Pretreatment Prostate-specific Antigen Level Research Articles

Pretreatment Nomogram Predicting Ten-Year Biochemical Outcome of Three-Dimensional Conformal Radiotherapy and Intensity-Modulated Radiotherapy for Prostate Cancer

To update our previously published nomogram predicting for biochemical outcome with 10-year data from a larger cohort of patients treated with three-dimensional conformal radiotherapy (RT) or intensity-modulated RT for localized prostate cancer. From 1988 to 2004, 2253 patients were treated with three-dimensional conformal RT or intensity-modulated RT for clinical Stage T1-T3 prostate cancer. Prescription doses ranged from 64.8 to 86.4 Gy. The median follow-up time was 7 years. The nomogram was developed using a proportional hazards regression model predicting for the probability of biochemical relapse after RT according to the nadir plus 2 ng/mL definition of prostate-specific antigen (PSA) relapse. The 10-year PSA relapse-free survival rate was 62%. The nomogram incorporated the following variables to predict likelihood of PSA failure after RT: pretreatment PSA level, Gleason score, radiation dose, use of neoadjuvant androgen deprivation, and clinical stage. The concordance index of this long-term nomogram was 0.72. A nomogram predicting the 10-year probability of biochemical control after three-dimensional conformal RT or intensity-modulated RT for prostate cancer was reasonably accurate and discriminating. The nomogram also provided evidence that long-term biochemical control can be achieved after conformal RT for the treatment of localized prostate cancer.

Prostate‐specific antigen half‐life and pretreatment prostate‐specific antigen: Crucial predictors for prostate‐specific antigen trend in delayed‐combined androgen blockade therapy

To elucidate the crucial predictors for prostate-specific antigen (PSA) trends and determine the usage of anti-androgen treatment during delayed-combined androgen blockade (CAB) leading to a PSA level below 0.2 ng/mL. From January 2001 to December 2004, 105 prostate cancer patients were enrolled. Medical castration and anti-androgen treatment were used sequentially and termed delayed-CAB. The first goal was to maintain an undetectable PSA level. The nadir PSA was determined after medical castration only. Anti-androgen was given if a PSA level of more than 0.2 ng/mL was observed and the subsequent PSA response was assessed. All cases were divided into two groups based on whether the PSA was lower (n = 59) or higher (n = 46) than 0.2 ng/mL. An analysis of the difference between the two groups was calculated. The median of the initial PSA level in the lower group was lower than in the higher group with a 95% cut-off level of 40 ng/mL. The median PSA half-life in the lower group was also reduced with a 95% cut-off of 3.6 months. In a multivariate analysis, the pretreatment PSA level and the PSA half-life exhibited a significant correlation between the two groups. Anti-androgen treatment was given to 26 cases in the higher group. The PSA increased in one case, decreased to less than 0.2 ng/mL in 17 cases and remained over 0.2 ng/mL in eight cases. Both the PSA half-life and the pretreatment PSA level were useful markers for predicting the PSA trends to determine the optimal use of anti-androgen treatment during delayed-CAB.

Prediagnostic Prostate-Specific Antigen Velocity and Probability of Detecting High-Grade Prostate Cancer

Men with high-grade prostate cancer experience a survival benefit when androgen suppression therapy is combined with radiotherapy (RT) compared with RT alone. We evaluated whether an association exists between the pretreatment prostate-specific antigen (PSA) velocity and high-grade prostate cancer at diagnosis, controlling for known predictors of high-grade disease. The study cohort consisted of 358 men with Stage T1c-T4 prostate cancer treated with external beam RT from 1989 to 2002. Univariate and multivariate logistic regression analyses were used to assess whether an association exists between the pretreatment PSA velocity, PSA level, age, clinical T stage, and Gleason score 4+3 or greater compared with Gleason score 3+4 or less prostate cancer. Of the 358 men, 73 had a Gleason score of 4+3 or greater. The median PSA velocity was 2.71 ng/mL/yr (interquartile range 1.09 to 12.6) for men with a Gleason score of 4+3 or greater and 1.24 ng/mL/yr (interquartile range 0.71 to 3.37) for men with a Gleason score of 3+4 or less. All clinical covariates were significantly associated (P < or = 0.05) with a Gleason score of 4+3 or greater on univariate analysis. On multivariate analysis, the PSA velocity (odds ratio 1.06, 95% confidence interval 1.02 to 1.10, P = 0.004), age (odds ratio 1.07, 95% confidence interval 1.02 to 1.13, P = 0.008), and clinical T stage (odds ratio 2.17, 95% confidence interval 1.21 to 3.92, P = 0.01) were significantly associated with the detection of Gleason score 4+3 or greater prostate cancer. The prediagnostic PSA velocity, patient age, and clinical T stage were significantly associated with high-grade prostate cancer at diagnosis. Because a biopsy Gleason score of 4+3 or greater is associated with a prostatectomy Gleason score of 7 or greater in the vast majority of cases, these parameters can identify men at high risk of harboring occult high-grade prostate cancer, permitting improved selection of RT fields and the use of androgen suppression therapy.

