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Alan Pollack

Publications and source records attributed to Alan Pollack.

At least 73 records · Page 4Linked to original sources

Free prostate-specific antigen improves prostate cancer detection in a high-risk population of men with a normal total PSA and digitalrectal examination.

OBJECTIVES: Uncertainty exists regarding optimal prostate cancer screening parameters for high-risk populations. The purpose of this study is to report the use of percent free prostate-specific antigen (PSA) as an indication for biopsy in men at increased risk for developing prostate cancer who have a normal digital rectal examination (DRE) and total PSA level between 2 and 4 ng/mL. METHODS: African-American men and men with at least one first-degree relative with prostate cancer are eligible for enrollment into the Prostate Cancer Risk Assessment Program (PRAP) at our institution. Between October 1996 and April 2002, 310 asymptomatic high-risk men with no history of prostate cancer, benign prostatic hyperplasia (BPH), or prostatic intraepithelial neoplasia (PIN) were screened in the PRAP with DRE and total PSA. Percent free PSA was obtained in men with a total PSA between 2 and 10 ng/mL. Men with a normal DRE and total PSA between 2 and 4 ng/mL were advised to undergo transrectal ultrasound-guided (TRUS) biopsies of the prostate if the percent free PSA was less than 27%. Other indications for biopsy included an abnormal DRE or a total PSA greater than 4 ng/mL. The primary endpoint evaluated was prostate cancer detection in high-risk men with a benign prostate examination, a normal total PSA between 2 and 4 ng/mL, and percent free PSA less than 27%. RESULTS: Of the 310 men, 174 (56%) were African American and 202 (65%) had at least one first-degree relative with prostate cancer. Sixty-two of the 310 men were referred for prostate biopsy, and 40 of 62 had biopsy performed. Twenty-one of 40 men were diagnosed with prostate cancer for a cancer detection rate of 53% in all men undergoing biopsy and an overall cancer detection rate of 6.8% in this high-risk population. Thirty-seven high-risk men (median age 54 years) with a total PSA level between 2 and 4 ng/mL (median 2.7 ng/mL) and a normal DRE were found to have a percent free PSA level of less than 27% (median 16%, range 8% to 25%). Twenty-three of these 37 men (62%) proceeded with the recommended prostate biopsy. Prostatic adenocarcinoma was diagnosed in 12 of 23 men for a cancer detection rate of 52% in men undergoing biopsy and 32% in all men with a normal DRE, a total PSA between 2 and 4 ng/mL, and a percent free PSA less than 27%. All positive biopsies demonstrated clinically significant Gleason score 6 or 7 disease. In all men electing radical prostatectomy, bilateral organ-confined disease (pT2bN0M0) was confirmed. CONCLUSIONS: In this unique population of men at high risk for prostate cancer, a percent free PSA of less than 27% was found to be useful for detecting early-stage but clinically significant cancers in men with a total PSA value between 2 and 4 ng/mL and normal DRE findings.

Biopsy, Needle↗

Positive prostate biopsy laterality and implications for staging.

OBJECTIVES: To examine the effect of including positive prostate biopsy information in palpation staging (2002 system) and the influence of this information on freedom from biochemical failure (bNED). Prostate biopsy laterality status (unilateral versus bilateral positive) is part of clinical staging using American Joint Commission on Cancer criteria, but is rarely used. METHODS: From April 1, 1989 to September 30, 1999, 1038 patients with palpable T1-T3Nx-0M0 prostate cancer were treated with three-dimensional conformal radiotherapy alone. Kaplan-Meier bNED curves were compared using the log-rank test. The Cox proportional hazards regression model of bNED was used for multivariate analysis. RESULTS: The median follow-up was 46 months. The proportion of patients with bilateral positive biopsies by palpation category T1c was 24%, by T2a was 17%, by T2b was 26%, by T2c was 65%, and by T3 was 53%. No statistically significant difference was noted in bNED on the basis of biopsy laterality status for the palpation T stages T1c, T2a, T2b, or T3. A statistically significant difference in the 5-year bNED in the T2c stage was found; those with unilateral positive biopsies fared worse (46% versus 74%, respectively, P = 0.04). CONCLUSIONS: Inclusion of positive biopsy laterality status into clinical staging causes stage migration without reflecting a change in outcome and should not be used.

