Risk Of Biochemical Progression Research Articles

EAU RISK GROUPS APPLIED ON PATIENTS TREATED WITH RADICAL PROSTATECTOMY - ANALYSIS OF PATHOLOGY SPECIMENS AND PATIENT SURVIVAL

Purpose: The European Association of Urology (EAU) classifies patients with prostate cancer into three risk groups - low-risk, intermediate- and high-risk depending on the probability of biochemical progression after treatment with curative intent (either radical prostatectomy or radiotherapy). The aim of the present study is to analyze our experience with patients who underwent radical prostatectomy and to look for the relationship between the pathological results from the operation and the distribution of patients into risk groups. Material/Methods: A single-center, non-interventional study was conducted. The study was performed after analysis of patients undergoing radical prostatectomy (either open or laparoscopic) at the Clinic of Urology in St. Anna Hospital in Varna. The number of patients available for analysis was 201. Data were analyzed with IBM SPSS version 23. Results: We found that high-risk patients had unfavorable results from the examination of the pathology specimens- patients with pT3a and pT3b were more often from the high-risk group. High-risk patients were also at increased risk of PSA progression and development of distant metastases. Conclusions: The EAU-risk groups will probably undergo changes connected with the improved methods for the diagnosis of prostate cancer. But still, it is a valid tool which correctly predicts the unfavorable pathology of the removed specimen and also the risk of biochemical progression after radical prostatectomy.

Impact of uni- or multifocal perineural invasion in prostate cancer at radical prostatectomy

BackgroundAim of this study was to correlate perineural invasion (PNI) with other clinical-pathological parameters in terms of prognostic indicators in prostate cancer (PC) cases at the time of radical prostatectomy (RP).MethodsProspective study of 288 consecutive PC cases undergoing RP. PNI determination was performed either in biopsy or in RP specimens classifying as uni- and multifocal PNI. The median follow-up time was 22 (range, 6–36) months.ResultsAt biopsy PNI was found in 34 (11.8%) cases and in 202 (70.1%) cases at the time of surgery. Among those identified at RP 133 (46.1%) and 69 (23.9%) cases had uni- and multi-PNI, respectively. Presence of PNI was significantly (P<0.05) correlated with unfavorable pathological parameters such higher stage and grade. The percentage of extracapsular extension in PNI negative RP specimens was 18.6% vs. 60.4% of PNI positive specimens. However, the distribution of pathological staging and International Society of Urological Pathology (ISUP) grading did not vary according to whether PNI was uni- or multifocal. The risk of biochemical progression increased 2.3 times in PNI positive cases was significantly associated with the risk of biochemical progression (r=0.136; P=0.04). However, at multivariate analysis PNI was not significantly associated with biochemical progression [hazard ratio (HR): 1.87, 95% confidence interval (CI): 0.68–3.12; P=0.089]. Within patients with intermediate risk disease, multifocal PNI was able to predict cases with lower mean time to biochemical and progression free survival (chi-square 5.95; P=0.04).ConclusionsPNI at biopsy is not a good predictor of the PNI incidence at the time of RP. PNI detection in surgical specimens may help stratify intermediate risk cases for the risk of biochemical progression.

Identification of curable high-risk prostate cancer using radical prostatectomy alone: who are the good candidates for undergoing radical prostatectomy among patients with high-risk prostate cancer?