Prostate cancer progression in the presence of undetectable or low serum prostate‐specific antigen level

The serum prostate-specific antigen (PSA) level after definitive treatment for prostate cancer (PC) is a powerful predictor of outcome. Occasionally, PC progression can occur despite low or undetectable PSA levels. The authors report on the clinical and pathologic characteristics of patients who experienced PC progression with undetectable or low PSA levels. From an electronic database of all patients with PC who were treated at The University of Texas M. D. Anderson Cancer Center between 1999 and 2004, a group of 46 patients was identified who had progression to metastatic PC detected with concomitant PSA levels from 0.1 ng/mL to 2 ng/mL. Patient charts were reviewed for tumor stage, Gleason score, pretreatment PSA level, and the presence of atypical histologic variants (ie, ductal, sarcomatoid, or small cell cancers). The nadir PSA level after treatment and the PSA level at the time metastatic PC was detected were determined. The patients were followed semiannually, and imaging studies were obtained at the discretion of treating physicians. The sites of metastasis and histologic confirmation were reported when available. Twenty-three of 46 patients underwent radical prostatectomy, 11 patients received radiation therapy, and 12 received hormone treatment as their initial form of therapy. Progression to metastatic disease with concomitant, undetectable PSA levels occurred in 10 patients, including 3 patients who had not received treatment with hormones. The sites of metastasis included bone (n = 35 patients), liver (n = 7 patients), retroperitoneal lymph nodes (n = 5 patients), lungs (n = 4 patients), and brain (n = 1 patient). Aggressive and locally advanced PC were common features in these patients: Eighty-five percent had Gleason scores >or=7, 63% had clinical T3 or T4 tumors, and 41% had pretreatment PSA levels >10 ng/mL. Atypical histologic variants were observed in 21 patients (46%) and in 8 of 10 patients who progressed with undetectable PSA levels. In 10 patients (22%), metastasis were detected in the presence of an undetectable PSA level. Eight of those patients had small cell carcinoma. In 19 patients (41%), progression to metastasis occurred without any increase in their PSA from the nadir level. Thirty-one patients (67%) were asymptomatic at the time metastasis was detected, and the detection of metastasis in these patients occurred only because of routine imaging studies. Progression of PC may occur despite undetectable or low PSA levels. Complete physical evaluation and imaging studies may be indicated in the surveillance of patients with high-grade, locally advanced tumors, especially when atypical histologic variants are present.

Staging for prostate cancer

The American Joint Committee on Cancer (AJCC) staging system for prostate cancer is based primarily based on clinical tumor (T) classification. In this article, the authors summarize arguments for incorporating additional pretreatment parameters and creating a new staging system for prostate cancer. Men with localized prostate cancer who received treatment with external beam radiation alone were analyzed using the 1997 AJCC staging system compared with a system that included pretreatment prostate-specific antigen (pPSA) level and Gleason score (GS). Multivariate analyses using a Cox proportional-hazards model were carried out to evaluate T classification, GS, and pPSA as predictors of overall survival (OS), disease-specific survival (DSS), and freedom from PSA failure (FFPF). RESULTS.: Based on pretreatment characteristics in a series of contemporary patients, only 0.6% of patients were classified with AJCC stage I disease, 16.0% were classified with AJCC stage III disease, and 83.4% were classified with AJCC stage II disease. Multivariate analyses indicated the independent statistical significance of T classification, GS, and pPSA in predicting OS, DSS, and FFPF (model chi-square value, P < .0001 for each). Using these 3 predictors, subsets of patients who had similar outcomes were combined to provide examples of the insensitivity of the AJCC system for predicting outcomes. Incorporating pPSA and GS allowed the identification of differences in OS, DSS, and FFPF for subsets of patients with AJCC stage II disease (P < .0001, P = .005, and P < .0001, respectively). The current AJCC staging system does not divide contemporary patients with prostate cancer into prognostic subgroups and does not identify patients who have comparable biochemical control and survival. The AJCC staging system for prostate cancer should be changed to incorporate pPSA, GS, and risk stratification.

