Biomedical subjects

Patrick A Kupelian

Publications and source records attributed to Patrick A Kupelian.

At least 19 recordsLinked to original sources

PubMed2004

Early prostate-specific antigen (PSA) kinetics following prostate carcinoma radiotherapy: prognostic value of a time-and-PSA threshold model.

BACKGROUND: The goal of the current study was to analyze the prognostic value of early prostate-specific antigen (PSA) kinetics, with PSA assessed as reaching or failing to reach discrete threshold values at fixed time points during follow-up after external-beam radiotherapy (EBRT) for prostate carcinoma. METHODS: The authors conducted a retrospective review of PSA follow-up for 839 patients treated between May 1987 and December 2000 at the Cleveland Clinic Foundation (Cleveland, OH). They also assessed the impact on bRFS of PSA levels lower than defined threshold values at given time points during follow-up. RESULTS: During a median follow-up of 74 months (range, 24-189 months), 540 patients (64.4%) maintained bRFS, whereas 299 patients (35.6%) did not maintain bRFS. The median nadir among patients with sustained bRFS was 0.4 ng/mL, with a median time to nadir of 28.9 months. Patients who did not maintain bRFS reached a median nadir of 1.3 ng/mL at a median of 15 months (P < 0.0001 for both nadir level and time to nadir). Reaching PSA thresholds of 3.0, 2.0, 1.0, 0.5, and 0.2 ng/mL at any time during follow-up was correlated with improved bRFS (P < 0.0001, each threshold). Patients whose PSA levels crossed the appropriate thresholds within 3 and 6 months of follow-up, irrespective of the time or level of eventual nadir, exhibited significantly improved bRFS when compared with patients whose PSA levels reached those thresholds at any time during follow-up and patients whose PSA levels never reached those thresholds (all thresholds: P < 0.0001). CONCLUSIONS: Despite previous conclusions that early PSA assessment may lack prognostic value, the data obtained in the current study suggest that the kinetics of early PSA decline is predictive of long-term bRFS when assessed using a time-and-PSA threshold model. After EBRT for prostate carcinoma, PSA levels below various discrete PSA thresholds were indicative of statistically meaningful long-term outcome differences between experimental arms as early as 90 days after radiotherapy. If the time-and-PSA threshold model is shown to be predictive of prostate carcinoma mortality as well, then it may allow the scientific community to evaluate promising treatment concepts and technologies at a highly accelerated pace.

Adenocarcinoma↗

PubMed2004

Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy.

CONTEXT: 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. OBJECTIVE: To delineate patients who may benefit from salvage radiotherapy for prostate cancer recurrence by identifying variables associated with a durable response. DESIGN, SETTING, AND PATIENTS: 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. MAIN OUTCOME MEASURE: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗

PubMed2004

Recurrence-free survival rates after external-beam radiotherapy for patients with clinical T1-T3 prostate carcinoma in the prostate-specific antigen era: what should we expect?

BACKGROUND: The objective of the current study was to report biochemical recurrence-free survival (bRFS) rates among men with T1-T3 prostate carcinoma who were treated with external-beam radiotherapy (RT) at the Cleveland Clinic Foundation (Cleveland, OH). METHODS: In total, 1352 patients were identified between 1987 and 2000 with a minimum follow-up of 1 year (median follow-up, 55 months; range, 12-189 months). The median radiation dose was 74.0 grays (Gy) (range, 63.0-83.0 Gy). The median radiation doses for patients who received < 68.0 Gy (n = 201), 68.0-72.0 Gy (n = 373), and > or = 72.0 Gy (n = 778) were 66.6 Gy, 70.0 Gy, and 78.0 Gy, respectively. The RT techniques used were standard RT in 41% of patients, 3-dimensional conformal RT in 34% of patients, and intensity-modulated RT in 25% of patients. Androgen-deprivation (AD) therapy lasting < or = 6 months was administered to 34% of patients. RESULTS: The 5-year and 7-year bRFS rates were 63% and 59%, respectively. On multivariate analysis, T classification (P < 0.001), pretreatment prostate-specific antigen level (P < 0.001), biopsy Gleason score (P = 0.001), radiation dose (P < 0.001), and year of therapy (P < 0.001) were independent predictors of biochemical failure. Age, race, AD therapy, and RT technique did not predict for biochemical failure. For patients with low-risk tumors, the 5-year bRFS rates for those who received RT doses of < or = 68.0 Gy, 68.0-72.0 Gy, and > or = 72.0 Gy were 52%, 82%, and 93%, respectively (P < 0.001); for patients with intermediate-risk tumors, the respective 5-year bRFS rates were 27%, 51%, and 83% (P < 0.001); and for patients with high-risk tumors, the respective 5-year bRFS rates were 21%, 29%, and 71%, respectively (P < 0.001). CONCLUSIONS: The most significant therapeutic factor affecting bRFS rates after RT was radiation dose, rather than AD therapy use or radiation technique.

