Preradiotherapy Prostate-specific Antigen Research Articles

Prostate-specific membrane antigen-based imaging for stereotactic irradiation of low-volume progressive prostate cancer: a single-center experience.

Prostate-specific membrane antigen (PSMA) is a transmembrane protein that may be expressed on the surface of prostate cancer (PC) cells. It enables a more sensitive and specific diagnosis PC, compared to conventional anatomical imaging. The integration of PSMA-based imaging in the personalized radiotherapy of PC patients and the evaluation of its impact on target volume definition if stereotactic body radiotherapy (SBRT) is planned for locally recurrent or oligometastatic disease. The data from 363 examinations were analyzed retrospectively. Inclusion criteria were histologically verified PC and clinical data suggesting local recurrence or distant metastasis. Whole-body 99mTc-PSMA-I&S single-photon emission computed tomography (SPECT)/CT or 18F-JK-PSMA-7 positron emission tomography/computer tomography (PET/CT) was carried out, and the evaluation of the scans and biological tumor volume contouring was performed at the Department of Nuclear Medicine. The target volume delineation on topometric CT (TCT) scan was performed at the Department of Oncotherapy. The comparison of the two volumes was performed by image fusion and registration. From 363 PSMA isotope-based examinations, 84 lesions of 64 patients were treated with SBRT. In 50 patients, 70 lesions were examined for intermodality comparison. The target volume defined by the PSMA density was significantly smaller than the tumor size defined by the TCT scan: GTVCT (gross tumor volume on the TCT), 27.58 ± 46.07 cm3; BTVPSMA (biological target volume on the PSMA-based examination), 16.14 ± 29.87 cm3. During geometrical analyses, the Dice similarity coefficient (DSC) was 0.56 ± 0.20 (0.07-0.85). Prostate-specific antigen (PSA) control was performed to evaluate the response: mean pre-radiotherapy (pre-RT) PSA was 16.98 ng/ml ( ± SD: 33.81), and post-RT PSA at 3 months after SBRT was 11.19 ng/ml ( ± SD: 32.85). Three-month post-therapy PSMA-based imaging was performed in 14 cases, in which we observed a decrease or cessation of isotope uptake. Conventional imaging control was performed in 42 cases (65.6% of all cases): 22 (52.4%) complete remissions, 14 (33.3%) partial remissions, four (9.5%) stable diseases, and two (4.8%) progressive diseases were described. PSMA-based imaging is a promising diagnostic method for specifying the stage and detecting the low-volume progression. Our results suggest that PSMA-based hybrid imaging can influence treatment decisions and target volume delineation for SBRT.

Clinical Outcome of Salvage Radiotherapy for Locoregional Clinical Recurrence After Radical Prostatectomy.

Objectives: To assess the clinical outcomes of prostate cancer patients treated with salvage radiotherapy (SRT) for locoregional clinical recurrence (CR) after radical prostatectomy (RP). Methods: Records of 60 patients with macroscopic locoregional recurrence after prostatectomy and referrals for SRT were retrospectively investigated in the multi-institutional database. The median radiation dose was 70.2 Gy. Biochemical failure was defined as the prostate-specific antigen (PSA) ≥ nadir + 2 or initiation of androgen deprivation therapy (ADT) for increased PSA. Results: Median recurrent tumor size was 1.1 cm and pre-radiotherapy PSA level was 0.4 ng/ml. At a median follow-up of 83.1-month after SRT, 7-year biochemical failure-free survival (BCFFS), locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), and overall survival (OS) were 67.0%, 89.7%, 83.6%, and 91.2%, respectively. Higher Gleason's scores were associated with unfavorable BCFFS, DMFS, and OS. Pre-SRT PSA ≥0.5 ng/ml predicted worse BCFFS, LRFFS, and DMFS. In multivariate analyses, a Gleason's score of 8 to 10 was associated with decreased BCFFS (hazard ratio [HR] 3.12, 95% confidence interval [CI] 1.11-8.74, P = .031) and OS (HR 17.72, 95% CI 1.75-179.64, P = .015), and combined ADT decreased the risks of distant metastasis (HR 0.18, 95% CI 0.04-0.92, P = .039). Two patients (3.3%) experienced late grade 3 urinary toxicity. Conclusions: SRT for locoregional CR after RP achieved favorable outcomes with acceptable long-term toxicities. Higher Gleason's scores and pre-radiotherapy PSA level were unfavorable prognostic variables. Combined ADT may decrease the risks of metastases.

Post-Prostatectomy Radiotherapy in a Single Tertiary Institution: Outcomes Relating to Pre-Radiotherapy Prostate Specific Antigen