MABまたは女性ホルモン剤併用による初期内分泌療法にてもPSA低下が不充分な前立腺癌症例の検討

The prostate specific antigen (PSA) level usually is lowered in response to initial endocrine therapy even in advanced cases of prostate cancer, but in some cases, it is not. We examined the cases in which the PSA level was not sufficiently lowered by initial endocrine therapy with maximal androgen blockade (MAB) or estrogenic drugs. The subjects were 20 patients with prostate cancer diagnosed between January 1992 and December 2005 whose PSA level was not lowered below 10 ng/ml after initial endocrine therapy with MAB or estrogenic drugs. We investigated the frequency of cases, pretreatment PSA levels, PSA nadir levels after initial endocrine therapy and throughout the therapy, PSA response to second line therapy, and the prognosis. The PSA level was not lowered below 10 ng/ml after initial endocrine therapy with MAB or estrogenic drugs in 4.9% of the cases. Cancer-specific survival rates in all cases were extremely poor, 75.0% at 1 year and 14.7% at 3 years. Prognosis tended to be worse in patients with a higher PSA nadir level throughout the therapy and on whom second therapy was not effective, although the difference was not statistically significant. The patients whose PSA levels were not lowered sufficiently by MAB or estrogenic drugs had an extremely poor prognosis. These results are useful in planning the therapy, and in explaining the status or future prospective of the disease to patients and their families.

Critical Assessment of Ideal Nodal Yield at Pelvic Lymphadenectomy to Accurately Diagnose Prostate Cancer Nodal Metastasis in Patients Undergoing Radical Retropubic Prostatectomy

Objectives To study the relation between the number of removed and examined lymph nodes at pelvic lymph node dissection and the rate of lymph node invasion (LNI). Methods A total of 858 patients aged 45 to 85 years were predominantly treated with extended pelvic lymph node dissection before radical retropubic prostatectomy. The pretreatment prostate-specific antigen level was 0.24 to 49.9 ng/mL (median 5.8). Most lesions were Stage T1c (55.2%) or T2 (40.7%), with a biopsy Gleason sum of 6 or less (62.2%) or 7 (25.1%). Receiver operating characteristic curve coordinates were used to determine the probability of finding LNI according to the number of removed and examined lymph nodes. Moreover, the association between the number of removed lymph nodes and LNI was tested in univariate and multivariate logistic regression models. Results From 2 to 40 nodes (mean 15, median 14) were removed and examined, and 88 patients (10.3%) had LNI. The LNI rate increased with the number of removed nodes ( P <0.001): 2 to 10 nodes removed, 5.6% LNI rate; 10 to 14 nodes removed, 8.6% LNI rate; 15 to 19 removed, 10.2% LNI rate; and 20 to 40 removed, 17.6% LNI rate. On multivariate analysis, the number of examined nodes predicted for LNI ( P <0.001), after accounting for prostate-specific antigen level, clinical stage, and biopsy Gleason sum. The receiver operating characteristic coordinate plot indicated that the removal of 28 nodes yielded a 90% ability to detect LNI. Conversely, the assessment of 10 or fewer nodes was associated with a virtually zero probability of finding LNI. Conclusions We have provided a critical assessment of the concept that the nodal yield at pelvic lymph node dissection is closely associated with the rate of LNI.

The predictive value of 2-year posttreatment biopsy after prostate cancer radiotherapy for eventual biochemical outcome

To determine the value of a 2-year post-radiotherapy (RT) prostate biopsy for predicting eventual biochemical failure in patients who were treated for localized prostate cancer. This study comprised 164 patients who underwent a planned 2-year post-RT prostate biopsy. The independent prognostic value of the biopsy results for forecasting eventual biochemical outcome and overall survival was tested with other factors (the Gleason score, 1992 American Joint Committee on Cancer tumor stage, pretreatment prostate-specific antigen level, risk group, and RT dose) in a multivariate analysis. The current nadir + 2 (CN + 2) definition of biochemical failure was used. Patients with rising prostate-specific antigen (PSA) or suspicious digital rectal examination before the biopsy were excluded. The biopsy results were normal in 78 patients, scant atypical and malignant cells in 30, carcinoma with treatment effect in 43, and carcinoma without treatment effect in 13. Using the CN + 2 definition, we found a significant association between biopsy results and eventual biochemical failure. We also found that the biopsy status provides predictive information independent of the PSA status at the time of biopsy. A 2-year post-RT prostate biopsy may be useful for forecasting CN + 2 biochemical failure. Posttreatment prostate biopsy may be useful for identifying patients for aggressive salvage therapy.