Adult↗

PubMed2004

Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy > or =72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer.

PURPOSE: To review the biochemical relapse-free survival (bRFS) rates after treatment with permanent seed implantation (PI), external beam radiotherapy (EBRT) <72 Gy (EBRT <72), EBRT > or =72 Gy (EBRT > or =72), combined seeds and EBRT (COMB), or radical prostatectomy (RP) for clinical Stage T1-T2 localized prostate cancer treated between 1990 and 1998. METHODS AND MATERIALS: The study population comprised 2991 consecutive patients treated at the Cleveland Clinic Foundation or Memorial Sloan Kettering at Mercy Medical Center. All cases had pretreatment prostate-specific antigen (iPSA) levels and biopsy Gleason scores (bGSs). Neoadjuvant androgen deprivation for < or =6 months was given in 622 cases (21%). No adjuvant therapy was given after local therapy. RP was used for 1034 patients (35%), EBRT <72 for 484 (16%), EBRT > or =72 for 301 (10%), PI for 950 (32%), and COMB for 222 patients (7%). The RP, EBRT <72, EBRT > or =72, and 154 PI patients were treated at Cleveland Clinic Foundation. The median radiation doses in EBRT <72 and EBRT > or =72 case was 68.4 and 78.0 Gy, respectively. The median follow-up time for all cases was 56 months (range 12-145). The median follow-up time for RP, EBRT <72, EBRT > or =72, PI, and COMB was 66, 75, 49, 47, and 46 months, respectively. Biochemical relapse was defined as PSA levels >0.2 for RP cases and three consecutive rising PSA levels (American Society for Therapeutic Radiology Oncology consensus definition) for all other cases. A multivariate analysis for factors affecting the bRFS rates was performed using the following variables: clinical T stage, iPSA, bGS, androgen deprivation, year of treatment, and treatment modality. The multivariate analysis was repeated excluding the EBRT <72 cases. RESULTS: The 5-year bRFS rate for RP, EBRT <72, EBRT > or =72, PI, and COMB was 81%, 51%, 81%, 83%, and 77%, respectively (p <0.001). The 7-year bRFS rate for RP, EBRT <72, EBRT > or =72, PI, and COMB was 76%, 48%, 81%, 75%, and 77%, respectively. Multivariate analysis, including all cases, showed iPSA (p <0.001), bGS (p <0.001), year of therapy (p <0.001), and treatment modality (p <0.001) to be independent predictors of relapse. Because EBRT <72 cases had distinctly worse outcomes, the analysis was repeated after excluding these cases to discern any differences among the other modalities. The multivariate analysis excluding the EBRT <72 cases revealed iPSA (p <0.001), bGS (p <0.001), and year of therapy (p = 0.001) to be the only independent predictors of relapse. Treatment modality (p = 0.95), clinical T stage (p = 0.09), and androgen deprivation (p = 0.56) were not independent predictors for failure. CONCLUSION: The biochemical failure rates were similar among PI, high-dose (> or =72 Gy) EBRT, COMB, and RP for localized prostate cancer. The outcomes were significantly worse for low-dose (<72 Gy) EBRT.

Aged↗

PubMed2004

Monotherapy for stage T1-T2 prostate cancer: radical prostatectomy, external beam radiotherapy, or permanent seed implantation.

BACKGROUND AND PURPOSE: To review the freedom from biochemical recurrence (FBR) rates after permanent prostate brachytherapy (PPB), external beam radiotherapy (RT) to a minimum 70Gy, or radical prostatectomy (RP) for clinically localized stage T1-T2 adenocarcinoma of the prostate. PATIENTS AND METHODS: The study cohort consisted of 1819 consecutively treated clinical stage T1-T2 (AJCC 1997) localized prostate cancer patients between 1992 and 1998. All patients received monotherapy treatment without additional adjuvant therapy. The distribution by treatment modality was as follows: RT for 340, RP for 746, and PPB for 733 cases. The median follow-up time was 58 months for all cases (51 months for PPB cases, 56 months for RT cases, and 64 months for RP cases). Biochemical relapse was defined as to be detectable PSA levels in RP cases, and the ASTRO consensus panel definition for the RT and PPB cases. RESULTS: The 7-year FBR rates for PPB vs EBRT vs RP were 74, 77, and 79%, respectively. Multivariate analysis identified iPSA (P < 0.001) and bGS (P < 0.001) as independent predictors of relapse. Treatment modality, age, clinical T-stage, and race were not independent predictors of failure. CONCLUSIONS: Pretreatment PSA levels, and biopsy Gleason score determined outcome in this study cohort. Biochemical failure rates in this study cohort are similar between PPB, RT, and RP as monotherapy for clinically localized prostate cancer.

