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1.  Contemporary Radical Prostatectomy 
Prostate Cancer  2011;2011:645030.
Purpose. Patients diagnosed with clinically localized prostate cancer have more surgical treatment options than in the past. This paper focuses on the procedures' oncological or functional outcomes and perioperative morbidities of radical retropubic prostatectomy, radical perineal prostatectomy, and robotic-assisted laparoscopic radical prostatectomy. Materials and Methods. A MEDLINE/PubMed search of the literature on radical prostatectomy and other new management options was performed. Results. Compared to the open procedures, robotic-assisted radical prostatectomy has no confirmed significant difference in most literatures besides less blood loss and blood transfusion. Nerve sparing is a safe means of preserving potency on well-selected patients undergoing radical prostatectomy. Positive surgical margin rates of radical prostatectomy affect the recurrence and survival of prostate cancer. The urinary and sexual function outcomes have been vastly improved. Neoadjuvant treatment only affects the rate of positive surgical margin. Adjuvant therapy can delay and reduce the risk of recurrence and improve the survival of the high risk prostate cancer. Conclusions. For the majority of patients with organ-confined prostate cancer, radical prostatectomy remains a most effective approach. Radical perineal prostatectomy remains a viable approach for patients with morbid obesity, prior pelvic surgery, or prior pelvic radiation. Robot-assisted laparoscopic prostatectomy (RALP) has become popular among surgeons but has not yet become the firmly established standard of care. Long-term data have confirmed the efficacy of radical retropubic prostatectomy with disease control rates and cancer-specific survival rates.
doi:10.1155/2011/645030
PMCID: PMC3200259  PMID: 22110994
2.  The Association Between Total and Positive Lymph Node Counts, and Disease Progression in Clinically Localized Prostate Cancer 
The Journal of urology  2006;175(4):1320-1325.
Purpose
We examined the association between the number of LNs removed, the number of positive LNs and disease progression in patients undergoing pelvic lymph node dissection and radical retropubic prostatectomy for clinically localized prostate cancer.
Materials and Methods
We analyzed 5,038 consecutive patients who underwent radical retropubic prostatectomy between 1983 and 2003. Clinicopathological parameters, including the administration of neoadjuvant hormonal therapy, preoperative prostate specific antigen, specimen Gleason score, surgeon and pathological stage, were collected prospectively in our prostate cancer database. We excluded men treated with radiation or chemotherapy before surgery. BCR was defined as 2 postoperative prostate specific antigen increases greater than 0.2 ng/ml. Cox models were used to determine whether the number of nodes removed or the number of positive nodes predicted freedom from BCR after adjustment for prognostic covariates.
Results
The 4,611 eligible patients had a median of 9 LNs (IQR 5 to 13) removed. Positive nodes were found in 175 patients (3.8%). Overall the number of LNs removed did not predict freedom from BCR (HR per additional 10 nodes removed 1.02, 95% CI 0.92 to 1.13, p = 0.7). Results were similar in patients receiving and not receiving neoadjuvant hormonal therapy. Finding any LN involvement was associated with a BCR HR of 5.2 (95% CI 4.2 to 6.4, p <0.0005). However, in men without nodal involvement an increased number of nodes removed correlated significantly with freedom from BCR (p = 0.01).
Conclusions
Nodal disease increased the risk of progression. Extensive lymphadenectomy enhances the accuracy of surgical staging. However, we were unable to determine that removing more nodes improves freedom from BCR uniformly. Since the proportion of patients with prostate cancer with positive nodes is low, the value of extensive lymphadenectomy requires a multi-institutional, randomized clinical trial.
doi:10.1016/S0022-5347(05)00685-3
PMCID: PMC1950746  PMID: 16515989
prostate; prostatic neoplasms; lymph nodes; lymph node excision; neoplasm recurrence; local
3.  Evaluating PSA Density as a Predictor of Biochemical Failure after Radical Prostatectomy: Results of a Prospective Study after a Median Follow-Up of 36 Months 
ISRN Urology  2013;2013:984951.