Nadir prostate-specific antigen within 12 months after radiotherapy predicts biochemical and distant failure

Objectives To determine whether nadir prostate-specific antigen (PSA) levels within 12 months (nadir PSA12) after completion of radiotherapy (RT) can be used as an early marker of recurrence risk. Methods A total of 4839 patients were treated with RT and without hormonal therapy from 1986 to 1995 for Stage T1-T2 prostate cancer at nine institutions. Of these 4839 patients, 4833, with a median follow-up of 6.3 years, met the criteria for analysis. The study endpoints included freedom from PSA failure, initiation of androgen deprivation, or documented local or distant failure (PSA-DFS); freedom from clinically apparent distant metastasis (DMFS); and overall survival (OS). Results Patients with a nadir PSA12 of 2.0 ng/mL or less had an 8-year PSA-DFS, DMFS, and OS rate of 55%, 95%, and 73%, respectively, compared with 40%, 88%, and 69%, respectively, for patients with a nadir PSA12 of more than 2.0 ng/mL. Multivariate analysis confirmed that a nadir PSA12 of greater than 2 ng/mL was an independent predictor of PSA-DFS, DMFS, and OS. Classification and regression tree analysis identified the nadir PSA12 levels after RT associated with PSA-DFS, DMFS, and OS. Nadir PSA12, combined with the pretreatment PSA level, identified patients at particularly high risk of distant metastasis. Conclusions The results of this large, multi-institutional study have demonstrated that nadir PSA12 is predictive of clinical outcomes for patients with localized prostate cancer after RT. A high pretreatment PSA level and high nadir PSA12 will identify patients at particularly high risk who might benefit from early adjuvant therapy.

Efficacy of primary hormonal therapy for patients with localized and locally advanced prostate cancer: A retrospective multicenter study

A retrospective review of patients with localized and locally advanced prostate cancer was performed to evaluate the efficacy of primary hormonal therapy and predict long-term prognosis in these patients. A total of 628 patients who were diagnosed with stage T1c to T3 prostate cancer were treated with primary hormonal therapy at participating institutions. The patients were classified based on pretreatment prostate-specific antigen (PSA) level, Gleason score, and time to nadir PSA level. Disease-specific and progression-free survival rates were investigated, and compared among the subgroups. The mean age of patients was 74.5 years, and median pretreatment PSA level was 14.0 ng/mL. A total of 399 patients (63.5%) were treated with combined androgen blockade (CAB), and 229 patients (36.5%) were treated with castration monotherapy. The disease-specific survival rate of all 628 patients was 89.1% at 8 years. The group that showed a good response to primary hormonal therapy (Group G, pretreatment PSA level < or =20 ng/mL, Gleason score < or =7, and time to nadir PSA < or =6 months) accounted for approximately one-third of the total number of T1c-T3 patients. Disease-specific and progression-free survival rates at 8 years in Group G were 98.9% and 82.0%, respectively. These rates increased to 100% and 87.3%, respectively, in patients receiving CAB treatment in Group G. The results indicate the usefulness of primary hormonal therapy, especially CAB treatment, for patients showing a good response to hormonal therapy in long-term control of localized and locally advanced prostate cancer.

Multi-institutional analysis of long-term outcome for stages T1–T2 prostate cancer treated with permanent seed implantation