Aged↗

Quality-of-life questionnaire results 2 and 3 years after radiotherapy for prostate cancer in a randomized dose-escalation study.

OBJECTIVES: To assess patient-reported prostate cancer-specific quality of life 2 and 3 years after radiotherapy to the prostate in a randomized dose-escalation trial of 70 versus 78 Gy conducted from 1993 to 1998. METHODS: Two years after completing radiotherapy, a questionnaire that assessed bladder, rectal, and sexual function was sent to 301 patients in the study. Three years after treatment, a second questionnaire was sent to the 175 patients with adequate follow-up. RESULTS: Three years after radiotherapy, urinary incontinence was reported by 35% of patients, but only 6% required the use of a pad or other protective device. Patients reported increased leakage with a full bladder (urge incontinence) between the 2 and 3-year questionnaires (42% versus 50%; P = 0.03). At 3 years, 33% of patients reported rectal bleeding compared with 47% at 2 years (P = 0.006). Patients in the 78-Gy arm reported more frequent bowel movements at 3 years and less change in bowel function at 2 years than patients in the 70-Gy arm. Before radiotherapy, 84% of patients reported erections adequate for intercourse at least a few times during the previous year. After 2 and 3 years, this had decreased to 49% and 41%, respectively (P <0.02). CONCLUSIONS: By patient-reported questionnaire, 78 Gy produced an increase in bowel movement frequency and no increase in bladder or sexual side effects at 3 years compared with 70 Gy. Comparing the results 2 and 3 years after radiotherapy, the symptoms of rectal bleeding had improved, erectile function had decreased, and urinary urge incontinence had increased.

Adenocarcinoma↗

Mindless or mindful? Radiation oncologists' perspectives on the evolution of prostate cancer treatment.

The evolution of radiation therapy treatment for prostate cancer has been striking over the last 10 years. Advances in brachytherapy (BT), external beam radiotherapy (EBRT), and the combination of EBRT + BT have led to improved biochemical and clinical results. This article describes these advances in the context of the treatment decision process. Key to this process is the assignment of patient risk, which is based on the results of conventional radiation dose and techniques. Using the 1992 AJCC palpation staging system, Gleason score, and pretreatment prostate-specific antigen, two different risk assessment algorithms were compared. Both gave comparable approximations of risk, although the single factor high-risk model was superior in differentiating those patients with the highest probability of failing treatment after radiotherapy. Such criteria are the foundation for treatment selection. Objective findings support BT alone or EBRT alone for low-risk patients, high-dose EBRT or EBRT + BT for intermediate-risk patients, and EBRT + androgen deprivation for high-risk patients. In summary, advances in radiation oncology have led to significant gains in prostate cancer control. Clinical prognostic factor-based patient selection is central to the optimization of outcome.

Brachytherapy↗

Treatment of prostate cancer with regional lymph node (N1) metastasis.

Prostate cancer with pathologically documented regional lymph node positive disease has been associated with a dismal prognosis in the past. Clinical and/or biochemical progression is evident within 5 years in over 50% treated with external-beam radiotherapy (EBRT) alone, radical prostatectomy (RP) alone, or androgen deprivation (AD) alone. By 10 years after treatment, greater than 75% progress and over half succumb to prostate cancer. In contrast, the results with the combination of EBRT + AD or RP + AD have been very promising. Ten-year biochemical progression and overall survival rates are roughly 20% and 70%, respectively, for patients with subclinical lymph node involvement. Patients with a 10-year life expectancy should be treated aggressively with long-term AD combined with either EBRT or RP.

Androgen Antagonists↗

Hazard rates of disease progression after external beam radiotherapy for clinically localized carcinoma of the prostate.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Carcinoma↗

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.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗

Clinical, demographic and psychosocial correlates of complementary and alternative medicine use by men diagnosed with localized prostate cancer.

