RoachCAPRAMSKPartinKaiserECE (25% risk) AUC0.740.740.760.720.69 Sen/Spec1.00/00.63/0.701.00/00.87/0.460.37/0.91 PPV/NPV0.22/ NA0.39/0.860.22/0.830.31/0.920.54/0.84SVI (25% risk) AUC0.760.780.790.760.81 Sen/Spec0.47/0.850.22/0.960.28/0.960.03/0.990.39/0.94 PPV/NPV0.27/0.930.39/0.910.47/0.920.40/0.900.42/0.93ECE/SVI (40% risk) AUC---0.760.79 Sen/Spec---0.64/0.720.52/0.86 PPV/NPV---0.48/0.830.61/0.82ECE, SVI, or +margin (20% risk) AUC----0.75 Sen/Spec----0.91/0.35 PPV/NPV----0.44/0.87Detectable 1st Postop PSA (20% risk) AUC----0.81 Sen/Spec----0.36/0.95 PPV/NPV----0.34/0.96 Open table in a new tab

Does Early Prostate Specific Antigen Doubling Time after Radical Prostatectomy, Calculated Prior to Prostate Specific Antigen Recurrence, Correlate with Prostate Cancer Outcomes? A Report from the SEARCH Database Group

Short prostate specific antigen doubling time following recurrence after radical prostatectomy portends a poor prognosis. Prostate specific antigen doubling time is traditionally calculated using prostate specific antigen values 0.2 ng/ml or greater. We determined whether early prostate specific antigen doubling time, calculated from the first detectable postoperative prostate specific antigen up to and including the first recurrence value, correlates with prostate cancer outcomes. Cox models were used to examine the association between early prostate specific antigen doubling time and castration resistant prostate cancer, metastases, and all cause and prostate cancer specific mortality in 674 men who underwent radical prostatectomy between 1988 and 2014 and had a biochemical recurrence. Early prostate specific antigen doubling time was examined as a log transformed continuous and a categorical variable. After adjusting for multiple clinicopathological characteristics, log transformed early prostate specific antigen doubling time was not associated with any outcome. However, when early doubling time was categorized as 15 or greater, 9 to 14.9, 3 to 8.9 and less than 3 months, on multivariable analysis men with early doubling time less than 3 months were at increased risk for castration resistant prostate cancer (HR 6.20, p = 0.004), metastases (HR 5.26, p = 0.001), prostate cancer specific mortality (HR 5.06, p = 0.026) and all cause mortality (HR 1.63, p = 0.065) compared to those with an early doubling time of 15 months or greater. However, the association with all cause mortality was not significant. Those with an early prostate specific antigen doubling time of 3 to 8.9 months were at increased risk for castration resistant prostate cancer (HR 3.56, p = 0.015), all cause mortality (HR 1.67, p = 0.006) and prostate cancer specific mortality (HR 3.17, p = 0.044) but not metastases (p = 0.13). Early prostate specific antigen doubling time less than 9 months, calculated using prostate specific antigen values before and up to biochemical recurrence, is associated with an increased risk of castration resistant prostate cancer, metastases, and prostate cancer specific and all cause mortality among men with biochemical recurrence after radical prostatectomy. Early prostate specific antigen doubling timeallows for risk stratification at biochemical recurrence and before prostate specific antigen doubling timeis calculable, enabling these men to be referred for early aggressive secondary treatment and/or clinical trials.