Purpose. To evaluate the predictive ability of PSA density for biochemical relapse after radical prostatectomy in patients operated for clinically localized disease and to compare its predictive strength with preoperative PSA and Gleason score. Patients and Methods. The study evaluated 244 patients with localized disease who underwent an open retropubic radical prostatectomy between February 2007 and April 2011. PSA was measured every 3 months after surgery with a mean follow-up period of 36 months. Two consecutive rises >0.2 ng/mL were considered as biochemical relapse. Results. Biochemical recurrence was observed in 71 (29.1%). A great correlation was found between relapse and PSA (P = 0.005), PSA density (P = 0.002), Gleason score (P = 0.015), pathological stage (P = 0.001), positive surgical margins (P = 0.021), and invasion of seminal vesicles (P < 0.001) and lymph nodes (P < 0.001). We also found that PSA density was associated with adverse pathological findings. In univariate and multivariate analysis both PSA (P = 0.006) and PSA density (P = 0.009) were found to be significant predictors for relapse in contrast to tumor grade. Conclusion. PSA density is a valuable parameter in estimating the danger of biochemical failure and it may increase predictive potential through the incorporation in preoperative nomograms.
doi:10.1155/2013/984951
PMCID: PMC3671563  PMID: 23762630
4.  Younger patients have poorer biochemical outcome after radical prostatectomy in high-risk prostate cancer 
Asian Journal of Andrology  2011;13(5):719-723.
The aim of this study was to investigate the prognostic significance of patient age with respect to tumour aggressiveness in men who underwent radical prostatectomy (RP) for prostate cancer. In this study, we reviewed the records of 743 patients who received RP without neoadjuvant or adjuvant therapy at our institution and were followed up for >2 years postoperatively. For our analyses, the patients were divided into two groups according to age: younger (<60 years) and older (≥60 years). Through uni- and multivariate analyses, associations of various clinicopathological parameters, including biochemical recurrence-free survival, with patient age, were evaluated among all patients, and the patients were stratified according to their D'Amico risk classification. Among all subjects, younger (n=126) and older (n=617) patients showed no significant differences regarding pathological parameters and biochemical recurrence-free survival (P=0.288). For the high-risk group (n=206), younger patients had a lower rate of biochemical recurrence-free survival following surgery than older patients (P=0.017), despite the fact that no significant differences were observed regarding various known prognostic parameters between the two age groups. In addition, multivariate analysis revealed that age was an independent predictor of biochemical recurrence-free survival among the high-risk group (P=0.003). Our results showed that relatively younger patients have a comparable biochemical outcome compared with their older counterparts following RP performed for prostate cancer. However, among patients with high-risk disease, younger patients have a worse biochemical outcome following RP compared with older patients.
doi:10.1038/aja.2011.39
PMCID: PMC3739588  PMID: 21706038
age factors; biochemical outcome; prostate; prostatic neoplasms; prostatectomy
5.  The prognostic significance of percentage of tumour involvement according to disease risk group in men treated with radical prostatectomy 
Asian Journal of Andrology  2011;13(6):828-832.
We investigated the prognostic significance of percentage of tumour involvement (PTI) according to the clinicopathological features of prostate cancer among patients who underwent radical prostatectomy (RP). A retrospective study of 534 patients who underwent RP between September 2003 and March 2008 without any neoadjuvant or adjuvant therapy was performed. The associations of PTI with various clinicopathological features and biochemical recurrence-free survival were examined via uni- and multivariate analyses. The predictive accuracy of the multivariate model was assessed with a receiver operating characteristics-derived area under the curve. PTI was demonstrated to be significantly associated with preoperative prostate-specific antigen (PSA) level (P=0.001), pathological Gleason score (P<0.001), extraprostatic tumour extension (P<0.001), seminal vesicle invasion (P<0.001) and positive surgical margin (P<0.001) in univariate analyses. When patients were stratified into disease risk groups, PTI was an independent predictor of biochemical recurrence-free survival in multivariate analysis only among the low-risk group (P=0.033) but not the intermediate- (P=0.287) or the high-risk groups (P=0.828). The addition of the PTI did not significantly increase the accuracy of the multivariate model devised for the prediction of biochemical recurrence-free survival among both total patients (P=0.459) and the low-risk group (P=0.268), respectively. In conclusion, although PTI appeared to be a more significant prognostic factor among patients with low-risk disease than among those with higher risk diseases, overall, the PTI may not provide additional prognostic information beyond what can already be obtained via established prognostic factors.
doi:10.1038/aja.2011.111
PMCID: PMC3739551  PMID: 21946230
biochemical recurrence-free survival; percentage of tumour involvement; prognosis; prostate cancer; prostatectomy
6.  Independent predictors of biochemical recurrence after radical prostatectomy: a single center experience 
Introduction
The aim of study was to establish pretreatment and postoperative factors which could predict the early biochemical recurrence after radical prostatectomy.
