Biochemical Disease-free Survival Rates Research Articles

Effect of Pelvic Lymph Node Irradiation in Salvage Therapy for Patients with Prostate Cancer with a Biochemical Relapse Following Radical Prostatectomy

Radiation therapy (RT) as salvage treatment for a biochemical relapse following prostatectomy has been shown to be of benefit measured by serum prostate-specific antigen (PSA) control. However, identifying a target volume for RT has not been well established in this setting. In this study, the results of postoperative RT delivered to extended fields (EFs), prostatic fossa, and pelvic lymph nodes encompassing at least the obturator lymph nodes are compared with treatment of limited fields (LFs), prostatic fossa only, as salvage treatment for patients with a biochemical relapse. Between 1987 and 1999, 68 patients were referred for postprostatectomy RT. Of these patients, 46 were treated for salvage intent by RT alone without adjuvant hormones, 21 patients were treated to EFs and 25 treated to LFs. All patients were treated using 4-field plans. The mean field sizes measured 15 × 14 cm (AP/PA fields) and 12 × 14 cm LFs for the EFs and 10 × 10 cm (AP/PA fields) and 10 × 10 cm (lateral fields) for the LFs. The mean total doses for the EFs and LFs were 6300 and 6200 cGy, respectively, using 180-cGy daily increments. All patients treated to the EFs received boost doses to the prostatic fossa after 4500 cGy total dose to the pelvis. The 10-year actuarial biochemical diseasefree survival (DFS) rates for the EF and LF groups were 52% and 47%, respectively (P = 0.523). The distant metastasis-free survival (DMFS) rates were 77% and 78% (P = 0.925), and overall survival (OS) rates were 88% and 68% (P = 0.615) for the EF and LF group, respectively. A subset analysis of patients with adverse pathologic features (including tumor-involved surgical margins, lymph node involvement, seminal vesicle involvement, extracapsular extension, and/or perineural invasion) showed biochemical DFS rates of 57% and 44% (P = 0.217) for the EF and LF groups, respectively. The DMFS rates were 84% and 72% (P = 0.423), and OS rates 92% and 61% (P = 0.366) for the EF and LF groups, respectively. For patients with increasing PSA levels after a radical prostatectomy, salvage irradiation is a viable option for biochemical control. Our results suggest that EF radiation with coverage of pelvic lymph nodes shows a trend toward better PSA control in those with adverse pathologic features, although statistical significance was not achieved because of the limited number of patients who satisfied the restricted criteria excluding use of adjuvant hormones.

High-dose-rate iridium-192 afterloading therapy combined with external beam radiotherapy for T1c-T3bN0M0 prostate cancer

Objectives To determine the efficacy of radiotherapy (RT) for T1c-T3bN0M0 prostate cancer in a prospective clinical trial of concurrent external beam RT and fractionated iridium-192 high-dose-rate brachytherapy. Methods Included in the study were 98 patients with T1c-T3bN0M0 prostate cancer who were diagnosed between October 1997 and September 2002 and underwent high-dose-rate brachytherapy with external beam RT. Treatment consisted of external beam RT (four ports) to the prostate of 16 fractions of 2.3 Gy to a total dose of 36.8 Gy and high-dose-rate brachytherapy of 4 fractions of 6.0 Gy within 30 hours to a total dose of 24.0 Gy. No patient received adjuvant hormonal therapy after RT. Results The most recent prostate-specific antigen level was 0.0 to 3.9 ng/mL (median 0.4). Seven patients (7.1%) developed recurrence and treatment was considered a failure (bone metastasis in two and biochemical failure in five). The overall biochemical disease-free survival (bDFS) rate was 95.9% at 2 years and 92.9% at 5 years. The bDFS rate by T stage was 98.6% at 2 years and 95.9% at 5 years for Stage T1c-T2b and 88.0% and 84.0% for Stage T3a-b, respectively ( P = 0.047). The 2-year and 5-year bDFS rate was better in patients with an initial prostate-specific antigen level of less than 20 ng/mL compared with 20 ng/mL or greater (98.6% and 97.1% versus 93.1% and 82.8%, respectively, P = 0.0261). Acute toxicity was mild to moderate (Radiation Therapy Oncology Group grade 1-2) and consisted of cystourethritis or proctitis in 29 (29.6%) of 98 patients. Conclusions With a low complication rate and satisfactory bDFS rates, this combination therapy can be considered an alternative method for clinical Stage T1c-T3b prostate cancer and is expected to improve patient quality of life. Additional long-term follow-up is needed to confirm this treatment.

