Systemic Progression Research Articles

The Association Between Sarcopenia and Oncologic Outcomes After Radical Prostatectomy.

Sarcopenia is associated with inferior perioperative and oncologic outcomes in patients undergoing surgery for multiple malignancies. The purpose of this study was to evaluate the association between sarcopenia and outcomes after radical prostatectomy (RP) for men with prostate cancer. Using a representative computed tomographic image from the L3 level, preoperative skeletal muscle indices (SMI) calculated for 698 patients who underwent RP between 2007 and 2010. Patients were classified as sarcopenic if they had a SMI<55cm2/kg2 according to international consensus. The associations between sarcopenia and biochemical recurrence (BCR), systemic progression (SP), and all-cause mortality (ACM) were investigated by Cox proportional hazards regression. Sarcopenic patients were older than nonsarcopenic patients (mean age, 63.0 vs. 60.4 years, P< .001) but were otherwise similar with regard to clinical and pathologic characteristics. There was no significant difference in the perioperative complication rate after RP between sarcopenic and nonsarcopenic patients (16.5% vs. 17.4%, P= .82). At a median follow-up after surgery of 6.0 years, 152 patients were diagnosed with BCR, patients were diagnosed with SP, and 50 patients died. In multivariable analysis, the presence of sarcopenia was not significantly associated with the risks of BCR, SP, or ACM. Similar results were obtained when analyzing SMI as a continuous variable. Sarcopenia was not found to be independently associated with perioperative complications or oncologic outcomes after RP. As such, the presence of sarcopenia may not be prognostic marker for inferior outcomes among men with localized prostate cancer undergoing RP.

Oncological outcomes following radical prostatectomy for patients with pT4 prostate cancer.

ABSTRACTObjectives:Radical prostatectomy (RP) for locally advanced prostate cancer may reduce the risk of metastasis and cancer-specific death. Herein, we evaluated the outcomes for patients with pT4 disease treated with RP.Materials and methods:Among 19,800 men treated with RP at Mayo Clinic from 1987 to 2010, 87 were found to have pT4 tumors. Biochemical recurrence (BCR)-free survival, systemic progression (SP) free survival and overall survival (OS) were estimated using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazards regression models were used to assess the association of clinic-pathological features with outcome.Results:Median follow-up was 9.8 years (IQR 3.6, 13.4). Of the 87 patients, 50 (57.5%) were diagnosed with BCR, 30 (34.5%) developed SP, and 38 (43.7%) died, with 11 (12.6%) dying of prostate cancer. Adjuvant androgen deprivation therapy was administered to 77 men, while 32 received adjuvant external beam radiation therapy. Ten-year BCR-free survival, SP-free survival, and OS was 37%, 64%, and 70% respectively. On multivariate analysis, the presence of positive lymph nodes was marginally significantly associated with patients' risk of BCR (HR: 1.94; p=0.05), while both positive lymph nodes (HR 2.96; p=0.02) and high pathologic Gleason score (HR 1.95; p=0.03) were associated with SP.Conclusions:Patients with pT4 disease may experience long-term survival following RP, and as such, when technically feasible, surgical resection should be considered in the multimodal treatment approach to these men.

Breast cancer brain metastases – A 12 year review of treatment outcomes

BackgroundBreast cancer (BC) is the 2nd commonest cause of brain metastases (BM). This retrospective review investigates the applicability of prognostic scores and highlights different outcomes for patients with HER2 positive compared to triple negative (TN) subtypes. MethodsTwo hundred and seventy four patients received whole brain radiotherapy for BC BM (01/2000–12/2011). The primary objective was to determine factors influencing overall survival (OS). All information relevant to primary BC, disease recurrence, treatment, outcome and cause of death (either neurological (NP) or systemic progression (SP)) were collected. Univariate (UV) and multivariate (MV) Cox regression analysis were used. ResultsOne hundred and forty four patients (53%) were ER positive, 104 (38%) HER2 positive and 57 (21%) TN. Median age at BM was 53 (27–81) years and median OS from BM diagnosis 7.3 (5.7–8.9) months.On MV analysis, Her2 status, RPA score, surgery, stereotactic radiotherapy, and absence of TN disease were independent prognostic factor for OS. NP was the cause of death in 69.2% of HER2 positive patients and 17.3% had SP. Of the TN patients, 29.8% had NP and 54.4% SP (p < 0.001). ConclusionA consistent OS advantage is noted for HER2 positive BM cases and inclusion of BC subtype in the breast GPA score should improve the prognostic factors' sensitivity. The unique presentations, response to treatment and causes of death for HER2 positive patients means more aggressive focal therapy should be considered and studied in the context of clinical trials. For TN BM patients with poor performance status, best supportive care may be appropriate.