Objective: Timing of post-radical prostatectomy (RP) radiotherapy (RT) in patients with high risk prostate cancer continues to be debated. This is a retrospective review aiming to evaluate the influence of pre-RT prostate specific antigen (PSA) values on postprostatectomy RT outcomes in one Australian center. Method: Eligible patients were treated at the Royal Adelaide Hospital between January 2004 and December 2013, excluding those with nodal or distant metastatic disease pre-RT, or those who received neoadjuvant androgen deprivation therapy pre-RT. The primary endpoint of biochemical failure-free survival (bFFS) was defined as time from RP to date of biochemical failure (bF). Covariates of Gleason score, post-RP PSA, and pre-RT PSA were further analysed in relation to bFFS. Results: 103 of 122 patients underwent final analysis (8 were excluded for the above reasons; 11 had missing data). Median follow-up from RP was 60 months. Kaplan-Meier (KM) estimates of 1, 2, 3, 4 and 5-year survival probabilities were 93.5%, 83.4%, 82.4%, 76.6% and 71% respectively. There was no statistically significant correlation between bFFS and pathological T-stage (p=0.1), surgical margin involvement (p=0.7), or RT total dose (p=0.8). Analysis based on KM survival distributions and log-rank tests suggest that pathological Gleason score may have some influence on bFFS (p=0.04). Doubling the pre-RT PSA whilst holding all other factors and covariates constant, increases the hazard of bF at a particular time-point by approximately 19% on average. Conclusion: This single-institution retrospective study provides reasonable evidence for influence of pre-RT PSA on post-RP RT outcomes, arguing for earlier referral for RT.

Pre-radiotherapy PSA progression is anegative prognostic factor in prostate cancer patients using 5‑alpha-reductase inhibitors.

To investigate the impact of 5‑alpha-reductase inhibitor (5-ARI) use on radiotherapy outcomes for localized prostate cancer. We included 203patients on a5-ARI from our institutional database comprising over 2500patients who had been treated with either external beam radiotherapy (EBRT) or brachytherapy for localized prostate cancer. Patients received a5-ARI for urinary symptoms or active surveillance. Cancer progressions at the time of definitive treatment were analyzed according to the following criteria:(a) progression of Gleason score or increase in cancer volume on biopsy, (b)first biopsy positive for cancer after being treated for urinary symptoms with a5-ARI, and (c)prostate-specific antigen (PSA) progression with or without aprevious cancer diagnosis. Biochemical failure (BF) was defined by the Phoenix definition. Log-rank test was used for survival analysis. At amedian follow-up of 38.2months (standard deviation 22.2months), 10(4.9%) patients experienced BF. Concerning prostate cancer progression criteria, 52% of men demonstrated none, 37% showed only one criterion, and 11% showed two. Using univariate analysis, PSA progression (p= 0.004) and appearance of apositive biopsy (p< 0.001) were significant predictive factors for BF, while Gleason progression (p= 0.3) was not. In multivariate analysis adjusted for cancer aggressiveness, rising PSA (hazard ratio, HR,5.7; 95% confidence interval, CI,1.1-28.8; p= 0.04) and the number of cancer progression factors (HR2.9, 95%CI1.2-7.0, p= 0.02) remained adverse risk factors. PSA progression experienced during 5‑ARI treatment before radiotherapy is predictive of worse biochemical outcome. Such details should be considered when counseling men prior to radiation therapy.

Post-prostatectomy salvage radiation therapy in prostate cancer upon identification of biochemical failure.

127 Background: Prostate Specific Antigen (PSA) values post-prostatectomy are used as an indication for salvage radiation therapy. It has been suggested that initiation of therapy at lower PSA values lead to better outcomes. This study investigates outcomes of salvage radiation therapy at specific PSA thresholds. Methods: One hundred two prostate cancer patients were treated with salvage radiotherapy at our institution with curative intent, 19 of whom had Gleason score ≤6, 52 of whom had Gleason 7, and 31 with Gleason ≥8. Median follow-up after radiotherapy was 51 months. The median PSA prior to salvage radiotherapy was 0.33 ng/mL, and the median time from prostatectomy to radiotherapy was 24.6 months. Positive margins were identified in 52 patients, and perineural invasion was positive in 83. The median dose delivered was 64.8 Gy. Results: The 5-year actuarial freedom from biochemical failure rates for NCCN low, intermediate, and high risk groups were 100%, 77%, and 62%, p=0.2449. The 5-year actuarial freedom from biochemical failure rates for Gleason score ≤6, Gleason 7, and Gleason ≥8 patients were 87%, 72%, and 49%, p=0.0187. Patients with pre-radiotherapy PSA ≤0.5 ng/mL had better 5-year biochemical control relative to patients with higher pre-radiotherapy PSA, 76% versus 51%, p=0.0211. The pathological margin status did not predict for biochemical control after salvage radiation across the different Gleason grades. Very few interval biochemical failures are observed after the 5-year point of follow-up. The 5-year overall survival for the entire cohort is 92%, with prostate cancer specific survival of 96%. Conclusions: Salvage radiotherapy demonstrated favorable efficacy with durable PSA control and few failures 5 years post radiation. Initiation of salvage radiotherapy for PSA ≤0.5 ng/mL demonstrated improved biochemical control, supporting the adoption of early referral to radiation oncology once post-prostatectomy biochemical failure is identified. [Table: see text]

Hypofractionated External Beam Radiotherapy to Boost the Prostate with ≥85 Gy/Equivalent Dose for Patients with Localised Disease at High Risk of Lymph Node Involvement: Feasibility, Tolerance and Outcome