To assess long-term prostate-specific antigen (PSA) outcome after permanent prostate brachytherapy (BT) and identify predictors of improved disease-free survival. Eleven institutions combined data on 2,693 patients treated with permanent interstitial BT monotherapy for T1-T2 prostate cancer. Of these patients, 1,831 (68%) were treated with I-125 (median dose, 144 Gy) and 862 (32%) were treated with Pd-103 (median dose, 130 Gy). Criteria for inclusion were: available pre-BT PSA, BT > or =5 years before data submission, BT between 1988-1998, and no androgen deprivation before failure. The median follow-up was 63 months. Among patients where the I-125 dose to 90% of the prostate (D90) was > or =130 Gy, the 8-year PSA relapse-free survival (PRFS) was 93% compared with 76% for those with lower D90 dose levels (p < 0.001). A multivariable analysis identified tumor stage (p = 0.002), Gleason score (p < 0.001), pretreatment PSA level (p < 0.001), treatment year (p = 0.001), and the isotope used (p = 0.004) as pretreatment and treatment variables associated with PRFS. When restricted to patients with available postimplantation dosimetric information, D90 emerged as a significant predictor of biochemical outcome (p = 0.01), and isotope was not significant. The 8-year PRFS was 92%, 86%, 79%, and 67%, respectively, for patients with PSA nadir values of 0-0.49, 0.5-0.99, 1.0-1.99, and >2.0 ng/mL (p < 0.001). Among patients free of biochemical relapse at 8 years, the median nadir level was 0.1 ng/mL, and 90% of these patients achieved a nadir PSA level <0.6 ng/mL. Outcome after permanent BT for prostatic cancer relates to tumor stage, Gleason score, pretreatment PSA, BT year, and post-BT dosimetric quality. PSA nadir < or =0.5 ng/mL was particularly associated with durable long-term PSA disease-free survival. The only controllable factor to impact on long-term outcome was the D90 which is a reflection of implant quality.

Results of radiation therapy combined with neoadjuvant hormonal therapy for stage III prostate cancer: comparison of two different definitions of PSA failure

We herein report the clinical outcome of radical radiation therapy combined with neoadjuvant hormonal therapy (NHT) for stage III (International Union Against Cancer [UICC] 1997: UICC 97) prostate cancer. Prostate-specific antigen (PSA) failure-free survival was assessed according to two different definitions, and the appropriateness of each definition is discussed. Between October 1997 and December 2000, 27 patients with stage III prostate cancer were enrolled in this study. The median pretreatment PSA level was 29 ng/ml (range, 7.4-430 ng/ml). The Gleason score (GS) was 7 or more in 22 patients (81%). All patients received 3 months of NHT with a luteinizing hormone-releasing hormone (LH-RH) analogue, in combination with an antiandrogen (flutamide), given during the first 2 weeks, followed by 70-Gy external-beam radiation therapy (EBRT) in 35 fractions. The initial 46 Gy was given with a four-field technique, while the remainder was given with a dynamic conformal technique. No adjuvant hormonal therapy (AHT) was given. The median follow-up time was 63 months. PSA levels decreased to the normal range (<4 ng/ml) after irradiation in all but one patient. The 5-year PSA failure-free survival was 34.8% according to the American Society for Therapeutic Radiology and Oncology (ASTRO) definition and it was 43.0% according to the "nadir plus 2" definition. Discordance of the results between the two definitions was seen in two patients. The 5-year overall and cause-specific survivals were 83.0% and 93.3%, respectively. No severe acute or late adverse effects were observed. Seventy Gy of EBRT following 3 months of NHT produced therapeutic results comparable to those reported in other studies which used long-term AHT. The value of long-term AHT for Japanese men should be tested in a clinical trial.

The Clinical Potential of Pretreatment Serum Testosterone Level to Improve the Efficiency of Prostate Cancer Screening

ObjectivesThe aim of the present study was to evaluate the clinical value of the pretreatment serum testosterone (T) level as a potential predictor of prostate cancer risk in screening for prostate cancer. Materials and methodsThe subjects were 420 patients suspected of having prostate cancer who underwent prostate biopsy, and whose pretreatment T levels were recorded. We checked for association between the presence of prostate cancer and the following clinical factors: pretreatment serum T level, age, pretreatment prostate-specific antigen (PSA) level, digital rectal examination findings, ratio of free to total PSA, prostate volume, and PSA density (PSAD). ResultsOverall, there was no significant difference in mean pretreatment T level between patients diagnosed with cancer (3.9±2.4ng/ml) and patients diagnosed with benign prostate disease (BPD; 3.7±1.7ng/ml); diagnosis was based on prostate biopsy. However, among patients with PSA <10ng/ml, the pretreatment T level was significantly higher in patients diagnosed with prostate cancer (4.2±2.6ng/ml) than in patients diagnosed with BPD (3.6±1.4ng/ml) (p=0.007); a similar trend was observed among patients with PSAD <0.15ng/ml/cc. Multivariate analysis indicated that pretreatment T level was an independent significant predictor of positive prostate biopsy (p=0.020). Additionally, the serum T level was significantly lower in patients with a Gleason score ≥7 (3.7±2.1ng/ml) versus a score <7 (4.2±1.7ng/ml) (p=0.030). Also, serum T levels were significantly higher in well-differentiated prostate cancer (4.8±2.1ng/ml) versus moderately differentiated (3.8±1.3ng/ml) or poorly differentiated (3.7±1.4ng/ml) (p<0.01). ConclusionsAmong relatively low-risk patients, serum T level was an independent significant predictor of positive prostate biopsy, suggesting that the efficiency of prostate cancer screening can be improved by including measurement of serum T level.

