Clinical predictors of Gleason score upgrading: implications for patients considering watchful waiting, active surveillance, or brachytherapy

BACKGROUND: Brachytherapy, active surveillance, and watchful waiting are increasingly being offered to men with low-risk prostate cancer. However, many of these men harbor undetected high-grade disease (Gleason pattern > or =4). The ability to identify those individuals with occult high-grade disease may help guide treatment decisions in this patient cohort. METHODS: The authors identified 175 cases of low-risk prostate cancer treated with radical prostatectomy. By using logistic regression analysis, 11 a priori-defined preoperative risk factors were evaluated for their ability to predict upgrading from Gleason 6 at biopsy to Gleason > or =7 at radical prostatectomy. An internally validated nomogram using all clinical variables was subsequently created to help physicians identify patients who had undetected high-grade disease. RESULTS: A total of 60 (34%) patients were upgraded to high-grade disease. On multivariate analyses, both prostate-specific antigen (PSA) level (P = .02) and the level of pathologist expertise (P = .007) were predictive of upgrading. The predictive nomogram contained these variables plus age, digital rectal examination, transrectal ultrasound results, biopsy scheme applied (sextant vs extended), presence of prostatic intraepithelial neoplasia, prostate gland volume, and percentage of cancer in the biopsy. The nomogram provided acceptable discrimination (C statistic 0.71). CONCLUSIONS: The authors identified significant predictors of upgrading for patients diagnosed with low-risk prostate cancer. A nomogram based on these study findings could help physicians further risk-stratify patients with low-risk prostate cancer before embarking on treatment. Caution should be exercised in recommending nonradical therapy to individuals with a high probability of undetected high-grade disease.     

Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer.

PURPOSE: Although models exist that place patients into discrete groups at various risks for disease recurrence after surgery for prostate cancer, we know of no published work that combines pathologic factors to predict an individual's probability of disease recurrence. Because clinical stage and biopsy Gleason grade only approximate pathologic stage and Gleason grade in the prostatectomy specimen, prediction of prognosis should be more accurate when postoperative information is added to preoperative variables. Therefore, we developed a postoperative nomogram that allows more accurate prediction of probability for disease recurrence for patients who have received radical prostatectomy as treatment for prostate cancer, compared with the preoperative nomogram we previously published. PATIENTS AND METHODS: By Cox proportional hazards regression analysis, we modeled the clinical and pathologic data and disease follow-up for 996 men with clinical stage T1a-T3c NXM0 prostate cancer who were treated with radical prostatectomy by a single surgeon at our institution. Prognostic variables included pretreatment serum prostate-specific antigen level, specimen Gleason sum, prostatic capsular invasion, surgical margin status, seminal vesicle invasion, and lymph node status. Treatment failure was recorded when there was either clinical evidence of disease recurrence, a rising serum prostate-specific antigen level (two measurements of 0.4 ng/mL or greater and rising), or initiation of adjuvant therapy. Validation was performed on this set of men and a separate sample of 322 men from five other surgeons' practices from our institution. RESULTS: Cancer recurrence was noted in 189 of the 996 men, and the recurrence-free group had a median follow-up period of 37 months (range, 1 to 168 months). The 7-year recurrence-free probability for the cohort was 73% (95% confidence interval, 68% to 76%). The predictions from the nomogram appeared to be accurate and discriminating, with a validation sample area under the receiver operating characteristic curve (ie, a comparison of the predicted probability with the actual outcome) of 0.89. CONCLUSION: A postoperative nomogram has been developed that can be used to predict the 7-year probability of disease recurrence among men treated with radical prostatectomy.     

Preoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy

An existing preoperative nomogram predicts the probability of prostate cancer recurrence, defined by prostate-specific antigen (PSA), at 5 years after radical prostatectomy based on clinical stage, serum PSA, and biopsy Gleason grade. In an updated and enhanced nomogram, we have extended the predictions to 10 years, added the prognostic information of systematic biopsy results, and enabled the predictions to be adjusted for the year of surgery. Cox regression analysis was used to model the clinical information for 1978 patients treated by two high-volume surgeons from our institution. The nomogram was externally validated on an independent cohort of 1545 patients with a concordance index of 0.79 and was well calibrated with respect to observed outcome. The inclusion of the number of positive and negative biopsy cores enhanced the predictive accuracy of the model. Thus, a new preoperative nomogram provides robust predictions of prostate cancer recurrence up to 10 years after radical prostatectomy.     

