Prediction of clinical progression after radical prostatectomy in a nationwide population-based cohort
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Abstract:
The aim of this study was to create a model for predicting progression-free survival after radical prostatectomy for localized prostate cancer.The risk of biochemical recurrence (BCR) was modelled in a cohort of 3452 men aged 70 years or younger who were primarily treated with radical prostatectomy after being diagnosed between 2003 and 2006 with localized prostate cancer [clinical stage T1c-T2, Gleason score 5-10, N0/NX, M0/MX, prostate-specific antigen (PSA) < 20 ng/ml]. The cohort was split into two: one cohort for model development (n = 3452) and one for validation (n = 1762). BCR was defined as two increasing PSA values of at least 0.2 ng/ml, initiation of secondary therapy, distant metastases or death from prostate cancer. Multivariable Cox proportional hazard regression was applied, predictive performance was assessed using the bootstrap resampling technique to calculate the c index, and calibration of the model was evaluated by comparing predicted and observed Kaplan-Meier 1 year BCR.The overall 5 year progression-free survival was 83% after a median follow-up time of 6.8 years in the development cohort and 7.3 years in the validation cohort. The final model included T stage, PSA level, primary and secondary Gleason grade, and number of positive and negative biopsies. The c index for discrimination between high and low risk of recurrence was 0.68. The probability of progression-free survival ranged from 22% to 97% over the range of risk scores in the study population.This model is based on nationwide population-based data and can be used with a fair predictive accuracy to guide decisions on clinical follow-up after prostatectomy. An online calculator for convenient clinical use of the model is available at www.npcr.se/nomogram.Keywords:
Biochemical recurrence
Progression-free survival
Evaluation: The ability of highly-trained dogs’ olfactory system to detect prostate cancer specific volatile organic compounds (VOCs) in men after undergoing radical prostatectomy and the eventual biochemical recurrence (BCR) was assessed. Materials and methods: One hundred-fourteen consecutivemen with clinical localized PCa undergoing radical prostatectomy between November 2011 and May 2013 were investigated. For each patient urine and serum samples were collected prior to radical prostatectomy, forty-five days and every six months during the successive follow-up (mean: 28 months; median: 28 months; range 1937 months). Two dogs were trained to sit when they detected PCa specific volatile organic compounds (VOCs) in the urine samples. Results: Preoperatively, both dogs were able to detect PCa specific VOC’s in the urine samples of men with PCa with 100% accuracy. Forty-five days post-radical prostatectomy, 104 (91.2%) patients had a serum prostate-specific antigen (PSA) levels 0.01 but 1 ng/ml. Forty-five days following surgery, neither dog detected prostate cancer specific VOC’s in the urine samples of the 104 men with a serum PSA level 0.01ng/ml and 1ng/ml (i.e. persistent disease). During the successive followup 9 of 110 patients (8.1%) had BCR. Both dogs were able to detect PCa VOC’s in the urine samples of 7 of these 9 patients (77.7%). Conclusions: Highlytrained dogs are able to detect BCR in men who have previously undergone radical prostatectomy alone for PCa. Our understanding of the use of the canine olfactory system in PCa detection continues to evolve.
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To assess the pathological features of Gleason score 6 prostate cancers after radical prostatectomy in the low (<4 ng/mL) and intermediate range of prostate-specific antigen level (4-10 ng/mL), as such prostate cancers are considered to be well differentiated tumours with a low risk for recurrence after therapy.In all, 1354 patients with T1c prostate cancer and PSA levels of <10.0 ng/mL had a radical retropubic prostatectomy. Patients with Gleason score 6 tumours were divided into two groups, those with PSA levels of <4 and 4.0-10.0 ng/mL. Extracapsular extension, positive surgical margins, biochemical recurrence (BCR) and mean time to BCR were evaluated.Of the 1354 patients, there were 437 (32.3%) with Gleason score 6 prostate cancers. Patients in the low PSA group had less extraprostatic disease than those with a higher level (5.9% vs 14.5%) and both groups had an almost equal proportion of positive surgical margins (9.4% vs 11.0%). In the low PSA group there was statistically significantly shorter BCR than in the high PSA group, with a mean time to BCR of 1.7 vs 3.1 years.These results show a statistically significantly higher rate of extraprostatic disease and earlier BCR in men with a high than a low PSA level even in Gleason score 6 prostate cancer. As the rate of BCR and extracapsular extension are significantly related to prostate cancer mortality, these findings further support the concept of screening using low PSA levels.