Localized pancreatic cancer (LPC) with isolated positive peritoneal cytology (PPC): A single-institution experience.

411 Background: Natural history (NHx) and overall survival (OS) of patients (pts) with LPC and PPC without gross metastasis (GM) at initial diagnosis are rarely studied. We assessed rate, time and pattern of disease recurrence (REC), impact of local therapy (Rx) and OS in this pt cohort from our institution. Methods: The Virginia Mason Pancreatic Cancer (PC) Database (Picozzi et.al. Proc GI Cancer Symp 2011) was used to identify pt cohort. Inclusion criteria were 1) laparoscopic PPC and 2) no other evidence of GM (radiographic/ laparoscopic). Local progression (LP) was defined as primary tumor growth with change/cessation of chemoRx. Systemic progression (SP) was defined as radiological/pathological metastastic progression. The database provided OS. Results: 39/884 (4.4%) pts initiating Rx at VMMC from 2003-2014 met these criteria. 13/39 pts were included in a prior report (Clark et.al. Am J Surg 2010). Pt characteristics include: 21/39 (54%) male; median (med) age 65 (range 49 – 83) yrs; 25/39 (64%) head lesions; med tumor size 39 (range 25 - 100) mm. Med pt follow-up is 13 mo. All pts received gemcitabine-combination chemoRx as initial Rx. 14/39 (36%) pts also received local Rx (13 consolidative chemoXRT, 1 surgery). 3 month (mo) disease control (DC) was 86% (31/36 pts, 3 pts followed &lt;3 mo). 6 mo progression - free survival (PFS) was 72% (26/36 pts). 6/36 pts (16%, range 9+-15+ mo) are progression – free. 30/36 pts (83%) progressed (med time 8.1 mo). REC pattern was local (13/30 pts, 43%), distant (9/30 pts, 30%) and combined (8/30 pts, 27%). Pts given local Rx did not differ statistically from pts given systemic Rx only with respect to 3 mo DC, 6 mo PFS, REC rate, time, or pattern, or OS. OS for LPC with PPC was significantly better than pts with GM (n = 277) identified from the database from 2003-2014 (med OS 15 vs. 9.3 mo, p = 0.0002; 1-yr OS 68 vs. 32%, p = 0.01; 2-yr OS 34 vs. 12%, p = 0.007). Conclusions: 1)LPC with PPC is a rare PC pt cohort with high response rates to chemoRx and superior OS to those with GM. 2) However, long-term disease free OS was not seen. 3)Local Rx did not clearly alter pt cohort NHx. 4)This is the largest pt series of this pt cohort compiled from a US institution; their further study seems of value.

Gleason grading after neoadjuvant hormonal therapy retains prognostic value for systemic progression following radical prostatectomy.

The Gleason grading system in prostatectomy specimens following receipt of neoadjuvant therapy has been considered inaccurate. However, with continuing expansion of novel therapeutics, it is important to understand whether the Gleason system can be effectively utilized in this setting. The aim of this study was to assess the ability of the Gleason grading system to predict systemic progression among prostatectomy specimens treated with neoadjuvant hormone therapy (NHT). This was a single-institution retrospective analysis from 1987 to 2009 of 13,427 patients who underwent radical prostatectomy (RP) without NHT and 1148 patients with NHT. NHT consisted of leuprolide alone (n = 415), antiandrogen therapy alone (n = 400) and combined treatment (n = 333). Kaplan-Meier analysis estimated 15-year systemic progression-free survival among NHT and non-NHT patients. Cox proportional hazard regression models estimated risk of systemic progression following RP according to NHT use and nonuse. Median duration of NHT was 3 months (interquartile range (IQR) 2-4) whereas median follow-up after RP was 8.3 years (IQR 5-10.8). NHT patients were more likely to be D'Amico high risk, have locally advanced pathologic T stage (≥ pT3), pathologic Gleason scores (GS) of 8-10 and lymph node involvement (P<0.0001 for all). NHT use was associated with lower rates of positive surgical margins, more downgrading to pT0 and less GS upgrading from biopsy (P ≤ 0.001 for all). GS could not be assigned to only 3% of NHT patients. On multivariate analysis, pathologic GS remained a predictor of systemic progression (SP) following NHT (hazard ratio (HR) 1.6, P = 0.005), but the association was less strong compared with non-NHT patients (HR 2.9, P < 0.0001). Utilization of the Gleason system appears feasible among hormonally pretreated prostatectomy specimens and shows continued prognostication for systemic progression. Confirmatory investigations are needed before the Gleason system can be reliably applied in the setting of neoadjuvant therapy.

