High Risk Of Cancer Recurrence Research Articles

Total Nasal Reconstruction Using a Prelaminated Free Radial Forearm Flap and Porous Polyethylene Implants

Reconstruction of total nasal defects remains one of the most difficult problems in plastic surgery as the nose combines aesthetics and function. Standard techniques using either forehead or nasolabial flaps do not have a place in the case of extensive scarring on the face or areas with high risk of cancer recurrence on the face. In these cases, microsurgical free tissue transfer for the soft tissue reconstruction in combination with bone grafts or implants for the nasal skeleton are ideal. We report the use of prelaminated radial forearm flap with porous polyethylene implants for total nasal reconstruction.

Does Her2/neu status affect adjuvant chemotherapy utilization? A population based analysis

11549 Background: Adjuvant chemotherapy (aC) is a standard treatment for patients with breast cancer (BC) who have a moderate to high risk of cancer recurrence. More recently, adjuvant trastuzumab (aTZ) has also become a standard treatment option for patients with Her2/neu positive BC who are candidates for aC. We conducted a population-based study in Nova Scotia, Canada, to determine if patients with Her2/neu positive BC have a greater chance of receiving aC compared to those with Her2/neu negative BC. Methods: All patients diagnosed with stage I-III BC between October 2005 and September 2006 in NS, Canada, were identified through the provincial cancer registry. A retrospective chart review was performed to abstract relevant clinical and pathological variables including: age, menopausal status, comorbidities, TNM stage, grade, multifocality, lymphovascular invasion, hormone receptor status, Her2/neu status, referral to medical oncology (MO) and receipt of aC and trastuzumab (aTZ). Logistic regression model with multivariate analyses was performed to determine variables associated with MO referral and/or aC treatment. Results: 630 patients were identified; 523 were reviewed and 421 underwent Her2/neu testing (IHC with Tab250 and DAKO A0485 antibodies, and FISH for equivocal IHC results). Of those tested, Her2/neu was positive in 59 (14%) and negative in 362 (86%) with 43 (73%) vs 182 (50%) undergoing aC treatment, respectively (p=0.001). In the Her2/neu positive cohort, 37/59 received aTZ (63%). Patients not tested for Her2-neu were older (median age 71 vs 59) and more likely to be post menopausal with T1 tumors; only 8/102 (8%) received aC. In multivariate analyses MO referral was associated with age <60, premenopausal status, ≥T2 tumor and node-positive disease while receipt of aC was associated with age <60, ≥T2 tumors, node-positive disease, negative hormone receptor status and positive Her2/neu status. Conclusions: Patients with Her2/neu positive BC were more likely treated with aC compared to those with Her2/neu negative disease, even after accounting for patient and disease-risk characteristics. No significant financial relationships to disclose.

Long-Term Rates of Undetectable PSA with Initial Observation and Delayed Salvage Radiotherapy after Radical Prostatectomy

BackgroundRandomized trials have shown an improvement in progression-free survival rates with adjuvant radiation therapy (ART) after radical prostatectomy for patients with a high risk of cancer recurrence. Less is known about the relative advantages and disadvantages of initial observation with delayed salvage radiation therapy (SRT). ObjectiveTo examine the results of SRT in a large single-surgeon radical prostatectomy series. Design, Setting, and ParticipantsFrom a radical prostatectomy database, we identified 859 men with positive surgical margins (SM+), extracapsular tumor extension (ECE), or seminal vesicle invasion (SVI) who chose to defer ART. Following a period of initial observation, 192 ultimately received SRT for prostate-specific antigen (PSA) progression. MeasurementsSurvival analysis was performed to examine the outcomes of initial observation followed by SRT. Results and LimitationsIn patients with SM+/ECE and SVI, the 7-yr PSA progression-free survival rates with observation were 62% and 32%, respectively. Among those who had PSA progression, 56% and 26%, respectively, maintained an undetectable PSA for 5 yr after SRT. The long-term rates of undetectable PSA associated with an SRT strategy were 83% and 50% for men with SM+/ECE and SVI, respectively. In the subset of 716 men who did not receive any hormonal therapy, the corresponding long-term rates of undetectable PSA were 91% and 75%, respectively. ConclusionsFollowing radical prostatectomy, initial observation followed by delayed SRT at the time of PSA recurrence is an effective strategy for selected patients with SM+/ECE. Some patients with SVI may also benefit from this strategy. However, additional prospective studies are necessary to further examine the survival outcomes following SRT.