Radiotherapy of prostate cancer

Radiotherapy(RT) is one of the principle treatment options for prostate cancer. Modern RT and surgery show similar progression-free survival in localized prostate cancer. Adjuvant RT compared to observation significantly diminishes the risk of prostate-specific antigen(PSA) progression and local failure for patients at the highest risk for recurrence after radical prostatectomy, including with seminal vesicle invasion, extraprostatic extension, extensive positive margins, and detectable postoperative PSA. Salvage RT is effective at controlling local recurrence and reduces the risk of distant metastasis and prostate cancer-specific mortality (PCSM) for patients with PSA or local recurrence after prostatectomy. Hypofractionated radiotherapy of recent years' reports shows similar cancer control rates without an increased risk of late toxicity in comparison to conventional regimens. The addition of androgen-deprivation therapy(ADT) to radiation improves the overall survival and biochemical progression-free survival(bPFS) for intermediate-risk and high-risk patients. Key words: Prostatic neoplasms; Radiotherapy(RT); Adjuvant radiotherapy; Salvage radiotherapy; Hypofractionated radiotherapy

Adjuvant and salvage radiotherapy after prostatectomy: American Society of Clinical Oncology clinical practice guideline endorsement.

To endorse the American Urological Association (AUA)/American Society for Radiation Oncology (ASTRO) guideline on adjuvant and salvage radiotherapy after prostatectomy. The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing clinical practice guidelines developed by other professional organizations. The guideline on adjuvant and salvage radiotherapy after prostatectomy was reviewed for developmental rigor by methodologists. An ASCO endorsement panel then reviewed the content and recommendations. The panel determined that the guideline recommendations on adjuvant and salvage radiotherapy after prostatectomy, published in August 2013, are clear, thorough, and based on the most relevant scientific evidence. ASCO endorsed the guideline on adjuvant and salvage radiotherapy after prostatectomy, adding one qualifying statement that not all candidates for adjuvant or salvage radiotherapy have the same risk of recurrence or disease progression, and thus, risk-benefit ratios are not the same for all men. Those at the highest risk for recurrence after radical prostatectomy include men with seminal vesicle invasion, Gleason score 8 to 10, extensive positive margins, and detectable postoperative prostate-specific antigen (PSA). Physicians should discuss adjuvant radiotherapy with patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invasion, positive surgical margins, extraprostatic extension) and salvage radiotherapy with patients with PSA or local recurrence after prostatectomy. The discussion of radiotherapy should include possible short- and long-term adverse effects and potential benefits. The decision to administer radiotherapy should be made by the patient and multidisciplinary treatment team, keeping in mind that not all men are at equal risk of recurrence or clinically meaningful disease progression. Thus, the risk-benefit ratio will differ for each patient.

The PROCAINA (PROstate CAncer INdication Attitudes) Project (Part I): a survey among Italian radiation oncologists on postoperative radiotherapy in prostate cancer

Radiotherapy (RT) has an established role in the postoperative treatment of prostate cancer patients with extracapsular extension, positive surgical margins or a detectable post-operative prostate-specific antigen (PSA). Despite the large number of patients treated with postoperative RT, some issues about optimal technique, doses, volumes, timing and association with androgen deprivation are still subject of debate. The aim of this survey was to determine the patterns of choice of Italian radiation oncologists in two different clinical cases of postoperative prostate cancer patients. During the 2010 National Congress of the Italian Association of Radiation Oncology (AIRO), four clinical cases were presented to the attending radiation oncologists. Two of them were cases of postoperative prostate cancer, differing in T stage of the primary tumour according to the TNM classification, preoperative staging procedures, preoperative PSA (iPSA), Gleason score of biopsies and definitive pathological specimen after surgery and postoperative PSA. For each clinical case, the radiation oncologists were asked to: (a) give indication to new pre-treatment procedures for staging; b) give indication to postoperative treatment; (c) to define specifically, where indicated, the total dose, type of fractionation, treatment volumes, type of technique, type of image-guided setup control; (d) indicate whether adjuvant hormonal therapy should be prescribed; (e) define criteria that mostly influenced the prescription. A descriptive statistical analysis was then performed. A total of 300 questionnaires were distributed amongst radiation oncologists attending the congress; 128 were completed and considered for this analysis (41%). Some important differences were shown in prescribing and performing postoperative radiotherapy, and some significant differences with international guidelines and data available from the literature were also reviewed and discussed. Despite the results of clinical trials, significant differences still exist among Italian radiation oncologists in deciding postoperative treatment in prostate cancer patients. These patients probably deserve a more uniform approach based on updated, detailed and evidence-based recommendations.