Adenocarcinoma↗

PubMed2003

Pretreatment nomogram that predicts 5-year probability of metastasis following three-dimensional conformal radiation therapy for localized prostate cancer.

PURPOSE: There are several nomograms for the patient considering radiation therapy for clinically localized prostate cancer. Because of the questionable clinical implications of prostate-specific antigen (PSA) recurrence, its use as an end point has been criticized in several of these nomograms. The goal of this study was to create and to externally validate a nomogram for predicting the probability that a patient will develop metastasis within 5 years after three-dimensional conformal radiation therapy (CRT). PATIENTS AND METHODS: We conducted a retrospective, nonrandomized analysis of 1,677 patients treated with three-dimensional CRT at Memorial Sloan-Kettering Cancer Center (MSKCC) from 1988 to 2000. Clinical parameters examined were pretreatment PSA level, clinical stage, and biopsy Gleason sum. Patients were followed until their deaths, and the time at which they developed metastasis was noted. A nomogram for predicting the 5-year probability of developing metastasis was constructed from the MSKCC cohort and validated using the Cleveland Clinic series of 1,626 patients. RESULTS: After three-dimensional CRT, 159 patients developed metastasis. At 5 years, 11% of patients experienced metastasis by cumulative incidence analysis (95% CI, 9% to 13%). A nomogram constructed from the data gathered from these men showed an excellent ability to discriminate among patients in an external validation data set, as shown by a concordance index of 0.81. CONCLUSION: A nomogram with reasonable accuracy and discrimination has been constructed and validated using an external data set to predict the probability that a patient will experience metastasis within 5 years after three-dimensional CRT.

Adenocarcinoma↗

PubMed2003

Long-term multi-institutional analysis of stage T1-T2 prostate cancer treated with radiotherapy in the PSA era.

PURPOSE: To report the long-term outcome for patients with Stage T1-T2 adenocarcinoma of the prostate definitively irradiated in the prostate-specific antigen (PSA) era. METHODS AND MATERIALS: Nine institutions combined data on 4839 patients with Stage T1b, T1c, and T2 adenocarcinoma of the prostate who had a pretreatment PSA level and had received >or=60 Gy as definitive external beam radiotherapy. No patient had hormonal therapy before treatment failure. The median follow-up was 6.3 years. The end point for outcome analysis was PSA disease-free survival at 5 and 8 years after therapy using the American Society for Therapeutic Radiology and Oncology (ASTRO) failure definition. RESULTS: The PSA disease-free survival rate for the entire group of patients was 59% at 5 years and 53% at 8 years after treatment. For patients who had received >or=70 Gy, these percentages were 61% and 55%. Of the 4839 patients, 1582 had failure by the PSA criteria, 416 had local failure, and 329 had distant failure. The greatest risk of failure was at 1.5-3.5 years after treatment. The failure rate was 3.5-4.5% annually after 5 years, except in patients with Gleason score 8-10 tumors for whom it was 6%. In multivariate analysis for biochemical failure, pretreatment PSA, Gleason score, radiation dose, tumor stage, and treatment year were all significant prognostic factors. The length of follow-up and the effect of backdating as required by the ASTRO failure definition also significantly affected the outcome results. Dose effects were most significant in the intermediate-risk group and to a lesser degree in the high-risk group. No dose effect was seen at 70 or 72 Gy in the low-risk group. CONCLUSION: As follow-up lengthens and outcome data accumulate in the PSA era, we continue to evaluate the efficacy and durability of radiotherapy as definitive therapy for early-stage prostate cancer. Similar studies with higher doses and more contemporary techniques will be necessary to explore more fully the potential of this therapeutic modality.

Adenocarcinoma↗

PubMed2003

Improvement in relapse-free survival throughout the PSA era in patients with localized prostate cancer treated with definitive radiotherapy: year of treatment an independent predictor of outcome.