AimsTo evaluate the tolerance and preliminary outcome of prostate cancer patients at high risk of lymph node involvement treated with normofractionated whole pelvic radiotherapy (WPRT) followed by a hypofractionated boost to the prostate with an intensity-modulated radiotherapy (IMRT) technique. Materials and methodsBetween 2004 and 2011, 78 T1-4N0M0 prostate cancer patients at high risk of lymph node involvement (70 patients with a Roach index ≥ 15%; 57 with T-stage ≥ 3a; 40 with Gleason score ≥ 8) underwent WPRT to a median normofractionated dose of 50.4 Gy (range 48.0–50.4 Gy) with conformal three-dimensional techniques for most patients. A 24 Gy boost (4 Gy/six fractions, twice weekly) was delivered to the prostate with IMRT. The total median delivered dose was 74.4 Gy, equivalent to 85.2 Gy in 2 Gy/fractions (α/β = 1.5 Gy). All patients underwent androgen deprivation for a total median time of 10.8 months. The maximum gastrointestinal and genitourinary acute and late toxicity scores were recorded according to the Radiation Therapy Oncology Group scoring system. ResultsAll patients completed treatment as planned. Only 1% of patients presented with grade 3 genitourinary or gastrointestinal acute toxicity and none scored ≥ grade 4. With a median follow-up of 57 months, the 5 year probability of late grade ≥2 genitourinary and gastrointestinal toxicity-free survival was 79.1 ± 4.8% and 84.1 ± 4.5%, respectively. The 5 year biochemical disease-free survival, local relapse-free survival and distant metastasis-free survival were 84.5 ± 4.5%, 96.0 ± 2.8% and 86.4 ± 4.4%, respectively. A pre-radiotherapy prostate-specific antigen ≤0.3 ng/ml was associated with a better 5 year biochemical disease-free survival (P = 0.036) and distant metastasis-free survival (P = 0.049). ConclusionsThe use of a hypofractionated IMRT boost after WPRT may allow a minimally invasive dose escalation to successfully treat patients with non-metastatic prostate cancer at high risk of lymph node involvement. Higher prostate-specific antigen values before radiotherapy may require alternative adjuvant treatments to further optimise the outcome of this high-risk group of patients.

Comparison of calcaneal bone density in operative versus non-operative army personnel

Purpose: To study the response of nonmalignant prostatic tissue to ionizing irradiation in terms of the resultant changes in serum prostate specific antigen (PSA) levels.Methods and Materials: Weekly serum PSA values were determined during radiotherapy (RT)_in nine patients (“treatment group”) without clinical evidence of prostate cancer (PC), and who received pelvic RT for other indications. Slopes fr the rate of change in PSA was determined using model: log PSA = β0 + β1∗week + β2∗week2 + error. These results are compared with 17 normal volunteers (“control group”) who were not exposed to ionizing irradiation. an attempt is made to compare any similarities and differences in subsets of 64 T1–T4NOMO PC patients who received pelvic RT.Results: An elevation in the serum PSA levels were noted in eight of nine patients in the “treatment group” with a median time of 4.2 weeks to reach the maximum serum PSA values. After an initial increase, PSA values declined. In some patients, manifold increase in PSA was noted, for exampel, from 1.8 to 13.5 ng/ml and 3.3 to 9.8 ng/ml in two patients. The PSA increase ranged from 50–650%. The median slope was 0.601 week−1 (range 0.192–3.045 week−1). No such increases were seen in the “control group” (median slope = 0.03 week−1; range, 0.18–0.13 week−1). When diffrences between the mean increase/decrease for each week compared to pretreatment values were analyzed, the irradiated group had statistically significant elevations in the PSA for weeks 3 (p = 0.034), 4 (p = 0.24). A similar ternd of increasing PSA levels during radiotherapy was noted in prostate cancer patients whose initial PSA values were ≤ 20 ng/ml: whereas positive slopes (i.e., increasing PSA levels during radiotherapy course) was seen in 7.1% of those with > 20 ng/ml preradiotherapy PSA values, such trends were seen in52.7% of those with ≤ 20 ng/ml preradiotherapy PSA values.Conclusion: (a) Incidental exposure of noncancerous prostate to ionizing irradiation appears to lead to an initial elevation followed by a decline in serum PSA. (b) Similar elevations in serum (PSA) levels are seen in over 50% of prostate cancer patients with ≤ 20 ng/ml pretreatment PSA. (c) Acinal cell death and sudden release of PSA into the circulation is the most likely explanation for our observations, although other mechanism cannot be excluded. (d) Our observations have to be considered in modeling PSA kinetics induced by RT and in correlating such kinetics to long-term outcomes. (e0 Our findings in the control group indicate that there appears to be no significant variation in serum PSA over many weeks under physiological conditions in normal healthy ambulatory men.