Effect of metformin on prostate cancer outcomes after radical prostatectomy

ObjectiveRecent studies have shown a relative risk reduction in the incidence of prostate cancer in patients taking metformin. However, there are conflicting findings on the effect of metformin on established cases of prostate cancer. In this study we evaluated the effect of metformin on survival and pathologic outcomes in established prostate cancer. Materials and methodsWe retrospectively identified 12,052 patients who underwent radical prostatectomy between 1997 and 2010 at Mayo Clinic. Among these, 885 (7.3%) were diabetics, including 323 taking and 562 not taking metformin. Kaplan-Meier method was utilized to calculate rates of biochemical recurrence (BCR), systemic progression (SP), and all-cause mortality (ACM). Cox models were used to estimate the metformin hazard ratio (HR) adjusted for clinical and pathologic variables. Results and conclusionsMedian follow-up was 5.1 years. In univariate analysis, metformin HR (95% confidence intervals) was not significant for BCR (1.13 [0.84, 1.52]; P = 0.40), SP (1.37 [0.69, 2.72]; P = 0.37), and ACM (1.32 [0.84, 2.05]; P = 0.23). After adjusting for covariates of interest, the HRs for metformin among diabetics remained nonsignificant for BCR (0.91 [0.67, 1.24]; P = 0.55), SP (0.83 [0.39, 1.74]; P = 0.62); and ACM (1.16 [0.73, 1.86]; P = 0.53). No significant difference was seen between metformin users and nonusers in the final pathologic Gleason score (P = 0.33), stage (P = 0.1), rate of positive surgical margins (P = 0.29), or tumor volume (P = 0.76). Metformin use was not associated with a risk reduction in BCR, SP, or ACM. Besides presenting survival data, our results describing metformin's effect on final pathology are unique.

767 OUTCOMES OF RADICAL PROSTATECTOMY IN PT4 PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: Recent evidence suggests that radical prostatectomy (RP) in locally advanced prostate cancer (LAPC) may reduce the risk of cancer specific deaths and metastasis. We present our outcomes of RP in LAPC with pT4 disease. METHODS: Among 19,800 men treated with RP at Mayo Clinic from 1987 to 2010, 87 (0.4%) were found to have pT4 disease. The Kaplan-Meier method was utilized to calculate survival estimates of biochemical failure (BCR), systemic progression (SP), cancer specific survival and overall survival (OS) of the whole cohort and stratified by pathological Gleason score and PSA level of greater or less than 12.2ng/mL. Multivariable Cox proportional hazards regression were used to assess the association of BCR, SP and OS with clinical pathological features. RESULTS: Median follow up for the whole cohort was 9.8 years (IQR3.6, 13.4). Approximately 46% patients presented with palpable extra capsular disease. Five-year survival estimates for the whole cohort for BCR, SP and OS were 48%, 77% and 91% respectively (Figure). Five and 10 years cancer specific survival were 91% and 70% respectively. Ten (11.5%) patients experienced local recurrence. Seventyseven (88.5%) and 32 (36.8%) patients received adjuvant androgen deprivation therapy and radiation therapy respectively. Forty patients (46%) had node positive disease on final pathology. The Multivariate analysis results, summarized as Hazard Ratios (HR) with confidence Intervals (CIs), revealed only positive lymph nodes as a predictor of BCR (HR: 1.94; CI: {1.01,3.73}; p 0.05). However, both positive lymph nodes and pathologic Gleason score were predictors of SP with HR of 2.96(CI {1.20, 7.30}, p 0.02) and HR of 1.95(CI {1.05, 3.61}; p 0.03), respectively. CONCLUSIONS: RP for LAPC with pT4 is technically feasible. Future directions should include greater utilization of RP in multimodality decision making for LAPC.

Intraventricular (IVe) topotecan for women with neoplastic meningitis (NM) associated with "responsive" malignancies.