A nomogram for predicting low-volume/low-grade prostate cancer: a tool in selecting patients for active surveillance

BACKGROUND: The authors reported previously that assessment of the number of positive biopsy cores, maximum tumor length in a core, Gleason score, and prostate volume in an extended biopsy enhanced the accuracy of predicting low-volume/low-grade prostate cancer. On the basis of those findings, they developed a nomogram to predict the probability of low-volume/low-grade prostate cancer specifically for men with a single positive biopsy core. METHODS: The study cohort comprised 258 men who underwent radical prostatectomy without neoadjuvant therapy. Prostate cancer was diagnosed in only 1 core of an extended biopsy scheme. Low-volume/low-grade cancer was defined as pathologic organ-confined disease and a tumor volume<0.5 cc with no Gleason grade 4 or 5 cancer. Patient age, prostate-specific antigen (PSA) level, prostate volume, PSA density (PSAD), and tumor length in a biopsy core were examined as variables. A fitted multiple logistic regression model was used to establish the nomogram. RESULTS: One hundred thirty-three patients (51.6%) had low-volume/low-grade cancer. To establish the nomogram, age, PSAD, and tumor length were adopted as variables. The fitted model suggested that older age, higher PSAD values, and greater tumor length would reduce the probability of low-volume/low-grade cancer. The nomogram predicted low-volume/low-grade cancer with good discrimination (an area under the receiver operating characteristic curve of 0.727). Calibration of this nomogram showed good predicted probability. CONCLUSIONS: The authors established a nomogram with which to predict low-volume/low-grade cancer in men with 1 positive biopsy core in an extended biopsy scheme, and they recommend this nomogram for use in selecting men for active surveillance.     

Critical assessment of tools to predict clinically insignificant prostate cancer at radical prostatectomy in contemporary men

BACKGROUND: Overtreatment of prostate cancer (PCa) is a concern, especially in patients who might qualify for the diagnosis of insignificant prostate cancer (IPCa). The ability to identify IPCa prior to definitive therapy was tested. METHODS: In a cohort of 1132 men a nomogram was developed to predict the probability of IPCa. Predictors consisted of prostate-specific antigen (PSA), clinical stage, biopsy Gleason sum, core cancer length and percentage of positive biopsy cores (percent positive cores). IPCa was defined as organ-confined PCa (OC) with tumor volume (TV) <0.5 cc and without Gleason 4 or 5 patterns. Finally, an external validation of the most accurate IPCa nomogram was performed in the same group. RESULTS: IPCa was pathologically confirmed in 65 (5.7%) men. The 200 bootstrap-corrected predictive accuracy of the new nomogram was 90% versus 81% for the older nomogram. However, in cutoff-based analyses of patients who were qualified by our and the older nomograms as high probability for IPCa, respectively 63% and 45% harbored aggressive PCa variants at radical prostatectomy (Gleason score 7-10, ECE, SVI, and/or LNI). CONCLUSIONS: Despite a high accuracy, currently available models for prediction of IPCa are incorrect in 10% to 20% of predictions. The rate of misclassification is even further inflated when specific cutoffs are used. As a consequence, extreme caution is advised when statistical tools are used to assign the diagnosis of IPCa.     

Clinically significant Gleason sum upgrade: external validation and head-to-head comparison of the existing nomograms

BACKGROUND:

Several nomograms have been developed for the purpose of predicting the likelihood of an increase in Gleason sum (GS) from biopsy information compared with the GS determined after examination of the “entire prostate” in patients with prostate cancer. In this study, the authors evaluated and compared the ability of 4 nomograms (published by Capitanio et al, Chun et al, Kulkarni et al, and Moussa et al) to predict GS upgrades for patients with biopsy GS ≤6 prostate cancer who underwent radical prostatectomy (RP) at their center.

