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M L Blute

Publications and source records attributed to M L Blute.

At least 19 recordsLinked to original sources

Contralateral adrenal metastasis of renal cell carcinoma: treatment, outcome and a review.

OBJECTIVE: To report the surgical treatment of patients with renal cell carcinoma (RCC) metastatic to the contralateral adrenal gland and compare our experience with previous reports, as such metastases are found in 2.5% of patients with metastatic RCC at autopsy, and the role of resecting metastatic RCC at this site is not well defined. PATIENTS AND METHODS: We retrospectively identified 11 patients who had surgery for metastatic RCC to the contralateral adrenal gland between October 1978 and April 2001. The patients' medical records were reviewed for clinical, surgical and pathological features, and the patients' outcome. RESULTS: The mean (median, range) age of the patients at primary nephrectomy was 60.9 (64, 43-79) years; all had clear cell (conventional) RCC. Synchronous contralateral adrenal metastasis occurred in two patients. The mean (median, range) time to contralateral adrenal metastasis after primary nephrectomy for the remaining nine patients was 5.2 (6.1, 0.8-9.2) years. All patients were treated with adrenalectomy; there were no perioperative complications or mortality. Seven patients died from RCC at a mean (median, range) of 3.9 (3.7, 0.2-10) years after adrenalectomy for contralateral adrenal metastasis; one died from other causes at 3.4 years, one from an unknown cause at 1.7 years and two were still alive at the last follow-up. CONCLUSIONS: The surgical resection of contralateral adrenal metastasis from RCC is safe; although most patients died from RCC, survival may be prolonged in individual patients. Hence, in the era of cytoreductive surgery, the removal of solitary contralateral adrenal metastasis seems to be indicated.

Adrenal Gland Neoplasms↗

Rationale for combination therapy of intraurethral prostaglandin E(1) and sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy.

Corpus cavernosum smooth muscle relaxation and hence penile erection are regulated in part by increases in smooth muscle synthesis of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). The object of this study was to determine 30-month follow-up results in motivated patients desiring noninvasive medical therapy using sildenafil citrate (Viagra) in combination with intraurethral prostaglandin E(1) (PGE(1)) (Medicated Urethral System for Erection [MUSE]). Twenty-eight patients (mean +/- s.d. age, 59 +/-7.3 y; 17 who had undergone radical prostatectomy and 11 who had a diagnosis of organic erectile dysfunction) were included in this study. Detailed history taking and physical examinations were performed and vascular risk factors noted. In these patients, treatment with either 100 mg of sildenafil citrate and/or 1000 microg of MUSE had failed. None of these patients desired intracavernosal injection. Duplex Doppler ultrasonography after redosing was carried out on all patients. Dynamic infusion corpus cavernosography/cavernosometry was obtained in 17 of 28 patients, and combination therapy was initiated using 100 mg of sildenafil citrate orally 60 min before intercourse and 500 microg of MUSE intraurethrally immediately before intercourse. Independently, either 100 mg of sildenafil citrate or 1000 microg of MUSE was not efficacious in inducing an erection sufficient for vaginal penetration in any of the 28 patients. After initiating a combination therapy, at 30 months, all 28 patients were reporting erections sufficient for vaginal penetration, with 3.6 intercourse episodes per month. None of the patients crossed over to intracavernosal therapy or penile prosthesis. During therapy, eight of 28 patients reduced the dose of sildenafil citrate to 50 mg. Combination therapy with MUSE and sildenafil may be more efficacious in the salvage of patients who desire noninvasive therapy but in whom single-treatment modalities fail. Although both cAMP- and cGMP-mediated vasodilation can lead to penile erection, combining therapies that incorporate both pathways may succeed when single therapies fail.

Aged↗

Role of HPC2/ELAC2 in hereditary prostate cancer.