Identifying Node-Positive Prostate Cancer Patients Who May Benefit From Adjuvant Pelvic Radiation Following Prostatectomy

Identifying Node-Positive Prostate Cancer Patients Who May Benefit From Adjuvant Pelvic Radiation Following Prostatectomy

Seminal vesicle invasion: what is the best adjuvant treatment after radical prostatectomy?

• To evaluate the biochemical-failure free survival according to different adjuvant treatments in patients who underwent radical prostatectomy (RP) with seminal vesicle invasion (SVI). • Between 1994 and 2008, 4090 men underwent RP in nine centres. Of these, 310 men had a SVI. • Exclusion criteria were: detectable postoperative prostate-specific antigen, lymph node metastases and follow-up <18 months. • Therefore, the study group included 199 patients. Of these, 41 received adjuvant radiotherapy (RT) only, 26 received adjuvant androgen deprivation therapy (ADT) only, 50 received adjuvant ADT combined with RT and 82 were monitored. The endpoint for this analysis was biochemical no evidence of disease (bNED). • Preoperative prostate-specific antigen level, specimen Gleason score, age, clinical stage, surgical margin status and adjuvant treatment were evaluated in a multivariable analysis with respect to bNED survival. • After a mean (range) follow-up of 60.3 (18-185) months, 88 (44.2%) patients had a biochemical relapse. • The estimated 5- and 7-year bNED survival were 32.6% and 25.9% for the observation group, 44.4% and 28.6% for the RT only group, 48.4% and 32.3% for the ADT only group and 82.8% and 62.1% for the adjuvant ADT combined with RT group. • On multivariate analysis, only adjuvant ADT combined with RT (P < 0.001) was an independent prognostic factor of biochemical relapse. • RP appeared to be insufficient as a single treatment for patients with SVI. • The findings of the present study suggest that adjuvant ADT combined with RT after RP for patients with SVI confers a substantial benefit on 5-year bNED survival.

Persistently elevated prostate-specific antigen at six weeks after radical prostatectomy helps in early identification of patients who are likely to recur

To determine the prognostic factors of biochemical recurrence in patients who failed to achieve an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP) for prostate cancer. We reviewed data on 240 men who underwent RP as first-line treatment and who had a PSA assay available at 6 weeks after surgery. Persistent detectable PSA was defined as a PSA level ≥ 0.1 ng/ml at 6 weeks after surgery. Overall, 83 men presented persistently elevated PSA after RP and 81 had a biochemical recurrence. Median follow-up was 44 months. In univariate analysis, these factors were associated with biochemical recurrence: preoperative PSA level (P < 0.0001), biopsy and pathologic Gleason score (P < 0.001), capsular involvement (P = 0.0001), positive surgical margins (P < 0.0001), pathological stage ≥ T3 (P = 0.0001), and detectable post-operative PSA ≥ 0.1 ng/ml (P = 0.0001). In a multivariate analysis, only the detectable post-operative PSA level ≥ 0.1 ng/mL (P = 0.001), positive surgical margins (P = 0.002), and pathological stage ≥ T3 (P < 0.001) were significant. The individual, five-year, PSA-free survival rate for men with post-operative PSA <0.1 ng/ml and ≥ 0.1 ng/ml were 59 and 42%, respectively (P < 0.001). A majority of patients who failed to achieve an undetectable PSA after surgery had a subsequent biochemical recurrence in the outcome. A systematic PSA assay 6 weeks after RP could be useful to early identify patients who are likely to recur.

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.