Telomerase activity in transthoracic fine-needle biopsy aspirates from non-small cell lung cancer as prognostic factor of patients’ survival

Evaluation of the relationship between telomerase activity in transthoracic fine-needle biopsy (TFNB) aspirates collected from peripheral non-small cell lung cancer (NSCLC), cancer advancement, risk of death and free of cancer recurrence survival. The study group consisted of 93 patients with peripheral infiltration of the lung. All of them had TFNB of the focal pulmonary lesion performed. The aspirates were subjected to standard cytological evaluation. Telomerase activity in the specimens was determined with the PCR-ELISA PLUS method. Cancer advancement, manner of treatment and survival were assessed in patients with NSCLC. A benign lesion of the lung was recognised in 14 cases. NSCLC was newly diagnosed in 79 subjects. Nobody with benign infiltration had a detectable level of telomerase in lung infiltration. Increased telomerase activity was observed in 56 (70.9%) patients with lung cancer. It was significantly more often detected in patients with non-operable NSCLC (clinical stage IIIB plus IV) and patients with distant metastases (stage IV alone). Cox hazard analysis revealed that presence of telomerase activity in primary NSCLC is an independent prognostic factor of survival. Increased telomerase activity in TFNB aspirates was related to 7 times higher relative risk of death during the study [RR=6.9 (CI: 1.8-26.8); p<0.05] and 2.5 times higher risk of cancer recurrence after radical treatment [RR=2.5 (CI: 0.3-9.3); p<0.05]. Telomerase activity in aspirates collected through TFNB of primary peripheral NSCLC could be a helpful independent prognostic factor of distant metastases and risk of death or cancer recurrence.

Diet High in Meat, Fat, and Refined Grains Is Associated With Increased Risk for Colon Cancer Recurrence and Death

Patients treated for colon cancer who consumed a diet high in meat, refined grains, fat, and desserts had an increased risk of cancer recurrence and death compared with patients who consumed a diet high in fruits and vegetables, poultry, and fish, according to a study in the August 15, 2007 issue of The Journal of the American Medical Association. Previous research has indicated that diet and other lifestyle factors have a significant influence on the risk of developing colon cancer. However, few studies have assessed the influence of diet on colon cancer recurrence and survival, according to researchers led by Dr. Jeffrey A. Meyerhardt, MD, MPH, of the Dana-Farber Cancer Institute, Boston, MA. “This is the first study, to our knowledge, in a potentially cured population of colon cancer survivors to address the effect of diet,” they write. Meyerhardt et al examined the influence of 2 distinct dietary patterns on cancer recurrence and survival in a group of 1009 stage III colon cancer patients enrolled in a clinical trial of postoperative chemotherapy in addition to other treatment. Patients reported dietary intake using a food frequency questionnaire during and 6 months after supplemental chemotherapy. Two major dietary patterns were identified: “prudent” and “Western.” The prudent pattern was characterized by high intakes of fruits and vegetables, poultry, and fish, whereas the Western pattern was characterized by high intakes of meat, fat, refined grains, and dessert. During a median follow-up of 5.3 years, 324 patients had cancer recurrence, 223 patients died with cancer recurrence, and 28 died without documented cancer recurrence. The researchers found that intake of a Western dietary pattern after cancer diagnosis was associated with a significant increase in the risk of cancer recurrence or death. Compared with patients in the lowest Western dietary pattern quintile (bottom 20%), those in the highest quintile (top 20%) experienced a 3.3 times higher risk for cancer recurrence or death. Patients in the highest quintile of Western dietary pattern were 2.9 times more likely to have their cancer recur than those in the lowest quintile. Similarly, a significantly higher overall risk of death with increasing Western dietary pattern was observed. In contrast, the prudent dietary pattern was not significantly associated with cancer recurrence or death. “Studies have shown an improved disease-free survival among patients who receive adjuvant chemotherapy following the surgical resection of stage III colon cancer,” the researchers write. “Because this was an observational study, causality cannot and should not be drawn from these data. Nonetheless, the data suggest that a diet characterized by higher intakes of red and processed meats, sweets and desserts, french fries, and refined grains increases the risk of cancer recurrence and decreases survival. Further analyses are under way to better delineate specific nutrients or food groupings that may have the strongest association,” the authors write. See JAMA “Association of Dietary Patterns with Cancer Recurrence and Survival in Patients with Stage III Colon Cancer.” 2007;298:754–764.