The HPC2/ELAC2 gene on chromosome 17p was recently identified as a candidate gene for hereditary prostate cancer (HPC). To confirm these findings, we screened 300 prostate cancer patients (2 affected members/family) from 150 families with HPC for potential germ-line mutations using conformation-sensitive gel electrophoresis, followed by direct sequence analysis. The minimum criteria for our families with HPC was the presence of 3 affected men with prostate cancer. A total of 23 variants were identified, including 13 intronic and 10 exonic changes. Of the 10 exonic changes, 1 truncating mutation was identified, a Glu216Stop nonsense mutation. This nonsense variant was found in 2 of 3 affected men in a single family. The remaining nine alterations included five missense, three silent, and one variant in the 3' untranslated region. To additionally test for potential associations of polymorphic variants and increased risk for disease, we genotyped two common polymorphisms, Ser217Leu and Ala541Thr, in 446 prostate cancer patients from 164 families with HPC and 502 population-based controls. The frequency of the Leu217 variant was similar for patients (32.3%) and controls (31.8%), as was the frequency of the Thr541 variant (5.4% among patients versus 5.2% among controls). In contrast to previous reports, we found no association of the joint effects of Leu271 and Thr541 (odds ratio, 1.04; 95% confidence interval, 0.57-1.89). Overall, our results did not reveal any association between these two common polymorphisms and the risk for HPC. The finding of a nonsense mutation in the HPC2/ELAC2 gene confirms its potential role in genetic susceptibility to prostate cancer. However, our data also suggest that germ-line mutations of the HPC2/ELAC2 are rare in HPC and that the variants Leu217 and Thr541 do not appear to influence the risk for HPC. Cumulatively, these results suggest that alterations within the HPC2/ELAC2 gene play a limited role in genetic susceptibility to HPC.

Adult↗

Outcomes for men with clinically nonmetastatic prostate carcinoma managed with radical prostactectomy, external beam radiotherapy, or expectant management: a retrospective analysis.

BACKGROUND: With a lack of data from randomized trials, the optimal management of men with nonmetastatic prostate carcinoma is controversial. The authors sought to define the outcomes of three common strategies for managing patients with nonmetastatic prostate carcinoma: expectant management, radiotherapy, and radical prostatectomy. METHODS: The authors conducted a retrospective cohort study with standardized collection of key prognostic data, including centralized assignment of Gleason grades from original biopsy specimens. Participants included all Connecticut hospitals (the expectant management cohort) and three academic medical centers in other states (the radiotherapy and surgery cohorts). Two thousand three hundred eleven consecutive men ages 55-74 years who were diagnosed during 1971-1984 with nonmetastatic prostate carcinoma and were treated at the participating sites were included. RESULTS: Kaplan-Meier estimates with 95% confidence intervals (95% CI) of overall survival at 10 years for each cohort were as follows: expectant management cohort, 42% of patients (95% CI, 38-46%); radiotherapy cohort, 52% of patients (95% CI, 46-58%); and radical prostatectomy cohort, 69% of patients (95% CI, 67-71%); for disease specific mortality, the estimates were as follows: expectant management cohort, 75% of patients (95% CI, 71-79%); radiotherapy cohort, 67% of patients (95% CI, 61-73%); and radical prostatectomy cohort, 86% of patients (95% CI, 84-88%). There were large differences in distributions of important prognostic factors among men in the different treatment groups. CONCLUSIONS: These data provide precise estimates of the outcomes of patients who have been treated with different modalities for nonmetastatic prostate carcinoma in the recent past. Direct comparisons of outcomes between treatment groups are inadvisable because of the different characteristics of patients who select these alternative management strategies.

Aged↗

Predicting prostate carcinoma volume and stage at radical prostatectomy by assessing needle biopsy specimens for percent surface area and cores positive for carcinoma, perineural invasion, Gleason score, DNA ploidy and proliferation, and preoperative serum prostate specific antigen: a report of 454 cases.