Materials and method
754 patients had undergone radical prostatectomy since January 2002 to December 2008 in our department and were included in this prospective study. Exclusion criteria were: neoadjuvant or adjuvant treatment (radiation or hormonal treatment) and N+. Following parameters were evaluated: age, PSA at time of biopsy, time period from biopsy to operation, biopsy and postoperative Gleason score, stage, high grade intraepithelial neoplasias, perineural invasion. Biochemical recurrence was detected if PSA value after radical prostatectomy was ≥0.2 ng/ml. All factors likely to be predictive were evaluated by univariate analysis (Log-rank test). Multivariate analysis using Cox model was completed for all factors with p value <0.1 at univariate analysis.
Results
Final analysis was done using data of 496 patients. We detected 53 (10.7%) biochemical recurrences. Calculated actuarial biochemical recurrence free survival reached 64%. Multivariate analysis highlighted that PSA >10 ng/ml (HR 2.45, p = 0.008), pathological stage ≥pT3 (HR 2.371, p = 0.02), postoperative Gleason score ≥7 (HR 2.149, p = 0.049), positive surgical margins (HR 2.482, p = 0.014) and absence of high grade intraepithelial neoplasia in removed prostate (HR 0.358, p = 0.006) are independent factors influencing biochemical recurrence after radical prostatectomy.
Conclusion
Patients with higher PSA, locally advanced disease, positive surgical margins, and Gleason score ≥7 are at the highest risk for biochemical recurrence.
doi:10.5173/ceju.2011.01.art4
PMCID: PMC3921706  PMID: 24578855
prostate; prostate cancer; radical prostatectomy; biochemical recurrence
7.  Significance of Neoadjuvant Hormonal Therapy in Radical Retropubic Prostatectomy: A Retrospective Single-Surgeon Study 
Yonsei Medical Journal  2013;54(2):410-415.
Purpose
The purpose of this study was to evaluate whether neo-adjuvant hormonal therapy (NHT) prior to radical retropubic prostatectomy (RRP) for prostate cancer (PCa) is beneficial in terms of surgical outcomes and for preventing or delaying biochemical recurrence via single-surgeon case series study.
Materials and Methods
Fifty-three men underwent RRP by a single surgeon. The patients were divided into two groups according to whether or not NHT was performed prior to RRP. The study was analyzed retrospectively. We evaluated clinical parameters, surgical parameters, and biochemical recurrence rate. Group 1 (n=34) was treated with RRP only, while Group 2 (n=19) underwent RRP along with NHT.
Results
There were no significant differences in clinical, operation-related and pathological factors between the two groups (p>0.05). There was also no significant difference in biochemical recurrence rate between the two groups at the last follow-up, although Group 2 tended to have a lower PCa recurrence rate than Group 1 and the initial prostate-specific antigen (PSA) level was significantly higher in Group 2 than Group 1 (p=0.0496).
Conclusion
The present single-surgeon case series study revealed a trend toward a lower rate of PCa recurrence in NHT+RRP treated patients compared to those treated with RRP alone, but this did not reach statistical significance, despite the fact that NHT+RRP patients exhibited higher serum PSA levels preoperatively. Prospective studies with a longer duration of observation and a greater number of patients would be helpful in evaluating NHT more definitively.
doi:10.3349/ymj.2013.54.2.410
PMCID: PMC3575985  PMID: 23364975
Neo-adjuvant hormonal therapy; radical retropubic prostatectomy; single surgeon study
8.  Robotic-assisted prostatectomy and open radical retropubic prostatectomy for locally-advanced prostate cancer: multi-institution comparison of oncologic outcomes 
Prostate International  2013;1(1):31-36.
Purpose:
Robotic-assisted laparoscopic prostatectomy (RALP) offers reportedly comparable oncologic outcomes for localized disease compared with open radical retropubic prostatectomy (ORRP). However, the oncologic efficacy of RALP in locally-advanced prostate cancer (PCa) is less clear. We report and compare our experience with RALP and ORRP in men with locally advanced PCa.