Proton therapy for prostate cancer: the initial Loma Linda University experience

Purpose We analyzed results of conformal proton radiation therapy for localized prostate cancer, with emphasis on biochemical freedom from relapse. Methods and materials Analyses were performed for 1255 patients treated between October 1991 and December 1997. Outcomes were measured on primarily in terms of biochemical relapse and toxicity. Results The overall biochemical disease-free survival rate was 73%, and was 90% in patients with initial PSA ≤4.0; it was 87% in patients with posttreatment PSA nadirs ≤0.50. Rates dropped with rises in initial and nadir PSA values. Long-term survival outcomes were comparable with those reported for other modalities intended for cure. Conclusions Conformal proton radiation therapy at the reported dose levels yielded disease-free survival rates comparable with other forms of local therapy, and with minimal morbidity. Dose-escalation strategies are being implemented to further improve long-term results.

Improved Biochemical Disease-Free Survival of Men Younger Than 60 Years With Prostate Cancer Treated With High Dose Conformal External Beam Radiotherapy

We report the long-term prostate specific antigen relapse-free survival rates and predictors of biochemical outcome for patients 60 years or younger with prostate cancer treated with high dose conformal external beam radiotherapy. We retrospectively reviewed the records of 740 patients with prostate cancer treated with 3-dimensional conformal radiotherapy or intensity modulated external beam radiotherapy. Patients who also received androgen deprivation therapy were excluded from this analysis. Median radiation dose was 75.6 Gy and median followup was 88 months with a minimum followup of 24 months. Median followup for patients 60 years or younger in this report was 54 months (range 24 to 132). Biochemical failure was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. Biochemical failure developed in 20 (21%) of the 96 men 60 years or younger, which was similar to the 22% failure rate observed in 644 patients older than 60. The 5 and 7-year biochemical disease-free survival rates were 82% and 79% in younger men, and 79% and 78% in older men, respectively (p = 0.48). For younger patients who received 81 Gy or greater, the 7-year prostate specific antigen relapse-free survival rates for favorable, intermediate and unfavorable risk patients were 96%, 87% and 50%, respectively. Multivariate analysis revealed that among patients 60 years or younger the most important predictor of biochemical relapse was radiation doses less than 75.6 Gy followed by Gleason score greater than 7. Men with prostate cancer 60 years or younger treated with high dose radiotherapy have an excellent biochemical outcome and fare as well as older patients. The use of conventional dose levels in patients 60 years or younger was associated with an 8-fold increase in the biochemical relapse rate and these doses should not be considered appropriate for the treatment of localized prostate cancer.

Identification of Factors Predicting Response to Adjuvant Radiation Therapy in Patients With Positive Margins After Radical Prostatectomy

Radical prostatectomy (RP) is a highly effective treatment for patients with prostate cancer. However, patients with positive surgical margins after radical prostatectomy have less than ideal outcomes with 5-year progression rates between 36% and 50%. Postoperative radiation therapy (RT) is often advocated for improving these outcomes. We identified predictors of response to adjuvant RT given for positive margins after RP. We retrospectively reviewed the clinical records of men who underwent RP between 1987 and 1999 at our institution and who received adjuvant RT for positive surgical margins. Only patients in whom prostate specific antigen (PSA) was undetectable after RP as well as before the initiation of RT were included. Numerous clinicopathological variables, including pre-RP PSA, pathological stage, margin length and location, and extracapsular extension or seminal vesicle involvement, were assessed for their adverse effect on the biochemical recurrence rate after adjuvant RT. A total of 62 men met our inclusion criteria. Median age at surgery was 60.7 +/- 6.1 years and median PSA at presentation was 9.0 ng/ml (range 1.4 to 64.9). The median RT dose was 60.0 +/- 3.6 Gy. RT was started a median of 5.0 +/- 3.6 months after RP. The 5 and 10-year biochemical disease-free survival rates for the whole group were 90.2% and 87.9%, respectively. Of all parameters tested only Gleason score 4 + 3 or greater (p = 0.037) and pre-RP PSA greater than 10.9 ng/ml (p = 0.040) were predictive of biochemical recurrence after adjuvant RT on univariate analysis. On multivariate analysis only pre-RP PSA greater than 10.9 ng/ml remained an independent predictor (p = 0.031). In the setting of true adjuvant RT in patients with positive margins after RP and undetectable PSA those with predominant Gleason grade 4 or greater, or PSA greater than 10.9 ng/ml at presentation are at increased risk for recurrence after adjuvant RT.