Prospective Study Evaluating Postoperative Radiotherapy Plus 2-Year Androgen Suppression for Post–Radical Prostatectomy Patients With Pathologic T3 Disease and/or Positive Surgical Margins

To determine the efficacy of a combined approach of postoperative radiotherapy (RT) plus 2-year androgen suppression (AS) for patients with pathologic T3 disease (pT3) and/or positive surgical margins (PSM) after radical prostatectomy (RP). A total of 78 patients with pT3 and/or PSM after RP were treated with RT plus 2-year AS, as per a pilot, prospective study. Androgen suppression started within 1 month after the completion of RT and consisted of nilutamide for 4 weeks and buserelin acetate depot subcutaneously every 2 months for 2 years. Relapse-free rate, including freedom from prostate-specific antigen (PSA) relapse, was estimated using the Kaplan-Meier method. A Cox regression analysis was performed to evaluate prognostic factors for relapse. Prostate-specific antigen relapse was defined as a PSA rise above 0.2 ng/mL, with two consecutive increases over a minimum of 3 months. The median age was 61 years at the time of RP. The median interval between RP and postoperative RT was 4.2 months. Forty-nine patients had undetectable PSA (<0.2 ng/mL), and 29 had persistently detectable postoperative PSA at the time of the protocol treatment. Median follow-up from RT was 6.4 years. Relapse-free rates at 5 and 7 years were 94.4% and 86.3%, respectively. Survival rates were 96% at 5 years and 93.1% at 7 years. On Cox regression analysis, persistently detectable postoperative PSA and pT3b-T4 were significant predictors for relapse. The combined treatment of postoperative RT plus 2-year AS yielded encouraging results for patients with pT3 and/or PSM and warrants a confirmatory study.

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.

Defining the ideal cutpoint for determining PSA recurrence after radical prostatectomy

Objectives To determine the ideal cutpoint for defining prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). Although various cutpoints have been used, a recent study suggested that 0.4 ng/mL may be the most appropriate. Methods A retrospective survey of 358 men undergoing RP at the West Los Angeles Veterans Affairs Medical Center between 1991 and 2001 was undertaken. The 3-year and 5-year risk of PSA recurrence was estimated by Kaplan-Meier analyses using various cutpoints of postoperative PSA to define recurrence: greater than 0.1, greater than 0.2, greater than 0.3, greater than 0.4, and greater than 0.5 ng/mL. The 1 and 3-year risk of PSA progression after a detectable PSA level (PSA rising to a higher cutpoint) was evaluated for each definition of PSA recurrence using Kaplan-Meier analyses. Multivariate analysis using a Cox proportional hazards model was used to determine the clinical variables that were significant independent predictors of PSA recurrence at each cutpoint. Results For patients with a detectable postoperative PSA value from 0.11 to 0.2 ng/mL, the 1 and 3-year risk of PSA progression was 64% (95% confidence interval [CI] 46% to 82%) and 93% (95% CI 74% to 99%), respectively. For patients with a PSA value from 0.21 to 0.3 ng/mL, the 1 and 3-year risk of PSA progression was 86% (95% CI 69% to 97%) and 100% (95% CI 87% to 100%), respectively. The use of higher PSA cutpoints to define recurrence resulted in a lower 5-year risk of PSA recurrence. The 5-year risk of PSA recurrence using a greater than 0.1 ng/mL cutpoint resulted in a 43% (95% CI 36% to 50%) risk of recurrence compared with only 23% (95% CI 18% to 30%) for a greater than 0.5 ng/mL cutpoint. In multivariate analysis, PSA and biopsy Gleason score were significant independent predictors of biochemical recurrence, regardless of the definition of PSA recurrence used ( P ≤0.002). Conclusions PSA and biopsy Gleason score were significant predictors of biochemical failure, regardless of the definition of failure used. However, the definition of PSA recurrence dramatically affected the perceived success of therapy. Patients with a postoperative PSA value greater than 0.2 ng/mL are at very high risk of developing an additional rise in PSA. On the basis of this finding, a PSA value greater than 0.2 ng/mL is an appropriate cutpoint to define PSA recurrence after RP.