Methods:
Patients with locally advanced PCa (stage T3 or greater) were identified in both robotic and open cohorts. Clinicopathologic features including age, clinical stage, prostate-specific antigen, surgical margins, and Gleason score were reviewed. We further examined the incidence of positive surgical margins, the effect of the surgical learning curve on margins, and the need for adjuvant therapy.
Results:
From 1997 to 2010, 1,011 patients underwent RALP and 415 patients were identified who underwent radical retropubic prostatectomy (RRP) across four institutions. 140 patients in the RALP group and 95 in the RRP group had locally advanced PCa on final pathology. The overall robotic positive margin rate 47.1% compared with 51.4% in the RRP group. A trend towards a lower positive margin rate was seen after 300 cases in the RALP group, with 66.7% positive margin rate in the first 300 cases compared with 41.8% in the latter 700 cases. In addition, a lower incidence of biochemical recurrence was also noted in the latter cases (30.6% vs. 9.5%).
Conclusions:
Up to 2 out of 3 men undergoing RALP for locally-advanced PCa had positive margins during our initial experience. However, with increasing surgeon experience the overall positive margin rate decreased significantly and was comparable to the positive margin rate for patients with locally advanced disease undergoing ORRP over four academic institutions. We also noted a lower incidence of biochemical recurrence with increasing RALP experience, suggesting better oncologic outcomes with higher volume. Given this data, RALP has comparable oncologic outcomes compared to ORRP, especially with higher volume surgeons.
doi:10.12954/PI.12001
PMCID: PMC3821519  PMID: 24223399
Prostate neoplasms; Oncologic outcomes; Prostatectomy
9.  Adjuvant Effect of IV Clodronate on the Delay of Bone Metastasis in High-Risk Prostate Cancer Patients: A Prospective Study 
Purpose
High-risk prostate cancer patients undergoing treatment often experience biochemical recurrence. The use of bisphosphonates as an adjuvant treatment delays skeletal events, yet whether or not bisphosphonates also delay metastastic development remains to be determined.
Materials and Methods
A total of 140 high-risk prostate cancer patients who were undergoing definitive treatment and who had clinically organ-confined disease and who suffered from biochemical recurrence were administered intravenous (IV) clodronate. The patients were treated with a radical retropubic prostatectomy (RP) or curative radiotherapy (RTx). Upon androgen deprivation therapy initiation, tri-monthly IV clodronate was added to the treatment to prevent bone demineralization. Twenty-six out of 60 operated cases and 45 out of 80 irradiated cases received bisphosphonate. The length of time until the first bone metastasis was recorded and analyzed.
Results
No statistical difference was found for the type of primary treatment (RP or RTx) on the time to the first bone metastasis (95% confidence interval [CI], 0.40 to 2.43; p=0.98). However, there was a clear advantage favoring the group that received bisphosphonate (p<0.001). The addition of bisphosphonate delayed the appearance of the first bone metastasis by seven-fold (95% CI, 3.1 to 15.4; p<0.001).
Conclusion
Treatment with tri-monthly IV clodronate delayed the time to the first bone metastasis in high-risk prostate cancer patients who were experiencing an increase in the prostate specific antigen level after definitive treatment.
doi:10.4143/crt.2011.43.4.231
PMCID: PMC3253865  PMID: 22247708
Prostatic neoplasms; Clodronic acid; Osteoporosis; Androgen antagonists; Zoledronic acid; Hormone antagonists
10.  Bcl-2 as a Predictive Factor for Biochemical Recurrence after Radical Prostatectomy: An Interim Analysis 
Purpose
The objective of this study was to determine Bcl-2 expression in localized prostate cancer and its potential role as a predictive factor for biochemical recurrence (BCR).
Materials and Methods
This study included 171 Korean patients with newly diagnosed adenocarcinoma of the prostate who underwent radical prostatectomy (RP) without neoadjuvant therapy at a single center between February 2005 and May 2009. RP specimens obtained from these patients were analyzed for the expression of Bcl-2 using tissue microarray. The values of Bcl-2 and other clinicopathologic factors were evaluated. Statistical analysis was performed with contingency table analysis, chi-square tests, and a Cox proportional hazard model.