Influence of follow-up bias on PSA failure after external beam radiotherapy for localized prostate cancer: Results from a 10-year cohort analysis

Purpose To estimate the biases inherent in prostate cancer outcome that arise from different failure end points and variations in follow-up time and intensity using a cohort of men with long follow-up. Methods and materials The study cohort consisted of 205 men with T1–T2N0-Nx prostate cancer treated with conventional radiotherapy between 1991 and 1993. The median follow-up was 103 months. Outcome was assessed using different definitions of biochemical failure, including the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria and the “nadir plus two” criteria (any rise of 2 ng/mL greater than the current nadir). Patient subgroups were created according to where patients had received their last 2 years of follow-up. Patients were also stratified according to whether they were initially present in the departmental database (under regular surveillance) or were uncovered after more vigorous investigation (previously “lost to follow-up”). Results In this series with maximized follow-up, the 10-year biochemical disease-free survival rate did not change significantly with varying definitions of failure, 49% and 45% for ASTRO and “nadir plus two” criteria, respectively. Patients followed by outside physicians ( n = 99) were faring better at 10 years than those followed at the treating institution by either their radiation oncologist ( n = 50) or their medical oncologist or urologist ( n = 52). This was by all measures of outcome, including overall survival, and metastasis-free survival. Patients previously lost to follow-up ( n = 43) who were tracked down also appeared to be doing better than those on our database for whom information had been readily available ( n = 161). This, however, may have been an artifact of the ASTRO criteria, which underestimates failure when insufficient prostate-specific antigen values are available. Conclusion The ASTRO definition of failure underestimates late failure. This bias may be compensated for by the use of cohorts with long follow-up or the use of the “nadir plus two” definition of failure. The use of institutional prostate cancer databases may overestimate failure rates because patients followed outside of the treating institution fared better with respect to both survival and biochemical recurrence. Vigorous attempts to obtain follow-up beyond the hospital walls may correct this bias.

Long-term results of three-dimensional conformal adjuvant and salvage radiotherapy after radical prostatectomy

Objectives To evaluate the efficacy and toxicity of three-dimensional conformal radiotherapy (3D-CRT) in the adjuvant and salvage setting after radical prostatectomy (RP). Methods From 1986 to 1997, 38 patients received adjuvant 3D-CRT, with a median time from RP to 3D-CRT of 2.8 months, and 57 patients were treated with salvage RT for a rising prostate-specific antigen with a median time to 3D-CRT of 27.7 months. The median radiation dose was 64.8 Gy. The median follow-up from completion of RT was 7.0 years (range 1.0 to 14.2). Results Overall, the 8-year actuarial rate of biochemical disease-free survival was 40% in all patients. The 8-year biochemical disease-free survival rate was 45% (standard error [SE] 8%) and 30% (SE 7%) for the adjuvant and salvage group, respectively, from RT completion. When measured from the date of RP, the 5 and 8-year biochemical disease-free survival rate for salvage radiotherapy was 58% and 37%, respectively. The corresponding results for adjuvant RT were similar at 53% and 45%. On multivariate analysis, the Gleason score was the only prognostic factor predictive of prostate-specific antigen failure in the salvage group. No prognostic factor was significant in the adjuvant group. The prevalence of major complications after 3D-CRT was low using physician-reported data. Conclusions Long-term biochemical control can be achieved in both adjuvant and salvage settings. For patients receiving salvage RT, a Gleason score greater than 7 was predictive of prostate-specific antigen failure. Prospective trials are needed to improve further on these results.