(IN)-efficacy of salvage radiotherapy for rising PSA or clinically isolated local recurrence after radical prostatectomy

Purpose: To determine the efficacy of external beam radiotherapy (RT) as salvage treatment for prostate-specific antigen (PSA) failure or local recurrence after radical prostatectomy.Methods and Materials: Between 1991 and 1997, 98 patients underwent salvage RT to the prostatic bed at the Toronto Sunnybrook Regional Cancer Centre for PSA failure or local recurrence after radical prostatectomy. Thirty-six patients were treated for persistently detectable postoperative PSA levels (Group A), 26 for a delayed PSA rise (Group B), and 36 for palpable and/or biopsy-proven local recurrence (Group C). None had clinically apparent distant metastasis at the time of salvage RT. Freedom from PSA failure was defined as the maintenance of PSA ≤0.2 ng/mL. Cox regression analyses were performed to identify factors predictive of relapse.Results: The median follow-up from radical prostatectomy and RT was 5.11 and 4.21 years for Group A, 5.31 and 3.32 years for Group B, and 7.85 and 3.95 years for Group C, respectively. The initial PSA response rate was encouraging at a range of 86—94%. The complete PSA response rate (PSA ≤0.2 ng/mL) was lower, however and ranged from 53% to 62%. The actuarial relapse-free rate, including freedom from PSA failure, at 4 years was 26%, 39%, and 14% for Groups A, B, and C, respectively. At the time of the last follow-up, 49, 20, and 1 patient had PSA failure alone, distant metastasis, and local progression, respectively. The actuarial survival rate at 4 years was 89%, 95%, and 94% for Groups A, B, and C, respectively. On Cox regression analysis, the significant predictors for relapse were PSA level before salvage RT and Gleason score for Group A, none for Group B, and margin status for Group C.Conclusion: The efficacy of salvage RT for PSA failure or local recurrence after RT was limited, reflected by very low relapse-free rates. Salvage RT appeared more efficacious for patients with a delayed PSA rise than for those with either persistently detectable postoperative PSA levels or clinically palpable local recurrence. Other strategies such as a combination of salvage RT and hormonal therapy need to be explored.

Salvage radiotherapy after radical prostatectomy for prostate adenocarcinoma: analysis of efficacy and prognostic factors

Objectives. To determine the probability of biochemical control for patients treated with salvage irradiation and identify prognostic factors associated with successful salvage. The optimal management of prostate cancer in patients with an elevated prostate-specific antigen (PSA) level after radical prostatectomy remains unclear. Methods. We reviewed the records of 54 patients with node-negative prostate cancer treated with radiotherapy alone between 1991 and 1998 for isolated biochemical relapse after prostatectomy. The median preoperative PSA level was 15 ng/mL, and the median salvage PSA level was 1.3 ng/mL. Complete pathologic information was recorded, as was the interval to postoperative PSA failure. Radiotherapy was delivered to the prostatic fossa using appropriate techniques. The primary endpoint was biochemical failure, measured from radiotherapy initiation to the first detectable PSA level. Biochemical control rates were determined using Kaplan-Meier methods. The median follow-up was 45 months. Results. The initial complete response rate was 76%. Only seminal vesicle status demonstrated borderline significance for the rate of the initial complete response. The 5-year actuarial biochemical control rate was 35%. The presence of seminal vesicle invasion, Gleason score greater than 6, and an immediately detectable postoperative PSA level all predicted for decreased 5-year biochemical control. Gleason score and detectable postoperative PSA retained significance on multivariate analysis. Those with a salvage PSA level of 1.2 ng/mL or less had a trend toward a decreased 5-year biochemical control rate ( P = 0.07). Conclusions. Salvage radiotherapy yields a 76% complete response rate, with 35% of treated patients free of a detectable PSA at 5 years. Those with favorable biochemical and pathologic tumor features are most likely to remain disease free.

