Validation of a Genomic Risk Classifier to Predict Prostate Cancer-specific Mortality in Men with Adverse Pathologic Features

Background

Risk of prostate cancer-specific mortality (PCSM) is highly variable for men with adverse pathologic features at radical prostatectomy (RP); a majority will die of other causes. Accurately stratifying PCSM risk can improve therapy decisions.

Prostate cancer in men aged less than 50 years at diagnosis

Purpose

Prostate cancer (CaP) in younger men (age ≤50 years) appears to present differently compared with older men. This study describes CaP characteristics and outcomes in Australian young men.

Methods

The South Australian Prostate Cancer Clinical Outcomes Collaborative database was used to identify men diagnosed with CaP 1998–2012. Men were stratified by age at diagnosis into groups ≤50, 50–70 and ≥70 years. Primary outcomes of cumulative biochemical recurrence (BCR) and cumulative prostate cancer-specific mortality (PCSM) were assessed at 5 and 10 years.

Results

In total, 7018 men were included. At time of diagnosis, 182 (2.6 %) were aged ≤50 years. Median follow-up exceeded 4 years. Younger men had a greater proportion of T stage <2 disease, lower median PSA and higher rates of Gleason score <7 (all p < 0.001). They were more likely to experience active surveillance (AS) (4.9, 3.1, 1.5 %) or radical prostatectomy (RP) (70, 55, 8 %) and less likely radiotherapy (13, 24, 29 %) as their principal modality (all p < 0.001). Although only 4.9 % underwent AS, 48 % of men ≤50 years were eligible for AS. Men ≤50 years had both the lowest unadjusted cumulative BCR and PCSM at 10 years. After multivariate analysis, BCR was not significantly different. Sample size limited multivariate analysis of PCSM.

Conclusions

In our cohort, men ≤50 years with CaP had less aggressive clinical characteristics, but were more likely to undergo RP. They appear to experience lower unadjusted PCSM, but similar rates of adjusted BCR. Further studies are needed to assess whether AS is appropriately utilised in these men.

     

New Prostate Cancer Grading System Predicts Long-term Survival Following Surgery for Gleason Score 8–10 Prostate Cancer

Background

The newly proposed five-tiered prostate cancer grading system (PCGS) divides Gleason score (GS) 8–10 disease into GS 8 and GS 9–10 on the basis of biochemical recurrence (BCR) following radical prostatectomy (RP) as an outcome. However, BCR does not necessarily portend worse survival outcomes.

Prostate cancer at the peripheral end of prostate biopsy specimen predicts increased risk of positive resection margin after radical prostatectomy: results of a prospective multi-institutional study

Purpose

To test a novel technique of processing prostate biopsy specimen by marking the peripheral end (PE) as a predictive tool for positive resection margin after radical prostatectomy (RP) or for locally advanced carcinoma of the prostate (PC).

Methods

Prospective, multi-institutional study of a consecutive cohort of men who underwent prostate biopsy with marking the peripheral biopsy end and subsequent RP at the same institution.

Results

The study cohort comprised 445 men with a mean age of 63 years (40–77 years). Overall, PE-positive cores were found in 174 men (39.1 %) and R1 status was diagnosed in 132 men after RP (29.7 %). In the multivariate analysis, the presence of at least one PE-positive core was correlated with an increased risk of R1 status (OR 2.29, 95 % CI 1.31–4.00, p = 0.003) and was the strongest predictor followed by Gleason score, PSA and percentage of positive cores. Including all predictive parameters, a nomogram with a concordance index of 72.1 % was calculated. In the pT3/pT4 subgroup, PE positivity was the only predictive factor for R1 status (OR 3.03, 95 % CI 1.36–6.75, p = 0.006). In pT2 stage, no single factor was predictive for R1 status. PE-positive biopsies were not predictive for pT3/pT4 stages.

Conclusions

PC at the peripheral end of prostate biopsy specimen predicts an increased risk of R1 status in subsequent RP. This simple and cheap technique may contribute to an increased accuracy of risk stratification for curative treatment for PC.     