BACKGROUND: DNA ploidy analysis of prostate carcinoma is a generally accepted prognostic marker, particularly when tumors are extraprostatic at the time of surgery. In the past decade, the DNA content of prostate carcinoma frequently has been assessed in needle biopsy specimens based on the assumption that ploidy, in conjunction with serum prostate specific antigen (PSA) and Gleason score, provides valuable pretreatment information. METHODS: Between 1995 and 1998, the authors identified a consecutive series of 454 prostate carcinomas, verified by needle biopsies and followed by radical retropubic prostatectomies (RRP). Based on the needle biopsies, DNA ploidy and MIB-I immunostaining were measured by digital image analysis (DIA). The authors also quantified the percent of nuclei in four categories from the DNA histograms. The DIA data were combined with the age of the patient at diagnosis, the serum PSA, Gleason score, percent cores and percent surface area positive for carcinoma, and status of perineural invasion in multivariate models using tumor volume and risk of extraprostatic extension (EPE) at RRP as the outcome variables. RESULTS: Joint predictors of tumor volume at RRP were the percent cores positive for carcinoma (P < 0.0001), serum PSA (P < 0.0001), the percent surface area positive for carcinoma (P < 0.0001), and the percent nuclei classified by DNA quantification to be in the "S-phase" category (P = 0.03). Joint predictors of risk of EPE were the percent cores positive for carcinoma (P = 0.0004), a Gleason score of 7 (P < 0.0001), a Gleason score of 8 or 9 (P < 0.0001), serum PSA (P = 0.006) and perineural invasion (P = 0.02). CONCLUSIONS: After adjusting for traditional prognostic markers, DNA ploidy interpretation and MIB-I quantitation of prostate carcinoma did not appear to jointly predict either outcome variable in the multivariate models. However, a quantitative measure related to both ploidy and proliferation, the percent of nuclei in the putative "S-phase" category from the DIA histograms, was found to jointly predict for tumor volume.

Adult↗

Pathologic staging of renal cell carcinoma: significance of tumor classification with the 1997 TNM staging system.

BACKGROUND: The TNM staging system for renal cell carcinoma was revised by the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) in 1997. The 1997 TNM staging system for renal cell carcinoma reclassifies tumors using criteria for size and for extent of renal vein/vena cava involvement that are different from the criteria used in the 1987 staging system. The current study investigated the prognostic significance of tumor classification and other factors using the new staging system. METHODS: Records from 1547 renal cell carcinoma patients (1039 males and 508 females; mean age, 63.4 years; mean follow-up, 7.1 years) who underwent surgical resection between 1970 and 1998 were analyzed retrospectively. Tumors were staged using the 1987 and 1997 TNM criteria, and Kaplan-Meier estimates of survival and disease recurrence were compared for both staging systems. The Peto-Peto log rank test and the generalized Wilcoxon test were used to assess univariate significance of prognostic factors on survival. Cox proportional hazards regression analysis was then completed to assess the significance of the revised staging system. RESULTS: Tumor classification using the 1987 TNM staging system (P = 0.0001) and the 1997 TNM staging system (P = 0.0001) was a significant predictor of cause specific survival. Using 1997 TNM staging criteria, 641 patients were reclassified from the T2 classification to the T1 classification, 114 patients were reclassified from the T3c classification to the T3b classification, 11 patients were reclassified from the T4b classification to the T3c classification, and 3 patients were reclassified from the T4b classification to the T3b classification. Patients with reclassified tumors had outcomes similar to patients with tumors that remained in the same tumor classification. Patient stratification was improved using the new staging system. Prognostic discrimination for cause specific survival at 10 years was noted for the 1987 and 1997 TNM classifications (T1, 97% vs. 91%; T2, 84% vs. 70%; T3a, 53% vs. 53%; T3b, 48% vs. 42%; and T3c, 29% vs. 43%). CONCLUSIONS: The revised classification of renal cell carcinoma was a significant predictor of cause specific survival for the cohort of patients described in this report. Using the new system, the stratification of patients was improved. Patients who had their tumors reclassified as a result of the new staging system had outcomes similar to those of patients who had tumors that remained in the same classification. Based on an analysis of this cohort, tumor classification is valid, and the T1 subclassification is warranted. However, additional revision may be required to optimize staging.

Adolescent↗

Risk of prostate carcinoma death in patients with lymph node metastasis.