A randomized comparative study of endocrine monotherapy and a combination of estramustine phosphate with the endocrine therapy in patients with untreated stage D prostate cancer

We investigated the clinical efficacy and the prolongation of survival with combination therapy of estramustine phosphate (EMP) and endocrine therapy in untreated patients with progressive prostate cancer. We randomly divided 57 patients with untreated stage D prostate cancer into two groups, an endocrine monotherapy group and a group receiving combination treatment, consisting of endocrine therapy plus EMP. Treatment was continued until deterioration. There were no significant differences in the improvement rating for subjective/objective symptoms or in progression-free survival between the two groups. However, overall survival was significantly prolonged in the combination therapy group (log-rank test, P = 0.0394; generalized Wilcoxon's test, P = 0.0145). In particular, overall survival was significantly prolonged, compared to that in the endocrine monotherapy group, in patients in the combination therapy group who were less than 74 years old, those with a performance status (PS) of 1 to 3, a pretreatment prostate-specific antigen (PSA) level of more than 20 ng/ml, moderately or poorly differentiated carcinoma, or a partial response (PR) based on the PSA level 12 weeks after the start of treatment. There was no significant difference in the incidence of side effects between the combination therapy and the endocrine monotherapy groups. A combination of EMP with endocrine therapy may be useful for initial treatment in younger patients (aged 73 or younger) and in patients at high risk of progressive prostate cancer.

Six-Month Androgen Suppression Plus Radiation Therapy Compared With Radiation Therapy Alone for Men With Prostate Cancer and a Rapidly Increasing Pretreatment Prostate-Specific Antigen Level

We evaluated whether treatment with 6 months of androgen-suppression therapy (AST) and radiation therapy (RT) compared with RT was associated with the time to prostate-specific antigen (PSA) recurrence, prostate cancer-specific mortality (PCSM), and all-cause mortality (ACM) in men with a pretreatment PSA velocity more than 2 ng/mL/yr. The study cohort comprised 241 men with clinically localized or locally advanced prostate cancer treated with RT and AST or RT from 1989 to 2002. Cox regression and Gray's formulation were used to assess whether treatment was associated significantly with the time to PSA recurrence or ACM and PCSM, respectively, adjusting for known prognostic factors. Despite the significantly longer median follow-up, younger age at diagnosis, higher proportion of Gleason score 7 to 10, and advanced T-category cancers, significantly lower estimates of PSA recurrence (P < .001), PCSM (P = .007), and ACM (P < .001) were observed in men who were treated using RT and AST compared with RT. Treatment with RT and AST compared with RT was associated with a longer time to PSA recurrence (adjusted hazard ratio [HR], 0.22; 95% CI, 0.14 to 0.35; P < .001), PCSM (HR, 0.23, 95% CI, 0.09 to 0.64; P = .005), and ACM (HR, 0.30; 95% CI, 0.16 to 0.58; P < .001). Treatment using 6 months of AST and RT compared with RT in men with a pretreatment PSA velocity greater than 2 ng/mL/yr was associated with a longer time to PSA recurrence, PCSM, and ACM.