Knowledge and Attitudes about Microsatellite Instability Testing among High-Risk Individuals Diagnosed with Colorectal Cancer

For individuals meeting Bethesda criteria for hereditary nonpolyposis colorectal cancer syndrome, the microsatellite instability (MSI) test is recommended as a screening evaluation before proceeding to genetic testing. The MSI test is new to the medical setting, but will be increasingly used to screen patients at high risk for hereditary nonpolyposis colorectal cancer. The main goals of this study were to examine knowledge about and exposure to the MSI test among individuals considering the test, to evaluate perceived benefits and barriers to undergoing the MSI test, and to identify the demographic, medical, and psychosocial correlates of the perceived benefits and barriers to undergoing the test. One hundred and twenty-five patients completed a survey after being offered the test, but prior to making the decision whether to pursue MSI testing. Results indicated low levels of knowledge about and previous exposure to the MSI test. Participants held positive attitudes about the potential benefits of the test and perceived few barriers to undergoing the test. Motivations were similar to those cited by individuals considering other genetic tests. Participants with nonmetastatic disease, with lower perceived risk for cancer recurrence, and who reported more self-efficacy endorsed more benefits from the test. Higher levels of cancer-specific psychological distress were associated with more perceived barriers to having the test. These findings suggest that individuals considering the MSI test know very little about it but hold positive attitudes about the test's utility. More distressed patients, patients who perceive themselves at higher risk for cancer recurrence, and patients with metastatic disease might be less motivated to have the MSI test.

Correlation of TLK1B in Elevation and Recurrence in Doxorubicin-Treated Breast Cancer Patients with High eIF4E Overexpression

Tousled-like kinase 1B (TLK1B), a mammalian threonine kinase, facilitates the repair of DNA breaks. Eukaryotic initiation factor 4E (eIF4E) overexpression leads to the upregulation of TLK1B. Doxorubicin, commonly used in the adjuvant setting for breast cancer, causes DNA breaks. We hypothesized that the degree of TLK1B elevation is correlated with eIF4E overexpression and translates clinically to an increased risk for recurrence in breast cancer patients treated with doxorubicin-based adjuvant chemotherapy. We prospectively accrued 152 patients with stage I to III breast cancer treated with a doxorubicin-based chemotherapy in an adjuvant setting. Standardized treatment and surveillance protocols were used. eIF4E and TLK1B protein levels were quantified using Western blots, and patients were divided into tertiles based on previously reported stratification of eIF4E and TLK1B levels. Primary end points were cancer recurrence and death. Statistical analysis included Spearman's correlation, Kaplan-Meier survival analysis, log rank test, and the Cox proportional hazard model. The degree of TLK1B overexpression was highly correlated with the degree of eIF4E elevation (r=0.25, p=0.0025, Spearman rank correlation). Patients whose tumors were in the highest tertile for eIF4E overexpression had a higher risk for cancer recurrence and cancer death (p=0.015 and 0.049, respectively, log rank test). After adjusting for T-stage, nodal status, age, and estrogen receptor and progesterone receptor status, patients with tumors in the highest tertile of TLK1B overexpression treated with doxorubicin were 1.7-fold more likely to suffer recurrence than those in the low TLK1B group treated similarly (p=0.0078, CI, 1.17 to 2.75, Cox model). TLK1B overexpression was highly correlated with the level of eIF4E elevation. High TLK1B in cancer specimens was associated with a higher risk for cancer recurrence in patients treated with doxorubicin-based adjuvant chemotherapy.

Prognostic Value of Histologic Tumor Regression, Thymidylate Synthase, Thymidine Phosphorylase, and Dihydropyrimidine Dehydrogenase in Rectal Cancer UICC Stage II/III After Neoadjuvant Chemoradiotherapy