BACKGROUND: The presence of lymph node metastasis is a poor prognostic sign for patients with prostate carcinoma. Results of published reports on survival among patients with lymph node metastasis are difficult to assess because of treatment selections. The extent to which lymph node status will have an impact on a patient's survival is uncertain. METHODS: The authors analyzed 3463 consecutive Mayo Clinic patients who underwent radical prostatectomy and bilateral pelvic lymphadenectomy for prostate carcinoma between 1987 and 1993. Of these patients, 322 had lymph node metastasis at the time of surgery, and 297 lymph node positive patients also received adjuvant hormonal therapy within 90 days of surgery. The progression free rate and the cancer specific survival rate were used as outcome endpoints in univariate and multivariate Cox proportional hazards models. The median follow-up was 6.3 years. Progression was defined by elevation of serum prostate specific antigen (PSA) > or = 0.4 ng/mL after surgery, development of local recurrence, or distant metastasis documented by biopsy or radiographic examination. RESULTS: The 5-year and 10-year progression free survival rates (+/- standard error [SE]) for patients with lymph node metastasis were 74% +/- 2% and 64% +/- 3%, respectively, compared with 77% +/- 1% and 59% +/- 2%, respectively, for patients without lymph node metastasis. The 5-year and 10-year cancer specific survival rates were 94% +/- 1% and 83% +/- 4%, respectively, compared with 99% +/- 0.1% and 97% +/- 0.5%, respectively, for patients without lymph node metastasis. Among patients with a single lymph node metastasis, the 5-year and 10-year cancer specific survival rates were 99% +/- 1% and 94% +/- 3%, respectively. After adjustment for extraprostatic extension, seminal vesicle invasion, Gleason grade, surgical margins, DNA ploidy, preoperative serum PSA concentration, and adjuvant therapy, the hazard ratio for death from prostate carcinoma among patients with a single lymph node metastasis compared with patients who were without lymph node metastasis was 1.5 (95% confidence interval, 0.5-5.0; P = 0.478), whereas the hazard ratio for death from prostate carcinoma was 6.1 (95% confidence interval, 1.9-19.6; P = 0.002) for those with two positive lymph nodes and 4.3 (95% confidence interval, 1.4-13.0; P = 0.009) for those with three or more positive lymph nodes. There was no significant difference in the progression free survival rate among patients with or without lymph node metastasis in multivariate analysis after controlling for all relevant variables, including treatments (hazard ratio,1.0; 95% CI, 0.7-1.3; P = 0.90). CONCLUSIONS: Patients with prostate carcinoma who have multiple regional lymph node metastases had increased risk of death from disease, whereas patients with single lymph node involvement appeared to have a more favorable prognosis after radical prostatectomy and immediate adjuvant hormonal therapy. Excellent local disease control was achieved by using combined surgery and adjuvant hormonal therapy in patients with positive lymph nodes.

Adult↗

Stage pT1 conventional (clear cell) renal cell carcinmoa: pathological features associated with cancer specific survival.

PURPOSE: The features predictive of aggressive behavior in stage pT1 conventional (clear cell) renal cell carcinoma are not completely known. We evaluated pathological features in a large series of stage pT1 conventional renal cell carcinoma cases and examined the association of these features with cancer specific survival. MATERIALS AND METHODS: Patients with solitary stage pT1 conventional renal cell carcinoma who underwent radical nephrectomy between 1970 and 1997 were eligible for study. For each of the 46 patients who died of renal cell carcinoma we selected a stratified random sample of at least 3 year matched controls who were still alive or dead of other causes. The study included 277 patients. We evaluated patient age at nephrectomy, sex, tumor size, Fuhrman grade, necrosis and sarcomatoid component. Univariate and multivariate Cox proportional hazards models were fit to assess the features associated with cancer specific survival. RESULTS: Multivariate modeling revealed that tumor size, Fuhrman grade and necrosis were jointly significantly associated with cancer specific survival. Of the 4.5, 5 and 6 cm. tumor size cutoffs examined on univariate analysis a cutoff of 5 cm. or greater was most predictive of cancer specific survival. CONCLUSIONS: In stage pT1 conventional renal cell carcinoma Fuhrman grade, tumor necrosis and tumor size together were jointly significantly associated with cancer specific survival. Specifically of the tumor size cutoffs analyzed the 5 cm. cutoff was most predictive of cancer specific survival.

Adult↗

Chemoprevention for prostatic carcinoma: The role of flutamide in patients with prostatic intraepithelial neoplasia.

High-grade prostatic intraepithelial neoplasia (HGPIN) is believed to be a precursor for prostatic adenocarcinoma. The prevalence of prostatic intraepithelial neoplasia (PIN) increases with advancing age. Autopsy studies suggest that PIN may precede the development of prostatic adenocarcinoma by up to 10 years. As such, HGPIN is believed to be a marker of increased risk. This provides a potential opportunity for chemoprevention. Flutamide is 1 agent with potential activity and limited side effects that may act to prevent or delay the onset of prostatic adenocarcinoma in men with HGPIN. A clinical trial is currently underway to assess the efficacy of flutamide.