Impact of initial local therapy on survival in men later receiving chemotherapy for prostate cancer: a population-based,propensity-weighted multivariable analysis

Purpose

Prostate cancer remains a common disease that is frequently treated with multimodal therapy. The goal of this study was to assess the impact of treatment of the primary tumor on survival in men who go onto receive chemotherapy for prostate cancer.

Methods

Using surveillance, epidemiology and end results (SEER)-Medicare data from 1992 to 2009, we identified a cohort of 1614 men who received chemotherapy for prostate cancer. Primary outcomes were prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM). We compared survival among men who had previously undergone radical prostatectomy (RP), radiation therapy (RT), or neither of these therapies. Propensity score adjusted Cox proportional hazard models and weighted Kaplan–Meier curves were used to assess survival.

Results

Compared to men who received no local treatment, PCSM was lower for men who received RP ± RT (HR 0.65, p < 0.01) and for those who received RT only (HR 0.79, p < 0.05). Patients receiving neither RP nor RT demonstrated higher PCSM and ACM than those receiving treatment in a weighted time-to-event analysis. Men who received RP + RT had longer mean time from diagnosis to initiation of chemotherapy (100.7 ± 47.7 months) than men with no local treatment (48.8 ± 35.0 months, p < 0.05).

Conclusion

In patients who go on to receive chemotherapy, treatment of the primary tumor for prostate cancer appears to confer a survival advantage over those who do not receive primary treatment. These data suggest continued importance for local treatment of prostate cancer, even in patients at high risk of failing local therapy.

     

Preoperative sex steroids are significant predictors of early biochemical recurrence after radical prostatectomy

Purpose

We sought the association of preoperative serum total testosterone (tT), hypogonadism, 17β estradiol (E₂), and sex hormone-binding globulin (SHBG) with early biochemical recurrence (BCR) after radical prostatectomy (RP).

Methods

Sex steroids were assessed the day before surgery (7–11 a.m.) in a cohort of 605 patients with a median follow-up of 24 months following RP. Cox regression models tested the association between predictors [including age, body mass index (BMI), prostate-specific antigen (PSA), clinical stage, biopsy Gleason scores, tT, hypogonadism, E₂, and SHBG] and early BCR (defined as a PSA ≥ 0.1 ng/ml that occurred within 24 months after RP).

Results

Early BCR was found in 34 (5.6 %) patients. Patients with BCR did not differ in terms of age, BMI, serum PSA, tT, E₂, and SHBG levels, rate of hypogonadism, and clinical stage as compared with those without BCR (all p ≥ 0.05). Conversely, patients with BCR showed a greater prevalence of biopsy Gleason scores ≥4 + 3 (all p ≤ 0.001). At multivariable Cox regression analysis, tT [hazard ratio (HR): 1.43; p = 0.03] E₂ (HR: 1.05; p = 0.04), SHBG (HR: 1.29; p = 0.02), and biopsy Gleason scores equal to 4 + 3 (HR: 3.37; p = 0.04) and ≥8 (HR: 20.06; p < 0.001) achieved independent predictor status for early BCR. Conversely, no significant associations were found for all the other predictors.

Conclusions

Current findings show that preoperative serum sex steroids are independent predictors of early BCR in a homogeneous, large cohort of nonscreened patients treated with RP.     

Development and validation of nomograms to predict the recovery of urinary continence after radical prostatectomy: comparisons between immediate,early, and late continence

Purpose

Few studies have been conducted on the serial evaluation of predictors for recovery of urinary continence (RC) after radical prostatectomy (RP) among same cohort. We developed and validated nomograms to predict immediate (≤1), early (≤3), and late (≤12 months) RC from a contemporary series and compared each nomogram with regard to the significance of predictors for RC.

Methods

Among consecutive men who received robot-assisted or open retropubic RP between 2004 and 2011, 872 (74.7 %) and 296 (25.3 %) were randomly assigned to subcohorts for the development of nomograms and for the split-sample external validation. The final multivariate model was selected based on the stepwise procedure, and the regression coefficient-based nomograms were developed based on final models.