Long-term cancer control of radical prostatectomy in men younger than 50 years of age: update 2003

Objectives To compare the cancer control in men younger than 50 years with that in older men treated with radical retropubic prostatectomy (RRP) for localized prostate cancer in a contemporary series. In the 1970s and 1980s, men younger than 50 years old represented approximately 1% of newly diagnosed prostate cancer cases. However, with the widespread use of serum prostate-specific antigen (PSA) testing and increased public awareness of prostate cancer, this figure has risen (3.7% to 4%). Previous studies, mostly carried out before the PSA era, reported conflicting data with respect to cancer control for these younger men treated with RRP. Methods We analyzed the data from 2897 men who underwent RRP between April 1982 and September 2001. Preoperative PSA level, clinical and pathologic stage, and biochemical recurrence were compared between 341 men younger than 50 years old and 2556 men 50 years old or older. Disease-free (PSA less than 0.2 ng/mL) survival rates were compared using Kaplan-Meier analysis. Pathologic staging was compared using logistic regression analysis. Results Men younger than 50 years old had pathologic variables and 5, 10, and 15-year biochemical disease-free survival rates comparable to men aged 50 to 59 years (88%, 81%, and 69% versus 87%, 78%, and 71%, respectively). However, younger men had a lower incidence of extraprostatic extension (25% versus 31%; P <0.02), seminal vesicle involvement (2% versus 6%; P <0.03), and positive surgical margins (3% versus 9%; P <0.03), a greater organ-confined disease rate (65% versus 49%; P <0.0001), and a trend toward greater 5, 10, and 15-year biochemical disease-free survival rates, which did not reach statistical significance, compared with men aged 60 to 69 years (84%, 74%, and 67%, respectively; P <0.09). Furthermore, younger men not only had a lower rate of extraprostatic extension (25% versus 36%; P <0.001), seminal vesicle involvement (2% versus 10%; P <0.001), and positive surgical margins (3% versus 9%; P <0.001) and a greater organ-confined disease rate (65% versus 36%; P <0.0001), they also demonstrated significantly ( P <0.003) greater 5, 10, and 15-year biochemical disease-free survival rates compared with men aged 70 years or older (72%, 58%, and 58%, respectively). Conclusions Men diagnosed with prostate cancer who are younger than 50 years of age and are candidates for RRP tend to have a greater probability of organ-confined disease than older men. Younger men also demonstrate greater long-term cancer control rates than older men.

Modifying the American Society for Therapeutic Radiology and Oncology Definition of Biochemical Failure to Minimize the Influence of Backdating in Patients With Prostate Cancer Treated With 3-dimensional Conformal Radiation Therapy Alone

Adoption of the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definition has been critical for evaluating and comparing outcome following treatment with radiation. However, since its almost universal adoption, several points have remained controversial, notably backdating the date of failure to the point midway between the posttreatment prostate specific antigen (PSA) nadir and the first increase. We evaluated the impact of backdating on no biochemical evidence of disease (bNED) control and suggest changes in the definition. Between April 1, 1989 and November 30, 1998, 1,017 patients with nonmetastatic prostate cancer were treated with 3-dimensional conformal radiation therapy alone. bNED control was defined using the ASTRO consensus definition. bNED failure was calculated from the time midway between the posttreatment PSA nadir and the first of the 3 consecutive increases in PSA (date of failure A). Four alternate failure time points were chosen, including backdating to the date of the first increase in PSA after the nadir, the date between the first and second consecutive PSA increases, the date between the second and third consecutive PSA increases, and the date of the third increase in PSA after the nadir (dates of failure 1 to 4). Kaplan-Meier estimates were calculated for all definitions of failure as well as hazard functions with time. Subset analyses based on prognostic group and followup time were also performed. The 10-year Kaplan-Meier bNED control rates were 64%, 52%, 47%, 42% and 39% using dates of failure A and 1 to 4, respectively. These differences persisted when patients were stratified by prognostic group. These same differences in bNED control were observed for the long-term followup subset, in which 10-year bNED control rates were 48%, 47%, 44%, 41% and 39% using dates of failure A and 1 to 4, respectively. Adoption of the ASTRO consensus definition has been crucial for evaluating outcome in the radiation oncology community. However, the date of failure should be moved from the current point to one closer to the point at which failure is declared. Additional analysis with large numbers of patients from multiple institutions is necessary to determine the point.