Histologic tumor regression (TR) in rectal cancer after preoperative chemoradiotherapy (CT/RT) may be useful as a surrogate end point for early treatment efficacy, but little is known about its prognostic value. The aim of this follow-up study was to evaluate whether TR is able to predict prognosis in rectal cancer patients. Furthermore, the prognostic value of thymidylate synthase (TS)-gene, thymidine phosphorylase (TP)-gene, and dihydropyrimidine dehydrogenase (DPD)-gene expression after neoadjuvant CT/RT was determined. Forty patients with rectal cancer cUICC stage II/III, receiving preoperative 5-fluorouracil (5-FU) based CT/RT were studied for therapy-induced TR and categorized as "responders" or "nonresponders" according to their TR-grade. Posttherapeutical TS-gene, TP-gene, and DPD-gene expression on surgical resection specimens was quantified by TaqMan real-time PCR after microdissection. During a median follow-up of 58 months, cancer recurrence occurred in 28%. A significant correlation was seen between disease-free survival and lymph node status (P<0.001). All patients, who developed cancer recurrence had a posttherapeutical positive lymph node status. The majority of patients with cancer recurrence were "responders" (91%) after CT/RT. There was a significant correlation between posttherapeutical TS-gene expression and cancer recurrence within the subgroup of "responders." TS-gene expression was significantly higher in patients with cancer recurrence than in those, who are disease-free up to date (P=0.028). In conclusion, lymph node status remains the most important prognostic marker in rectal cancer patients, whereas posttreatment TR by itself has no prognostic significance. Furthermore, measurement of posttherapeutical TS-gene expression may help to identify patients at higher risk for cancer recurrence.

Poorly Differentiated Prostate Cancer Treated With Radical Prostatectomy: Long-Term Outcome and Incidence of Pathological Downgrading

Patients with high grade (Gleason score 8 to 10) prostate cancer on biopsy are at high risk for cancer recurrence after local treatment, such as radiation therapy and radical prostatectomy. We examined long-term outcomes in patients with high grade prostate cancer on biopsy who were treated with radical prostatectomy alone. We also investigated the impact on outcomes of changes in the radical prostatectomy Gleason score. Of 5,662 patients who underwent radical prostatectomy during 20 years 238 had a biopsy Gleason score of 8 to 10. We analyzed the rate of biochemical recurrence in this subgroup according to the Gleason grade of cancer in the radical prostatectomy specimen. Ten-year biochemical recurrence-free probability in the cohort was 39%. However, 45% of patients (95% CI 38 to 51%) with Gleason score 8 to 10 cancer on biopsy had a Gleason score of 7 or less in the radical prostatectomy specimen. These patients had a 10-year biochemical recurrence-free probability of 56% compared to 27% in those with a final Gleason score that remained 8 to 10 (p = 0.0004). On multivariate analysis neither prostate specific antigen nor biopsy features, including total number of cores, number of cores with cancer and percent of cancer in the cores, was a significant predictor of downgrading. However, clinical stage and biopsy Gleason score were significant with 58% of cT1c and 51% of biopsy Gleason score 8 cancers downgraded. Almost 65% of cT1c Gleason score 8 cancers were downgraded compared to 11% of cT3 Gleason score 9 cancers. Patients diagnosed with poorly differentiated prostate cancer (Gleason score 8 to 10) on biopsy do not uniformly have a poor prognosis. Of the patients 39% remain free of cancer recurrence 10 years after radical prostatectomy. Of these cancers 45% have a lower Gleason score in the radical prostatectomy specimen and a correspondingly more favorable long-term outcome. Predictors of downgrading are lower clinical stage (cT1c) and Gleason score 8 in the biopsy specimen.

Up-regulation of TLK1B by eIF4E overexpression predicts cancer recurrence in irradiated patients with breast cancer

The overexpression of eukaryotic initiation factor 4E (eIF4E), which is a critical component of the RNA helicase complex important in the translation of messenger RNAs with long and/or complex 5' untranslated regions, appears to impact malignant transformation and predict cancer recurrence in patients with breast cancer, independent of nodal status. Tousled-like kinase (TLK1B) is a mammalian threonine kinase with a long 5' untranslated regions in the messenger RNA. In vitro, malignant cells with eIF4E overexpression appear to have corresponding TLK1B elevation. Additionally TLK1B phosphorylates histone 3, which is a protein that is involved in chromatin assembly, plays an integral role in radioresistance in cell lines. Our hypothesis is that patients with breast cancer with high eIF4E overexpression have increased TLK1B and a higher risk for recurrence after adjuvant radiation therapy. One hundred fifty-eight patients with stage I to III breast cancer were accrued in a prospective study that was designed to detect cancer recurrence in patients who had been treated with adjuvant radiation therapy. A standardized surveillance and treatment protocol was used to maximize treatment homogeneity and to detect the study primary end point, cancer recurrence. All patients received adjuvant radiation therapy either for high-risk node-positive disease or as a part of breast conservation therapy. TLK1B and eIF4E levels were quantified by Western blot. Statistical analysis was performed and included Spearman correlation, survival analysis by the Kaplan-Meier method, log-rank test, and Cox proportional hazard model. Both eIF4E (15.4 +/- 0.6, mean +/- SD) and TLK1B (18.8 +/- 1.5) were increased in all breast cancer specimens. Increasing eIF4E overexpression was correlated highly with increasing TLK1B (r = 0.35; P < .0001, Spearman coefficient). Tertile distribution of patients, based on the degree of eIF4E and TLK1B increase, demonstrated that the patients in the highest eIF4E group and the highest TLK1B group had a higher rate of cancer recurrences (P = .015 and .049, log rank test, respectively). After adjustment for stage of disease, age, and estrogen/progesterone receptor status, data showed that patients in the highest TLK1B group had a 3.0-fold increase in relative risk for cancer recurrence after adjuvant radiation therapy (P = .036; 95% CI, 1.0-5.0), compared with patients in the low TLK1B group. The overexpression of eIF4E is correlated with TLK1B increase in cancer specimens from patients with stage I to III breast cancer. High TLK1B increase in tumor specimens was associated with a higher risk for cancer recurrence after adjuvant radiation therapy. Resistance to radiotherapy may be 1 mechanism whereby eIF4E overexpression in breast cancer portends a worse prognosis.