PURPOSE: In patients treated with radical prostatectomy in the prostate-specific antigen (PSA) era, it has been demonstrated that the year of treatment in the PSA era is associated with better pathologic parameters and outcomes, independently of other well-recognized parameters such as clinical stage, pretreatment PSA level, or Gleason score. The purpose of the present study was to study a similar phenomenon with definitive radiotherapy (RT). METHODS AND MATERIALS: The inclusion criteria were as follows: clinical Stage T1-T2, available pretreatment PSA level and biopsy Gleason score, treatment delivered before January 2000 with standard fractionation external beam radiotherapy to at least 70 Gy, no adjuvant androgen deprivation (AD), all neoadjuvant AD limited to < or =6 months, and a minimum of 3 years of PSA follow-up. A total of 467 cases treated between January 1986 and December 1999 were included. Short-course AD in the adjuvant or neoadjuvant setting for < or =6 months was given in 124 cases (27%). The median radiation dose was 74 Gy (range 70.0-78.0). A conformal technique was used in 293 cases (63%). The median follow-up was 62 months (range 37-189). A total of 4931 follow-up PSA levels were available for analysis (average 11 per patient). A multivariate analysis for factors affecting biochemical relapse-free survival rates using the proportional hazards model was performed for all cases using the following variables: age (continuous variable), race (black vs. white), clinical T stage (T1-T2a vs. T2b-T2c), pretreatment PSA (continuous variable), biopsy Gleason score (continuous variable), use of AD (yes vs. no), radiation dose (continuous variable), and year of treatment (continuous variable: 1986-1999). RESULTS: The projected 8-year biochemical relapse-free survival rate was 74%. The projected 5-year biochemical relapse-free survival rate for the 143 patients treated in the 1986-1995 period was 58% vs. 82% for the 324 patients treated in the 1996-1999 period (p <0.001). The difference was attributable to a multitude of factors (earlier stage cancer, higher radiation doses, shorter follow-up). To study the confounding effects of these factors on the year of therapy, a multivariate analysis was performed. The multivariate analysis revealed the initial PSA level (p <0.001), Gleason score (p <0.001), RT dose (p = 0.045), and year of treatment (p <0.001) to be independent predictors of outcome. Age (p = 0.41), race (p = 0.14), T stage (p = 0.10), and use of AD (p = 0.58) were not. CONCLUSION: When controlling for tumor, treatment, and follow-up parameters, the year in which RT was performed was still an independent predictor of outcome, consistent with observations made for radical prostatectomy patients. This indicates a more favorable presentation of localized prostate in current years probably related to a combination of factors such as screening and increased patient awareness leading to earlier diagnosis. Outcome predictions should be based on contemporaneous series.

Adenocarcinoma↗

PubMed2003

Localized prostate cancer: radiation or surgery?

The treatment of localized prostate cancer remains controversial because of the lack of conclusive well-controlled or randomized studies comparing outcomes of radiotherapy to outcomes of radical prostatectomy. A comparison of different therapies should include issues of cancer control, morbidity, quality of life (QOL), salvage of primary treatment failures, late effects, and cost. The available data suggest that these two modalities provide similar rates of cancer control at 10 years, and that except for the youngest patients, choice of therapy should be based on toxicity and QOL issues.

Counseling↗

PubMed2002

The use of treatments for erectile dysfunction among survivors of prostate carcinoma.

BACKGROUND: The objectives of this survey were to describe the prevalence of using a treatment for erectile dysfunction (ED) among men after therapy for localized prostate carcinoma and to construct models explaining the variance in trying a treatment, treatment success, and adherence to treatment. METHODS: A postal survey was sent to 2636 men in The Cleveland Clinic Foundation's Prostate Cancer Registry who were treated initially with either definitive radiotherapy or prostatectomy for localized prostate carcinoma. The survey asked about demographic items, past and current sexual functioning, and the partner's sexual function. Men were asked about their current and intended use of medical treatments for ED. Standardized questionnaires included the Sexual Self-Schema Scale-Male Version, the International Index of Erectile Function, urinary and bowel symptom scales from the Los Angeles Prostate Cancer Index), and the Short-Form Health Survey. RESULTS: The return rate was 49%. Differences between men who returned the questionnaire and men who did not respond suggest that the sample was weighted toward men who were more interested in staying active sexually. ED was a problem for 85% of men, and 59% of this group used at least 1 treatment for ED. Only 38% of men found that a medical treatment was at least somewhat helpful in improving their sex lives, however, and 30% of respondents still were using at least 1 treatment at the time of the survey. Factors that were associated with the efficacy of treatments for ED and with their continued use included having a sexual partner, younger age, choosing a treatment for prostate carcinoma that was more likely to spare some sexual function, and not having had neoadjuvant or current antiandrogen therapy. Men who tried a greater number of treatments for ED were more likely to find one that worked. Men were more likely to continue using treatments for ED that produced greater improvements in sexual function. CONCLUSIONS: The success of medical treatments for men with ED among long-term survivors of prostate carcinoma is limited. Men prefer noninvasive treatments, although invasive treatments are more effective. Sexual counseling for men and their partners is recommended, because it may increase the use of medical therapies for ED. Creating more realistic expectations in both partners also may enhance treatment adherence.

Adult↗

PubMed2002

Factors affecting recurrence rates after prostatectomy or radiotherapy in localized prostate carcinoma patients with biopsy Gleason score 8 or above.