METHODS:

The entire study cohort included 942 patients with a biopsy GS ≤6. Predictive performances of the nomograms were compared using area under the receiver operating characteristic curve (AUC‐ROC) analysis, calibration plots, and decision curve analysis (DCA) in the entire cohort, in patients with low‐risk prostate cancer (LRPC), and a subgroup of those patients who underwent extended biopsy with ≥10 cores.

RESULTS:

Patients with a GS ≥7 at prostatectomy included 319 of 942 patients (33.9%) in the entire study cohort, 263 of 814 patients (32.2%) with LRPC, and 84 of 301 patients (27.9%) with LRPC who underwent extended biopsy. With an AUC‐ROC of 0.637 to 0.647 in the different subgroups of patients with low‐risk cancer, the Kulkarni et al nomogram demonstrated significantly higher discriminative ability compared with the other nomograms. The same nomogram provided a small clinical benefit at DCA. All nomograms were poorly calibrated.

CONCLUSIONS:

The available prognostic tools had limited ability to predict clinically significant upgrading in patients with biopsy GS ≤6 and, thus, the authors concluded that these tools are not ready for clinical application. Cancer 2011;. © 2011 American Cancer Society.     

The addition of interleukin-6 soluble receptor and transforming growth factor beta1 improves a preoperative nomogram for predicting biochemical progression in patients with clinically localized prostate cancer.

PURPOSE: Several preoperative prostate cancer nomograms have been developed that predict risk of progression using pretreatment prostate-specific antigen (PSA) level, clinical stage, and biopsy Gleason grade. We describe the development and performance of a new nomogram. The nomogram adds new markers to the standard clinical predictors that reflect the biologic behavior of prostate cancer: pretreatment plasma levels of interleukin-6 soluble receptor (IL6SR) and transforming growth factor beta1 (TGF-beta1). PATIENTS AND METHODS: Between November 7, 1994 and December 22, 1997, 714 patients with stage cT1c to cT3a prostate cancer and no prior therapy were treated with radical prostatectomy at the Methodist Hospital, Houston TX. Plasma levels of IL6SR and TGF-beta1 were measured in banked preoperative plasma. With these data, a nomogram was developed to predict the probability of PSA progression within 5 years of surgery. The nomogram was validated with bootstrapping to assess its discrimination and calibration performance. RESULTS: In the multivariable Cox model, PSA (P =.004), IL6SR (P <.001), TGF-beta1 (P <.001), primary Gleason grade (P <.002), and secondary Gleason grade (P =.029) were associated with PSA progression, whereas clinical stage (P =.696) was not. The nomogram seemed to be well calibrated and had a bootstrap-corrected area under the receiver operating characteristic curve (ie, concordance index) of 0.83. For comparison, a nomogram that omitted IL6SR and TGF-beta1 achieved a concordance index of only 0.75. CONCLUSION: We found that pretreatment plasma levels of IL6SR and TGF-beta1 improved the ability to predict biochemical progression by a prognostically substantial margin. A nomogram including the pretreatment levels of these molecular markers, along with standard clinical markers, has been developed and internally validated.     

Optimizing patient selection for prostate monotherapy

PURPOSE: Patients at low risk for prostate-specific antigen (PSA) failure following definitive local therapy are those with PSA of 10 or less, biopsy Gleason Score of 6 or less, and 1992 American Joint Committee on Cancer (AJCC) clinical Stage T1c or T2a. However, low-risk patients managed with radical prostatectomy and found to have prostatectomy Gleason score > or = 3+4 have a less favorable PSA outcome when compared to patients with prostatectomy Gleason score < or = 3+3. This study was performed to determine whether the percentage of positive prostate biopsy cores could predict upgrading from a biopsy Gleason score of 6 or less to a prostatectomy Gleason score > or = 3+4 in low-risk patients to optimize selection for prostate only radiation therapy. METHODS AND MATERIALS: Concordance testing of the biopsy Gleason score and the primary and secondary prostatectomy Gleason grades was performed in 427 prostate cancer patients treated with radical prostatectomy and at low risk for PSA failure. Logistic regression multivariable analysis was performed to test the ability of the established prognostic factors and the percentage of positive prostate biopsies (<34%, 34-50%, >50%) to predict for upgrading from biopsy Gleason score of 6 or less prostatectomy Gleason score > or = 3+4. PSA failure-free survival was reported using the actuarial method of Kaplan and Meier and comparisons were made using a log-rank test. RESULTS: Twenty-nine percent of the 427 study patients were upgraded from a biopsy Gleason score of 6 or less to a prostatectomy Gleason score > or = 3+4. The presence of greater than 50% positive biopsies was the only significant factor for predicting the upgrading from biopsy Gleason score of 6 or less to prostatectomy Gleason score > or = 3+4 on logistic regression multivariable analysis with the variables treated as continuous and categorical. Specifically, upgrading occurred in 26% vs. 59% of patients with 50% or less vs. greater than 50% positive biopsies, respectively. This translated into a 5-year PSA failure-free survival which was significantly higher (92% vs. 62%, p = 0.00001) for men with 50% or less vs. greater than 50% positive prostate biopsies, respectively. CONCLUSION: The presence of greater than 50% positive biopsies was associated with higher rates of pathologic upgrading which translated into lower 5-year PSA failure-free survival following radical prostatectomy (RP). Therefore, the percentage of positive biopsies may be useful in optimizing the selection of low-risk patients for prostate only radiation therapy such as external beam radiation or implant monotherapy.     