BackgroundCurrently, there is no consensus regarding which patients with high-risk prostate cancer (PCa) would benefit the most by radical prostatectomy (RP). We aimed to identify patients with high-risk PCa who are treatable by RP alone.MethodsWe retrospectively reviewed data on 315 patients with D’Amico high-risk PCa who were treated using RP without neoadjuvant or adjuvant therapy at the institutions of the Yamaguchi Uro-Oncology Group between 2009 and 2013. The primary endpoint was biochemical progression-free survival (bPFS) after RP. Risk factors for biochemical progression were extracted using the Cox proportional hazard model. We stratified the patients with high-risk PCa into 3 subgroups based on bPFS after RP using the risk factors.ResultsAt a median follow-up of 49.9 months, biochemical progression was observed in 20.5% of the patients. The 2- and 5-year bPFS after RP were 89.4 and 70.0%, respectively. On multivariate analysis, Gleason score (GS) at biopsy (≥ 8, HR 1.92, p < 0.05) and % positive core (≥ 30%, HR 2.85, p < 0.005) were independent predictors of biochemical progression. Patients were stratified into favorable- (0 risk factor; 117 patients), intermediate- (1 risk factor; 127 patients), and poor- (2 risk factors; 57 patients) risk groups, based on the number of predictive factors. On the Cox proportional hazard model, this risk classification model could significantly predict biochemical progression after RP (favorable-risk, HR 1.0; intermediate-risk, HR 2.26; high-risk, HR 5.03; p < 0.0001).ConclusionThe risk of biochemical progression of high-risk PCa after RP could be stratified by GS at biopsy (≥ 8) and % positive core (≥ 30%).

Increased expression of putative cancer stem cell markers in the bone marrow of prostate cancer patients is associated with bone metastasis progression

The number of cells positive for the α-6 and α-2 integrin subunits and the c-Met receptor in primary tumors and bone biopsies from prostate cancer patients has been correlated with metastasis and disease progression. The objective of this study was to quantify disseminated tumour cells present in bone marrow in prostate cancer patients using specific markers and determine their correlation with metastasis and survival. Patients were included at different stage of prostate cancer disease, from localised to metastatic castration-resistant prostate cancer. Healthy men were used as a control group. Bone marrow samples were collected and nucleated cells separated. These were stained for CD45, α-2, α-6 integrin subunits and c-Met and samples were processed for analysis and quantification of CD45-/α2+/α6+/c-met + cells using flow cytometry. Clinical and pathological parameters were assessed and survival measured. Statistical analyses were made of associations between disease specific parameters, bone marrow flow cytometry data, prostate-specific antigen (PSA) progression free survival and bone metastases progression free survival. For all markers, the presence of more than 0.1% positive cells in bone marrow aspirates was significantly associated with the risk of biochemical progression, the risk of developing metastasis and death from prostate cancer. Quantification of cells carrying putative stem cell markers in bone marrow is a potential indicator of disease progression. Functional studies on isolated cells are needed to show more specifically their property for metastatic spread in prostate cancer.

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The link between obesity and oncologic outcomes after RP remains ill-defined. Understanding the effect of surgical proficiency and obesity-related changes in tumor biology on prostate cancer outcomes is paramount to explain the suggested association. The unique and difficult challenges of performing RP in obese men implore adherence to strict surgical principles to optimize the cancer cure. Controlling for margin status, tumor burden, and D'Amico risk category, the BMI was not associated with BCR after RP in the present cohort. Numerous series that revealed an association between the BMI and BCR after RP did not control for margin status 1 Magheli A. Rais-Bahrami S. Trock B.J. et al. Impact of body mass index on biochemical recurrence rates after radical prostatectomy: an analysis utilizing propensity score matching. Urology. 2008; 72: 1246-1251 Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar , 2 Bassett W.W. Cooperberg M.R. Sadetsky N. et al. Impact of obesity on prostate cancer recurrence after radical prostatectomy: data from CaPSURE. Urology. 2005; 66: 1060-1065 Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar or other adverse pathologic risk factors, such as tumor volume. 3 Freedland S.J. Grubb K.A. Yiu S.K. et al. Obesity and risk of biochemical progression following radical prostatectomy at a tertiary care referral center. J Urol. 2005; 174: 919-922 Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar Editorial CommentUrologyVol. 81Issue 5PreviewThe presented series evaluates the effect of obesity on adverse pathologic features at prostatectomy and the BCR rates after surgery. This is a topic that has been studied previously, with varying conclusions. An explanation for the observed inconsistencies in the published data could be the multiple factors that can influence the observed outcomes. Two of the factors that must be considered are surgical proficiency and potential obesity-related changes on tumor biology. Full-Text PDF

Elective irradiation of pelvic lymph nodes during postprostatectomy salvage radiotherapy