BACKGROUND: To review the biochemical recurrence-free survival (bRFS) rates of treatment with either external beam radiotherapy or radical prostatectomy in patients with biopsy Gleason score 8 or above in the prostate specific antigen (PSA) era. METHODS: A total of 297 localized prostate carcinoma patients diagnosed with biopsy Gleason score 8 or above were treated between 1987 and 2000 at the Cleveland Clinic with either prostatectomy or radiotherapy (RT). All patients had pretreatment PSA (iPSA) levels. Androgen deprivation was given as part of the initial treatment in 154 patients (52%). Radical prostatectomy (RP) was the primary treatment in 115 patients (39%) and 182 patients (61%) received RT. The median radiation dose was 70.2 Gy (range, 60.0-78.0 Gy). The median follow-up time was 42 months (range, 1-153 months). RESULTS: For the 297 patients, the 5 and 8-year bRFS rates were 45% (95% confidence interval [CI] 38-52%) and 31% (95% CI 20-42%), respectively. The 5-year bRFS rates for iPSA 10 or less versus. iPSA above10 were 66% (95% CI 54-78%) versus 31% (95% CI 22-40%), respectively (P < 0.001). The 5-year bRFS rates for use of androgen deprivation versus no androgen deprivation were 62% (95% CI 52-72%) versus 35% (95% CI 27-42%), respectively (P < 0.001). The 5-year bRFS rates for RT patients versus RP patients were 47% (95% CI 38-57%) versus 42% (95% CI 31-53%), respectively (P = 0.051). For RT patients, the 5-year bRFS rates for use of androgen deprivation versus no androgen deprivation were 71% versus 29%, respectively (P < 0.001). For RP patients, the 5-year bRFS rates for use of androgen deprivation versus no androgen deprivation were 39% versus 43%, respectively (P = 0.90). Multivariate time-to-failure analysis using the proportional hazards model showed iPSA level (P < 0.001) and the use of androgen deprivation (P = 0.001) to be the only independent predictors of biochemical recurrence. Age (P = 0.44), race (P = 0.80), clinical T stage (P = 0.10), biopsy Gleason scores (P = 0.39), and treatment modality (P = 0.13) were not independent predictors of biochemical failure. A total of 104 patients had Stage T1 or T2 disease, low iPSA levels (</= 10 ng/mL), and a high Gleason score (>/= 8). For all 104 patients, the 5-year bRFS rate was 64%. For 52 of the 104 patients who received 6 months of androgen deprivation or less, the 5-year bRFS rate was 78%. CONCLUSION: Patients with localized prostate carcinoma with a biopsy Gleason score 8 or less have lower recurrence rates if iPSA levels are 10 or less. Biochemical control rates were encouraging for patients with biopsy Gleason score 8 or above, clinical Stage T1-T2, and iPSA levels less than or equal to 10 ng/mL treated with adjuvant androgen deprivation given only for 6 months or less. If longer follow-up confirms these findings, these patients might not need prolonged androgen deprivation for periods exceeding 6 months following local therapy.

Adult↗

PubMed2002

Defining sexual outcomes after treatment for localized prostate carcinoma.

BACKGROUND: The objective of this survey was to identify factors associated with good sexual outcomes in a large group of survivors of localized prostate carcinoma. METHODS: A postal survey was sent to 2636 men in the Cleveland Clinic Foundation's Prostate Cancer Registry who either were treated with definitive radiotherapy or underwent prostatectomy for localized prostate carcinoma. The survey asked about demographic items, past and current sexual functioning, partner's sexual function and health, and a number of factors hypothesized to affect sexual satisfaction. Standardized questionnaires included the Sexual Self-Schema Scale-Male Version, the International Index of Erectile Function (IIEF), urinary and bowel symptom scales from the Los Angeles Prostate Cancer Index, and the Short Form Health Survey (SF-36). RESULTS: The return rate was 49%, yielding a sample of 1236 men at an average of 4.3 years post-treatment. Comparing responders with nonresponders suggested that the sample may have been somewhat biased toward men who were more interested in maintaining sexual function. At the time they were diagnosed with prostate carcinoma, 36% of men had erectile dysfunction (ED). Within the past 6 months, however, 85% of men reported having ED. Only 13% of men were having reliable, firm erections spontaneously, and another 8% of men were having erections with the aid of a medical treatment. Men were as distressed about loss of desire and trouble having satisfying orgasms as they were about ED. Of the 84% of men who reported having a current sexual partner, 66% indicated that she had a sexual problem. Younger age was associated strongly with better sexual outcome (global IIEF score). With demographic factors taken into account, better sexual outcome was related significantly to medical factors, including not having neoadjuvant or current antiandrogen therapy, undergoing bilateral nerve-sparing prostatectomy or brachytherapy, and having better mental and physical health composite scores on the SF-36. Sexual factors that were associated with a better outcome included having normal erections before treatment for prostate carcinoma, choosing a treatment based on the hope that it would preserve sexual function, having more sexual partners in the past year, and having a sexually functional partner. CONCLUSIONS: The great majority of men who survive prostate carcinoma do not achieve a return to functional sexual activity in the years after treatment. The priorities a man places on sexuality and on having a sexually functional partner are important factors in sexual satisfaction at follow-up, over and above the influence of age and medical factors.