Association between percentage of tumor involvement and Gleason score upgrading in low-risk prostate cancer

To find the predictors of Gleason score upgrading in a cohort of low-risk prostate cancer patients, data were analyzed comprising 1,632 consecutive men with low-risk prostate cancer who underwent radical prostatectomy between 1993 and 2009. Assessment focused on preoperative parameters including patient age, race, diagnostic prostate-specific antigen (PSA) levels, clinical stage and biopsy Gleason score, along with pathological parameters including percentage of tumor involvement (PTI), tumor laterality, pathological stage, extra-capsular extension, seminal vesicle invasion, and surgical margins. These parameters were analyzed using univariate and multivariate methods. Kaplan?CMeier curves compared differences in biochemical disease-free survival in men having cancers with and without Gleason score upgrading. Cases involving pathological Gleason score upgrading were identified in 723 (44.3?%) of 1,632 patients. Kaplan?CMeier PSA recurrence-free survival curves showed a difference in outcome between men with and without Gleason score upgrading (p?<?0.001). Of Gleason score upgraded patients, 35 (4.8?%) men had PTI of <5?%, 237 (32.8?%) had PTI of 5?C9.9?%, 177 (24.5?%) had PTI of 10?C14.9?%, and 274 (37.9?%) had PTI????15?% (p?<?0.001). PTI (p?<?0.001) along with diagnostic PSA, patient age, diagnostic biopsy Gleason score, pathologic stage, and surgical margin status were independent predictors of pathological Gleason score upgrading on multivariate logistic regression. PTI correlates closely with Gleason score upgrading in a low-risk prostate cancer cohort. Low-risk prostate cancer patients with clinical findings suggestive of high PTI or large volume cancers should not benefit from active surveillance strategies.     

Use of preoperative plasma endoglin for prediction of lymph node metastasis in patients with clinically localized prostate cancer.

PURPOSE: Current predictive tools and imaging modalities are not accurate enough to preoperatively diagnose lymph node metastases in patients with prostate cancer. The aim of the study was to evaluate whether preoperative plasma endoglin improves the prediction of lymph node metastases in patients with clinically localized prostate cancer. EXPERIMENTAL DESIGN: Endoglin levels were measured using a commercially available ELISA assay in banked plasma from 425 patients treated with radical prostatectomy and bilateral lymphadenectomy for clinically localized prostatic adenocarcinoma at two university hospitals between July 1994 and November 1997. Logistic regression analyses were undertaken to evaluate whether endoglin improves the accuracy of a standard preoperative model for prediction of lymph node metastasis and to build a predictive nomogram. RESULTS: Preoperative plasma endoglin levels were higher in patients with higher preoperative total serum prostate-specific antigen (PSA; Spearman correlation coefficient 0.296, P < 0.001), positive surgical margins (P = 0.03), higher pathologic Gleason sum (P = 0.04), and lymph node metastasis (P < 0.001). In a preoperative multivariable logistic regression analysis that included PSA and clinical stage, only preoperative endoglin (odds ratio, 1.17; 95% confidence interval, 1.09-1.26; P < 0.001) and biopsy Gleason sum (odds ratio, 18.57; 95% confidence interval, 1.08-318.36; P = 0.04) were associated with metastasis to lymph nodes. The addition of endoglin to a standard preoperative model (including PSA, clinical stage, and biopsy Gleason sum) significantly improved its accuracy for prediction of lymph node metastasis from 89.4% to 97.8% (P < 0.001). CONCLUSIONS: Preoperative plasma endoglin improves the accuracy for prediction of pelvic lymph node metastasis in patients treated with radical prostatectomy for clinically localized prostate cancer by a statistically and clinically significant margin.     