Progress in systemic chemotherapy of primary breast cancer: an overview.

Substantial progress has been made in the multidisciplinary management of primary breast cancer during the last 30 years. Adjuvant chemotherapy has been shown to significantly reduce the annual risk of cancer recurrence and mortality, and these effects persist even 15 years after diagnosis. Combination chemotherapy is superior to single-agent therapy and anthracycline-containing regimens. Those that combine an anthracycline with 5-fluorouracil and cyclophosphamide are more effective than regimens without an anthracycline. Six cycles of a single regimen appear to provide optimal benefit. Dose reductions below the standard range are associated with inferior results. Dose increases that require growth factor or hematopoietic stem cell support are under investigation; at this time, the existing results provide no compelling reason to use this strategy outside a clinical trial. Regimens using fixed crossover designs with two non-cross-resistant regimens are being evaluated. The addition of a taxane to anthracycline-containing regimens is currently under intense scrutiny, and preliminary analysis of the first three clinical trials has shown encouraging, albeit not compelling, results. For patients with estrogen receptor-positive breast cancer, the sequential administration of chemotherapy and 5 years of tamoxifen therapy provides additive benefits. No compelling evidence exists to combine ovarian ablation with chemotherapy. Most side effects and toxic effects are self-limited, although premature menopause requires monitoring and preventive interventions to preserve bone mineral density. The small risk of acute leukemia is of concern, and additional research to develop safer regimens is clearly indicated. The overall effect of optimal local/regional treatment combined with an anthracycline-containing adjuvant chemotherapy and a taxane (and, for patients with estrogen receptor-positive tumors, 5 years of tamoxifen therapy) is a greater than 50% reduction in annual risks of recurrence of and death from breast cancer. For most patients at intermediate or high risk of cancer recurrence, the benefits of adjuvant chemotherapy exceed by far its unwanted effects.

High Expression of Somatostatin Receptors and Messenger Ribonucleic Acid for Its Receptor Subtypes in Organ-Confined and Locally Advanced Human Prostate Cancers1

To evaluate the potential application of somatostatin (SST) analogs as an adjuvant treatment for prostate cancer, we characterized the binding sites for SST octapeptide analogs on prostate cancers in patients treated with radical prostatectomy. The affinity and density of binding sites for SST analog RC-160 on 80 surgical specimens of prostate cancers were determined by ligand competition assays. The expression of messenger ribonucleic acid (mRNA) for SST receptor subtype 1 (SSTR1), subtype 2 (SSTR2), and subtype 5 (SSTR5) was also investigated in 22 samples by RT-PCR. Fifty-two of 80 specimens (65%), showed a single class of specific binding sites for RC-160 with a mean dissociation constant (K(d)) of 9.44 nmol/L and a mean maximal binding capacity of 754.8 fmol/mg membrane protein. The mRNA for SSTR1 was detected in 86% of samples, whereas the incidences of mRNA for SSTR2 and SSTR5 were 14% and 64%, respectively. The expression of SSTR2 and/or SSTR5 was 100%, consistent with the presence of RC-160 binding. In patients at high risk of cancer recurrence (stage pT3 and/or Gleason score of 8-10), the incidence of RC-160 binding (65.7%) was similar to that observed in the low risk group (64.3%). The demonstration of the high incidence of octapeptide-preferring SSTRs in organ-confined and locally advanced prostate cancers supports the merit of further investigations of the application of SST analogs and their radionuclide and cytotoxic derivatives for adjuvant treatment of patients at high risk of cancer recurrence after radical prostatectomy. Such approaches could be also considered for patients with advanced prostate cancer at the time of relapse.