2015 Background: A prior study of intra-CSF topotecan (TOPO) for unselected pts w/ NM reported PFS 6 mo of 19%, and OS of 15 wks (Groves, NeuroOncol 2008;10:208). We postulated that greater activity might occur in pts w/ malignancies considered sensitive to topoisomerase inhibitors. Methods: We reviewed outcome of women with NM and adenocarcinoma of the breast, ovary or lung receiving IVe TOPO (0.4 mg 2x/wk x 4wk, Q wk x 4, Q 2wk x 2, Q mo x 3, Q 2mo x 3, and Q 3mo x 4) until progression (PROG) or adverse events (AE). All had baseline CSF cytology, and MRI of brain and spine. CSF cytology was obtained at each treatment (Rx), and brain/spine MRI Q 3mo. Neuro-specific PROG was defined as recurrent + CSF cytology; PROG of NM on MRI; all-cause neurologic worsening; pt refusal; or death. PFS/OS were measured from 1st TOPO Rx. All pts signed consent; the study was IRB approved. Results: 17 women (breast -12; lung-3; ovary - 2) were treated via Ommaya reservoirs; 7 (41%) had VP shunts w/ valves, adjusted for Rx. Median (med) age was 53 (41-79), and KPS 70 (50-90). At presentation, 11(65%) had + CSF cytology and 14 (82%) had NM on MRI [brain-11 (65%); spine-10 (59%)]. 15 (88%) had no prior intrathecal Rx. 13 pts (76%) received focal RT for CNS disease, and 8 (47%), chemotherapy for extracranial disease. Med.number of Rx were 13/pt (range, 3-50); med. duration of TOPO Rx was 14 wks (range, 1-109). Med. neuro-specific PFS was 13 wks; PFS6 was 41%, and PFS12, 29 %. Med. OS was 33 wks (range, 5-180), w/ 4 alive at 13+, 30+, 33+, and 180+ wks. 4 pts (24%) lived &gt; 95 wks. Of 11 w/ baseline + CSF cytology, 7 (64%) cleared CSF of malignant cells (med. duration clear = 47 wk (range, 9-104). AE included arachnoiditis (18%), leukoencephalopathy (18%), and Ommaya infections (12%). Rx was stopped for neuro PROG (29%); systemic PROG (23%); refusal (18%); AE (12%); or persistent negative CSF (6%); 12% are still on Rx. Conclusions: Promising activity of IVe TOPO was observed in women with NM from breast, lung and ovarian cancer. PFS 6 and 12, OS and cytologic response were twice that noted in prior studies of NM pts w/ unselected malignancies. This data supports our plan for a phase II study targeting this select cohort.

1327 THE PRESENCE OF EXTRAPROSTATIC EXTENSION INCREASES THE RISK OF DEATH FROM PROSTATE CANCER AFTER RADICAL PROSTATECTOMY FOR PATIENTS WITH PT3B DISEASE

INTRODUCTION AND OBJECTIVES: Patients with pathologic T3b (seminal vesicle invasion) prostate cancer are at increased risk for disease recurrence and cancer-related mortality following radical prostatectomy (RP). Clinicopathologic features which stratify the risk of disease progression in these patients continue to be defined. We sought to determine the prognostic significance of extraprostatic extension (EPE) in patients with pT3b tumors with regard to the risks of subsequent biochemical recurrence (BCR), systemic progression (SP), and death from prostate cancer. METHODS: We reviewed 16,453 patients who underwent RP without prior therapy at our institution from 1987-2009 to identify patients noted to have pT3bN0 disease. Survival was estimated using the Kaplan Meier method and compared with the log rank test. The association of EPE with outcome was evaluated on Cox multivariate hazards regression models, controlling for Gleason score, preoperative PSA, tumor volume, and surgical margin status. RESULTS: A total of 1,132 patients with pT3b disease at RP were identified. Mean postoperative follow-up was 10.6 years (range 0-23.3). Of these, 693 (61%) also had pathologic evidence of EPE. Men with EPE, compared to those without, had a higher mean preoperative PSA (21.1 ng/ml vs 14.1 ng/ml; p 0.0001) and an increased rate of pathologic Gleason score 8-10 (28.1% vs 16.9%; p 0.0001). Overall, compared to patients without EPE, patients with EPE had an increased risk of BCR (63% vs 53%), SP (22% vs 14%), and death from prostate cancer (14% vs 8%) (p 0.0001 for all). Moreover, on multivariate analysis, the presence of EPE remained associated with significantly increased risks of BCR (HR 1.32, p 0.003), SP (HR 1.56, p 0.01), and death from prostate cancer (HR 1.7, p 0.03). In addition, increased Gleason score and higher tumor volume were significant predictors of death from prostate cancer (HR 2.31, p 0.0001; and HR 1.33, p 0.0006). On the other hand, administration of adjuvant hormonal therapy was associated with significantly lower risks of BCR (HR 0.32, p 0.0001), SP (HR 0.42, p 0.0001), and prostate cancer death (HR 0.49, p 0.009). CONCLUSIONS: The presence of EPE in patients with pT3b prostate cancer is significantly associated with increased risks of BCR, SP, and death from prostate cancer following RP. As the presence of EPE portends poorer outcomes in this patient population, consideration of adjuvant therapy should be given to pT3b patients with this pathologic finding.