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Radical retropubic prostatectomy
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Tumour density (TD) may be an independent prognostic factor in men with prostate cancer. The purpose of this study was to evaluate the association between prostate cancer TD and recurrence following radical prostatectomy.Between 1995 and 2007, 645 patients from The Ottawa Hospital or Memorial Sloan-Kettering Cancer Center who had cancer and prostate volumes measured from radical prostatectomy specimens. Tumour density was defined as the relative tumour to prostate volume (tumour volume/prostate volume) and recurrence was defined as a prostate-specific antigen (PSA) >0.2 ng/mL and rising, or postoperative use of radiation or hormonal therapy. Associations between TD and recurrence are adjusted for preoperative PSA, prostatectomy Gleason sum, tumour stage and margin status.Median follow-up was 40.8 months. Tumour density was associated with preoperative PSA, Gleason sum, tumour stage and surgical margin status (all p < 0.0001). As a continuous variable, TD predicted recurrence-free survival (adjusted HR 1.34 per 10% increase in TD; p = 0.04). As a categorical variable, the group of patients with a TD of >10% had a 2.7 times greater hazard of recurrence compared to patients with a TD <5% (95%CI 1.41, 5.19; p = 0.003). Despite the independent association between TD and recurrence, the clinical value of TD remains in question as the discriminative performance (area under the curve) of predictive models only improved from 0.865 to 0.876.Prostate cancer TD is associated with known prognostic factors and is also independently predictive of recurrence following radical prostatectomy.
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Radical retropubic prostatectomy
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van Oort I M, Bruins H M, Kiemeney L A L M, Knipscheer B C, Witjes J A & Hulsbergen‐van de Kaa C A (2010) Histopathology 56 , 464–471 The length of positive surgical margins correlates with biochemical recurrence after radical prostatectomy Aims: To evaluate the prognostic role of the length of a positive surgical margin (+SM) for biochemical recurrence (BCR) after radical prostatectomy (RP) for prostatic cancer. Methods and results: Consecutive RP specimens ( n = 267) with +SM were analysed. All RP specimens were sectioned at 4‐mm intervals and completely embedded. Data were analysed using Kaplan–Meier survival analysis and proportional hazards models. In 267 patients the length of +SM ranged from 0.4 to 174.5 mm (median 11.2 mm) and correlated with preoperative prostate specific antigen (PSA) ( P < 0.001), pathological stage ( P < 0.001), tumour volume ( P = 0.001), number of +SM ( P < 0.001), Gleason grade at +SM ( P < 0.001) and Gleason score ( P = 0.015). Patients with detectable postoperative PSA levels ( n = 34) or adjuvant therapy ( n = 59) were excluded from BCR analysis. In the remaining 174 patients the 5‐year risk of BCR was 29%; in patients with +SM ≤10 mm and >10 mm this was 21% and 39%, respectively. On multivariable analysis BCR was associated with an increasing length of +SM (≤10 mm versus >10 mm; hazard ratio 2.15; 95% confidence interval 1.12, 4.15; P = 0.022). Conclusions: The length of +SM is an independent prognostic factor for BCR in patients with undetectable PSA after RP.