Results

Age at surgery, membranous urethral length (MUL), and robot-assisted RP were significant for RC at 1, 3, and 12 months. Saving the neurovascular bundle (NVB) and prostate volume were significant only for RC at 12 months. Odds ratios for age and MUL were constant over time, whereas the odds ratio for robot-assisted surgery decreased over time. Each developed nomogram was reasonably well fitted to the ideal line of the calibration plot. The split-sample external validation of nomograms indicated 63, 65, 71 % accuracy for each RC time point.

Conclusions

We developed nomograms for RC at each time point after RP and validated adequately. Saving the NVB and prostate volume may affect only late RC after RP. In contrast, age, MUL, and robot-assisted surgery seem to be consistently associated with immediate, early, and late RC.     

Low body mass index is associated with adverse oncological outcomes following radical prostatectomy in Korean prostate cancer patients

Purpose

The purpose of this study was to determine the impact of obesity on clinicopathological features and biochemical recurrence (BCR) following radical prostatectomy (RP) in Korean prostate cancer (PCa) patients.

Methods

A single-institutional retrospective analysis was performed on 880 PCa patients treated by RP without neoadjuvant therapy between July 2005 and December 2011. Patients were stratified according to body mass index (BMI) standards for Asian populations: obese (BMI ≥25 kg/m²), overweight (BMI 23–24.9 kg/m²), or normal weight (BMI <23 kg/m²). For analysis, overweight and obese patients were combined (n = 592, BMI ≥23 kg/m²) and compared with normal weight patients (n = 288, BMI <23 kg/m²). BCR was defined as prostate-specific antigen (PSA) ≥0.2 ng/ml following RP.

Results

Normal weight patients tended to be classified into the higher D’Amico risk category with smaller prostate volumes compared with obese and overweight patients. Normal weight patients had higher pathological Gleason scores and were at higher risk of BCR during the mean follow-up of 58.2 months. This translated to a higher 5-year BCR-free survival rate for obese and overweight patients compared with normal weight patients (77.8 vs. 70.3 %; p = 0.017). On multiple Cox-proportional hazards regression analysis incorporating variables of BMI category, PSA, positive surgical margins, pathological T stage, and Gleason score, higher BMI category remained a significant predictor of a lower risk of BCR (HR = 0.634, p = 0.028).

Conclusions

Obese and overweight Korean PCa patients have lower Gleason scores and a reduced risk of BCR compared with normal weight patients. These findings suggest that body fat influences pathological features and oncologic outcomes of PCa.     

Are all grade group 4 prostate cancers created equal? Implications for the applicability of the novel grade grouping

Background

According to the novel prostate cancer (PCa) grade grouping, men with Gleason score 8 should be included in the grade group 4 regardless of primary and secondary scores. We aimed at evaluating the effect of Gleason patterns on the risk of recurrence in men with grade group 4 PCa.

Impact of positive surgical margins and their locations after radical prostatectomy: comparison of biochemical recurrence according to risk stratification and surgical modality

Purpose

We investigated the influence of positive surgical margins (PSMs) and their locations on biochemical recurrence (BCR) according to risk stratification and surgical modality.

Methods

A total of 1,874 post-radical-prostatectomy (RP) patients of pT2–T3a between 2000 and 2010 at three tertiary centers, and who did not receive neoadjuvant/adjuvant therapy, were included in this study. Patients were stratified according to BCR risk: low risk (PSA <10, pT2a-b, and pGS ≤6), intermediate risk (PSA 10–20 and/or pT2c and/or pGS 7), and high risk (PSA >20 or pT3a or pGS 8–10). The median follow-up was 43 months.