Hazard Rates of Disease Progression After External Beam Radiotherapy for Clinically Localized Carcinoma of the Prostate

We established hazard rates for disease progression at different intervals after external beam radiotherapy alone in patients with clinically localized prostate cancer. We determined the likelihood of biochemical failure in those free of disease 5 years after radiotherapy and identified those at risk for early versus late biochemical failure. We reviewed the records of 964 patients treated with full dose external beam radiotherapy alone for T1 to T4, NxM0 prostate cancer. Followup prostate specific antigen (PSA) was measured 3 months after the completion of radiotherapy and every 3 to 6 months thereafter. Yearly hazard rates for biochemical failure were calculated each followup year. Median followup of the whole study group was 48 months. Overall 5 and 10-year biochemical disease-free survival rates were 63.7% and 53.6%, respectively. Patients had a peak overall hazard rate 2 years after treatment. The hazard rate then decreased until year 6, when it increased slightly and remained elevated even at year 10. This late increase in the overall hazard rate was associated with late increases in the hazard rate in men with favorable prognostic factors, namely pretreatment PSA less than 10 ng./ml., Gleason score less than 5, clinical T stage T1 or T2, posttreatment PSA nadir less than 0.99 ng./ml. or radiation dose less than 68 Gy. In 13 of the 307 patients (3.9%) with biochemical failure the failure occurred more than 5 years after initial treatment. The peak risk of biochemical failure is 2 years after radiotherapy. Patients are at slight but persistent risk for biochemical failure more than 5 years after treatment. Hazard rate calculations beyond the median followup of 4 years can underestimate the true hazard.

Outcome, morbidity, and prognostic factors in post-prostatectomy radiotherapy: an Australian multicenter study

Objectives To report the outcome and morbidity data for patients treated with post-prostatectomy radiotherapy (PPRT) in a multicenter collaboration. Methods The case records of all patients treated with PPRT from 1996 to 1998 were reviewed. Survival was calculated using Kaplan-Meier methods. Potential prognostic factors were evaluated using the Cox proportional hazards regression model. Prostate-specific antigen (PSA) remission was defined as a PSA level of 0.2 ng/mL or less. Acute and late morbidities were documented. Results We reviewed the data of 115 patients, with a median follow-up from the start of PPRT of 28.7 months. Patients were treated with adjuvant intent (n = 23), for local recurrence (n = 27), or for a detectable PSA level (n = 65). The overall and cause-specific survival rate at 5 years was 73.7% and 81.4%, respectively. The biochemical disease-free survival rate was 69.6% at 2 years and 50% at 5 years. Factors predicting for subsequent relapse on multivariate analysis were pre-PPRT PSA ( P = 0.013) and post-PPRT nadir ( P <0.0001). Patients with a PSA greater than 1 ng/mL fared significantly worse than those with lower levels ( P <0.0001). For patients with a pretreatment PSA of less than 1 ng/mL and an operative Gleason score of 7 or less, the 5-year projected biochemical disease-free survival rate was 71%. One case of grade 3 late proctitis was recorded, and 4 patients had continued grade 3 late urinary incontinence. Conclusions Early use of PPRT is effective and well tolerated in patients at risk of, or with proven, local recurrence.

Prostate Specific Antigen Bounce Phenomenon After External Beam Radiation for Clinically Localized Prostate Cancer.

We characterize the prostate-specific antigen (PSA) bounce in patients who underwent external beam radiation therapy for prostate cancer and correlate the PSA bounce with the development of biochemical disease progression. In this study 964 patients received full dose radiation therapy alone. Followup PSA values were obtained 3 months after completion of radiotherapy and every 3 to 6 months thereafter. Median followup of the entire study group was 48 months. All time intervals were calculated from the completion date of radiation therapy. PSA bounce was defined as an initial increase in serum PSA of at least 0.5 ng./ml., followed by a decrease to pre-bounce baseline serum PSA values no more than 60 months after external beam radiation therapy. Of the 964 patients 119 (12%) had a PSA bounce. PSA bounce was unrelated to age, race, pretreatment PSA, Gleason score, clinical T stage or radiation dose. Mean time to PSA bounce was 9 months from the time of therapy. The respective 1 and 5-year biochemical disease-free survival rates were 100% and 82.1% for patients with PSA bounce and 93.9% and 57.7% for those without PSA bounce (p = 0.0001). Of men with prostate cancer treated with external beam radiation therapy 12% experienced a transient increase in PSA (PSA bounce) followed by a return to pre-bounce levels after radiation. The PSA bounce phenomenon was not predictive of time to biochemical recurrence.