Results
Bcl-2 expression was immunohistologically-confirmed in 42 patients (24.6%). Bcl-2 expression was not associated with conventional clinicopathologic factors. Bcl-2 negative patients had a significantly longer mean BCR-free survival than Bcl-2-positive patients (p=0.036). Among several variables, a high Gleason score in the RP specimen (≥8), extraprostatic extension, seminal vesicle invasion (SVI), lymphovascular invasion (LVI), and Bcl-2 expression were significant predictors of BCR based on univariate analysis. Multivariate Cox proportional hazards analysis revealed that BCR was significantly associated with a high prostate specific antigen level (p=0.047), SVI (p<0.001), a positive surgical margin (p=0.004) and Bcl-2 expression (p=0.012).
Conclusion
Bcl-2 expression in RP specimens is associated with a significantly worse outcome, suggesting a potential clinical role for Bcl-2. Post-operative Bcl-2 could be a significant predictor of outcome after RP.
doi:10.4143/crt.2010.42.3.157
PMCID: PMC2953779  PMID: 20948921
Prostatic neoplasms; Proto-oncogene proteins; B-cell leukemia/lymphoma 2; Recurrence; Prostatectomy
11.  Neoadjuvant Hormonal Therapy Preceding Radical Prostatectomy for Clinically Localized Prostate Cancer: Early Postoperative Complications and Biochemical Recurrence 
Korean Journal of Urology  2011;52(1):19-23.
Purpose
The effect of neoadjuvant hormonal therapy (NHT) on radical retropubic prostatectomy (RRP) for prostate cancer is various and remains a controversy for urologists. We conducted this study to comparatively evaluate whether NHT before RRP is indicated and beneficial in the aspects of postoperative complications, positive surgical margin, and biochemical recurrence.
Materials and Methods
Between September 2006 and December 2009, 69 men were scheduled for RRP as a treatment for clinically localized and locally advanced prostate cancer and were divided into two groups. Group 1 (n=31, 44.9%) was treated with RRP only, and group 2 (n=38, 55.1%) underwent RRP with preoperative NHT. We evaluated clinical parameters, surgical parameters, and the positive margin rate in surgical specimens and the biochemical recurrence rate.
Results
There were no statistical differences in age, body mass index (BMI), preoperative biopsy Gleason score, initial serum prostate-specific antigen (PSA) levels, International Prostate Symptom Score (IPSS), or quality of life (QoL) between the two groups (p>0.05). We also observed no differences in the transfusion rate, mean catheterization time, or positive margin rate (p>0.05). However, the mean operative time was significantly higher in the RRP with preoperative NHT group than in the other group (p=0.034). There was no significant difference in the biochemical recurrence rate during the last follow-up according to NHT (p=0.102) or positive surgical margin (p=0.473).
Conclusions
These results suggest that there were no clinical benefits to the administration of NHT before RRP from the viewpoint of biochemical recurrence.
doi:10.4111/kju.2011.52.1.19
PMCID: PMC3037502  PMID: 21344026
Neoadjuvant therapy; Prostatectomy; Prostatic neoplasms
12.  Biochemical Recurrence-Free and Cancer-Specific Survival after Radical Prostatectomy at a Single Institution 
Korean Journal of Urology  2010;51(12):836-842.
Purpose
To analyze the biochemical recurrence-free and cancer-specific survival after radical prostatectomy in a consecutive series of patients with prostate cancer.
Materials and Methods
We retrospectively reviewed data for 1,822 patients who underwent radical prostatectomy with pelvic lymph node dissection at our institution between 1990 and 2009. After excluding 498 patients who were treated with neoadjuvant androgen deprivation therapy or who were followed up for ≤6 months, we included 1324 patients (mean age, 64.4 years; mean prostate-specific antigen [PSA] level, 12.3 ng/ml). We assessed patient age at the time of surgery, preoperative PSA concentration, biopsy and pathologic Gleason scores, pathologic stage, surgical margin status, disease progression, and survival.