8p22> loss concurrent with 8c gain is associated with poor outcome in prostate cancer

Objectives. A critical issue in the management of prostate cancer is the ability to distinguish patients at risk of disease recurrence. The aim of this study was to determine whether specific physical alterations of chromosome 8 may be associated with disease recurrence and poor outcome using postoperative prostate-specific antigen (PSA) values as surrogate end points. Methods. To test this hypothesis, we examined paired normal and tumor radical prostatectomy tissues from 25 patients with prostate cancer for chromosome 8 alterations using dual fluorescence in situ hybridization with a fluorescein-labeled 8p22-specific (8p) cosmid probe and a rhodamine-labeled 8-centromere-specific (8c) probe. The probes were enumerated in 200 nuclei per tissue. Results. Of the 25 tumors examined, 22 demonstrated distinct classes of genetic alterations, or nuclear types, including disomy for 8p and 8c (1 tumor), loss of 8p and disomy for 8c (10 tumors), or loss of 8p concurrent with gain of 8c (11 tumors). The presence of even a small population of tumor nuclei characterized by the loss of 8p concurrent with the gain of 8c was correlated with poor tumor grade ( P = 0.009), preoperative PSA values 11 ng/mL or higher ( P = 0.022), high tumor stage ( P = 0.086), and detectable, rising postoperative PSA values ( P = 0.086). These observations are consistent with the hypothesis that a gain of chromosome 8 is associated with poor outcome in prostate cancer. Conclusions. 8p loss concurrent with 8c gain may successfully predict disease recurrence and poor clinical outcome before the observation of detectable postoperative PSA values in patients with prostate cancer.

Patterns of Positive Specimen Margins and Detectable Prostate Specific Antigen After Radical Perineal Prostatectomy

Positive specimen margins and detectable postoperative prostate specific antigen (PSA) levels were analyzed after 200 consecutive radical perineal prostatectomies for clinical stages T1 and T2 adenocarcinoma of the prostate. Clinical parameters that correlated with lymph node metastases in concomitant pelvic lymphadenectomies were also noted. At a mean followup of 35 months 79 percent of the patients had undetectable PSA levels. Step-section pathological analysis of specimens obtained by either nerve sparing or extended radical modifications revealed that 41 percent of the tumors were organ confined and 56 percent had negative margins. Selective sacrifice of the posterolateral periprostatic fascia and the enclosed neurovascular bundle achieved negative margins and undetectable PSA levels despite capsular penetration in 15 percent of all patients. Of all positive margins with the perineal approach, solitary positive apical and posterolateral margins were infrequent (7 percent and 16 percent, respectively) but solitary positive anterior margins were more so (25 percent). Of those positive anterior margins 41 percent appeared to be artifactual and 45 percent might have been eliminated by avoiding avulsion of the puboprostatic ligaments. Pelvic lymphadenectomy could have been eliminated in 58 percent of the patients (clinical stage T2b or less, biopsy Gleason score 6 or less and PSA level 11 or less, for a node negative predictive value of 99 percent).

Effect of Radiation Therapy on Detectable Serum Prostate Specific Antigen Levels Following Radical Prostatectomy: Early Versus Delayed Treatment

Radiation therapy may be beneficial after radical prostatectomy in some patients with pathological stage C prostate cancer and in those with detectable postoperative prostate specific antigen (PSA) levels. A total of 64 men underwent postoperative radiation therapy following radical prostatectomy for pathological stage C disease (27), a detectable serum PSA level (11) or both conditions (26). Of the 27 men treated prophylactically for pathological stage C disease 18 (67%) had no evidence of recurrence after radiation within the first 6 months postoperatively (median followup 40 months, range 17 to 97). Of 22 men treated for delayed PSA elevation 15 (68%) currently are disease-free (median followup 27.5 months, range 15 to 47). Of 15 men treated within the first 6 months after radical prostatectomy for persistently detectable PSA levels 8 (53%) had an initial decrease in PSA to undetectable levels but only 5 (33%) had a durable complete response (median followup 36 months, range 8 to 56). We conclude that patients with pathological stage C disease who are most likely to benefit from postoperative radiation therapy are those with initially undetectable postoperative PSA levels. We observed no striking difference in treatment outcome between early and delayed adjuvant radiation therapy.