Success rates with salvage radiotherapy (SRT) in men who have a postprostatectomy biochemical relapse are suboptimal. One treatment-intensification strategy includes elective irradiation of the pelvic lymph nodes with whole pelvis radiotherapy (WPRT). An inter-institutional retrospective cohort study compared outcomes for patients who received SRT at 2 separate academic institutions with disparate treatment paradigms: almost exclusively favoring WPRT (n = 112) versus limiting treatment to the prostate bed (PBRT) (n = 135). Patients were excluded if they had lymph node involvement or if they received androgen-deprivation therapy. The Cox proportional hazards model was used to adjust for potential confounders. In total, 247 patients were analyzed with a median follow-up of 4 years. The pre-SRT prostate-specific antigen (PSA) level (adjusted hazard ratio [HR], 1.58; P < .0001) and a Gleason score of 8 to 10 (adjusted HR, 3.21; P < .0001) were identified as independent predictors of increased risk of biochemical PSA progression after SRT. However, WPRT was not independently associated with biochemical progression-free survival in the multivariate model (adjusted HR, 0.79; P = .20). Neither low-risk patients nor high-risk patients (defined a priori by a preoperative PSA level ≥20 ng/mL, a pathologic Gleason score between 8 and 10, or pathologic T3 tumor classification) benefited from WPRT. Overall survival was similar between treatment groups. When restricting the analysis to patients with pre-SRT PSA levels ≥0.4 ng/mL (n = 139), WPRT was independently associated with a 53% reduction in the risk of biochemical progression (adjusted HR, 0.47; P = .031). WPRT did not improve outcomes among the entire group but was independently associated with improved biochemical control among patients with pre-SRT PSA levels ≥0.4 ng/mL.

Abstract LB-477: Micro-RNA expression patterns to classify prostate cancer risk

Abstract Progression risk from early stage localized prostate cancer (CaP) to more aggressive and lethal phenotypes is not precisely predicted. This leads to the over-treatment of men whose disease might otherwise remain indolent. Tumor and serum microRNA (miR) expression show promise as functional biomarkers of CaP progression risk but considerable ambiguity exists over which miR are altered, in which direction and at what point in disease. To address these ambiguities we undertook a genome-wide miR expression comparison using a micro-array approach in key and isogenic CaP cell lines and non-malignant controls. Specifically, cell pairs that represent; Initiation (non-malignant RWPE-1 and RAS-transformed RWPE-2 cells); Progression (non-malignant HPr-1AR and LNCaP cells); Recurrence (LNCaP and LNCaP-C4-2 cells). Comparison between these cell line pairs identified 56 altered miR (≥1.5 fold, p&amp;lt;0.05). Specifically, 11 were altered in Initiation (2 down and 9 up-regulated), 43 in Progression (33 down and 10 up-regulated) and 19 in Recurrence (3 down and 16 up-regulated). Technical validation by Q-PCR supported these findings, as did biological validation in a test-set of 36 locally confined CaP tumors and matched normal pairs. Q-PCR analyses in a longitudinal tumor series from the murine CaP TRAMP model revealed that the expression of murine homologs of several miR (e.g. miR-138 and 205) was significantly altered prior to animals displaying palpable tumors. These findings supported further their utility as early stage disease markers. Importantly, biological validation included analyses in a publically available micro-array data-base of miR from 78 human locally tumors (cBio Cancer Genomics Portal). Approximately 800 miR were in common between the two micro-array platforms and 46, of the 56 miR identified in our cell line studies, were very significantly altered in these primary tumors. Enrichment analysis identified the TGF-β pathway as a key miR-targeted network and supported enhanced TGF-β signaling in the CaP cell lines. To test the ability of miR to discern disease risk at early stage we investigated the expression and association of the 56 miR identified above, with the 24 month risk of biochemical progression following radical prostatectomy, using a cohort of men who had surgery at RPCI. We measured expression of the 56 miR by Q-PCR in 33 men who displayed biochemically progression and 67 non-progressed CaP control patients. Samples were matched on age, PSA levels and Gleason score. We are now establishing the association of individual and multiple serum miR expression at baseline with stage, grade, pre-surgery PSA levels and risk of progression. In parallel we measured the expression of the 56 miR in the tumors of 32 men within this cohort, to measure tumor serum correlations. These analyses will determine the serum miR expression that best differentiate i) men by CaP prognostic variables and ii) who experience biochemical progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-477. doi:1538-7445.AM2012-LB-477