PURPOSE: We examined complementary and alternative medicine (CAM) use among men who received standard therapy for localized prostate cancer. MATERIALS AND METHODS: A total of 417 men completed a questionnaire 6 months after their treatment decision assessing clinical and psychosocial variables and use of 41 available CAM therapies grouped into the 2 general categories of herbal/dietary and nonherbal (i.e. mind-body, bioelectromagnetic, traditional/folk medicine, pharmacological/biological). RESULTS: The prostate cancer diagnosis prompted 19% of our sample to start using some form of CAM for prostate health, and 67% of men reported having used some form of CAM for prostate health before being diagnosed. Initiation of CAM was associated with being a member of an ethnic minority group and a higher level of education. Initiation of nonherbal CAM was associated with being married, while use of herbal CAM therapies was significantly associated with choosing observation. Herbal use before diagnosis was associated with being white, higher level of education and being single. Prostate specific antigen at diagnosis, Gleason score, quality of life, participant perceptions of seriousness of prostate cancer or self-reported worry about prostate cancer were not related to initiation or prior use. Of those men reporting current use almost 50% did not inform their treating physician of using CAM therapies. CONCLUSIONS: Initiation of CAM therapies as a result of a prostate cancer diagnosis was fairly low, although two-thirds of men had used it before diagnosis. Half of the patients did not inform their physicians about such use and physicians should continue to probe patients about CAM use.

Adult↗

Late rectal toxicity: dose-volume effects of conformal radiotherapy for prostate cancer.

PURPOSE: To identify dosimetric, anatomic, and clinical factors that correlate with late rectal toxicity after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. METHODS AND MATERIALS: We retrospectively analyzed the dose-volume histograms and clinical records of 163 Stage T1b-T3c prostate cancer patients treated between 1992 and 1999 with 3D-CRT, to a total isocenter dose of 74-78 Gy at The University of Texas M. D. Anderson Cancer Center. The median follow-up was 62 months (range 24-102). All late rectal complications were scored using modified Radiation Therapy Oncology Group and Late Effects Normal Tissue Task Force criteria. The 6-year toxicity rate was assessed using Kaplan-Meier analysis and the log-rank test. A univariate proportional hazards regression model was used to test the correlation between Grade 2 or higher toxicity and the dosimetric, anatomic, and clinical factors. In a multivariate regression model, clinical factors were added to the dosimetric and anatomic variables to determine whether they significantly altered the risk of developing late toxicity. RESULTS: At 6 years, the rate of developing Grade 2 or higher late rectal toxicity was 25%. A significant volume effect was observed at rectal doses of 60, 70, 75.6, and 78 Gy, and the risk of developing rectal complications increased exponentially as greater volumes were irradiated. Although the percentage of rectal volume treated correlated significantly with the incidence of rectal complications at all dose levels (p <0.0001 for all comparisons), the absolute rectal volume appeared to be a factor only at the higher doses of 70, 75.6, and 78 Gy (p = 0.0514, 0.0016, and 0.0021, respectively). The following variables also correlated with toxicity on the univariate analysis: maximal dose to the clinical target volume, maximal dose to rectum, maximal dose to the rectum as a percentage of the prescribed dose, and maximal dose delivered to 10 cm(3) of the rectum. Of the clinical variables tested, only a history of hemorrhoids correlated with rectal toxicity (p = 0.003). Multivariate analysis showed that the addition of hemorrhoids increased the risk of toxicity for each dosimetric variable found to be significant on univariate analysis (p <0.05 for all comparisons). CONCLUSION: Dose-volume histogram analyses clearly indicated a volume effect on the probability of developing late rectal complications. Therefore, dose escalation may be safely achieved by adherence to dose-volume histogram constraints during treatment planning and organ localization at the time of treatment to ensure consistent patient setup.

Aged↗

Interim report of toxicity from 3D conformal radiation therapy (3D-CRT) for prostate cancer on 3DOG/RTOG 9406, level III (79.2 Gy).