Clinicopathological predictors of systemic progression and prostate cancer mortality in patients with a positive surgical margin at radical prostatectomy

Although a positive surgical margin (PSM) at radical prostatectomy (RRP) has been consistently linked to an increased risk of biochemical recurrence, the impact of margin status on patient survival continues to be debated. We evaluated long-term outcomes of patients with a PSM at RRP and determined predictors of systemic progression (SP) and mortality in these men. We reviewed our institutional registry of 16,749 patients who underwent RRP between 1990 and 2008 to identify 2895 patients with a PSM. Median follow-up was 10.6 years. Postoperative survival was estimated using the Kaplan-Meier method. Cox proportional hazard regression models were used to analyze clinicopathological variables associated with SP and death from prostate cancer. A 15-year SP-free and cancer-specific survival was 90 and 93%, respectively. On multivariate analysis, higher tumor volume, increased pathological Gleason score and advanced pathological tumor stage were associated with significantly increased risks of SP and death from prostate cancer, whereas number and location of PSM did not predict mortality. The risks of SP and prostate cancer death in patients with a PSM remain low on long-term follow-up. Tumor variables are the primary determinants of cancer death. These results should be considered when evaluating patients with a PSM for adjuvant therapy.

340 LONG-TERM RISK OF CLINICAL PROGRESSION AFTER BIOCHEMICAL RECURRENCE FOLLOWING RADICAL PROSTATECTOMY: THE IMPACT OF TIME TO RECURRENCE