Long-Term Follow-Up of HLA-A2+ Patients with High-Risk, Hormone-Sensitive Prostate Cancer Vaccinated with the Prostate Specific Antigen Peptide Homologue (PSA146-154)

Twenty-eight HLA-A2+ patients with high-risk, locally advanced or metastatic, hormone-sensitive prostate cancer were immunized with a peptide homologue of prostate-specific antigen, PSA146-154, between July 2002 and September 2004 and monitored for clinical and immune responses. Fifty percent of the patients developed strong PSA146-154-peptide-specific delayed-type hypersensitivity skin responses, tetramer and/or IFN-γ responses within one year. Thirteen patients had stable or declining serum levels of PSA one year post-vaccination. A decreased risk of biochemical progression was observed in patients who developed augmented tetramer responses at six months compared to pre-vaccination levels (P = .02). Thirteen patients have died while 15 patients remain alive with a mean overall survival of 60 months (95% CI, 51 to 68 months) per Kaplan-Meier analysis. A trend towards greater overall survival was detected in men with high-risk, hormone-sensitive CaP who developed specific T-cell immunity following vaccination with PSA146-154 peptide.

Eligibility for Active Surveillance and Pathological Outcomes for Men Undergoing Radical Prostatectomy in a Large, Community Based Cohort

We analyzed competing active surveillance criteria in men who underwent radical prostatectomy in relation to outcome data in a large, community based cohort. We identified all men from the CaPSURE database who underwent radical prostatectomy from 1999 to 2007 and met inclusion criteria for the stringent prospective University of California-San Francisco and Johns Hopkins active surveillance protocols. Rates of pathological upgrading, up staging and biochemical recurrence were compared. We identified 2,837 men who underwent radical prostatectomy and had complete pathological and followup data available. Of these men 1,375 and 125 met University of California-San Francisco and Johns Hopkins criteria, respectively. When comparing men who met the 2 sets of criteria vs those who met University of California-San Francisco criteria only, there were no significant differences in the rate of upgrading (20% vs 27%, p = 0.07) and up staging (6% vs 8%, p = 0.39) at radical prostatectomy. At a median 36-month followup 5-year biochemical recurrence-free estimates were similar at 92% in men who met the 2 sets of criteria and 90% in those who met the University of California-San Francisco definition only. On multivariate analysis upgrading to 7 or greater (HR 2.2, 95% CI 1.2-4.2), up staging (HR 3.5, 95% CI 1.3-9.3), and upgrading plus up staging (HR 6.9, 95% CI 3.3-14.5) were associated with a higher risk of biochemical recurrence in patients who met University of California-San Francisco criteria. Men who met enrollment criteria for the 2 active surveillance protocols had a similar rate of upgrading, up staging and 5-year biochemical recurrence-free rates after radical prostatectomy. Further comparison between current protocols is warranted to establish universal inclusion criteria.

Prognostic significance of microscopic bladder neck invasion in prostate cancer

To assess the prognostic significance of microscopic bladder neck invasion (BNI+) after radical prostatectomy (RP). From January 1988 to December 2006, 1480 patients with clinically localized prostate cancer were surgically treated at one tertiary university hospital. The risk of biochemical progression, defined as a prostate-specific antigen (PSA) level after RP of >0.2 ng/mL, was assessed with univariate and multivariate analyses for clinical and pathological variables. We compared the biochemical progression-free survival (bPFS) of patients with BNI+ vs stages pT2, pT3a, pT3b and positive lymph nodes (N+). In a second analysis, we evaluated the bPFS of patients in different stages associated with BNI+ and compared them with those in the same stages with no BNI. BNI+ was found in 132 (9%) patients; the 5-year bPFS was 86%, 54%, 26% and 10% for stages pT2, pT3a, pT3b and N+, respectively, while it was 30% for BNI+ (P < 0.001). There was no difference in the 5-year bPFS between stage pT2 and pT2 + BNI (P = 0.32). Stages pT3a and pT3b had a better 5-year bPFS than stage pT3a + BNI (P = 0.003) and pT3b + BNI (P = 0.001), respectively. In the univariate analysis all variables were associated with BP. In the multivariate analysis, only BNI+ had no association with BP (odds ratio 1.14, 95% confidence interval 0.70-1.85; P = 0.59). Microscopic BNI+ in prostate cancer is not an independent risk factor for biochemical progression and should be regarded as a factor that worsens the prognosis of the underlying tumour stage. A longer follow-up is necessary to confirm these findings.