Adult↗

PubMed2002

Comparison of the efficacy of local therapies for localized prostate cancer in the prostate-specific antigen era: a large single-institution experience with radical prostatectomy and external-beam radiotherapy.

PURPOSE: To review biochemical relapse-free survival (bRFS) rates after either external-beam radiotherapy (RT) or radical prostatectomy (RP) for localized prostate cancer. PATIENTS AND METHODS: All 1,682 patients had pretreatment prostate-specific antigen (PSA) levels and biopsy Gleason scores (bGS) assigned. No adjuvant therapy was administered after local treatment. RP was the treatment in 1,054 patients (63%) and RT in 628 patients (37%). Median follow-up was 51 months (range, 1 to 134). The median follow-up for RP versus RT patients was 50.5 v 51.0 months. Biochemical relapse was considered detectable PSA levels (> 0.2 ng/mL) in RP patients and three consecutive rising PSA levels in RT patients. The analysis was repeated with a more stringent definition of biochemical control after either RP or RT-namely, reaching and maintaining a PSA level < or = 0.5 ng/mL-and excluding patients receiving any androgen deprivation (AD). RESULTS: Eight-year bRFS rates for RP versus RT were 72% and 70%, respectively (P =.010). Multivariate analysis indicated T stage (P <.001), pretreatment PSA (P <.001), bGS (P <.001), year of therapy (P <.001), and neoadjuvant AD (P =.019) to be the only independent predictors of relapse. Age (P =.78), race (P =.29), prior transurethral resection of prostate (P =.81), and treatment modality (P =.96) were not independent predictors of treatment failure. Fifty-one percent of RP patients had favorable tumors (T1 to T2A, pretreatment PSA < or = 10 ng/mL, bGS < or = 7), compared with only 34% of RT patients (P <.001). Repeat analysis with a stringent definition of biochemical failure and excluding patients receiving AD indicated no impact of treatment modality on outcome. CONCLUSION: Eight-year biochemical failure rates were identical between RT and RP in any subgroup. Outcome is determined mainly by pretreatment PSA levels, bGS, clinical T stage, and, for RT patients, radiation dose.

Adenocarcinoma↗

PubMed2002

Preoperative combined nested reverse transcriptase polymerase chain reaction for prostate-specific antigen and prostate-specific membrane antigen does not correlate with pathologic stage or biochemical failure in patients with localized prostate cancer undergoing radical prostatectomy.

PURPOSE: We report a prospective study examining the ability of preoperative nested reverse transcriptase polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) to predict pathologic stage and biochemical recurrence in patients with clinically localized prostate cancer treated with radical prostatectomy. PATIENTS AND METHODS: One hundred forty-one patients were entered onto the study. Preoperative evaluation included clinical T stage, serum PSA, biopsy Gleason score, and serum RT-PCR for PSA/PSM. Univariate and multivariate logistic regression models, Kaplan-Meier estimates, and Cox proportional hazards modeling were used to identify predictors of pathologic stage and biochemical failure. RESULTS: Seventy-three patients (51.8%) were RT-PCR positive for PSA, PSM, or both. In the multivariate logistic regression model, only initial PSA was an independent predictor of pathologic stage as defined by organ-confined disease (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00 to 1.13; P =.026) or organ-/specimen-confined disease (OR, 1.09; 95% CI, 1.02 to 1.16; P =.009). Overall Kaplan-Meier biochemical relapse-free survival (bRFS) was 85% at 59 months. Multivariate analysis of predictors for bRFS with the Cox proportional hazards model indicated that only initial PSA (OR, 1.05; 95% CI, 1.02 to 1.09; P =.004) and biopsy Gleason score (OR, 3.57; 95% CI, 1.37 to 9.58; P =.009) were independent predictors of biochemical failure. RT-PCR status did not predict pathologic stage or biochemical failure. Repeat analysis excluding 27 patients who received preoperative androgen-deprivation therapy did not change the results. CONCLUSION: Combined nested RT-PCR for PSA and PSM is not an independent predictor of pathologic stage or biochemical failure in patients with localized prostate cancer undergoing radical prostatectomy. This assay has no clinical utility in this patient population.

Antigens, Surface↗

PubMed2002

Preliminary observations on biochemical relapse-free survival rates after short-course intensity-modulated radiotherapy (70 Gy at 2.5 Gy/fraction) for localized prostate cancer.