Defining High Risk Prostate Cancer With Risk Groups and Nomograms: Implications for Designing Clinical Trials

Death from prostate cancer is usually preceded by metastases and it usually occurs in men with high risk disease who experienced biochemical failure with a short prostate specific antigen doubling time. We developed a model for determining disease specific survival in prostate cancer. We used the model for defining high risk prostate cancer that was developed by the Radiation Therapy Oncology Group and combined it with the Kattan nomogram for predicting the risk of metastases. We selected 414 Radiation Therapy Oncology Group intermediate and high risk patients who were treated with external beam radiotherapy alone. Excluded were patients with low risk disease. The Kaplan-Meier product limit method was used to estimate the probability of freedom from biochemical failure, overall survival and disease specific survival. A significant difference was observed in freedom from biochemical failure, disease specific survival and overall survival among the 3 tertiles created by the nomogram using the cutoff points less than 8.5%, 8.5% to 15% and greater than 15% (p <0.001, 0.0002 and 0.0003, respectively). Only the risk of metastases using the categorized nomogram score (less than 8.5% and 8.5% to 15% vs greater than 15%), not preradiotherapy prostate specific antigen or Radiation Therapy Oncology Group risk (Radiation Therapy Oncology Group 2 vs 3), was a significant predictor of disease specific and overall survival for intermediate/high risk patients and intermediate/high risk with 15% or less risk for metastases. We combined a risk group stratification scheme for disease specific survival with a nomogram predicting the risk of metastases and created a model that may be useful for designing phase III trials with metastases and disease specific survival as study end points.

E-Cadherin Protein Expression Predicts Prostate Cancer Salvage Radiotherapy Outcomes

Radiotherapy for biochemical prostate cancer recurrence after prostatectomy achieves durable salvage rates of only 40% to 50%. Improved methods of identifying patients unlikely to benefit from salvage radiotherapy are needed. Altered expression of the adhesion molecule E-cadherin may be associated with the invasive and metastatic phenotype. We examined the relationship between E-cadherin expression and outcomes after salvage radiotherapy. E-cadherin expression was examined by immunohistochemistical analysis of a tissue microarray of prostatectomy tissues from patients who underwent salvage radiotherapy. The relation between E-cadherin staining, other risk factors and biochemical failure after salvage radiotherapy was analyzed using Kaplan-Meier and Cox regression methods. Of 37 analyzable cases 25 showed aberrant E-cadherin expression, while the remainder had normal expression. At a median clinical followup of 40 months univariate analysis demonstrated that E-cadherin staining was not associated with Gleason score, extracapsular extension, surgical margin status, pre-prostatectomy or pre-radiotherapy prostate specific antigen, complete biochemical response after radiotherapy or adjunctive hormonal therapy but it was associated with seminal vesicle invasion. Two-year failure-free survival was 55% in patients with aberrant E-cadherin expression compared with 92% in patients with normal E-cadherin expression (p = 0.02). Multivariate analysis confirmed that aberrant E-cadherin expression was associated with salvage radiotherapy failure (p = 0.03). Aberrant E-cadherin staining is associated with increased biochemical failure rates after salvage radiotherapy. Patients with biochemical failure after prostatectomy and aberrant E-cadherin expression are likely to have subclinical disseminated disease. Early systemic therapy may be warranted in these patients.

Current Status of Prostate-Specific Antigen in the Radiotherapeutic Management of Prostatic Cancer.

The current data involving the use of prostate-specific antigen (PSA) in the radiotherapeutic management of localized prostatic cancer is reviewed. Controversies and ongoing debate notwithstanding, a number of general conclusions have been made. (1) PSA as a screening test has increased prostate cancer detection rates and is recommended as part of routine screening to supplement digital rectal examination. (2) Preradiotherapy PSA levels are correlated with tumor stage but also provide prognostic information that is independent of tumor stage and histological grade. (3) Following the completion of radiotherapy, PSA levels must decline to normal values to assure a successful treatment outcome. Disagreement persists as to what constitutes a normal PSA value after radiotherapy, and in what time frame after treatments such a level must be achieved. (4) Different proposed models of PSA decline after radiotherapy are discussed, but it remains premature to assess their relative success as predictors of subsequent clinical events. (5) Postradiotherapy prostate biopsy results (negative versus positive) correlate reasonably well with post-treatment PSA status (normal versus elevated). (6) The management of patients with a rising PSA following radiotherapy must be individualized, with early hormonal intervention being an attractive, although unproven, therapeutic option for selected patients. (7) PSA data confirm the value of adjuvant radiotherapy for positive surgical margins and strengthens the indications for its use. (8) Preliminary data regarding PSA levels following transperineal interstitial brachytherapy implantation of the prostate appear favorable.

Predicting the outcome of salvage radiotherapy for recurrent prostate cancer after radical prostatectomy

4514 Background: Salvage radiotherapy may potentially cure patients with recurrent prostate cancer after radical prostatectomy (RP). However, the outcome is highly dependent on patient selection factors and current diagnostic modalities for locally recurrent prostate lack acceptable sensitivity and specificity. We developed a model to predict the likelihood of a durable response to salvage radiotherapy for patients with post-RP biochemical recurrence (BCR). Methods: Using multivariable Cox proportional hazards regression analysis, we modeled the clinical data for 1540 patients who received salvage radiotherapy at 1 of 17 North American tertiary referral centers for post-RP BCR. The primary endpoint was disease progression after salvage radiotherapy, defined as a serum prostate-specific antigen (PSA) value ≥ 0.2 ng/mL followed by another increase, initiation of systemic therapy, or clinical recurrence. The median follow-up was 53 months. Results: Disease progression was observed in 866 patients and the 5- and 10-year progression-free probability was 38% (95% CI, 35–40) and 19% (95% CI, 15–23), respectively. Significant variables in the nomogram were: pre-radiotherapy PSA (P &lt; .001), RP Gleason score (P &lt; .001), neoadjuvant androgen-deprivation therapy (P&lt; .001), negative surgical margins (P &lt; .004), PSA at BCR (P = .011), PSADT (P = .029), and regional lymph node metastasis (P = .034). The nomogram was accurate and discriminating with a concordance index of 0.68. Published models predicting the probability of metastasis progression or PCSM for BCR patients based on disease-free interval, prostatectomy Gleason score, and/or PSA doubling time discriminated poorly for a durable response to salvage radiotherapy among patients in our cohort (concordance index, 0.56–0.61). Conclusions: A nomogram has been developed that predicts the 5-year progression-free probability after salvage radiotherapy for men with post-RP BCR. This represents the first model to predict the outcome of salvage therapy for BCR and is useful for quantifying the anticipated benefit of salvage radiotherapy for prostate cancer recurrence. Published predictive models for metastasis progression or PCSM are of limited clinical utility in selecting patients for salvage radiotherapy. No significant financial relationships to disclose.