PURPOSE: A prospective Phase I dose escalation study was conducted to determine the maximally tolerated radiation dose in men treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. This is a preliminary report of toxicity at Level III (79.2 Gy) on 3D Oncology Group/Radiation Therapy Oncology Group (RTOG) 9406. METHODS AND MATERIALS: Between November 26, 1996 and October 1, 1998, 173 patients with clinically organ-confined prostate cancer (T1 and T2) were accrued to a Level III dose of 79.2 Gy. One hundred sixty-nine patients were available for analysis of toxicity. Patients were registered to two groups according to the risk of seminal vesicle invasion (SVI) on the basis of presenting PSA and Gleason score. Group 1 patients had a calculated risk of SVI <15%, and Group 2 patients had a risk of SVI > or = 15%. For Group 1 patients, the planning target volume (PTV) margins were 5-10 mm around the prostate only. For Group 2 patients, the same margins were applied to the prostate and seminal vesicles (PTV(1)) for the initial 55.8 Gy; then treatment volume was reduced to the prostate only (PTV(2)). To reduce the rectal dose on dose Level III, the minimum PTV dose was limited to 73.8 Gy, whereas the minimum gross target volume dose was 79.2 Gy, both in 44 fractions. The incidence of > or = 3 Grade late effects was compared to that in a similar group of patients treated on RTOG 7506 and 7706 studies. RESULTS: Acute tolerance to 79.2 Gy was excellent with no patients experiencing > or = Grade 3 acute toxicity. The acute toxicity rate was comparable to that reported for previous lower dose levels. With the median follow-up of 3.3 years (range: 0.4-4.4 years), a total of 4 patients (2.4%) experienced Grade 3 late toxicity, three cases of which were related to the bladder, and one related to the rectum. There were no Grade 4 or 5 late complications noted during the period of observation. These results are also comparable to those reported at dose Levels I and II. The expected incidence of > or = 3 Grade 3 late toxicity was calculated using historical data from two previous RTOG prostate cancer trials, 7506 and 7706. The calculated risk accounted for the difference in follow-up duration between patients in this study and the historical experience. The observed rate of > or = Grade 3 late effects for Group 1 (two cases) is significantly lower (p = 0.0002) than the 17.6 cases that would have been expected from the historical control. The observed rate for Group 2 (two cases) was also significantly lower (p = 0.0037) than the 12.1 cases expected. CONCLUSION: Based on excellent tolerance of 3D-CRT for stages T1 and T2 prostate cancer, further biological dose escalation has been pursued to Levels IV and V, 74 Gy and 78 Gy, respectively, at 2 Gy per day, in an attempt to reduce the total treatment duration. This trial has closed. A Phase III comparative RTOG trial is being developed to determine whether high-dose 3D-CRT improves efficacy.

Adult↗

Prostate biopsy status and PSA nadir level as early surrogates for treatment failure: analysis of a prostate cancer randomized radiation dose escalation trial.

PURPOSE: A positive biopsy after external beam radiotherapy in patients free of any evidence of treatment failure is not synonymous with eventual recurrence. Although biopsy positivity is a predictor of outcome, the utility of biopsy status as a surrogate end point, the effect of radiation dose on biopsy status, and the interrelationships of these associations to prostate-specific antigen (PSA) nadir level are not well-defined. These issues were investigated in a cohort of men with Stage T1-T3 prostate cancer who were randomized to receive between 70 Gy and 78 Gy and were prospectively biopsied at about 2 years after the completion of radiotherapy (RT). METHODS AND MATERIALS: Of the 301 assessable patients in the trial, 168 underwent planned sextant or greater prostate post-RT biopsies in the absence of biochemical or clinical failure; this group constituted the study cohort. Of the 168 patients, 87 were in the 70-Gy arm and 81 in the 78-Gy arm. Biopsies were classified into four groups: negative (no tumor), atypical/suspicious cells (not diagnostic of carcinoma), carcinoma with treatment effect (CaTxEffect), and carcinoma without treatment effect (CaNoTxEffect). Any diagnosis of carcinoma in the specimen was classified as biopsy positive. Freedom from failure (FFF) included biochemical failure and/or clinical failure. Kaplan-Meier curves were calculated from the completion of RT. For those alive in the study cohort, the median follow-up was 65 months. RESULTS: The rate of biopsy without tumor was 42%; with atypical cells, it was 28%, with CaTxEffect 21%, and with CaNoTxEffect 9%. The overall biopsy positivity rate (CaTxEffect + CaNoTxEffect) was 30%; 28% in the 70-Gy group and 32% in the 78-Gy group (p = 0.52). The distribution of PSA nadir levels was 73% 0.5-1.0, 5% >1.0-2.0, and 1% >2.0 ng/mL. Significantly more patients randomized to 78 Gy had a PSA nadir of 2.0 ng/mL. CONCLUSION: For patients free of treatment failure at the time of prostate biopsy 2 years after RT, the prognosis of no tumor cells was the same as that of atypical/suspicious cells and CaTxEffect was the same as CaNoTxEffect. The biopsy positivity rate was not altered by dose, suggesting that most of the outcome differences between the 70-Gy and 78-Gy groups were due to events occurring before prostate biopsy at 2 years and/or were not entirely dependent on biopsy status. Biopsy status is a strong prognostic factor, but, as an early end point, it may be misleading. PSA nadir appears to have little clinical value in patients treated to doses of >/=70 Gy who are failure free 2 years after RT.