Results

PSMs were a significant predictor of BCR in both the intermediate- and high-risk-disease groups (P = .001, HR 2.1, 95 % CI 1.3–3.4; P < .001, HR 2.8, 95 % CI 2.0–4.1). Positive apical margin was a significant risk factor for BCR in high-risk disease (P = .003, HR 2.0, 95 % CI 1.2–3.3), but not in intermediate-risk disease (P = .06, HR 1.7, 95 % CI 0.9–3.1). Positive bladder neck margin was a significant risk factor for BCR in both intermediate- and high-risk disease (P < .001, HR 5.4, 95 % CI 2.1–13.8; P = .001, HR 4.5, 95 % CI 1.8–11.4). In subgroup analyses, robotic RP provided comparable BCR-free survival regardless of risk stratification. Patients with PSMs showed similar BCR-free survival between open and robotic RP (log-rank, P = .897).

Conclusions

Post-RP PSMs were a significantly independent predictor of disease progression in high-risk disease as well as intermediate-risk disease. Both positive apical and bladder neck margins are also significant risk factors of BCR in high-risk disease. Patients with PSMs showed similar BCR-free survival between open and robotic surgery.     

A Competing Risk Analysis of Cancer-Specific Mortality of Initial Treatment with Radical Prostatectomy versus Radiation Therapy in Clinically Localized High-Risk Prostate Cancer

Background

There is no consensus on the optimal treatment for localized high-risk prostate cancer (PC), and much debate exists regarding the ideal treatment approach. For these reasons, we evaluated the competing risks of PC-specific mortality after initial therapy with radical prostatectomy (RP) versus radiotherapy (RT) in men with clinically localized high-risk PC.

Methods

We reviewed patients treated with RP and RT combined with androgen-deprivation therapy between 1990 and 2009. High-risk PC is defined as clinical stage ≥T3a, serum prostate-specific antigen (PSA) >20 ng/mL, or a biopsy Gleason sum of 8–10 according to National Comprehensive Cancer Network guidelines. Competing risk analysis was conducted to assess the association of RP (n = 251) or RT (n = 125) with cancer-specific mortality (CSM). Thereafter, secondary analysis with propensity score matching was conducted to further elucidate patient characteristics, with optimal matching of 0.25 times the standard deviation of propensity scores.

Results

With an overall median follow-up of 76 months, 35 (9.3 %) men with high-risk PC died due to PC (23 in the RT group and 12 in the RP group). The 5-year estimates of cancer-specific survival rate for men treated with RP and RT were 96.5 % (95 % confidence interval [CI] 94.2–98.9) and 88.3 % (95 % CI 82.8–94.3), respectively. Cumulative incidence estimates for CSM were statistically increased amongst men treated with RT (p = 0.002). Propensity score matching extracted 168 men with high-risk PC from the total patient cohort. Cumulative incidence estimates for CSM were statistically different amongst men treated with RT (p < 0.001).

Conclusions

Initial treatment with RP versus RT was associated with a decreased risk of CSM in men with clinically localized high-risk PC.     

Oncologic outcomes after minimally invasive radical prostatectomy in patients with seminal vesicle invasion (pT3b) without adjuvant therapy

Purpose

To evaluate the long-term outcomes of patients with prostate cancer who have pathological pT3b N0–Nx, with postoperative PSA < 0.1 ng/ml and no systematic adjuvant treatment.

Materials and methods

Using a monocentric prospectively maintained database, we identified among 2,142 men who underwent minimally invasive radical prostatectomy, 104 pT3b N0–Nx patients, with postoperative PSA < 0.1 ng/ml and at least 5 years of follow-up. Patients were considered for salvage treatment at biochemical recurrence (PSA ≥ 0.2 ng/ml).

Results

The median time of follow-up was 83.5 months (interquartile range [IQR]: 69–99). Overall, 102 patients (98 %) had T2 clinical stage or less. Specimen Gleason score was 7 in 71 patients (68 %) and <7 in 15 (14 %). Thirty-eight patients (37 %) were upgraded for Gleason score after radical prostatectomy. The overall 5-year probability of freedom from biochemical recurrence for the entire cohort was 55.8 % (95 % CI 45.8–65.8) and 73.3 % for patients who had specimen Gleason score <7 (p = 0.005). In univariate analysis, specimen Gleason score and surgical margin status were significant predictors for biochemical failure after radical prostatectomy (p = 0.05 and 0.007, respectively). In multivariate analysis, only specimen Gleason score >7 was significantly associated with biochemical failure (p = 0.009).