Salvage radiotherapy (SR) in patients (pts) with prostate cancer (PC) and rising prostate specific antigen (PSA) after radical prostatectomy (RP): Results from a single-center study

14556 Background: In pts with PC and biochemical relapse after RP SR is well established. However, the significance of pre-radiotherapeutic variables for guidance of treatment decisions is less clear. We analyzed prognostic factors in a large cohort of pts treated with SR after RP. Methods: 163 pts with PC and persisting PSA-levels (n = 60) or PSA-elevation following undetectable PSA-levels (n = 103) after RP received three-dimensional conformal radiotherapy (RT). None received androgen depriving therapy between prostatectomy and start of RT. We evaluated the impact of age, stage, surgical margin status (SMS), Gleason score and PSA-kinetics by survival and regression analysis. Biochemical progression (BP) was defined as PSA-increases at 3 consecutive time points after the post RT nadir. To detect thresholds for significant prognostic variables, we calculated receiver operating characteristic (ROC) curves. Results: Medians for pre-RT variables were: 11.97 ng/ml for pre-prostatectomy PSA (Pre-OP PSA), 5.4 months for PSA doubling time (PSADT) and 0.339 ng/ml for pre-radiotherapy PSA (Pre-RT PSA). Probability for a projected 4-year PFS was 50% (median follow-up: 33.5 months). Logistic regression revealed a significant impact on the probability of BP for Pre-OP PSA (p = 0.036), PSADT (p = 0.024) and tumor-stage (p = 0.043), whereas Pre-RT PSA and SMS had a significant impact on achievement of undetectable post-RT PSA (p = 0.009 and p = 0.028 respectively). Analysis of ROC-curves for Pre-OP PSA, Pre-RT PSA, PSADT revealed an area under the curve not exceeding 0.704 for any of these parameters. Conclusions: By analyzing ROC-curves we could not detect clear thresholds for PSA kinetic variables. In accordance with recently published data we found similar independent significant variables predicting a therapeutic success. However, we observed a lower median Pre-RT PSA and a higher probability of PFS in our patient cohort. This suggests, that early radiotherapeutic intervention improves PFS. No significant financial relationships to disclose.

Postoperative radiotherapy after radical prostatectomy for prostate carcinoma: the experience of the Brescia Radium Institute

The purpose of this study was to evaluate the efficacy of postoperative radiotherapy in reducing the incidence of prostate carcinoma (PCa) recurrences after radical prostatectomy (RP), define the importance of the time interval between surgery and radiotherapy for prognosis and the toxicity of the treatment in comparison with radiotherapy or surgery alone. We examined 97 patients who consecutively underwent postoperative radiotherapy after RP between 1980 and 2003. The treatment was considered "adjuvant" if was conducted less than 6 months after RP, if there was no macroscopic residual disease and if there was no progressive increase in serum prostate-specific antigen (PSA) and "salvage" if performed more than 6 months after RP, for the presence of macroscopic recurrence or with rising PSA. Radiotherapy was salvage in 56 patients and adjuvant in 41. Age range was 60-70 years in 80% of patients, and the Karnofsky index was over 80 in 78% of cases. Histology revealed extracapsular spread in 60% of patients. Preradiotherapy PSA was higher than 1 ng/ml in 36%. Radiotherapy was performed on the surgical bed only in 80%, and the total dose was 70 Gy in 62% of cases. Recurrence-free survival (RFS) at 5 years and 10 years was 53+/-8% and 32+/-14.2%, respectively, for the whole sample; 76+/-9% and 38+/-2.7% for patients treated with adjuvant radiotherapy and 36+/-10% and 28+/-10% for those treated with salvage radiotherapy (p<0.01). Moreover, the 5-year RFS was better in the group treated with adjuvant radiotherapy and PSA less than or equal to 1 ng/ml (p<0.05). Treatment toxicity was acceptable. Postoperative radiotherapy improves RFS and reduces the risk of local recurrence. The best results are obtained with early postoperative treatment ("adjuvant"); adjuvant radiotherapy of high-risk forms yields better results if performed with PSA less than or equal to 1 ng/ml.