CA19‐9 as a predictor of recurrence in patients with colorectal cancer

Background and Objectives CA19-9 is a cancer-associated carbohydrate antigen that plays a role in the process of tumor progression as an adhesion molecule. Methods We evaluated the prognostic value of CA19-9 tumor expression and CA19-9 preoperative and postoperative serum levels in colorectal cancer patients treated by complete resection. The most powerful discrimination was achieved using the three CA19-9 markers in combination. Results CA19-9 tumor expression was identified by immunostaining in 71.0% (86/121) of primary carcinomas. Positive CA19-9 serum levels (≥37 U/ml) were restricted to cases with positive tumor expression, and CA19-9 was detected more frequently in preoperative serum (20.6%, 25/121) than in 1-month postoperative serum (6.6%, 8/121). Positive tumor expression, positive preoperative serum level, and positive postoperative serum level were all predictive of increased cancer mortality. Patients with three negative parameters had no recurrences and 97.1% 5-year survival, whereas patients with three positive parameters had 62.5% recurrence and 42.8% 5-year survival. Conclusions CA19-9 detection in tumor tissue and serum identified patients at high risk of cancer recurrence and death and may be useful in selecting patients for adjuvant therapy. J. Surg. Oncol. 1997;66:238–243. © 1997 Wiley-Liss, Inc.

CA19-9 as a predictor of recurrence in patients with colorectal cancer.

CA19-9 is a cancer-associated carbohydrate antigen that plays a role in the process of tumor progression as an adhesion molecule. We evaluated the prognostic value of CA19-9 tumor expression and CA19-9 preoperative and postoperative serum levels in colorectal cancer patients treated by complete resection. The most powerful discrimination was achieved using the three CA19-9 markers in combination. CA19-9 tumor expression was identified by immunostaining in 71.0% (86/121) of primary carcinomas. Positive CA19-9 serum levels (> or = 37 U/ml) were restricted to cases with positive tumor expression, and CA19-9 was detected more frequently in preoperative serum (20.6%, 25/121) than in 1-month postoperative serum (6.6%, 8/121). Positive tumor expression, positive preoperative serum level, and positive postoperative serum level were all predictive of increased cancer mortality. Patients with three negative parameters had no recurrences and 97.1% 5-year survival, whereas patients with three positive parameters had 62.5% recurrence and 42.8% 5-year survival. CA19-9 detection in tumor tissue and serum identified patients at high risk of cancer recurrence and death and may be useful in selecting patients for adjuvant therapy.

Selection of men at high risk for disease recurrence for experimental adjuvant therapy following radical prostatectomy

Objectives Following surgery, men with recurrent prostate cancer have an isolated elevation in serum prostate-specific antigen (PSA) well in advance of measurable metastatic disease. Rational patient selection for new forms of adjuvant therapy, for example, gene therapy, is imperative. Methods In a retrospective study of two cohorts, we used proportional hazards regression analysis to develop and validate a multifactor model for identifying men who are at high risk of cancer recurrence. The model cohort consisted of 216 men with clinical Stage T2b and T2c treated by 1 urologist. The validation cohort consisted of 214 men with Stage T2b and T2c disease. Results A model for log relative risk, R W , used serum PSA with a sigmoidal transformation (PSA ST), radical prostatectomy Cleason score (GS), and pathologic stage (PS) as specimen confined or nonspecimen confined: R W = (PSA ST × 0.06) + (GS × 0.54) + (PS × 1.87). Recurrence risk categories were determined as low risk if R W is less than 4.0, intermediate risk if it is 4.0 to less than 5.75, and high risk if R W, is more than 5.75. The observed Kaplan-Meier actuarial analysis of the three risk groups correlated well with the predictions determined for the model cohort. We then validated this model independently using a second cohort of 214 men with similar age, stage, and grade treated by 3 different urologists at two different institutions. Conclusions The recurrence rates for men in the high-risk group are similar to those for men with positive lymph nodes and justifies exploration of experimental adjuvant therapy within this group using this model of patient selection.