Pretreatment nomogram for prostate-specific antigen recurrence after radical prostatectomy or external-beam radiation therapy for clinically localized prostate cancer.

PURPOSE: To present nomograms providing estimates of prostate-specific antigen (PSA) failure-free survival after radical prostatectomy (RP) or external-beam radiation therapy (RT) for men diagnosed during the PSA era with clinically localized disease. PATIENTS AND METHODS: A Cox regression multivariable analysis was used to determine the prognostic significance of the pretreatment PSA level, 1992 American Joint Committee on Cancer (AJCC) clinical stage, and biopsy Gleason score in predicting the time to posttherapy PSA failure in 1,654 men with T1c,2 prostate cancer managed with either RP or RT. RESULTS: Pretherapy PSA, AJCC clinical stage, and biopsy Gleason score were independent predictors (P < .0001) of time to posttherapy PSA failure in patients managed with either RP or RT. Two-year PSA failure rates derived from the Cox regression model and bootstrap estimates of the 95% confidence intervals are presented in the format of a nomogram stratified by the pretreatment PSA, AJCC clinical stage, biopsy Gleason score, and local treatment modality. CONCLUSION: Men at high risk (> 50%) for early (< or = 2 years) PSA failure could be identified on the basis of the type of local therapy received and the clinical information obtained as part of the routine work-up for localized prostate cancer. Selection of these men for trials evaluating adjuvant systemic and improved local therapies may be justified.     

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.     

Ten-year survival after radical prostatectomy: specimen Gleason score is the predictor in organ-confined prostate cancer

Pathologic stage is a major prognostic factor in patients with clinically localized prostate cancer. However, disease recurrence occurs even in patients with organ-confined disease. With the advent of prostate-specific antigen (PSA) testing, the percentage of patients with pathologically organ-confined tumors has increased significantly. We studied clinical/pathologic factors that will predict disease recurrence in patients with pathologically organ-confined tumors. Patients with clinically localized newly diagnosed prostate cancer who had not received prior therapeutic intervention but who underwent radical prostatectomy as definitive treatment between 1990 and 1999, were included in this study. Clinical/pathologic parameters including age, race, clinical stage, preoperative PSA, and biopsy and specimen Gleason scores (grouped as 2-6, 7, and 8-10) were correlated with disease-free survival in patients with organ-confined disease. Metastasis-free and cancer-specific survival for the cohort was also assessed. A total of 1045 patients fulfilled our inclusion criteria. Overall, the 10-year estimates of PSA progression-free, metastasis-free, and cancer-specific survival were 75%, 91%, and 92%, respectively. Cancer was confined to the prostate in 532 of 1045 patients (51%), of whom 96% (511 of 532) remain PSA progression-free, compared to 65% (335 of 513) with extraprostatic disease (P = 0.0001). Interestingly, in patients with organ-confined disease, the specimen Gleason score was the only prognostic factor for disease recurrence after multivariable analysis. Radical prostatectomy provided excellent cancer control. For patients with pathologically organ-confined tumors, the specimen Gleason score is the only factor predictive of disease-free survival. Of note, Gleason scores of 8-10 are uncommon in these patients.     

Nomograms for clinically localized prostate cancer. Part I: radical prostatectomy

Many nomograms are currently available for patients' and physicians' use for prediction of pathologic stage based on preoperative parameters, such as prostate-specific antigen (PSA) level, clinical stage (tumor, node, metastasis), and Gleason score from prostate biopsy specimen. Based on the probability of final pathologic stage as well as patient comorbidity and life expectancy, patients and physicians can decide whether definitive local therapy, systemic therapy, or palliative therapy would be most appropriate. Nomograms have also been developed based on preoperative parameters for prediction of biochemical recurrence-free survival outcome following surgery. These nomograms can help patients understand the long-term cancer cure rates after radical prostatectomy.     