Hypofractionated radiotherapy as salvage for rising prostate-specific antigen after radical prostatectomy

To review the outcome of men receiving hypofractionated salvage radiotherapy for rising prostate-specific antigen (PSA) after radical prostatectomy. A retrospective analysis of 61 men referred for salvage radiotherapy for biochemical relapse after radical prostatectomy was conducted. Twenty-four men receiving hormonal therapy or with follow-up of less than 12 months were excluded. Thirty-seven men were identified, median age 64 years, median preoperative PSA 11 ng/ml (5.6-60 ng/ml), Gleason scores <7: 70%, Gleason scores > or = 7: 30%. Twenty-seven men had positive surgical resection margins, eight had seminal-vesicle involvement and one had lymph-node involvement. Diagnosis of failure after radical prostatectomy was made on rising PSA in all cases; 19 men also had positive magnetic resonance imaging, 11 abnormal digital rectal examination and nine positive biopsy. Radiotherapy was delivered conformally to the prostatic fossa, 50-52.5 Gy in 20 fractions over 4 weeks. Date of failure after radiotherapy was defined by the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria or as date of commencement of hormonal therapy for rising PSA. Median time from radical prostatectomy to radiotherapy was 30.6 months (8-68 months); median pre-radiotherapy PSA was 2.9 ng/ml (0.5-11.4 ng/ml). PSA response after radiotherapy was seen in 33 out of 37 (89%) patients. At median follow-up of 36 months (20-85 months), 28 out of 37 remained disease-free. Thirteen more patients have had two consecutive PSA rises. Actuarial 3-year disease-free survival is 74%. No patient has developed metastases or died of prostate cancer. Pre-radiotherapy PSA less than 2 ng/ml predicted disease-free survival (P = 0.027). No acute toxicity greater than Radiation Therapy Oncology Group (RTOG) G2 was observed. Salvage radiotherapy after radical prostatectomy achieved durable biochemical control in most patients. Outcome is improved if radiotherapy is delivered when PSA is less than 2 ng/ml. A policy of close monitoring after radical prostatectomy with early referral for salvage radiotherapy is advocated.

Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy: Stephenson AJ, Shariat SF, Zelefsky MJ, Kattan MW, Butler EB, Teh, BS, Klein EA, Kupelian PA, Roehrborn CG, Pistenmaa DA, Pacholke HD, Liauw SL, Katz, MS, Leibel SA, Scardino PT, Slawin KM, Department of Urology, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York, NY. JAMA

Salvage radiotherapy may potentially cure patients with disease recurrence after radical prostatectomy, but previous evidence has suggested that it is ineffective in patients at the highest risk of metastatic disease progression. To delineate patients who may benefit from salvage radiotherapy for prostate cancer recurrence by identifying variables associated with a durable response. Retrospective review of a cohort of 501 patients at 5 US academic tertiary referral centers who received salvage radiotherapy between June 1987 and November 2002 for detectable and increasing prostate-specific antigen (PSA) levels after radical prostatectomy. Disease progression after salvage radiotherapy, defined as a serum PSA value ⩾0.1 ng/mL above the postradiotherapy PSA nadir confirmed by a second PSA measurement that was higher than the first by any amount, by a continued increase in PSA level after treatment, or by the initiation of androgen deprivation therapy after treatment. Over a median follow-up of 45 months, 250 patients (50%) experienced disease progression after treatment, 49 (10%) developed distant metastases, 20 (4%) died from prostate cancer, and 21 (4%) died from other or unknown causes. The 4-year progression-free probability (PFP) was 45% (95% confidence interval [CI], 40%–50%). By multivariable analysis, predictors of progression were Gleason score of 8 to 10 (hazard ratio [HR], 2.6; 95% CI, 1.7–4.1; P < .001), preradiotherapy PSA level greater than 2.0 ng/mL (HR, 2.3; 95% CI, 1.7–3.2; P < .001), negative surgical margins (HR, 1.9; 95% CI, 1.4–2.5; P < .001), PSA doubling time (PSADT) of 10 months or less (HR, 1.7; 95% CI, 1.2–2.2; P = .001), and seminal vesicle invasion (HR, 1.4; 95% CI, 1.1–1.9; P = .02). Patients with no adverse features had a 4-year PFP of 77% (95% CI, 64%–91%). When treatment was given for early recurrence (PSA level ⩽2.0 ng/mL), patients with Gleason scores of 4 to 7 and a rapid PSADT had a 4-year PFP of 64% (95% CI, 51%–76%) and of 22% (95% CI, 6%–38%) when the surgical margins were positive and negative, respectively. Patients with Gleason scores of 8 to 10, positive margins, and receiving early salvage radiotherapy had a 4-year PFP of 81% (95% CI, 57%–100%) when the PSADT was longer than 10 months and of 37% (95% CI, 16%–58%) when the PSADT was 10 months or less. Gleason score, preradiotherapy PSA level, surgical margins, PSADT, and seminal vesicle invasion are prognostic variables for a durable response to salvage radiotherapy. Selected patients with high-grade disease and/or a rapid PSADT who were previously thought to be destined to develop progressive metastatic disease may achieve a durable response to salvage radiotherapy.