Low Testosterone and Risk of Biochemical Recurrence and Poorly Differentiated Prostate Cancer at Radical Prostatectomy

To evaluate, in a prospective study, the association between low testosterone and pathologic endpoints and the risk of biochemical progression. Androgens play a key role in prostate cancer progression. The results from 3 retrospective studies have suggested that low pretreatment testosterone is an independent predictor of adverse pathologic features in patients with localized prostate cancer. Routine preoperative total testosterone values were measured in 455 consecutive patients with clinically localized prostate cancer who underwent radical prostatectomy. The association of low testosterone levels (defined a priori as <220 ng/dL) with the pathologic endpoints and the risk of biochemical recurrence using a validated postoperative nomogram was evaluated in univariate and multivariate analyses. No association between low testosterone and the predicted risk of biochemical recurrence (P = .159) or actual disease progression (P = .9) was observed. On multivariate analysis, low testosterone was associated with a predominance of Gleason pattern 4-5 cancer (odds ratio 2.4, 95% confidence interval 1.01-5.7; P = .048). No association of low testosterone with tumor volume was observed (P = .9). In this prospective study, low pretreatment total testosterone was associated with Gleason pattern 4-5 cancer at prostatectomy, but not with disease progression thereafter. The clinical utility of the serum testosterone level for patients with localized prostate cancer is therefore marginal. These data are consistent with the hypothesis that tumors arising in a low-androgen environment might appear to be of higher grade but are not at increased risk of progression.

Percent Tumor Involvement and Risk of Biochemical Progression After Radical Prostatectomy

Percent tumor involvement has been associated with biochemical progression in organ confined disease, although its role in predicting outcome in men with more advanced disease pathology is unclear. We hypothesized percent tumor involvement may be a good correlate of outcome in all stages of prostate cancer. We examined the association between percent tumor involvement in the radical prostatectomy specimen and the outcome measures of pathological stage and biochemical progression using multivariate logistic regression and Cox proportional hazards analysis, respectively, in 2,220 patients from the Duke Prostate Center radical prostatectomy database. On multivariate analysis, percent tumor involvement significantly predicted the risk of positive margins (p <0.001), extracapsular extension (p <0.001), seminal vesicle invasion (p <0.001) and biochemical progression (HR 1.16, 95% CI 1.01-1.33, p = 0.035). The percent tumor involvement cut points of 5% or less, 6% to 20%, 21% to 50% and greater than 50% significantly separated men in groups with differing biochemical progression risk (p <0.001). In addition, these cut points were further able to stratify men among those with organ confined margin negative disease (p <0.001), either positive margins or extracapsular extension (p <0.001), and those with seminal vesicle invasion (p = 0.02). Percent tumor involvement was a significant predictor of biochemical progression and was able to further stratify men who were already assigned to narrowly defined pathological groups. If confirmed in other studies, percent tumor involvement may enable the clinician to identify the high risk patient who stands to benefit the most from adjuvant therapy.