Conclusion

SVI is an adverse prognostic factor, but it is not associated with a uniformly poor prognosis. Specimen Gleason score and surgical margin status are significant predictors of recurrence after radical prostatectomy in patients with prostate cancer and SVI.     

Preoperative characteristics of high-Gleason disease predictive of favourable pathological and clinical outcomes at radical prostatectomy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Men with high‐risk prostate cancer experience recurrence, metastases and death at the highest rate in the prostate cancer population. Pathological stage at radical prostatectomy (RP) is the greatest predictor of recurrence and mortality in men with high‐grade disease. Preoperative models predicting outcome after RP are skewed by the large proportion of men with low‐ and intermediate‐risk features; there is a paucity of data about preoperative criteria to identify men with high‐grade cancer who may benefit from RP. The present study adds comprehensive biopsy data from a large cohort of men with high‐grade prostate cancer at biopsy. By adding biopsy parameters, e.g. number of high‐grade cores and >50% involvement of any core, to traditional predictors of outcome (prostate‐specific antigen concentration, clinical stage and Gleason sum), we can better inform men who present with high‐grade prostate cancer as to their risk of favourable or unfavourable disease at RP.

OBJECTIVE

• ? To investigate preoperative characteristics that distinguish favourable and unfavourable pathological and clinical outcomes in men with high biopsy Gleason sum (8–10) prostate cancer to better select men who will most benefit from radical prostatectomy (RP).

PATIENTS AND METHODS

• ? The Institutional Review Board‐approved institutional RP database (1982–2010) was analysed for men with high‐Gleason prostate cancer on biopsy; 842 men were identified.
• ? The 10‐year biochemical‐free (BFS), metastasis‐free (MFS) and prostate cancer‐specific survival (CSS) were calculated using the Kaplan–Meier method to verify favourable pathology as men with Gleason <8 at RP or ≤ pT3a compared with men with unfavourable pathology with Gleason 8–10 and pT3b or N1.
• ? Preoperative characteristics were compared using appropriate comparative tests.
• ? Logistic regression determined preoperative predictors of unfavourable pathology.

RESULTS

• ? There was favourable pathology in 656 (77.9%) men. The 10‐year BFS, MFS and CSS were 31.0%, 60.9% and 74.8%, respectively.
• ? In contrast, men with unfavourable pathological findings had significantly worse 10‐year BFS, MFS and CSS, at 4.3%, 29.1% and 52.3%, respectively (all P < 0.001).
• ? In multivariable logistic regression, a prostate‐specific antigen (PSA) concentration of >10 ng/mL (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.38–3.62, P= 0.001), advanced clinical stage (≥ cT2b; OR 2.55, 95% CI 1.55–4.21, P < 0.001), Gleason pattern 9 or 10 at biopsy (OR 2.55, 95% CI 1.59–4.09, P < 0.001), increasing number of cores positive with high‐grade cancer (OR 1.16, 95% CI 1.01–1.34, P= 0.04) and >50% positive core involvement (OR 2.25, 95% CI 1.17–4.35, P= 0.015) were predictive of unfavourable pathology.

CONCLUSIONS

• ? Men with high‐Gleason sum at biopsy are at high risk for biochemical recurrence, metastasis and death after RP; men with high Gleason sum and advanced pathological stage (pT3b or N1) have the worst prognosis.
• ? Among men with high‐Gleason sum at biopsy, a PSA concentration of >10 ng/mL, clinical stage ≥ T2b, Gleason pattern 9 or 10, increasing number of cores with high‐grade cancer and >50% core involvement are predictive of unfavourable pathology.