Results
The mean follow-up time was 40 months (range, 6-193 months). The 5- and 10-year biochemical recurrence-free survival rates were 73.2% and 66.2%, respectively, and the 10-year cancer-specific survival rate was 92.4%. The mean time from surgery to biochemical recurrence was 18 months. In the multivariate analysis, Gleason score (4+3 vs. 2-6, p=0.004; 8-10 vs. 2-6, p<0.001), pathologic stage (pT3a vs. pT2, p=0.001; pT3b-4 vs. pT2, p<0.001; pN1 vs. pT2, p<0.001), and resection margin status (p<0.001) were statistically significant predictors of biochemical recurrence, with only pathologic stage (pT3b-4 vs. pT2, p=0.006; pN1 vs. pT2, p=0.010) being a statistically significant predictor of cancer-specific survival.
Conclusions
Radical prostatectomy resulted in favorable cancer control in more than 70% of patients after 5 years and a low (<10%) cancer-specific mortality rate after 10 years. The factors predictive of biochemical recurrence were Gleason score, pathologic stage, and resection margin status.
doi:10.4111/kju.2010.51.12.836
PMCID: PMC3016429  PMID: 21221203
Prostatectomy; Prostatic neoplasms
13.  External Validation of the Cancer of the Prostate Risk Assessment (CAPRA) Score in a Single-Surgeon Radical Prostatectomy Series 
Urologic oncology  2010;30(5):584-589.
SUMMARY
Objectives
Prostate cancer clinical staging has significant limitations in the ability to accurately risk-stratify patients for prompt treatment or expectant management. The University of California San Francisco Cancer of the Prostate Risk Assessment (UCSF CAPRA) was recently described as a straightforward staging system that uses clinical variables to generate a score ranging from 0 to 10. Our objective was to perform an external validation of the CAPRA score as a predictor of 5-year progression-free survival (PFS) in a single-surgeon radical retropubic prostatectomy (RRP) series.
Materials and Methods
We examined the performance characteristics of the preoperative CAPRA score (0–10) to predict biochemical progression-free survival (PFS) in 990 men who underwent RRP by a single surgeon from 2003 to 2009.
Results
CAPRA scores were significantly associated with the risk of early biochemical progression in our series. For example, 5-year PFS was markedly different for scores at the extremes of 0 to 1 versus ≥7 (95% vs. 40%, respectively). The concordance index was 0.764 for the prediction of biochemical progression using CAPRA scores in this cohort, which compares favorably with the concordance index of 0.66 in the original CaPSURE dataset.
Conclusions
Our results validate the UCSF-CAPRA score as a significant predictor of 5-year PFS in a single surgeon series. The CAPRA score is a simple preoperative tool that can be readily applied in clinical practice to help risk-stratify prostate cancer patients.
doi:10.1016/j.urolonc.2010.06.007
PMCID: PMC3137684  PMID: 20822930
CAPRA; staging; prostate cancer; prostatectomy; biochemical recurrence
14.  Poorly Differentiated Prostate Cancer Treated With Radical Prostatectomy: Long-Term Outcome and Incidence of Pathological Downgrading 
The Journal of urology  2006;176(3):991-995.
Purpose:
Patients with high grade (Gleason score 8 to 10) prostate cancer on biopsy are at high risk for cancer recurrence after local treatment, such as radiation therapy and radical prostatectomy. We examined long-term outcomes in patients with high grade prostate cancer on biopsy who were treated with radical prostatectomy alone. We also investigated the impact on outcomes of changes in the radical prostatectomy Gleason score.
Materials and Methods:
Of 5,662 patients who underwent radical prostatectomy during 20 years 238 had a biopsy Gleason score of 8 to 10. We analyzed the rate of biochemical recurrence in this subgroup according to the Gleason grade of cancer in the radical prostatectomy specimen.
Results:
Ten-year biochemical recurrence-free probability in the cohort was 39%. However, 45% of patients (95% CI 38 to 51%) with Gleason score 8 to 10 cancer on biopsy had a Gleason score of 7 or less in the radical prostatectomy specimen. These patients had a 10-year biochemical recurrence-free probability of 56% compared to 27% in those with a final Gleason score that remained 8 to 10 (p = 0.0004). On multivariate analysis neither prostate specific antigen nor biopsy features, including total number of cores, number of cores with cancer and percent of cancer in the cores, was a significant predictor of downgrading. However, clinical stage and biopsy Gleason score were significant with 58% of cT1c and 51% of biopsy Gleason score 8 cancers downgraded. Almost 65% of cT1c Gleason score 8 cancers were downgraded compared to 11% of cT3 Gleason score 9 cancers.