Age Factors↗

Contemporary identification of patients at high risk of early prostate cancer recurrence after radical retropubic prostatectomy.

OBJECTIVES: To develop a model that will identify a contemporary cohort of patients at high risk of early prostate cancer recurrence (greater than 50% at 36 months) after radical retropubic prostatectomy for clinically localized disease. Data from this model will provide important information for patient selection and the design of prospective randomized trials of adjuvant therapies. METHODS: Proportional hazards regression analysis was applied to two patient cohorts to develop and cross-validate a multifactorial predictive model to identify men with the highest risk of early prostate cancer recurrence. The model and validation cohorts contained 904 and 901 men, respectively, who underwent radical retropubic prostatectomy at Johns Hopkins Hospital. This model was then externally validated using a cohort of patients from the Mayo Clinic. RESULTS: A model for weighted risk of recurrence was developed: R(W)'=lymph node involvement (0/1)x1.43+surgical margin status (0/1)x1.15+modified Gleason score (0 to 4)x0.71+seminal vesicle involvement (0/1)x0.51. Men with an R(W)' greater than 2.84 (9%) demonstrated a 50% biochemical recurrence rate (prostrate-specific antigen level greater than 0.2 ng/mL) at 3 years and thus were placed in the high-risk group. Kaplan-Meier analyses of biochemical recurrence-free survival demonstrated rapid deviation of the curves based on the R(W)'. This model was cross-validated in the second group of patients and performed with similar results. Furthermore, similar trends were apparent when the model was externally validated on patients treated at the Mayo Clinic. CONCLUSIONS: We have developed a multivariate Cox proportional hazards model that successfully stratifies patients on the basis of their risk of early prostate cancer recurrence.

Adult↗

Is nephroureterectomy necessary in all cases of upper tract transitional cell carcinoma? Long-term results of conservative endourologic management of upper tract transitional cell carcinoma in individuals with a normal contralateral kidney.

OBJECTIVES: To evaluate the endoscopic management of upper urinary tract transitional cell carcinoma (TCC) as a first-line treatment in patients with a normal contralateral kidney. METHODS: During an 11-year period, 21 patients diagnosed with upper tract TCC were treated with conservative endourologic techniques using either neodymium:yttrium-aluminum-garnet laser or electrocautery at our institution. The 21 patients were followed up for a mean of 6.1 years (range 1 to 11.6). RESULTS: A total of 8 renal pelvic tumors and 13 ureteral tumors were found. All tumors were Stage T1 or less and grade 3 or less. All tumors were less than 2 cm in the greatest dimension (range 0.4 to 2). Of the 21 patients, 7 (33%) had one local recurrence and 1 (4.7%) developed two local recurrences. Of the 13 ureteral tumors, 6 (46%) recurred; 1 (12%) of the 8 renal pelvic tumors recurred. No recurrent tumor was shown to have an increase in grade. Of the 21 target renal units, 17 (81%) were preserved; 4 (19%) of 21 patients required nephroureterectomy because of tumor recurrence. Overall, 11 patients in the series died, 10 of non-TCC etiology and 1 secondary to invasive bladder TCC that developed after treatment for upper tract TCC. No patients died as a result of conservative management of their upper tract TCC. CONCLUSIONS: Endourologic techniques and conservative treatment of upper tract TCC is an evolving field; however, in properly selected patients, endoscopic treatment can be safely and effectively used as a first-line treatment for upper tract TCC.

Adult↗

Minimally invasive therapies for benign prostatic hyperplasia.

Currently, 3 categories of treatment are available for men with benign prostatic hyperplasia (BPH): (1) medicine, such as alpha-blockers and finasteride; (2) minimally invasive treatment, such as transurethral microwave thermotherapy and interstitial ablation using either radiofrequency or laser; and (3) surgical therapy. The 1990s have seen an explosion of transurethral technology to treat symptoms caused by bladder outlet obstruction secondary to BPH. Unlike surgical debulking procedures, the minimally invasive therapies attempt to treat patients without general or regional anesthesia, and even ambulatory procedures are performed in the office. Because of the demographics of patients with BPH, it is hoped that these minimally invasive options will relieve symptoms without any surgical complications and the side effects and compliance issues associated with medical therapy. It is important that urologists have a clear understanding of the clinical usefulness of these devices, so that the overall role of such treatment may be determined by science rather than marketing. Clinically, the degree of symptom score, peak flow, and quality-of-life improvement seen with all the minimally invasive techniques are similar. The techniques may differ in their ability to reach the maximum number of responders and achieve an acceptable duration of response, and the need for analgesia/sedation associated with each technique. This study will define the minimally invasive therapies and present the differences in catheter design and technique. The pathologic basis for these therapeutic options and the advantages and disadvantages of each will be discussed. Urologists must decide which therapy can be used in their office practice. The maximum numbers of responders and enhanced durability of the treatment can be achieved based on realistic expectations, proper selection of patients, and complete information on the potential of these devices.