     

Tumor Volume Adds Prognostic Value in Patients with Organ-Confined Prostate Cancer

Purpose

This study was designed to assess the independent prognostic value of tumor volume (TV) and whether adding TV provides additional prognostic information for predicting biochemical recurrence (BCR) after radical prostatectomy.

Methods

We reviewed the medical records of 1,129 patients who underwent radical prostatectomy between July 2005 and July 2011. TV was categorized as minimal (≤1.0 ml), moderate (1.1–5.0 ml), or extensive (>5.0 ml). Cox regression analysis was performed to identify independent predictors of BCR. The predictive accuracies of Cox’s proportional hazard regression models with and without TV were quantified and compared using time-dependent receiver operating characteristic curve analysis.

Results

Increasing TV was associated with higher prostate specific antigen, pathological Gleason score, and pathologic tumor stage. TV was an independent predictor of BCR in multivariate analysis (p < 0.001). When patients were stratified by organ-confined and nonorgan-confined tumor groups, TV remained an independent predictor of BCR in organ-confined tumors (p < 0.001). In the nonorgan-confined tumor group, a significant difference was found only between extensive versus minimal TV (p = 0.023). The predictive accuracy of the Cox regression model increased significantly by adding TV in organ-confined tumor group (0.748 vs. 0.704, p < 0.05) but not in nonorgan-confined group (0.742 vs. 0.734, p > 0.05).

Conclusions

TV was an independent prognostic predictor of BCR in organ-confined prostate cancers and provided additional prognostic information with increased predictive accuracy. In contrast, TV did not increase the predictive accuracy in nonorgan-confined tumor. TV should be considered as a prognosticator in organ-confined tumors.     

Characteristics of modern Gleason 9/10 prostate adenocarcinoma: a single tertiary centre experience within the Republic of Ireland

Introduction

The 2005 international society of urological pathology consensus statement on Gleason grading in prostate cancer revised Gleason scoring in clinical practice. The potential for grade migration with this refinement poses difficulties in interpreting historical series. We report the characteristics of a recent cohort of consecutive Gleason score 9 or 10 prostate cancers in our institution. The purpose of this study was to define the clinicopathologic variables and staging information for this high-risk population, and to identify whether traditional prostate staging techniques are adequate for this subcohort of men.

Materials and methods

A computational review of our pathology database was performed. Between May 2010 and September 2012, 1,295 consecutive biopsies were undertaken, 168 of which were high-grade tumours (12.97 %). This group were divided into two cohorts of which 84 (12.05 %) had a highest reported Gleason score of 9 (N = 79) or 10 (N = 5) and 84 were reported as Gleason 8. All biopsies were double-reported by pathologists with a special interest in uropathology.

Results

Men diagnosed with a Gleason pattern 5 tumour were statistically far more likely to have advanced disease on direct rectal examination of the prostate compared with Gleason sum 8 tumours (p < 0.001) and a positive first-degree family history of prostate cancer (p < 0.001). Overall, Gleason sum 9/10 prostate cancers were also found to be statistically more aggressive than Gleason sum 8 tumours on TRUS core biopsy analysis with significantly higher levels of perineural invasion (p < 0.0001) and extracapsular extension (p = 0.001) as well as a higher levels of tumour found within the core biopsy sample. Those men diagnosed with Gleason pattern 5 prostate cancer also had radiological indicators of increased tumour aggressiveness compared with Gleason sum 8 cancer with respect to bone (p = 0.0002) and visceral (p = 0.044) metastases at presentation.

Conclusions

This series of Gleason score 9/10 prostate cancers serves to highlight the large disease burden, adverse pathologic features, and locally advanced nature of this aggressive subtype, which has previously been under-described in the literature, and differs from historical series in having a large high-grade cohort demonstrating high rates of metastatic disease. A history of prostate cancer amongst first-degree relatives was particularly prevalent in this population raising the issue of screening in a high-risk population. The high incidence of visceral metastatic disease at presentation supports upfront staging with CT thorax, abdomen, and pelvis in patients with Gleason 9 or 10 prostate cancers.     