Brachytherapy in men aged ≤ 54 years with clinically localized prostate cancer

To report the biochemical progression-free survival (BPFS) in hormone-naive men aged < or = 54 years who underwent brachytherapy with or without supplemental external beam radiation therapy (EBRT), as despite favourable biochemical control rates with brachytherapy, there remains a reluctance to recommend non-extirpative approaches for young men with clinically localized prostate cancer. From April 1995 to October 2002, 108 hormone-naive patients aged < or = 54 years (median 52 years, range 45-54) had permanent interstitial brachytherapy for clinical stage T1c-T2c NXM0 (2002 American Joint Committee on Cancer staging) prostate cancer. No patient had a seminal vesicle biopsy or pathological lymph node staging. The mean (sd, median) follow-up was 5.3 (1.8, 4.8) years. BPFS was defined by a prostate-specific antigen (PSA) level of < or = 0.40 ng/mL after the nadir. Risk groups were assigned using the Memorial Sloan-Kettering Cancer Center criteria. Several clinical, treatment and dosimetric variables were evaluated for their effect on BPFS. For the entire group, the actuarial 8-year BPFS was 96%; for low- (57 men), intermediate- (47) and high- (four) risk patients, the BPFS rates were 96%, 100% and three of four, respectively. For biochemically disease-free patients, the median PSA level after treatment was 0.05 ng/mL. In a multivariate analysis, only pretreatment PSA level predicted biochemical control, while dosimetry variables after treatment were almost statistically significant. Hormone-naive patients aged < or = 54 years have a high probability of a good 8-year BPFS after permanent interstitial brachytherapy with or without supplemental EBRT.

Improved Biochemical Control and Clinical Disease-Free Survival with Intraoperative Versus Preoperative Preplanning for Transperineal Interstitial Permanent Prostate Brachytherapy

We hypothesized that intraoperative preplanning for transperineal interstitial permanent prostate brachytherapy may yield better prostate cancer control than preoperative preplanning. We tested this hypothesis by comparing treatment outcomes of patients who underwent implantation using these two preplanning methods. We analyzed the data of 135 consecutive patients with localized prostate cancer treated from 1996 to 2001 with transperineal interstitial permanent prostate brachytherapy+/-preimplantation hormonal therapy: 42 received preoperative preplanning (group 1), and 93 underwent intraoperative preplanning (group 2). Biochemical status was assessed using two failure definitions: American Society for Therapeutic Radiology and Oncology (ASTRO) (three consecutive rises in prostate-specific antigen level) and Houston (prostate-specific antigen level>or=current nadir+2 ng/mL). Clinical disease-free survival and postimplantation dosimetry were also examined. All disease control outcomes were superior for group 2. The 4-year ASTRO biochemical no evidence of disease rate was 80% for group 1 versus 94% for group 2. The 4-year Houston biochemical no evidence of disease rate was 82% for group 1 versus 96% for group 2. The 4-year clinical disease-free survival rate was 87% for group 1 versus 99% for group 2. Preplanning method (preoperative versus intraoperative) remained predictive of disease control outcomes in multivariate analyses with the covariates of pretreatment prostate-specific antigen level, Gleason score, clinical stage, and case sequence number (proxy for brachytherapist experience and "stage migration"). Dosimetric prostate coverage was superior for group 2. The mean percentage of the prescription dose delivered to 90% of the prostate volume (%D90) was 75% for group 1 versus 90% for group 2. A %D90>or=70% predicted for improved disease control; fewer group 1 than 2 patients met this dosimetric criterion (55% versus 87%). Intraoperative preplanning yielded superior disease control outcomes in this analysis, likely due at least in part to improved dosimetric prostate coverage with this method. Although not mandatory for obtaining high prostate brachytherapy efficacy, intraoperative preplanning nevertheless may offer an excellent means of improving dosimetric prostate coverage and therefore disease control outcomes.

A phase II trial of imatinib mesylate in patients with biochemical relapse of prostate cancer after definitive local therapy

To determine the biological effects of imatinib mesylate (STI-571, Gleevec; Novartis Pharmaceuticals, Inc., East Hanover, NJ, USA), as measured by prostate-specific antigen (PSA) kinetics in men with biochemical relapse of prostate cancer after definitive local therapy. Men with prostate cancer, who had had definitive local therapy, with nonmetastatic recurrent disease as manifested by a rising PSA level, were enrolled on this phase II trial. Men received 400 mg of imatinib mesylate orally twice daily and continuously until disease progression or unacceptable toxicity. The PSA level was measured monthly. In all, 20 men with biochemically relapsed prostate cancer were treated. The median pretreatment PSA level was 5.4 ng/mL. Of the 19 evaluable men, one achieved a >or= 50% reduction in PSA level and two had decreases of <50%. For the 16 men in whom the on-treatment PSA doubling time (PSADT) could be calculated (those with increasing PSA level) the median PSADT did not increase significantly (5.8 vs 7.2 months, P = 0.64). Eleven of 20 men discontinued therapy due to toxicity and the trial was stopped early due to toxicity. Based on the lack of PSA modulation and pronounced toxicities leading to early closure of this trial, further study of single-agent imatinib mesylate at this dose (400 mg twice daily) cannot be recommended in this patient population.