Adrenergic alpha-Antagonists↗

Introduction.

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5-alpha Reductase Inhibitors↗

Use of Gleason score, prostate specific antigen, seminal vesicle and margin status to predict biochemical failure after radical prostatectomy.

PURPOSE: We determine the importance of clinical and pathological variables for predicting biochemical progression in patients after surgery for specimen confined prostate cancer. We developed a simple scoring algorithm for biochemical progression in node negative cases and tested the algorithm performance on an independent group. MATERIALS AND METHODS: Our study included 2,518 patients with pT2N0 or pT3N0 disease treated between 1990 and 1993. Gleason score, preoperative prostate specific antigen (PSA), margin status, extraprostatic extension, seminal vesicle involvement, DNA ploidy and adjuvant treatment were primary variables analyzed univariately. The Cox proportional hazards model was used on 2,000 randomly selected patients to develop a multivariate scoring algorithm for the aforementioned factors to predict biochemical progression-free survival. The final model included Gleason score, preoperative PSA, margin status, seminal vesicle involvement and adjuvant treatment. The prognostic score derived from this model was validated by applying it to the remaining 518 patients. Harrell's measure of concordance (C) was used to compare competing models. RESULTS: For patients who did not receive adjuvant therapy the derived score based on the Cox model coefficient was Gleason +1 (PSA 4 to 10), +2 (PSA 10.1 to 20), +3 (PSA greater than 20), +2 (positive seminal vesicle) and +2 (positive margin). The score was reduced by 4 if adjuvant hormonal therapy was given and by 2 for only adjuvant radiotherapy. The 5-year progression-free survival was 94% for scores less than 5, 60% for 10 and 32% for greater than 12 (C = 0. 718). Applying the score to the independent validation data set (518) resulted in 5-year progression-free survival of 96% for scores less than 5, 53% for 10 and 30% for greater than 12 (C = 0.759). CONCLUSIONS: Progression-free survival determined by the model score group identified a wide range of risk levels for patients with specimen confined prostate cancer. This simple predictive model allows identification of patients at high risk for cancer progression with specimen confined disease who may be targeted for closer surveillance and adjuvant therapy, while those at lower risk may be simply observed.

Adenocarcinoma↗

PSA doubling time as a predictor of clinical progression after biochemical failure following radical prostatectomy for prostate cancer.