Impact of international variation of prostate cancer on a predictive nomogram for biochemical recurrence in clinically localised prostate cancer

Objective

Prostate cancer (PCa) incidence has been rising rapidly in Korea with aggressive clinicopathologic features compared to those observed in Western countries. Our aim was to develop a predictive nomogram for BCR-free survival based on the characteristics of PCa in Korean men and compared its predictive accuracy to an established Western nomogram.

Methods

A nationwide multicenter study was designed involving 723 Korean men with clinically localised PCa that had undergone radical prostatectomy. The Cox proportional hazards model was applied to 549 cases from four heavy volume institutions to define prognostic factors and develops the Korean nomogram, which was subjected to internal validation, external validation using a separate cohort of 295 cases, and head-to-head comparison with the updated Kattan nomogram.

Results

During the mean follow-up period of 44.8 months, BCR occurred in 251 patients (35.4 %) with aggressive clinicopathologic features. Similar to Western cases, preoperative prostate-specific antigen (PSA), pathologic tumour stage (pT), and Gleason score (GS) were independent prognostic factors and used to develop the Korean nomogram in conjunction with age and surgical margin status. The Korean nomogram performed well for predicting BCR-free 5- and 10-year survival on internal validation. On external validation, the Korean nomogram showed better calibration than the updated Kattan nomogram.

Conclusions

Preoperative PSA, pT, and GS were independent prognostic factor for BCR in clinically localised PCa in Korean men. The superior performance of the Korean nomogram for Korean PCa patients suggests that geographic variation in clinicopathologic factors should be considered in a predictive nomogram.     

Association of diabetes mellitus and metformin use with biochemical recurrence in patients treated with radical prostatectomy for prostate cancer

Purpose

The impact of diabetes mellitus (DM) and metformin use on biochemical recurrence (BCR) in patients treated with radical prostatectomy (RP) remains controversial.

Methods

We retrospectively evaluated 6,863 patients who underwent RP for clinically localized PC between 2000 and 2011. Univariable and multivariable Cox regression models addressed the association of DM and metformin use with BCR.

Results

Overall, 664 patients had a diagnosis of DM from which 287 (43 %) were on metformin and 377 (57 %) were on anti-diabetics other than metformin. DM and metformin were not associated with any clinicopathologic features (p values >0.05). Within a median follow-up of 25 months (interquartile range 35 months), 774 (11.3 %) patients experienced BCR. Actuarial 5-year biochemical-free survival was 83 % for non-diabetic, 79 % for diabetic patients without metformin use, and 85 % for diabetic patients with metformin use (log rank p = 0.17). In uni- and multivariable Cox regression analyses with the non-diabetic group as referent, DM without metformin use (HR = 0.99; 95 % CI 0.75–1.30, p = 0.65) and DM with metformin use (HR = 0.84, 95 % CI 0.58–1.22, p = 0.36) were not associated with BCR after RP. A subgroup analysis stratified by nodal status, surgical margins, tumor stage, and Gleason sum did not reveal any significant association between DM, use of metformin and risk of BCR.

Conclusions

We found no association between DM or metformin use and cancer-specific features or BCR in patients treated with RP. The effect of DM and metformin on complications, wound healing and overall survival needs to be assessed in similar cohorts.     

Insignificant disease among men with intermediate-risk prostate cancer

Purpose

A paucity of data exists on the insignificant disease potentially suitable for active surveillance (AS) among men with intermediate-risk prostate cancer (PCa). We tried to identify pathologically insignificant disease and its preoperative predictors in men who underwent radical prostatectomy (RP) for intermediate-risk PCa.

Methods

We analyzed data of 1,630 men who underwent RP for intermediate-risk disease. Total tumor volume (TTV) data were available in 332 men. We examined factors associated with classically defined pathologically insignificant cancer (organ-confined disease with TTV ≤0.5 ml with no Gleason pattern 4 or 5) and pathologically favorable cancer (organ-confined disease with no Gleason pattern 4 or 5) potentially suitable for AS. Decision curve analysis was used to assess clinical utility of a multivariable model including preoperative variables for predicting pathologically unfavorable cancer.