Long-term follow-up of prostascint scan pretreatment assessment in patients who undergo radiation therapy for a rising prostate specific antigen (PSA) after radical prostatectomy for prostate cancer

The Prostascint scan is a radioimmunoconjugate of a monoclonal antibody against prostate specific membrane antigen, which has high prostate tissue specificity. The purpose of our study was to evaluate long term failure patterns in patients who had undergone this scan as part of their pre treatment evaluation for a rising PSA after prostatectomy and went on to receive local radiotherapy (RT) to the prostatic bed. The study comprises of 59 patients who after radical prostatectomy for prostate cancer were referred to the department of radiation oncology for evaluation when their PSA started rising. All patients underwent imaging with Computerized Tomography (CT) scans of the abdomen and pelvis and an isotope bone scan. All patients also underwent a prostascint scan as part of the evaluation. The scans were read as negative, positive in the prostate bed alone, positive in the lymph node regions in the pelvis alone, positive in metastatic sites including lymph node regions outside the pelvis or positive in more than one of these areas. Regardless of the prostascint scan findings all patients were treated only with local radiotherapy to the prostatic bed to a dose of 66.6 Gy to 70.2 Gy in 1.8 Gy fractions. 7 patients had adjuvant short-term hormones for 3-6 months along with radiation. All patients were followed up with clinical evaluations, PSA tests and imaging where appropriate. The median follow-up from radiation was 41 months. The median follow-up after surgery was 79 months. Their postoperative stages were T2a: 5, T2b: 12, T2c: 14, T3a: 21, T3b: 6, T4a: 1. 46.5 % had Gleason 6 or less and 50% of the patients had positive margins. All the CT scans and bone scans were negative for metastatic disease. The mean PSA prior to RT was 0.9 ng/ml. The prostascint scan was negative in 15 patients, positive in the bed: 22, the bed and lymph node: 4, bed and metastatic site: 7, lymph nodes alone: 3, metastatic sites alone: 4, lymph node and metastatic sites: 2 and all 3 sites: 2. The 5-year biochemical relapse free survival (BRFS) in patients with a pre-RT PSA less than 1 was 57.9% which was statistically significantly better than those with a pre-RT PSA greater or equal to 1 ng/ml (p = 0.0027). The 5-year BRFS for patients with Gleason score 6 and below was 59.6 % compared to 42.8% for those with a higher Gleason score (p = 0.35). 19 patients have failed biochemically: 8/22 patients with scan positive in the bed alone, 5/15 patients with a negative scan and 6/22 in patients with a positive uptake outside the bed. The 5-year biochemical relapse free survival rates for patients with a negative scan (53.3%) positive scan in the bed alone (45.2%) or positive scan outside the bed (55.3%) were all not statistically different (p = 0.5) by log rank analysis. On multivariate analysis PSA less than 1 ng/ml was the only significant factor predicting improved BRFS. Prostascint Scan status had no effect on BRFS. 5-year BRFS rates were similar regardless of the pre-treatment prostascint scan status for patients who undergo post-prostatectomy salvage radiotherapy. Hence if other imaging studies are negative for metastatic disease, patients should still be considered for local therapy. Pre-radiotherapy PSA less than 1 ng /ml was the most important prognostic factor in our study

Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy.

Salvage radiotherapy may potentially cure patients with disease recurrence after radical prostatectomy, but previous evidence has suggested that it is ineffective in patients at the highest risk of metastatic disease progression. To delineate patients who may benefit from salvage radiotherapy for prostate cancer recurrence by identifying variables associated with a durable response. Retrospective review of a cohort of 501 patients at 5 US academic tertiary referral centers who received salvage radiotherapy between June 1987 and November 2002 for detectable and increasing prostate-specific antigen (PSA) levels after radical prostatectomy. Disease progression after salvage radiotherapy, defined as a serum PSA value > or =0.1 ng/mL above the postradiotherapy PSA nadir confirmed by a second PSA measurement that was higher than the first by any amount, by a continued increase in PSA level after treatment, or by the initiation of androgen deprivation therapy after treatment. Over a median follow-up of 45 months, 250 patients (50%) experienced disease progression after treatment, 49 (10%) developed distant metastases, 20 (4%) died from prostate cancer, and 21 (4%) died from other or unknown causes. The 4-year progression-free probability (PFP) was 45% (95% confidence interval [CI], 40%-50%). By multivariable analysis, predictors of progression were Gleason score of 8 to 10 (hazard ratio [HR], 2.6; 95% CI, 1.7-4.1; P<.001), preradiotherapy PSA level greater than 2.0 ng/mL (HR, 2.3; 95% CI, 1.7-3.2; P<.001), negative surgical margins (HR, 1.9; 95% CI, 1.4-2.5; P<.001), PSA doubling time (PSADT) of 10 months or less (HR, 1.7; 95% CI, 1.2-2.2; P =.001), and seminal vesicle invasion (HR, 1.4; 95% CI, 1.1-1.9; P =.02). Patients with no adverse features had a 4-year PFP of 77% (95% CI, 64%-91%). When treatment was given for early recurrence (PSA level < or =2.0 ng/mL), patients with Gleason scores of 4 to 7 and a rapid PSADT had a 4-year PFP of 64% (95% CI, 51%-76%) and of 22% (95% CI, 6%-38%) when the surgical margins were positive and negative, respectively. Patients with Gleason scores of 8 to 10, positive margins, and receiving early salvage radiotherapy had a 4-year PFP of 81% (95% CI, 57%-100%) when the PSADT was longer than 10 months and of 37% (95% CI, 16%-58%) when the PSADT was 10 months or less. Gleason score, preradiotherapy PSA level, surgical margins, PSADT, and seminal vesicle invasion are prognostic variables for a durable response to salvage radiotherapy. Selected patients with high-grade disease and/or a rapid PSADT who were previously thought to be destined to develop progressive metastatic disease may achieve a durable response to salvage radiotherapy.