OBJECTIVES: To characterize the clinical progression of disease in men who have undergone prostatectomy for clinically localized prostate cancer and have postoperative biochemical failure (elevated prostate-specific antigen [PSA] level) and to identify predictors of clinical disease progression, including the possible effect of PSA doubling time (PSADT). PATIENTS AND METHODS: Between 1987 and 1993, 2809 patients underwent radical retropubic prostatectomy for clinically localized (< or =T2) disease. In our database, all patients with postoperative biochemical failure (PSA level > or =0.4 ng/mL) were identified. The PSADT was estimated using log linear regression on all PSA values (excluding those values determined after administration of hormonal therapy) within 15 months after biochemical failure. All patients had regular PSA measurements from the time of surgery through the follow-up period. Systemic progression (SP) was defined as evidence of metastatic disease on a bone scan. Local recurrence (LR) was defined on the basis of digital rectal examination, transrectal ultrasonography, and biopsy. The SP-free survival and LR/SP-free survival (survival free of both LR and SP) after biochemical failure was estimated with use of the Kaplan-Meier method. Patients with prostate cancer treatment after biochemical failure had their follow-up censored from this study at the time of treatment. RESULTS: Postoperative biochemical failure occurred in 879 men (31%). The mean follow-up from time of biochemical failure was 4.7 years (range, 0.5-11 years). The mean time to biochemical failure was 2.9 years (median, 2.4 years). The overall mean SP-free survival from time of biochemical failure was 94% and 91% at 5 and 10 years, respectively. The mean LR/SP-free survival was 64% and 53% at 5 and 10 years, respectively. By using univariate analysis on the 587 patients with PSADT data, significant risk factors for SP were PSADT (P<.001) and pathologic Gleason score (P=.005); for LR/SP, significant risk factors included PSADT (P<.001) and pathologic Gleason score (P<.001). In multivariate Cox models analysis, only PSADT remained a significant risk factor for both SP and LR/SP (P<.001). Mean 5-year SP-free survival was 99%, 95%, 93%, and 64% for patients with PSADT of 10 years or longer, 1.0 to 9.9 years, 0.5 to 0.9 year, and less than 0.5 year, respectively; the respective mean LR/SP-free survivals were 87%, 62%, 46%, and 38%. The percentage of patients with PSADT of less than 0.5 year was considerably higher if the type of first clinical event was SP (48%) compared with LR (18%) (P<.001). CONCLUSIONS: For patients who have undergone radical prostatectomy, a rising PSA level suggests evidence of residual or recurrent prostate cancer. Many men remain free of clinical disease for an extended time after biochemical failure following radical prostatectomy for clinically localized prostate cancer. The PSADT appears to be an important predictor of SP and also of any clinical progression (local or systemic). These data may be useful when counseling men regarding the timing of adjuvant therapies.

Analysis of Variance↗

Defining prostate specific antigen progression after radical prostatectomy: what is the most appropriate cut point?

PURPOSE: The most appropriate definition of biochemical progression after radical prostatectomy and radiation therapy is uncertain. We analyzed the effect of using various prostate specific antigen (PSA) end point definitions for defining biochemical progression after radical prostatectomy and attempted to determine the best PSA cut point to use. Aspects of the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure after radiation therapy are also analyzed in our radical prostatectomy cases. MATERIALS AND METHODS: A total of 2,782 men with clinically localized prostate cancer (cT1-T2) who had undergone radical prostatectomy between 1987 and 1993 were reviewed. All patients had regular PSA determinations from surgery through followup. Analysis was limited to patients who did not receive adjuvant treatment within 90 days of radical prostatectomy. Biochemical, PSA progression-free percent after radical prostatectomy was determined by the Kaplan-Meier method using several PSA cut points, including 0.2, 0.3, 0.4 and 0.5 ng./ml. or greater, as well as 0.4 ng./ml. or greater and increasing. Progression-free percent was also assessed using the ASTRO definition, which is 3 increases in PSA. To determine which PSA level was most appropriate to define progression after radical prostatectomy, the percentage of patients with a continued PSA increase after reaching each cut point was determined. The relationship between the maximum PSA within 3 years of surgery and subsequent development of clinical disease was also assessed. RESULTS: Progression-free percent was dependent on the PSA cut point used. Biochemical progression-free percentages for cut points 0.2, 0.3, 0.4 and 0.5 ng./ml. or greater were 62%, 72%, 76% and 78% at 5 years, and 43%, 54%, 59% and 61% at 10 years, respectively. A subsequent increase in PSA was noted in 49%, 62% and 72% of patients who had PSA 0.2, 0.3 and 0.4 ng./ml., respectively. Subsequent clinical progression (local or systemic) was directly related to the maximum PSA attained within 3 years of radical prostatectomy (p=0.0001). Progression-free percent for definitions requiring multiple increases in PSA were dependent on when the event was said to occur. Backdating of events at or before the first PSA (ASTRO definition) resulted in poorer, short-term progression-free percent (78% at 5 years), with little apparent likelihood of long-term failure (78% at 10 years). Coding the event at the last PSA increase when all event criteria had been met resulted in more realistic progression-free percent estimates (85% at 5 and 59% at 10 years). CONCLUSIONS: Biochemical, PSA progression rates vary markedly depending on the method used to define PSA failure. Methods that require multiple increasing PSA values, for example the ASTRO definition, give misleading results, especially if the event time is backdated. Standards for defining PSA progression would allow more consistent and comparable progression estimates after radical prostatectomy. PSA 0.4 ng./ml. or greater may be the most appropriate cut point to use since a significant number of patients with lower PSA do not have a continued increase in it.

Adult↗