Adjuvant multimodality treatment in patients with high-risk prostate cancer following radical prostatectomy: Results of a prospective clinical phase-II trial

15557 Background: High risk prostate cancer (PCA) is associated with a high frequency of PSA relapse. Even with adjuvant androgen deprivation therapy about 50% of patients experience systemic recurrences within 5 years. Docetaxel has demonstrated significant activity in men with metastatic androgen independent PCA, zoledronic acid has been shown to significantly inhibit the development of osseous metastases. It was the aim of the current prospective clinical phase-II trial to evaluate safety and clinical efficacy of early multimodality treatment in high risk PCA after radical prostatectomy (RPE). Methods: Between 3/2004 and 12/2005 25 patients with high risk PCA following RPE were recruited. High risk PCA was defined by a risk of biochemical progression &gt; 70% according to the postoperative Kattan nomograms. Adjuvant therapy consisted of androgen deprivation with LHRH analogues for 12 months, zoledronic acid at 4mg every 3 months and docetaxel at 75 mg/qm for six consecutive cycles. Adjuvant treatment was initiated 4 to 6 weeks after surgery. Follow-up examination were undertaken every 3 months with PSA serum determinations; in case of PSA increase 2 consecutive measurements at 4 weeks intervals were performed. Time to progression defined the time interval between initiation of therapy and first PSA relapse. Results: The mean follow-up is 20.5 (6–31) months. Adjuvant multimodality treatment was well tolerated in all patients with grade 3/4 hematotoxicity in 3 (12%) and gastrointestinal toxicity in 5 (16%) patients; 2 (8%) developed significant oncolysis with surgical intervention. In none of the patients the dosage of docetaxel or the number of cycles had to be reduced. Currently, 4 (16%) patients have developed PSA relapse with 2 exhibiting osseous metastases and 2 having died. Median time to progression was 14.5 (10–16) months. Conclusions: The clinical efficacy appears to be lower than expected with a 16% progression rate and a 8% mortality rate after only 20 months of follow-up. Adjuvant multimodality treatment of high risk PCA after RPE can be applied without significant treatment-associated side effects. Currently ongoing clinical phase-III trials have to further validate the concept of adjuvant chemotherapy. No significant financial relationships to disclose.

Phase III results of adjuvant radiotherapy (RT) versus wait-and-see (WS) in patients with pT3 prostate cancer following radical prostatectomy (RP)(ARO 96–02/AUO AP 09/95)

5060 Background: Adjuvant RT for pT3 R1 or R0 patients (pts.) after RP remains controversial. Results of an EORTC-phase-III- study (with unknown PSA-status after RP) suggested a 20% better biochemical control (bNED) after 5 years for RT. Methods: 385 men with prostate cancer were randomized to either 60 Gy RT (arm A; n=193) or WS (arm B; n=192) before achieving an undetectable PSA. Pts. were stratified for Gleason-score, margin status, neoadjuvant hormonal treatment and stage (pT3A+B vs. C). When the undetectable PSA-level after RP was not achieved, the pts. were stated as progressive disease and left arm A/B and were irradiated. PSA-progression for pts. with undetectable PSA was stated after two consecutive increasing PSA out of the undetectable range. Primary endpoint was bNED. Study was powered to demonstrate a 15% increase in bNED for RT. Results: 78 pts. (20%) did not achieve an undetectable PSA and were stated as progressive disease (arm A: 45 pts., arm B: 33 pts.). Additionally, 34 pts. (23%) from the RT-arm did not receive RT. Therefore, 114 pts. had RT (arm A) and 159 pts. WS (arm B). Median follow up was 53.6 months for arm A and 53.7 months for arm B. BNED at 5 years increased to 72% for arm A (RT) compared with 54% for arm B (WS) (p=0.0015, hazard ratio 0.53). Pts. with a preop. PSA &gt; 10 ng/ml, tumor stage =pT3b, Gleason score =8 as well as positive margins profited significantly from adjuvant RT. The rate of late grade II side effects for the rectum was 1%. Conclusions: Adjuvant radiotherapy for pT3 prostate cancer significantly reduces the risk of biochemical progression after radical prostatectomy. The rate of side effects is very low. No significant financial relationships to disclose.