Aged↗

Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial.

PURPOSE: A randomized radiotherapy dose escalation trial was undertaken between 1993 and 1998 to compare the efficacy of 70 vs. 78 Gy in controlling prostate cancer. METHODS AND MATERIALS: A total of 305 Stage T1-T3 patients were entered into the trial and, of these, 301 with a median follow-up of 60 months, were assessable. Of the 301 patients, 150 were in the 70 Gy arm and 151 were in the 78 Gy arm. The primary end point was freedom from failure (FFF), including biochemical failure, which was defined as 3 rises in the prostate-specific antigen (PSA) level. Kaplan-Meier survival analyses were calculated from the completion of radiotherapy. The log-rank test was used to compare the groups. Cox proportional hazard regression analysis was used to examine the independence of study randomization in multivariate analysis. RESULTS: There was an even distribution of patients by randomization arm and stage, Gleason score, and pretreatment PSA level. The FFF rates for the 70- and 78 Gy arms at 6 years were 64% and 70%, respectively (p = 0.03). Dose escalation to 78 Gy preferentially benefited those with a pretreatment PSA >10 ng/mL; the FFF rate was 62% for the 78 Gy arm vs. 43% for those who received 70 Gy (p = 0.01). For patients with a pretreatment PSA 10 ng/mL who were treated to 78 Gy (98% vs. 88% at 6 years, p = 0.056). Rectal side effects were also significantly greater in the 78 Gy group. Grade 2 or higher toxicity rates at 6 years were 12% and 26% for the 70 Gy and 78 Gy arms, respectively (p = 0.001). Grade 2 or higher bladder complications were similar at 10%. For patients in the 78 Gy arm, Grade 2 or higher rectal toxicity correlated highly with the proportion of the rectum treated to >70 Gy. CONCLUSION: An increase of 8 Gy resulted in a highly significant improvement in FFF for patients at intermediate-to-high risk, although the rectal reactions were also increased. Dose escalation techniques that limit the rectal volume that receives >or=70 Gy to <25% should be used.

Aged↗

Intrafraction prostate motion during IMRT for prostate cancer.

PURPOSE: Although the interfraction motion of the prostate has been previously studied through the use of fiducial markers, CT scans, and ultrasound-based systems, intrafraction motion is not well documented. In this report, the B-mode, Acquisition, and Targeting (BAT) ultrasound system was used to measure intrafraction prostate motion during 200 intensity-modulated radiotherapy (IMRT) sessions for prostate cancer. METHODS AND MATERIALS: Twenty men receiving treatment with IMRT for clinically localized prostate cancer were selected for the study. Pre- and posttreatment BAT ultrasound alignment images were collected immediately before and after IMRT on 10 treatment days for a total of 400 BAT alignment procedures. Any ultrasound shifts of the prostate borders in relation to the planning CT scan were recorded in 3 dimensions: right-left (RL), anteroposterior (AP), and superior-inferior (SI). Every ultrasound procedure was evaluated for image quality and alignment according to a 3-point grading scale. RESULTS: All the BAT images were judged to be of acceptable quality and alignment. The dominant directions of intrafraction prostate motion were anteriorly and superiorly. The mean magnitude of shifts (+/-SD) was 0.01 +/- 0.4 mm, 0.2 +/- 1.3 mm, and 0.1 +/- 1.0 mm in the left, anterior, and superior directions, respectively. The maximal range of motion occurred in the AP dimension, from 6.8 mm anteriorly to 4.6 mm posteriorly. The percentage of treatments during which prostate motion was judged to be 5 mm. The extent of intrafraction motion was much smaller than that of interfraction motion. Linear regression analysis showed very little correlation between the two types of motion (r = 0.014, 0.029, and 0.191, respectively) in the RL, AP, and SI directions. CONCLUSION: Using an ultrasound-based system, intrafraction prostate motion occurred predominantly in the anterior and superior directions, but was clinically insignificant. Intrafraction motion was much smaller than interfraction motion, and the two types of movement did not correlate.