Conclusions:
Patients diagnosed with poorly differentiated prostate cancer (Gleason score 8 to 10) on biopsy do not uniformly have a poor prognosis. Of the patients 39% remain free of cancer recurrence 10 years after radical prostatectomy. Of these cancers 45% have a lower Gleason score in the radical prostatectomy specimen and a correspondingly more favorable long-term outcome. Predictors of downgrading are lower clinical stage (cT1c) and Gleason score 8 in the biopsy specimen.
doi:10.1016/j.juro.2006.04.048
PMCID: PMC2239297  PMID: 16890678
prostate; prostatic neoplasms; prostatectomy; mortality; biopsy
15.  Adjuvant Androgen Deprivation for High-Risk Prostate Cancer After Radical Prostatectomy: SWOG S9921 Study 
Journal of Clinical Oncology  2011;29(15):2040-2045.
Purpose
Men with high-risk features (extraprostatic extension or high Gleason grade) face a high risk of prostate cancer recurrence after radical prostatectomy. Clinical trials of adjuvant systemic therapy for such patients have been limited.
Patients and Methods
The SWOG (Southwest Oncology Group) S9921 study randomly assigned 983 men with high-risk features at prostatectomy to receive adjuvant therapy with androgen deprivation (ADT) alone or in combination with mitoxantrone chemotherapy. ADT consisted of goserelin and bicalutamide for 2 years.
Results
Although the final primary treatment comparison results are not ready for publication, this article reports results in the ADT-alone control arm with a median follow-up of 4.4 years. For these 481 men, the estimated 5-year biochemical failure-free survival is 92.5% (95% CI, 90 to 95), and 5-year overall survival is 95.9% (95% CI, 93.9 to 97.9).
Conclusion
The results of this trial, taken in context, make a compelling argument for counseling all high-risk patients with prostate cancer about adjuvant ADT. This article discusses the challenges in the design and implementation of clinical trials to take the next step forward in adjuvant therapy for prostate cancer because of the excellent survival achieved with currently available therapies and highlights the need for better molecular markers to personalize care.
doi:10.1200/JCO.2010.32.2776
PMCID: PMC3107759  PMID: 21502546
16.  First Danish Single-Institution Experience with Radical Prostatectomy: Biochemical Outcome in 1200 Consecutive Patients 
Prostate Cancer  2010;2011:236357.
Radical retropubic prostatectomy (RRP) as intended curative therapy for patients with clinically localized prostate cancer (PC) was initiated in 1995 in Denmark. This paper reports single-institution results from the first 1200 consecutive patients operated during a 15-year period. Median age at surgery was 63 years. Median PSA was 9 ng/mL. Palpable tumors (≤cT2) were present in 48% of patients. Gleason score at biopsy was ≤7 for 85% of patients. In sixty-five percent of patients, histopathology revealed localized PCa after RRP. Positive surgical margins were found in 39.2% of the cases. Biochemical recurrence (BR) occurred for 214 (18%) of patients. The estimated biochemical recurrence free survival (BRFS) was 71.7% and 63.2% after 5 and 10 years, respectively. When patients were stratified according to the D'Amico criteria, BRFS after 10 years was 75.3%, 59.7%, and 39.3% for low-, medium- and high-risk patients, respectively. In univariate analysis, clinical stage, PSA at diagnosis and type of surgery were significant predictors of BR. In multivariate analysis, Gleason score > 7, PSA > 10, and higher clinical stage were significant predictors of BR. Early Danish results in a population not subjected to screening demonstrate BRFS rates comparable with earlier reports from the prescreening era.
doi:10.1155/2011/236357
PMCID: PMC3215946  PMID: 22096651
17.  Discovery and Validation of a Prostate Cancer Genomic Classifier that Predicts Early Metastasis Following Radical Prostatectomy 
PLoS ONE  2013;8(6):e66855.
Purpose
Clinicopathologic features and biochemical recurrence are sensitive, but not specific, predictors of metastatic disease and lethal prostate cancer. We hypothesize that a genomic expression signature detected in the primary tumor represents true biological potential of aggressive disease and provides improved prediction of early prostate cancer metastasis.