Upgrading and Downgrading of Prostate Needle Biopsy Specimens: Risk Factors and Clinical Implications

The prostate biopsy Gleason grade frequently differs from the radical prostatectomy (RP) grade. Given the critical role that needle biopsy plays in treatment decisions, we sought to determine the risk factors for upgrading and downgrading the prostate biopsy specimen. We determined the significant predictors of upgrading (worse RP grade than biopsy grade) and downgrading (better RP grade than biopsy grade) among 1113 men treated with RP from 1996 to 2005 within the Shared Equal Access Regional Cancer Hospital (SEARCH) database who had undergone at least sextant biopsy. The Gleason sum was examined as a categorical variable of 2 to 6, 3+4, and 4+3 or greater. Overall, the disease of 299 men (27%) was upgraded and 123 (11%) was downgraded, and 691 men (62%) had identical biopsy and pathologic Gleason sum groups. Upgrading was associated with adverse pathologic features (P < or = 0.001) and the risk of biochemical progression (P = 0.001). Downgrading was associated with more favorable pathologic features (P < or = 0.01) and a decreased risk of progression (P = 0.04). On multivariate analysis, greater prostate-specific antigen levels (P < 0.001), more biopsy cores with cancer (P = 0.001), and obesity (P = 0.003) were all significantly and positively associated with upgrading. In contrast, biopsy Gleason sum 3+4 (P = 0.001) and obtaining eight or more biopsy cores (P = 0.01) were associated with a lower likelihood of upgrading. Men whose disease was upgraded were at a greater risk of adverse pathologic features and biochemical progression. Men with "high-risk" cancer (greater prostate-specific antigen levels, more positive cores, and obese) were more likely to have their disease category upgraded, and obtaining more biopsy cores reduced the likelihood of upgrading.

Is biopsy Gleason sum an independent predictor of biochemical progression following radical prostatectomy after adjusting for the pathological Gleason sum?

4652 Background: Biopsy Gleason sum is a known important predictor of PSA failure following radical prostatectomy (RP). However, it is unclear whether it remains predictive of outcome after surgery when the pathological Gleason sum is known. Methods: We determined the association between biopsy Gleason sum and biochemical progression after correcting for both pre-operative and post-operative characteristics including pathological Gleason sum among 1,931 men treated with RP between 1988 and 2005 within the SEARCH Database. Gleason sum was examined as a categorical variable of 2–6, 3+4, and ≥4+3. Results: Higher biopsy Gleason sums were associated with increased prevalence of extra-capsular extension (p &lt; 0.001), positive surgical margins (p &lt; 0.001), seminal vesicle invasion (p &lt; 0.001), positive lymph nodes (p &lt; 0.001), and biochemical progression (log rank, p &lt; 0.001). After adjusting for only pre-operative characteristics, both biopsy Gleason sums of 3+4 (p = 0.004) and ≥4+3 (p &lt; 0.001) were associated with increased risk of biochemical progression when compared to biopsy Gleason sums of 6 or less. After further adjusting for multiple pathological characteristics including pathological Gleason sum, the association between higher biopsy Gleason sum and risk of progression was little changed in that men with biopsy Gleason sums of 3+4 (p = 0.001) and ≥4+3 (p &lt; 0.001) were significantly more likely to progress. Furthermore, when stratified by pathological Gleason sum, higher biopsy Gleason sums were associated with increased risk of biochemical progression within each pathological Gleason sum category (log-rank, p ≤ 0.007). Conclusions: Biopsy Gleason sum remains a strong predictor of outcome even when the pathological Gleason sum is known. If confirmed at other centers, incorporation of biopsy Gleason sum into post-operative nomograms designed to predict risk of progression might improve model precision. No significant financial relationships to disclose.

Delay of Radical Prostatectomy and Risk of Biochemical Progression in Men With Low Risk Prostate Cancer