Biochemical Disease-Free Survival in Men Younger Than 60 Years With Prostate Cancer Treated With External Beam Radiation

We determined the biochemical failure rate in patients 60 years and younger, and older than 60 years old who were treated with external beam radiation for localized prostate cancer or locally advanced prostate cancer. We also evaluated prognostic factors in the 2 age groups. We reviewed the medical records of 964 patients who received full dose radiotherapy as the only treatment for prostate cancer. Followup prostate specific antigen was measured 3 to 6 months after the completion of radiotherapy and every 3 to 6 months thereafter. Biochemical failure was defined using the criteria established by the American Society for Therapeutic Radiology and Oncology Consensus Panel. Median followup in the whole study group was 48 months. Of the 98 men 60 years or younger 46 (47%) had biochemical failure, whereas 261 (30%) of the 866 older than 60 years old had biochemical failure. The 5 and 7-year biochemical disease-free survival rates were 55% and 47% in the younger men, and 65% and 59% in the older men, respectively. These rates were significantly lower in the younger men (p = 0.017 and 0.027, respectively). Multivariate regression showed that in men 60 years or younger initial prostate specific antigen, Gleason score and lower radiation doses were predictive of biochemical failure. Men with prostate cancer who are 60 years or younger and treated with radiotherapy may be at significant risk for long-term biochemical failure.

Biochemical outcome for hormone-naïve patients with high-risk prostate cancer managed with permanent interstitial brachytherapy and supplemental external-beam radiation.

The purpose of this article is to report the 5-year biochemical disease-free outcome for hormone-naive patients with high-risk disease who underwent permanent prostate brachytherapy. Multiple clinical and treatment parameters were also evaluated to determine whether any of these influence biochemical outcome. Sixty-six hormone-naïve patients underwent transperineal ultrasound-guided permanent prostate brachytherapy with generous periprostatic margins by use of either 103Pd or 125I for high-risk prostate cancer from April 1995 to October 1999. High-risk patients presented with two or three of the following risk factors: Gleason score > or = 7, prostate-specific antigen > or = 10 ng/mL, and clinical stage > or = T2b, 1997 AJCC. No patient underwent pathological lymph node staging. Only one patient was implanted with monotherapy, whereas 65 patients received supplemental external-beam radiation therapy before a prostate brachytherapy boost. The median patient age was 69 years (range, 50-81 years). No patient was lost to follow-up. The mean follow-up and median follow-up were 53.2 +/- 14.9 months and 53.7 months, respectively (range, 19.8-79.7 months). Follow-up was calculated from the day of implantation. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiology and Oncology consensus definition. Clinical parameters evaluated for biochemical disease-free survival included patient age, clinical stage, Gleason score, and pretreatment prostate-specific antigen. Treatment parameters included use of supplemental external-beam radiation therapy and choice of isotope. The 5-year actuarial biochemical disease-free survival rate was 79.9%. In multivariate analysis, preimplantation prostate-specific antigen (P = 0.008) was the only clinical or treatment parameter that predicted for biochemical failure. The mean and median posttreatment prostate-specific antigen levels were 0.13 +/- 0.22 ng/mL and < 0.1 ng/mL, respectively. At a median follow-up of 53.7 months, hormone-naive patients with high-risk disease who undergo permanent prostate brachytherapy have a high probability of 5-year biochemical disease-free survival and an apparent plateau on the biochemical disease-free survival curve.

Biochemical outcome for hormone-naive patients with Gleason score 3+4 versus 4+3 prostate cancer undergoing permanent prostate brachytherapy