Problems of the preoperative prediction of the pathological stage in prostate cancer

The pathological stage of the tumor is the most influential prognostic factor for progression after radical prostatectomy. However, as many as 50% of men undergoing radical prostatectomy are found to have extraprostatic disease in the pathological specimen. Accurate identification of the risks of disease extension and of disease recurrence prior to radical prostatectomy would thus be useful in counseling men presenting with clinically localized prostate cancer. Nomograms may help patients and physicians make more informed treatment decisions based on the probability of pathological stage. Partin and co-workers popularized the use of a pretreatment nomogram based on PSA (prostate specific antigen), clinical stage (TNM stage) and biopsy Gleason score to predict the pathological stage of localized prostate cancer. However, it may not be directly applicable to Japanese males, and the interpretation and comparison of data sets should be done with caution and careful consideration. Although attempts have been made to establish a nomogram for Japanese patients, been tried, it is still based on the data for a small number of patients. More data from a greater number of patients and validation analysis are essential. Recently, artificial neural networks (ANN) have been shown to be effective in predicting pathologic stage in men with clinically localized prostate cancer. The use of ANNs is a relatively new concept and the data is based on Western people; thus, the data analysis for Japanese patients is necessary. The present paper mainly outlines the usefulness and problems for the preoperative prediction of the pathological stage in prostate cancer by nomograms and artificial neural networks.     

The clinical utility of the percent of positive prostate biopsies in predicting biochemical outcome following external-beam radiation therapy for patients with clinically localized prostate cancer

PURPOSE: An investigation was performed of the clinical utility of the percent of positive prostate biopsies in predicting prostate-specific antigen (PSA) outcome following external-beam radiation therapy (RT) for men with PSA-detected or clinically palpable prostate cancer. METHODS AND MATERIALS: A Cox regression multivariable analysis was used to determine whether the percent of positive prostate biopsies provided clinically relevant information about PSA outcome following external beam RT in 473 men while accounting for the previously established risk groups based on the pretreatment PSA level, biopsy Gleason score, and the 1992 American Joint Commission on Cancer (AJCC) clinical T stage. RESULTS: Controlling for the known prognostic factors, the percent of positive prostate biopsies added clinically significant information (p = 0.02) regarding time to PSA failure following RT. Specifically, 76% of the patients in the intermediate risk group (1992 AJCC T(2b) or biopsy Gleason 7 or PSA > 10 ng/mL and < or = 20 ng/mL) could be classified into either an 30% or 85% 5-year PSA control cohort using the preoperative prostate biopsy data. CONCLUSION: The previously validated stratification of PSA outcome following radical prostatectomy (RP) using the percent of positive prostate biopsies in intermediate-risk patients is also clinically significant for men treated with external beam RT. The percent positive prostate biopsies should be considered in conjunction with the PSA level, biopsy Gleason score, and 1992 AJCC clinical T stage when counseling patients with newly diagnosed and clinically localized prostate cancer about PSA outcome following RP or external beam RT.     

Nomograms for clinically localized disease. Part III: watchful waiting

Patients with newly diagnosed, clinically localized prostate cancer need information concerning long-term outcomes to make informed decisions regarding treatment options. Several nomograms have been developed that can help in this decision process. By using a nomogram originally published in 1998, patients and clinicians can predict the 15-year clinical outcomes in the absence of aggressive treatment based on age and Gleason score at diagnosis. These predictions are based on patients diagnosed and treated before the routine use of PSA that has accelerated the diagnosis of prostate cancer by at least 5 years. Longer follow-up of contemporary patients will determine whether this nomogram remains accurate in the prostate-specific antigen (PSA) era. In view of the lead-time bias resulting from PSA testing, the outcomes of contemporary patients are likely to be better rather than worse than the results shown.     