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Histopathology
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INTRODUCTION AND OBJECTIVES: Cancer detection using sniffer dogs is a potential technology for clinical use and research. Here we evaluate the ability of highly-trained dogs’ olfactory system to detect biochemical recurrence (BCR) in men after undergoing radical prostatectomy for prostate cancer (PCa). METHODS: One hundred-fourteen consecutive men with clinical localized PCa undergoing radical prostatectomy between November 2011 and May 2013 were investigated. For each patient urine and serum samples were collected prior to radical prostatectomy, forty-five days and every six months during the successive follow-up (mean: 28 months; median: 28 months; range 19-37 months). Two dogs were trained to sit when they detected PCa specific volatile organic compounds (VOCs) in the urine samples. RESULTS: Preoperatively, both dogs were able to detect PCa specific VOC’s in the urine samples of men with PCa with 100% accuracy. Forty-five days post-radical prostatectomy, 104 (91.2%) patients had a serum prostate-specific antigen (PSA) levels 0.01 but 1 ng/ml. Forty-five days following surgery, neither dog detected prostate cancer specific VOC’s in the urine samples of the 104 men with a serum PSA level 0.01ng/ml and 1ng/ml (i.e. persistent disease). During the successive follow up 9 of 110 patients (8.1%) had BCR. Both dogs were able to detect PCa VOC’s in the urine samples of 7 of these 9 patients (77.7%). CONCLUSIONS: Highly trained dogs are able to detect BCR in men who have previously undergone radical prostatectomy alone for PCa. Our understanding of the use of the canine olfactory system in PCa detection continues to evolve
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Commonly available prostate specific antigen (PSA) assays have detection limits of greater than 0.05 ng/ml., limiting their ability to identify residual or recurrent prostate cancer after radical prostatectomy or to provide prognostic information within the first several years after surgery. We investigated the ability of a sensitive PSA assay to identify residual prostate cancer and men at risk for early recurrence after radical prostatectomy.We measured PSA in 1,037 serum samples obtained serially from 127 men after radical prostatectomy using the IMMULITE third generation PSA assay.The IMMULITE PSA assay has an analytical sensitivity of less than 0.002 ng./ml. and a clinically useful decision threshold of 0.01 ng./ml. With this assay our patients were classified into 3 groups: 1) 50 with a postoperative baseline PSA of less than 0.01 ng./ml. that did not change during an average of 36 months postoperatively, 2) 66 with increasing PSA that exceeded 0.01 ng./ml. in all cases by 30 months postoperatively (20 with clinical cancer recurrences) and 3) 11 with slowly increasing PSA of greater than 0.01 but less than 0.02 ng./ml. at an average of 36 months postoperatively.The IMMULITE PSA assay provides clinically useful information not previously available from PSA assays with conventional sensitivity, which is highly predictive of cancer activity in patients within 2 years after radical prostatectomy.
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Prostatic acid phosphatase
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We investigated whether the detection of prostate specific membrane antigen (PSMA) in blood preoperatively has predictive value for biochemical recurrence (BCR) after radical prostatectomy in patients with prostate cancer.All 134 patients scheduled to receive radical prostatectomy for prostate cancer were prospectively enrolled.The authors used nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay to detect PSMA mRNAbearing cells in peripheral blood, and analyzed the ability of PSMA mRNA positivity to predict BCR after surgery.PSMA-mRNA was detected in 24 (17.9%)patients by RT-PCR.Over a median follow-up of 20 months (range, 3 to 46 months), BCR developed in 15 patients (11.2%) and median time to BCR was 7 months (range, 3 to 25 months).Kaplan-Meier analysis revealed a significant difference between those positive or negative for PSMA in terms of recurrence-free actuarial probability (log rank P=0.0039).Multivariate analysis showed that positivity for PSMA mRNA (HR: 3.697, 95% CI 1.285-10.634,P=0.015) and a biopsy Gleason score of ≥7 (HR: 4.500, 95% CI 1.419-14.274,P=0.011) were independent preoperative predictors of BCR.The presence of PSMA mRNA in peripheral blood can be used to predict BCR after radical prostatectomy.
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Glutamate carboxypeptidase II
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