PURPOSE: To compare the preliminary biochemical relapse-free survival rates between short-course intensity-modulated radiotherapy (SCIM-RT) delivering 70 Gy in 28 fractions and three-dimensional conformal radiotherapy (3D-CRT) delivering 78 Gy in 39 fractions. METHODS AND MATERIALS: Between January 1998 and December 1999, 166 patients were treated with SCIM-RT and 116 with 3D-CRT. The SCIM-RT cases were treated to 70 Gy (2.5 Gy/fraction) using 5 intensity-modulated fields using a dynamic multileaf collimator. The BAT transabdominal ultrasound system was used for localization of the prostate gland in all SCIM-RT cases. The 116 3D-CRT cases were treated to 78.0 Gy (2.0 Gy/fraction). The study sample therefore comprised 282 cases; 70 Gy in 28 fractions is equivalent to 78 Gy in 39 fractions for late-reacting tissues, according to the linear-quadratic model. The median follow-up for all cases was 25 months (range 3-42). The median follow-up was 21 months for the SCIM-RT cases (range 3-31) and 32 months for the 3D-CRT cases (range 3-42). The follow-up period was shorter for the SCIM-RT cases, because SCIM-RT was started only in October 1998. Biochemical relapse was defined as 3 consecutive rising prostate-specific antigen levels after reaching a nadir. The analysis was then repeated with a more stringent definition of biochemical control: reaching and maintaining a prostate-specific antigen level of < or =0.5 ng/mL. Radiation Therapy Oncology Group toxicity scores were used to assess complications. RESULTS: For the 282 patients, the biochemical relapse-free survival rate at 30 months was 91% (95% confidence interval 88-95%). The biochemical relapse-free survival rate at 30 months for 3D-CRT vs. SCIM-RT was 88% (95% confidence interval 82-94%) vs. 94% (95% confidence interval 91-98%), respectively. The difference was not statistically significant between the two treatment arms (p = 0.084). The multivariate time-to-failure analysis using the Cox proportional hazards model for clinical parameters showed the pretreatment prostate-specific antigen level (p <0.001) and biopsy Gleason score (p <0.001) to be the only independent predictors of biochemical relapse. Clinical T stage (p = 0.66), age (p = 0.15), race (p = 0.25), and neoadjuvant androgen deprivation (p = 0.66) were not independent predictors of biochemical failure. SCIM-RT showed only a trend toward a better outcome on multivariate analysis (p = 0.058). Late rectal toxicity was limited; the actuarial combined Grade 2 and 3 late rectal toxicity rate at 30 months was 5% for SCIM-RT vs. 12% for 3D-CRT (p = 0.24). Grade 3 late rectal toxicity (rectal bleeding requiring cauterization) occurred in a total of 10 patients. The actuarial Grade 3 late rectal toxicity rate at 30 months was 2% for the SCIM-RT cases and 8% for the 3D-CRT cases (p = 0.059). Late urinary toxicity was rare in both groups. CONCLUSION: With the currently available follow-up period (< or =30 months), the hypofractionated intensity-modulated radiotherapy schedule of 70.0 Gy delivered at 2.5 Gy/fraction had a comparable biochemical relapse profile with the prior 3D-CRT schedule delivering 78.0 at 2.0 Gy/fraction. The late rectal toxicity profile has been extremely favorable. If longer follow-up confirms the favorable biochemical failure and low late toxicity rates, SCIM-RT will be an alternative and more convenient way of providing dose escalation in the treatment of localized prostate cancer.

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PubMed2002

Impact of biochemical failure on overall survival after radiation therapy for localized prostate cancer in the PSA era.