Objectives. To determine the effect of the dominant pattern in Gleason score 7 histologic findings on biochemical no evidence of disease survival for hormone-naive patients undergoing permanent prostate brachytherapy. Methods. A total of 114 hormone-naive patients with Gleason score 7 histologic findings underwent transperineal ultrasound-guided permanent prostate brachytherapy for clinical T1c-T3a NxM0 adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. Sixty-four patients were diagnosed with Gleason score 3+4 and 50 with Gleason score 4+3 prostate cancer. Twenty-one patients were implanted with either palladium 103 or iodine 125 monotherapy, and 93 patients received supplemental external beam radiotherapy with a brachytherapy boost. The median patient age was 69 years (range 49 to 79). The median follow-up was 46.4 months (range 20 to 80). The American Society for Therapeutic Radiology and Oncology consensus definition was used to determine the biochemical disease-free survival. Results. The actuarial 5-year biochemical disease-free survival rate was 90.3%. No statistically significant difference in outcome was found when stratified by the dominant pattern in Gleason score 7 histologic features (89.4% versus 91.5% for 3+4 and 4+3, respectively, P = 0.700). The biochemical no evidence of disease survival analysis in terms of the Gleason cohorts revealed no difference in terms of the choice of isotope, use of supplemental external beam radiotherapy, or preimplant prostate-specific antigen level. The median and mean postimplant prostate-specific antigen level was less than 0.1 ng/mL and 0.12 ± 0.20 ng/mL, respectively, without a significant difference between Gleason score 3+4 and 4+3. Conclusions. Our results indicate that the 5-year biochemical outcome with a hormone-naive prostate brachytherapy approach that uses multiple periprostatic seeds is not dependent on Gleason score 3+4 versus 4+3 histologic features.

Locally advanced prostate cancer

Standard therapy for clinically localized prostate cancer includes radical prostatectomy, external beam radiotherapy, or transperineal interstitial brachytherapy. Patients eligible for standard therapy are those with low risk features as defined by various risk group classifications, which generally include clinical stage T1 or T2a, serum prostate-specific antigen (PSA) less than 10 ng/mL, and biopsy Gleason sum of 6 or less. Although there has been important evolution in the performance of these techniques, particularly with respect to functional outcomes, these approaches for low-risk disease are relatively mature, and the cure rates with each of these therapies are similar in this patient population; locally advanced disease is more difficult to cure, however. Biochemical disease-free survival rates in men undergoing radical prostatectomy are clearly related to the pathologic stage. Prognostic groups can be defined based on pathologic stage with increasingly worse outcomes based on extracapsular extension (ECE), margin status, and the status of the lymph nodes and seminal vesicles. In patients with low risk features, the positive margin rate is generally low, making the presence or absence of ECE the dominant variable in predicting the likelihood of treatment failure. These observations suggest that more aggressive therapy is needed to cure those who are likely to have ECE or other adverse histologic features. Several nomograms predicting the likelihood of ECE or 5-year biochemical failure rates are now in routine clinical use, and can be used to select men at high risk of failure with single modality therapy for more aggressive treatment strategies. However, the optimal form of aggressive therapy for these patients is unknown.

Five-year biochemical outcome after prostate brachytherapy for hormone-naive men ≤ 62 years of age

Purpose: To evaluate 5-year biochemical disease-free outcome for hormone naı̈ve men 62 years of age or less who underwent transperineal ultrasound-guided permanent prostate brachytherapy. Methods and Materials: 76 patients underwent transperineal ultrasound guided prostate brachytherapy using either 103Pd or 125I for clinical T1b–T2b N×M0 (1997 AJCC) adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up, and no patient underwent pathologic lymph-node staging. 47 patients were implanted with either 103Pd or 125I monotherapy, and 29 patients received moderate-dose external-beam radiation therapy followed by a prostate brachytherapy boost. No patient received hormonal manipulation. The median patient age was 58 years (range, 48–62 years). The median follow-up was 37 months (range, 14–70 months). Follow-up was calculated from the day of implantation. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiation and Oncology (ASTRO) consensus definition. Results: The actuarial 5-year biochemical disease-free survival rate was 98.7%. For patients with low-, intermediate-, and high-risk disease, 97.7%, 100%, and 100%, respectively, were free of biochemical failure. The median posttreatment prostate-specific antigen (PSA) for the entire group was 0.2 ng/mL. When stratified by risk group, the median posttreatment PSA was 0.2, 0.15, and 0.1 for patients with low-, intermediate-, and high-risk disease, respectively. Conclusion: With a median follow-up of 37 months, hormone naı̈ve patients ≤ 62 years of age have a high probability of 5-year biochemical disease-free survival following permanent prostate brachytherapy with an apparent plateau on the PSA curve.