Does age matter in the selection of treatment for men with early‐stage prostate cancer?

The specific aim of the current study was to compare freedom from biochemical failure, distant metastases-free survival, and overall survival in men age < or = 55 years, men ages 60 to 69 years, and men age > or = 70 years presenting with localized prostate cancer. A matched pair analysis compared patients age < or = 55 years (Group 1) who were treated with 3-dimension conformal radiation without androgen deprivation to men age > or = 60 years and < 70 years (Group 2), and men age > or = 70 years (Group 3) who were treated at the Fox Chase Cancer Center between November 1989 and October 2001. The groups were matched for disease stage (T1/T2b vs. T2C/T3), Gleason grade (2-6 vs. 7-10), radiation dose (< 70 Gray [Gy] vs. > or = 70-76 Gy vs. > or = 76 Gy), and pretreatment prostate-specific antigen (PSA) level. Estimates of outcome were accomplished using Kaplan-Meier methodology and compared by age group using the log-rank test. Eighty-four men were identified according to the selection criteria. No statistically significant difference was found in the 5-year overall survival rates for Group 1, Group 2, and Group 3 (94%, 95%, and 87%, respectively) or the 5-year rate of freedom from biochemical failure in Group 1, Group 2, and Group 3 (82%, 76%, and 70%, respectively), or freedom from distant metastases (96%, 97%, and 98%, respectively). Men age < or = 55 years who present with localized prostate cancer do not appear to have a worse prognosis. External beam radiation therapy appears to be a viable treatment alternative and should be offered to men age < or = 55 years who present with organ-confined prostate cancer.

Erectile Function After Prostate Brachytherapy

Purpose: To evaluate erectile function after permanent prostate brachytherapy using a validated patientadministered questionnaire and to determine the effect of multiple clinical, treatment, and dosimetric parameters on penile erectile function. Methods and Materials: A total of 226 patients with preimplant erectile function determined by the International Index of Erectile Function (IIEF) questionnaire underwent permanent prostate brachytherapy in two prospective randomized trials between February 2001 and January 2003 for clinical Stage T1c-T2c (2002 American Joint Committee on Cancer) prostate cancer. Of the 226 patients, 132 were potent before treatment and, of those, 128 (97%) completed and returned the IIEF questionnaire after brachytherapy. The median follow-up was 29.1 months. Potency was defined as an IIEF score of >13. The clinical, treatment, and dosimetric parameters evaluated included patient age; preimplant IIEF score; clinical T stage; pretreatment prostate-specific antigen level; Gleason score; elapsed time after implantation; preimplant nocturnal erections; body mass index; presence of hypertension or diabetes mellitus; tobacco consumption; the volume of the prostate gland receiving 100%, 150%, and 200% of the prescribed dose (V100/150/200); the dose delivered to 90% of the prostate gland (D90); androgen deprivation therapy; supplemental external beam radiotherapy (EBRT); isotope; prostate volume; planning volume; and radiation dose to the proximal penis. Results: The 3-year actuarial rate of potency preservation was 50.5%. For patients who maintained adequate posttreatment erectile function, the preimplant IIEF score was 29, and in patients with brachytherapyrelated ED, the preimplant IIEF score was 25. The median time to the onset of ED was 5.4 months. After brachytherapy, the median IIEF score was 20 in potent patients and 3 in impotent patients. On univariate analysis, the preimplant IIEF score, patient age, presence of nocturnal erections, and dose to the proximal penis predicted for postimplant erectile function. However, in multivariate analysis, only the preimplant IIEF score and the D50 to the proximal crura were statistically significant predictors of brachytherapyrelated erectile function. Conclusions: Using a patient-administered validated quality-of-life instrument, brachytherapy-induced ED occurred in 50% of patients at 3 years. On multivariate analysis, preimplant erectile function and the D50 to the proximal crura were the best predictors of brachytherapy-related erectile function. Because the proximal penis is the most significant treatment-related predictor of brachytherapy-related ED, techniques to minimize the radiation dose to the proximal penis may result in improved rates of potency preservation. © 2005 Elsevier Inc. Brachytherapy, Erectile function, Prostate, Proximal penis, Quality of life.