Men newly diagnosed with prostate cancer are faced with multiple treatment options. Understanding these options and their associated side effects, and making a decision often requires time, resulting in a delay before receiving treatment. This is particularly pertinent in men with low risk disease who may be considered candidates for watchful waiting and, thus, may not experience strong pressure to undergo treatment promptly. Whether delays and especially prolonged delays, eg greater than 180 days, before RP negatively impact the disease outcome is unclear. We examined the association between time from diagnosis to surgery, and pathological features of the RP specimen and risk of biochemical progression in 895 men with low risk prostate cancer (prostate specific antigen less than 10 ng/ml and biopsy Gleason sum 6 or less) treated with RP between 1988 and 2004 in the Shared-Equal Access Regional Cancer Hospital Database using logistic regression and Cox proportional hazards, respectively. Time from biopsy to surgery was not significantly related to high grade disease in the RP specimen, positive surgical margins or extraprostatic extension (all p-trend >0.05). After adjustment for multiple clinical covariates a longer time from biopsy to surgery was significantly associated with an increased risk of biochemical progression (p-trend = 0.002). However, this increased risk of progression was only apparent in men with delays greater than 180 days (median 263, vs 90 or fewer days RR 2.73, 95% CI 1.51 to 4.94). Our data suggest that patients with low risk prostate cancer can be reassured that immediate treatment is not necessary. Whether long delays (greater than 180 days) decrease the likelihood of curability in some patients requires further study.

Delay of Radical Prostatectomy and Risk of Biochemical Progression in Men With Low Risk Prostate Cancer

Delay of Radical Prostatectomy and Risk of Biochemical Progression in Men With Low Risk Prostate Cancer

Prostate Size and Risk of High-Grade, Advanced Prostate Cancer and Biochemical Progression After Radical Prostatectomy: A Search Database Study

Prostate growth and differentiation are under androgenic control, and prior studies suggested that tumors that develop in hypogonadal men are more aggressive. We examined whether prostate weight was associated with tumor grade, advanced disease, or risk of biochemical progression after radical prostatectomy (RP). We evaluated the association of prostate weight with pathologic tumor grade, positive surgical margins, extracapsular disease, and seminal vesicle invasion using logistic regression and with biochemical progression using Cox proportional hazards regression among 1,602 men treated with RP between 1988 and 2003 at five equal-access medical centers, which composed the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. In outcome prediction models including multiple predictor variables, it was found that the predictor variable of prostate weight was significantly inversely associated with the outcomes of high-grade disease, positive surgical margins, extracapsular extension (all P < or = .004), and biochemical progression (comparing prostate weight < 20 v > or = 100 g: relative risk = 8.43; 95% CI, 2.9 to 24.0; P < .001). Similar associations were seen between preoperative transrectal ultrasound-measured prostate volume and high-grade disease, positive surgical margins, extracapsular extension (all P < or = .005), seminal vesicle invasion (P = .07), and biochemical progression (P = .06). Men with smaller prostates had more high-grade cancers and more advanced disease and were at greater risk of progression after RP. These results suggest that prostate size may be an important prognostic variable that should be evaluated for use pre- and postoperatively to predict biochemical progression.

THE PROSTATIC SPECIFIC ANTIGEN ERA IS ALIVE AND WELL: PROSTATIC SPECIFIC ANTIGEN AND BIOCHEMICAL PROGRESSION FOLLOWING RADICAL PROSTATECTOMY

Prostate specific antigen (PSA) has been shown to predict the presence of prostate cancer on biopsy, pathological stage, and biochemical progression following primary therapy. A recent study found only a weak association between PSA and tumor volume in the radical prostatectomy (RP) specimen and concluded that the PSA era is over. We examined the association between PSA and clinical progression in men undergoing RP. The study population consisted of 2,312 men treated with RP between 1992 and 2004 by a single surgeon. We evaluated the association between preoperative PSA and biochemical progression on multivariate analysis. Men with higher preoperative PSA concentrations had higher grade cancers in the biopsy and RP specimen, and more adverse pathological features. After adjusting for the clinical covariates of age, race, grade, stage, and year of surgery, preoperative PSA was significantly associated with the risk of biochemical progression. When only men with PSA less than 10 ng/ml were examined, PSA remained a significant predictor of biochemical progression on multivariate analysis (RR 1.30, 95% CI 1.18 to 1.44, p <0.001). For each 2-point increase in PSA, the risk of biochemical progression increased approximately 2-fold. Preoperative PSA was significantly associated with high grade disease and adverse pathological findings. After adjusting for clinical covariates, PSA was significantly associated with the risk of biochemical progression, even in men with PSA less than 10 ng/ml. Despite multiple limitations, PSA remains the best prostate cancer tumor marker available.