PSA based review of adjuvant and salvage radiation therapy vs. observation in postoperative prostate cancer patients

Because of the uncertainties regarding the efficacy of postoperative radiation therapy for early prostate cancer, treatment strategies following radical prostatectomy include: (1) observation alone in high-risk patients, (2) adjuvant radiation therapy (PSA undetectable) in high-risk patients, or (3) salvage radiation therapy for biochemical and clinical recurrence. Fifty-two patients treated with postoperative radiation therapy in either an adjuvant setting (13) or for salvage (39) were retrospectively reviewed. The actuarial biochemical disease-free survival (bNED) rates following radiation therapy were calculated using the life-table method. Univariate and multi variate analyses were used to define the clinical factors that predict biochemical failure following postoperative radiation therapy. In addition, the bNED survival rate for 36 high-risk surgery patients who were simply observed following prostatectomy was determined. The 3-year bNED survival rate for the adjuvant radiation group was 85% compared with 27% for salvage radiation and 43% for the observation group. These results are statistically significant. Factors that predict biochemical failure following postoperative radiation therapy include preoperative PSA level, pre-radiation therapy PSA level, and seminal vesicle involvement. At our institutions, adjuvant radiation therapy was a superior strategy compared with either observation alone or salvage radiation therapy for high-risk postoperative prostate cancer patients. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 29–36 (2000). © 2000 Wiley-Liss, Inc.

PSA based review of adjuvant and salvage radiation therapy vs. observation in postoperative prostate cancer patients

Because of the uncertainties regarding the efficacy of postoperative radiation therapy for early prostate cancer, treatment strategies following radical prostatectomy include: (1) observation alone in high-risk patients, (2) adjuvant radiation therapy (PSA undetectable) in high-risk patients, or (3) salvage radiation therapy for biochemical and clinical recurrence. Fifty-two patients treated with postoperative radiation therapy in either an adjuvant setting (13) or for salvage (39) were retrospectively reviewed. The actuarial biochemical disease-free survival (bNED) rates following radiation therapy were calculated using the life-table method. Univariate and multi variate analyses were used to define the clinical factors that predict biochemical failure following postoperative radiation therapy. In addition, the bNED survival rate for 36 high-risk surgery patients who were simply observed following prostatectomy was determined. The 3-year bNED survival rate for the adjuvant radiation group was 85% compared with 27% for salvage radiation and 43% for the observation group. These results are statistically significant. Factors that predict biochemical failure following postoperative radiation therapy include preoperative PSA level, pre-radiation therapy PSA level, and seminal vesicle involvement. At our institutions, adjuvant radiation therapy was a superior strategy compared with either observation alone or salvage radiation therapy for high-risk postoperative prostate cancer patients. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 29-36 (2000).

The impact of race on biochemical disease-free survival in early-stage prostate cancer patients treated with surgery or radiation therapy

Purpose: To assess the impact of race on biochemical freedom from recurrence in patients with early-stage prostate cancer treated either by radical prostatectomy or radiation therapy. Methods: Between July 1989 and December 1994, 693 patients with early-stage prostate cancer were treated with radiation (302 patients) or by radical prostatectomy (391 patients) at Barbara Ann Karmanos Cancer Institute/Wayne State University. Stage, Gleason score, race, pretreatment PSA, and follow-up PSA values were abstracted. There were 387 Caucasian males (CM) and 306 African-American males (AAM). None of the patients received hormone therapy. Radiation therapy was delivered using photon irradiation (249 patients, median dose 69 Gy) or mixed neutron/photon irradiation (53 patients, median dose 10 NGy + 38 PGy). Median follow-up was 36 months (range 2–70) for CM and 35 months (range 1–70) for AAM. Results: Thirty-seven percent of patients treated surgically were AAM, compared to 53% in the radiation group ( p = 0.0001). AAM had a higher median prostate-specific antigen (PSA) than CM (9.78 ng/ml vs. 8.0 ng/ml, p = 0.01). Thirty-three percent of AAM had a pretreatment PSA greater than 15 ng/ml compared to 20% of CM ( p = 0.00001). Disease-free survival (DFS) by race was equivalent at 36 months, 81% for CM and 77% for AAM ( p = NS). For patients with PSA ≤ 15, DFS rates were 87% and 85% for CM and AAM, respectively. DFS rates for patients with PSA > 15 were 61% for CM and 64% for AAM ( p = NS). Significant prognostic factors on multivariate analysis included pretreatment PSA ( p = 0.0001) and Gleason score ( p = 0.0001). Conclusion: Race does not appear to adversely affect biochemical disease-free survival in males treated for early-stage prostate cancer. African-American males with early-stage prostate cancer should expect similar biochemical disease-free survival rates to those seen in Caucasian males.