Should the Gleason grading system for prostate cancer be modified to account for high-grade tertiary components? A systematic review and meta-analysis

The Gleason system for grading prostate cancer assigns a score on the basis of the most prevalent and second most prevalent grade. Several studies have investigated the clinical significance of a tertiary grade in radical prostatectomy samples. A systematic search of the published work identified seven studies that reported the prognostic value of a tertiary Gleason grade. Three studies correlated the presence of a tertiary grade with pathological stage, and six with prostate-specific antigen recurrence or clinical progression. In the small number of studies available, the frequency of a tertiary grade was consistently higher in samples characterised with pathological variables of poor outcome, such as extra-prostatic extension and positive surgical margins, but not lymph-node metastases. In five studies the presence of a tertiary grade increased the risk of prostate-specific antigen recurrence after radical prostatectomy by a factor of 2.5. However, modification of the Gleason score to include a tertiary grade in Gleason 4+3 tumours might overestimate the risk of seminal-vesicle or lymph-node invasion. This systematic review has established the association of a tertiary grade with poorer outcome than that associated with no tertiary grade. A tertiary grade should, therefore, be included in the pathological reporting of prostate cancer and be considered in the interpretation and design of clinical trials. However, all studies assessed for this review were retrospective, potentially affected by selection bias, and based on radical prostatectomy samples or transurethral resections rather than biopsy samples. Therefore, more evidence is needed to warrant the adaptation of the Gleason system to account for the presence of a tertiary grade, especially when scoring prostatic biopsies and applying predictive algorithms.     

Ten-Year Survival After Radical Prostatectomy: Specimen Gleason Score Is the Predictor in Organ-Confined Prostate Cancer

Pathologic stage is a major prognostic factor in patients with clinically localized prostate cancer. However, disease recurrence occurs even in patients with organ-confined disease. With the advent of prostate-specific antigen (PSA) testing, the percentage of patients with pathologically organ-confined tumors has increased significantly. We studied clinical/pathologic factors that will predict disease recurrence in patients with pathologically organ-confined tumors. Patients with clinically localized newly diagnosed prostate cancer who had not received prior therapeutic intervention but who underwent radical prostatectomy as definitive treatment between 1990 and 1999, were included in this study. Clinical/pathologic parameters including age, race, clinical stage, preoperative PSA, and biopsy and specimen Gleason scores (grouped as 2-6, 7, and 8-10) were correlated with disease-free survival in patients with organ-confined disease. Metastasis-free and cancer-specific survival for the cohort was also assessed. A total of 1045 patients fulfilled our inclusion criteria. Overall, the 10-year estimates of PSA progression-free, metastasis-free, and cancer-specific survival were 75%, 91%, and 92%, respectively. Cancer was confined to the prostate in 532 of 1045 patients (51%), of whom 96% (511 of 532) remain PSA progression-free, compared to 65% (335 of 513) with extraprostatic disease (P = 0.0001). Interestingly, in patients with organ-confined disease, the specimen Gleason score was the only prognostic factor for disease recurrence after multivariable analysis. Radical prostatectomy provided excellent cancer control. For patients with pathologically organ-confined tumors, the specimen Gleason score is the only factor predictive of disease-free survival. Of note, Gleason scores of 8-10 are uncommon in these patients.     

Brachytherapy for clinically localized prostate cancer

Prostate brachytherapy is an effective treatment option for clinically organ-confined prostate carcinoma. Observed 5- and 10-year follow-up have documented prostate-specific antigen (PSA) levels that were comparable to published radical prostatectomy series and were better than several published external-beam radiation series. Between January 1987 and June 1988, a total of 152 consecutive patients with Stage T1 to T3 low to high Gleason grade prostate cancer were studied at Northwest Hospital in Seattle, Washington. Patients' median age was 70 years (range, 53 to 92 years). All patients received Iodine-125 prostate brachytherapy with or without a 45 Gy dose of external-beam radiation. The average preoperative PSA, clinical stage, and prostate needle biopsy Gleason sum were 11 ng/ml, T2, and (5), respectively, and were known in all but five patients. PSA follow-up, clinical examination, and biopsy results judged disease-free survival at 5 and 10 postoperative years. Elevation of PSA above 0.5 ng/ml or a positive biopsy or a positive bone scan was considered treatment failure. The authors provide an historical review of prostate brachytherapy in conjunction with up-to-date implant techniques and long-term outcome results.