Humans↗

Prostate specific antigen bounce phenomenon after external beam radiation for clinically localized prostate cancer.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Aged↗

Impact of androgen deprivation therapy on survival in men treated with radiation for prostate cancer.

A number of retrospective and randomized trials have studied the effect of external-beam radiation therapy (EBRT) plus androgen deprivation therapy (ADT) on locally advanced/high-risk prostate cancer. Of 6 published randomized trials that have compared EBRT plus ADT with EBRT alone, 2 have shown a highly significant overall survival benefit for EBRT plus ADT, and 2 have demonstrated an advantage for the combination in patient subsets based on Gleason score. The results from the positive trials of EBRT plus ADT versus EBRT alone, as well as a recent report of a comparison of short-term (6 months) ADT plus EBRT versus long-term (>6 months) ADT plus EBRT, suggest that short-term ADT plus EBRT preferentially lengthens the survival of patients with Gleason score 2 to 6 disease, whereas for Gleason score 8 to 10 disease, prolongation of survival requires long-term ADT plus EBRT. These data are far from clear-cut because there are factors that confound interpretation of the subgroup analyses. Retrospective data on patients with positive lymph node status support the assertion that EBRT plus ADT prolongs survival to a greater degree than either treatment given individually. The weight of the available investigations on the survival effect of EBRT plus ADT supports its use on a routine basis for patients with high-risk prostate cancer. The results with long-term ADT are much more convincing than short-term ADT, and, as a consequence, 2 to 3 years are recommended.

Androgen Antagonists↗

Hypoxic prostate/muscle pO2 ratio predicts for biochemical failure in patients with prostate cancer: preliminary findings.

OBJECTIVES: To investigate whether low partial pressure of oxygen (PO2) in prostate cancer (CaP) predicts for biochemical outcome after radiotherapy. We previously reported that hypoxic regions exist in human CaP. METHODS: Custom-made Eppendorf PO2 microelectrodes were used to obtain approximately 100 PO2 readings from both pathologically involved regions of the prostate (as determined by sextant biopsies) and normal muscle (as an internal control). Fifty-seven patients with localized disease were prospectively studied; all received brachytherapy implants (48 low dose rate and 9 high dose rate) under spinal anesthesia. Nine patients had received prior hormonal therapy. Biochemical failure was defined as two consecutive rises in prostate-specific antigen level, without a return to baseline. Cox proportional hazards regression analysis was used to evaluate the influence of hypoxia on biochemical control, while adjusting for prostate-specific antigen, Gleason score, stage, implant type (low dose rate versus high dose rate), perineural invasion, hemoglobin level, use of hormonal therapy, average (mean) of the median prostate PO2, average median muscle PO2, and prostate/muscle PO2 (P/M) ratio. RESULTS: With a median follow-up of 19 months (range 4 to 31), 9 patients developed biochemical failure. A threshold analysis of the P/M ratio demonstrated that biochemical control at 2 years differed significantly at a ratio of less than 0.05 versus 0.05 or greater (31% versus 92%, P <0.0001). However, the classic prognosticators were similar in these two groups. On multivariate analysis, the P/M ratio was the only predictor of biochemical control (P = 0.0002). CONCLUSIONS: To our knowledge, this is the first study to correlate the degree of hypoxia in CaP with treatment outcome after radiotherapy. The P/M PO2 ratio was the strongest predictor for biochemical control on stepwise multivariate analysis. Longer follow up with more patients is planned to confirm this result.

Aged↗