IS ANASTOMOTIC BIOPSY NECESSARY BEFORE RADIOTHERAPY AFTER RADICAL PROSTATECTOMY?

External beam radiotherapy may be given after radical prostatectomy as adjuvant (immediate) or therapeutic (delayed) treatment, the latter in response to evidence of disease recurrence. In patients receiving delayed radiotherapy the necessity of a positive anastomotic biopsy before treatment remains unclear. We determined whether a positive anastomotic biopsy predicted the response to radiation in this setting. We reviewed the records of 67 patients who received radiotherapy for biochemical or biopsy proved recurrent prostate cancer after radical prostatectomy. Patients underwent surgery at our institution or its affiliated hospitals, or were referred to our institution for radiotherapy. All patients had a negative metastatic evaluation before receiving radiotherapy. Biochemical failure after radiotherapy was defined as serum prostate specific antigen (PSA) 0.2 ng./dl. or greater on 2 or more consecutive occasions. Biochemical recurrence-free survival was calculated using the Kaplan-Meier method. Independent predictors of PSA failure after radiotherapy were identified using the multivariate Cox proportional hazards model. Of the 67 patients evaluated 33 and 34 received radiotherapy for biochemical failure and biopsy proved local recurrence, respectively. The 3-year recurrence-free survival rate was 49% in patients treated for biochemical failure and 39% in those with biopsy proved local recurrence. There was no significant difference in PSA-free survival in these 2 groups. Only pre-radiotherapy PSA 1 ng./dl. or greater (p = 0.02) and seminal vesicle invasion (p = 0.02) were significant independent predictors of biochemical failure. A positive anastomotic biopsy did not predict an improved outcome after radiotherapy following radical prostatectomy. Anastomotic biopsy was associated with a longer time to salvage radiotherapy. However, this delay did not translate into worse disease-free outcomes in patients who underwent anastomotic biopsy. High pre-radiotherapy PSA greater than 1 ng./ml. was the most significant predictor of biochemical failure after therapeutic radiotherapy. Decisions regarding local radiation therapy after radical prostatectomy may be made without documenting recurrent local disease.

RADIOTHERAPY FOR ISOLATED SERUM PROSTATE SPECIFIC ANTIGEN ELEVATION AFTER PROSTATECTOMY FOR PROSTATE CANCER

Elevated serum prostate specific antigen (PSA) may be the initial and only indication of disease recurrence after prostatectomy for prostate cancer. External beam radiotherapy may be given in this setting in an attempt to eradicate the disease but therapeutic outcomes after this approach require further description. We describe the intermediate term outcome in a large group of patients treated with radiotherapy and identify pre-therapy factors associated with disease outcome.We retrospectively studied a cohort of 166 consecutive patients treated with radiotherapy between July 1987 and May 1996. The Kaplan-Meier method was used to describe patient outcome for the overall study group, and statistical associations of pre-therapy variables with outcome were sought to identify predictive factors.At a median followup of 52 months 46% (95% confidence interval 38 to 55) of patients were expected to be free of biochemical relapse 5 years after radiotherapy. Multivariate analysis identified pathological classification (seminal vesicle invasion), tumor grade and preradiotherapy serum PSA as independent factors associated with biochemical relapse. Although in 1 of 6 patients a chronic complication was attributed to radiotherapy, it was often mild and self-limited in nature.In our current series approximately half of the patients treated with radiotherapy for an isolated elevation of serum PSA after prostatectomy were free of biochemical relapse at 5 years of followup. Radiotherapy may be given in this setting with modest long-term morbidity.

RADIOTHERAPY FOR ISOLATED SERUM PROSTATE SPECIFIC ANTIGEN ELEVATION AFTER PROSTATECTOMY FOR PROSTATE CANCER

Elevated serum prostate specific antigen (PSA) may be the initial and only indication of disease recurrence after prostatectomy for prostate cancer. External beam radiotherapy may be given in this setting in an attempt to eradicate the disease but therapeutic outcomes after this approach require further description. We describe the intermediate term outcome in a large group of patients treated with radiotherapy and identify pre-therapy factors associated with disease outcome. We retrospectively studied a cohort of 166 consecutive patients treated with radiotherapy between July 1987 and May 1996. The Kaplan-Meier method was used to describe patient outcome for the overall study group, and statistical associations of pre-therapy variables with outcome were sought to identify predictive factors. At a median followup of 52 months 46% (95% confidence interval 38 to 55) of patients were expected to be free of biochemical relapse 5 years after radiotherapy. Multivariate analysis identified pathological classification (seminal vesicle invasion), tumor grade and preradiotherapy serum PSA as independent factors associated with biochemical relapse. Although in 1 of 6 patients a chronic complication was attributed to radiotherapy, it was often mild and self-limited in nature. In our current series approximately half of the patients treated with radiotherapy for an isolated elevation of serum PSA after prostatectomy were free of biochemical relapse at 5 years of followup. Radiotherapy may be given in this setting with modest long-term morbidity.