You have accessJournal of UrologyProstate Cancer: Epidemiology and Natural History1 Apr 2011340 LONG-TERM RISK OF CLINICAL PROGRESSION AFTER BIOCHEMICAL RECURRENCE FOLLOWING RADICAL PROSTATECTOMY: THE IMPACT OF TIME TO RECURRENCE Stephen Boorjian, R. Houston Thompson, Matthew Tollefson, Laureano Rangel, Eric Bergstralh, and R. Jeffrey Karnes Stephen BoorjianStephen Boorjian Rochester, MN More articles by this author , R. Houston ThompsonR. Houston Thompson Rochester, MN More articles by this author , Matthew TollefsonMatthew Tollefson Rochester, MN More articles by this author , Laureano RangelLaureano Rangel Rochester, MN More articles by this author , Eric BergstralhEric Bergstralh Rochester, MN More articles by this author , and R. Jeffrey KarnesR. Jeffrey Karnes Rochester, MN More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.424AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The natural history of biochemical recurrence (BCR) after radical prostatectomy (RP) is variable, and does not always translate into systemic progression (SP) or prostate cancer death. We evaluated long-term clinical outcomes of patients with BCR, and determined predictors of disease progression and mortality in these men. METHODS We reviewed our institutional registry of 14,632 patients who underwent RP between 1990–2006 to identify 2,427 men with BCR (PSA ≥ 0.4 ng/ml) who did not receive neoadjuvant or adjuvant therapy. Median follow-up was 11.5 years (interquartile range (IQR) 7.8, 14.7) after RP and 6.6 years (IQR 3.3, 10.1) after BCR. Patients were grouped into quartiles according to the time from RP to BCR. Survival after BCR was estimated using the Kaplan-Meier method and compared using the log rank test. Cox proportional hazard regression models were used to analyze clinicopathologic variables associated with SP and death from prostate cancer. RESULTS Overall, 284 (11.7%) patients with BCR experienced SP and 556 (22.9%) died, with 140 (5.8%) dying from prostate cancer. A total of 399 (16.4%) men underwent salvage radiation (RT) and 209 (8.6%) received androgen deprivation therapy (ADT) at BCR and before SP. Ten-year SP-free and cancer-specific survival for patients after BCR was 84% and 91%. The median time from RP to BCR was 3.1 years (IQR 1.2, 5.9). Cancer-specific mortality 10 years after BCR was 9.9%, 9.3%, 7.8%, and 4.7% for patients who experienced BCR <1.2 years, 1.2–3.1 years, 3.1–5.9 years, and > 5.9 years after RP, respectively (p=0.10). On multivariate analysis (Table), time from RP to BCR was not significantly associated with the risk of SP (p=0.15) or cancer-specific mortality (p=0.29). Older patient age, increased pathologic Gleason score, advanced tumor stage, and rapid PSA velocity did predict SP and death from prostate cancer. Multivariate Analysis for Predictors of Systemic Progression (left) and Death from Prostate Cancer (right) Following BCR. Variable HR 95% CI p Value HR 95% CI p Value Patient age 1.02 1.00,1.05 0.04 1.06 1.02,1.10 0.001 Year of RP 0.95 0.91,1.00 0.05 0.99 0.91,1.07 0.77 Pathological Gleason score 1.40 1.20,1.60 <0.0001 1.53 1.27,1.86 <0.0001 Pathological tumor stage 1.20 1.03,1.40 0.02 1.33 1.07,1.66 0.01 Time interval from RP to BCR 0.95 0.89,1.02 0.15 0.94 0.83,1.06 0.29 Log-linear PSA velocity 1.32 1.23,1.40 <0.0001 1.37 1.25,1.49 <0.0001 Receipt of salvage RT 0.91 0.60,1.40 0.68 0.87 0.47,1.63 0.67 Receipt of salvage ADT 0.62 0.33,1.18 0.15 0.98 0.45,2.12 0.95 CONCLUSIONS Although only a minority of men experience SP and death from prostate cancer following BCR, an increased interval from RP to BCR is not independently associated with diminished risks of progression or mortality. Regardless of the timing of BCR, then, the decision to institute secondary therapies must balance the risk of disease progression based on clinical parameters with the cost and potential morbidity of treatment. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e137 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Stephen Boorjian Rochester, MN More articles by this author R. Houston Thompson Rochester, MN More articles by this author Matthew Tollefson Rochester, MN More articles by this author Laureano Rangel Rochester, MN More articles by this author Eric Bergstralh Rochester, MN More articles by this author R. Jeffrey Karnes Rochester, MN More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The Ability of Biomarkers to Predict Systemic Progression in Men with High-Risk Prostate Cancer Treated Surgically Is Dependent on ERG Status

The objective of this study was to assess the relationship of the tumor protein levels of TOP2A and MIB-1 and ERG status with cancer-specific outcomes in men with high-risk prostate cancer treated by radical prostatectomy (RP). A 150-pair case-control study was designed from RP patients who developed systemic progression (SP) within 6 years of RP (cases) and men who were free of disease at least 8 years after RP (controls). The cases and controls were matched on conventional prognostic clinical parameters. TOP2A and MIB-1 levels were assessed by immunohistochemical methods, and ERG status was assessed by quantitative reverse transcription-PCR. The prognostic abilities of TOP2A and MIB-1 were significantly better in ERG(-) patients, and TOP2A was superior to MIB-1. In receiver operating characteristic analysis, the TOP2A and MIB-1 scores exhibited AUCs of 0.81 and 0.78 for ERG(-) patients, versus 0.67 and 0.68 for ERG(+) patients, respectively. Clinical parameters attained an AUC of 0.65 in ERG(-) patients and 0.54 in ERG(+) patients. When both markers were incorporated into a model for ERG(-) patients, the AUC increased to 0.83, with TOP2A showing a stronger association with SP than MIB-1. The time to SP was significantly associated with TOP2A; higher 5-year SP rates were observed in patients with higher TOP2A protein levels. In addition, although patient numbers are small, the response to adjuvant androgen deprivation therapy is associated with ERG status, showing more significant treatment effect in ERG(+) patients.

PSA Doubling Time as a Predictor of Clinical Progression After Biochemical Failure Following Radical Prostatectomy for Prostate Cancer

PSA Doubling Time as a Predictor of Clinical Progression After Biochemical Failure Following Radical Prostatectomy for Prostate Cancer

PSA Doubling Time as a Predictor of Clinical Progression After Biochemical Failure Following Radical Prostatectomy for Prostate Cancer

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). 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. 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). 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.