PURPOSE: To study the impact of biochemical failure on overall survival rates during the first 10 years after definitive radiotherapy for localized prostate cancer. METHODS AND MATERIALS: The analysis was performed on 936 cases treated at a single institution between 1986 and 1998 with definitive radiotherapy. The median age of treatment was 69 years (range: 46-86 years). Pretreatment PSA levels (iPSA) and biopsy Gleason scores (bGS) were available for all cases. The clinical stage was T1/T2A in 63%, T2B/C in 27%, and T3 in 10%. The median iPSA level was 9.6 ng/mL (range: 0.4-692.9 ng/mL). The iPSA was < or =10 in 53% and >10 in 47%. The bGS was < or =6 in 59% and > or =7 in 41%. Androgen deprivation (AD) was administered in 181 cases (19%) for a median duration of 6 months (range: 1-6 months). All 181 cases received AD neoadjuvantly, i.e., before and/or during the radiotherapy. No AD was delivered after the completion of radiation. The median radiation dose was 70 Gy (range: 60-78 Gy). The radiotherapy technique was conformal in 376 (40%) cases. The American Society of Therapeutic Radiology and Oncology definition of biochemical failure (bF) was used; 316 cases (34%) had failed biochemically, and 620 (66%) had not. The end point was overall survival (OS). Time to death was determined from the time of definitive radiotherapy. The median PSA follow-up was 58 months. The median follow-up times for bF vs. no-bF cases were 77 and 49 months, respectively. A multivariate analysis of factors affecting OS using the proportional hazards model was performed for all cases using the following variables: age (>65 vs. < or =65 years), race (African-American vs. Caucasian), clinical T stage (T1-2A vs. T2B-C vs. T3), bGS (< or =6 vs. 7 vs. > or =8), iPSA (continuous variable), use of AD (yes vs. no), year of therapy (continuous variable), radiation dose (continuous variable), radiation technique (conformal vs. standard), and biochemical failure (yes vs. no). RESULTS: The 5-year OS rate for the entire group was 89% (95% CI [confidence interval]: 86-91%). The 5-year OS rates for bF vs. no-bF patients were 89% (95% CI: 86-93%) and 89% (95% CI: 86-92%), respectively. The 10-year OS rate for the entire group was 68% (95% CI: 61-75%). The 10-year OS rates for bF vs. no-bF patients were 65% (95% CI: 56-74%) and 77% (95% CI: 69-84%), respectively. The difference between bF and no bF was not significant in predicting overall survival in univariate analysis (log-rank test, p = 0.68). On multivariate analysis, bGS (p < 0.001), T stage (p = 0.003), radiation dose (p = 0.017), year of therapy (p = 0.031), and age (p = 0.020) were independent predictors of death. iPSA levels (p = 0.33), race (p = 0.80), radiation technique (p = 0.16), and use of AD (p = 0.09) were not predictive of OS. Biochemical failure (p = 0.052) showed only a trend for independently predicting overall survival on multivariate analysis. CONCLUSION: Biochemical failure after definitive radiotherapy for localized prostate cancer is not associated with increased mortality within the first 10 years after initial therapy, although a trend toward worse outcome was observed at 10 years. Longer follow-up from initial therapy is needed to fully understand the impact of biochemical failure on overall survival. With longer follow-up, significant differences might be observed at 15 or 20 years after therapy.

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PubMed2002

Validation study of the accuracy of a postoperative nomogram for recurrence after radical prostatectomy for localized prostate cancer.

PURPOSE: A postoperative nomogram for prostate cancer was developed at Baylor College of Medicine. This nomogram uses readily available clinical and pathologic variables to predict 7-year freedom from recurrence after radical prostatectomy. We evaluated the predictive accuracy of the nomogram when applied to patients of four international institutions. PATIENTS AND METHODS: Clinical and pathologic data of 2,908 patients were supplied for validation, and 2,465 complete records were used. Nomogram-predicted probabilities of 7-year freedom from recurrence were compared with actual follow-up in two ways. First, the area under the receiver operating characteristic curve (AUC) was calculated for all patients and stratified by the time period of surgery. Second, calibration of the nomogram was achieved by comparing the predicted freedom from recurrence with that of an ideal nomogram. For patients in whom the pathologic report does not distinguish between focal and established extracapsular extension (an input variable of the nomogram), two separate calculations were performed assuming one or the other. RESULTS: The overall AUC was 0.80 when applied to the validation data set, with individual institution AUCs ranging from 0.77 to 0.82. The predictive accuracy of the nomogram was apparently higher in patients who were operated on between 1997 and 2000 (AUC, 0.83) compared with those treated between 1987 and 1996 (AUC, 0.78). Nomogram predictions of 7-year freedom from recurrence were within 10% of an ideal nomogram. CONCLUSION: The postoperative Baylor nomogram was accurate when applied at international treatment institutions. Our results suggest that accurate predictions may be expected when using this nomogram across different patient populations.

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PubMed2002

Brain metastases from gynecological cancers: factors that affect overall survival.

We retrospectively reviewed factors that affected overall survival for patients with gynecological cancers that had metastasized to the brain. Between January 1985 to November 1999, we treated 25 patients with brain metastases from gynecological malignancies (cervix n=6, endometrium n=10, and ovary n=9). Various patient and tumor characteristics were identified and analyzed for their significance. Median age was 46 years old (range, 37-78 years) with the majority of tumors being adenocarcinoma (20/25 patients). The treatment consisted of whole brain radiation therapy (WBRT) in 11 patients, focal therapy (surgery and/or stereotactic radiosurgery [SRS]) in 6 patients, and combination therapy (WBRT and surgery and/or SRS) in 8 patients and resulted in median survivals of 6 months, 7 months and 11 months, respectively. Overall median survival was 7.3 months (range, 1 to 88 months). Cause of death was systemic in 9, neurologic in 8 and progression of primary in 2. Those with single lesions had better median survivals compared to those with multiple lesions (17 months vs. 3 months, p=0.017). Our results suggest that patients with a single lesion had improved outcomes. We encourage enrollment of patients with brain metastases onto prospective clinical trials.

Adult↗