Results

In the entire cohort, 221 of 1,630 (13.6 %) total patients had pathologically favorable cancer. Among 332 patients with TTV data available, 26 (7.8 %) had classically defined pathologically insignificant cancer. Between threshold probabilities of 20 and 40 %, decision curve analysis demonstrated that using multivariable model to identify AS candidates would not provide any benefit over simply treating all men who have intermediate-risk disease with RP.

Conclusion

Although a minority of patients with intermediate-risk disease may harbor pathologically favorable or insignificant cancer, currently available conventional tools are not sufficiently able to identify those patients.     

Nationwide practice patterns for the use of venous thromboembolism prophylaxis among men undergoing radical prostatectomy

Purpose

To examine the practice patterns and predictors of VTE prophylaxis following radical prostatectomy (RP).

Methods

This was a population-based observational study of 94,709 men with a diagnosis of prostate cancer (ICD-9 code 185) who underwent RP were identified from a hospital-based database from 2000 to 2010, including 68,244 (72.1 %) open RP (ORP) and 26,465 (27.9 %) robotic-assisted laparoscopic RP (RALP). VTE prophylaxis was classified as none, mechanical, pharmacologic, or combination.

Results

Following RP, 35,591 (52.2 %) received mechanical, 4,945 (7.2 %) pharmacologic, 7,720 (10.6 %) combination, and 20,438 (30.0 %) no VTE prophylaxis. A total of 245 VTE events (145 DVT, 114 PE) were identified, representing 0.25 % of all procedures. Men with >2 comorbidities (OR = 2.44; 95 % CI 1.78–3.35) and those who were black (OR = 1.44; 95 % CI 1.06–1.97) were more likely to have a VTE. Men who had RALP (OR = 0.61; 95 % CI 0.45–0.99), surgery at high-volume hospitals (OR = 0.45; 95 % CI 0.28–0.73), or received prophylaxis (OR = 0.67; 95 % CI 0.50–0.88) were less likely to develop a VTE.

Conclusion

Despite the observation that VTE prophylaxis reduces the risk of VTE by 40 %, VTE prophylaxis was not used in almost one-third of men who underwent radical prostatectomy.     

Parameters derived from the postoperative decline in ultrasensitive PSA improve the prediction of radical prostatectomy outcome

Purpose

Contemporary tools estimating increased risk of prostate cancer (PCa) relapse after radical prostatectomy (RP) are far from perfect and there has been an intensive search for additional predictive variables. We aimed to explore whether the parameters of postoperative ultrasensitive prostate-specific antigen (PSA) decline provide additional information for predicting PCa progression.

Methods

A total of 319 consecutive men, with at least 2 years of follow-up after RP for clinically localized PCa were subjected to this study. Intensive postoperative measurements of ultrasensitive PSA resulted in total of 4028 PSA values available for statistical evaluation. Biochemical recurrence (BCR) was defined as PSA ≥0.2 ng/ml. The accuracy of predictive models was quantified with the area under the curve.

Results

Over a median follow-up of 43 months (24–99 months), 107 patients (34 %) experienced BCR after RP. In patients with BCR, significantly higher values of PSA nadir (p < 0.001) and a decreased time interval from surgery to reach PSA nadir (p < 0.001) were observed. A multivariable Cox regression model confirmed that PSA nadir >0.01 ng/ml (HR 6.01, 95 % CI: 3.89–9.52) and time to PSA nadir <3 months (HR 2.86, 95 % CI: 1.74–5.01) were independent predictors of BCR. The inclusion of PSA nadir and the time to PSA nadir into the model resulted in improvement of predictive accuracy by 16 % over the model designed on the basis of established parameters.

Conclusions

Our results demonstrate that the level of PSA nadir and the time to PSA nadir determined by ultrasensitive assay significantly improve the identification of patients who are at high risk of disease recurrence after RP.