Methods
A nested case-control design was used to select 639 patients from the Mayo Clinic tumor registry who underwent radical prostatectomy between 1987 and 2001. A genomic classifier (GC) was developed by modeling differential RNA expression using 1.4 million feature high-density expression arrays of men enriched for rising PSA after prostatectomy, including 213 who experienced early clinical metastasis after biochemical recurrence. A training set was used to develop a random forest classifier of 22 markers to predict for cases - men with early clinical metastasis after rising PSA. Performance of GC was compared to prognostic factors such as Gleason score and previous gene expression signatures in a withheld validation set.
Results
Expression profiles were generated from 545 unique patient samples, with median follow-up of 16.9 years. GC achieved an area under the receiver operating characteristic curve of 0.75 (0.67–0.83) in validation, outperforming clinical variables and gene signatures. GC was the only significant prognostic factor in multivariable analyses. Within Gleason score groups, cases with high GC scores experienced earlier death from prostate cancer and reduced overall survival. The markers in the classifier were found to be associated with a number of key biological processes in prostate cancer metastatic disease progression.
Conclusion
A genomic classifier was developed and validated in a large patient cohort enriched with prostate cancer metastasis patients and a rising PSA that went on to experience metastatic disease. This early metastasis prediction model based on genomic expression in the primary tumor may be useful for identification of aggressive prostate cancer.
doi:10.1371/journal.pone.0066855
PMCID: PMC3691249  PMID: 23826159
18.  The natural history of metastatic progression in men with prostate-specific antigen recurrence after radical prostatectomy: long-term follow-up 
BJU international  2011;109(1):32-39.
OBJECTIVE
To describe metastasis-free survival (MFS) in men with prostate-specific antigen (PSA) recurrence following radical prostatectomy, and to define clinical prognostic factors modifying metastatic risk.
PATIENTS AND METHODS
We conducted a retrospective analysis of 450 men treated with prostatectomy at a tertiary hospital between July 1981 and July 2010 who developed PSA recurrence (≥0.2 ng/mL) and never received adjuvant or salvage therapy before the development of metastatic disease.
We estimated MFS using the Kaplan–Meier method, and investigated factors influencing the risk of metastasis using Cox proportional hazards regression.
RESULTS
Median follow-up after prostatectomy was 8.0 years, and after biochemical recurrence was 4.0 years. At last follow-up, 134 of 450 patients (29.8%) had developed metastases, while median MFS was 10.0 years.
Using multivariable regressions, two variables emerged as independently predictive of MFS: PSA doubling time (<3.0 vs 3.0–8.9 vs 9.0–14.9 vs ≥15.0 months) and Gleason score (≤6 vs 7 vs 8–10).
Using these stratifications of Gleason score and PSA doubling time, tables were constructed to predict median, 5- and 10-year MFS after PSA recurrence. In different patient subsets, median MFS ranged from 1 to 15 years.
CONCLUSIONS
In men undergoing prostatectomy, MFS after PSA recurrence is variable and is most strongly influenced by PSA doubling time and Gleason score. These parameters serve to stratify men into different risk groups with respect to metastatic progression.
Our findings may provide the background for appropriate selection of patients, treatments and endpoints for clinical trials.
doi:10.1111/j.1464-410X.2011.10422.x
PMCID: PMC3204323  PMID: 21777360
metastasis-free survival; natural history; prostate cancer; PSA recurrence
19.  Impact of Prostate Volume on Oncological and Functional Outcomes After Radical Prostatectomy: Robot-Assisted Laparoscopic Versus Open Retropubic 
Korean Journal of Urology  2013;54(1):15-21.
Purpose
We compared the impact of prostate volume on oncological and functional outcomes 2 years after robot-assisted laparoscopic prostatectomy (RALP) and open radical retropubic prostatectomy (ORP).
Materials and Methods
Between 2003 and 2010, 253 consecutive patients who had undergone prostatectomy by a single surgeon were serially followed over 2 years postoperatively. RALP was performed on 77 patients and ORP on 176. The patients were divided into two subgroups according to prostate volume as measured by transrectal ultrasound: less than 40 g and 40 g or larger. Recoveries of potency and continence were checked serially by interview 1, 3, 6, 9, 12, and 24 months postoperatively.
Results
RALP was associated with less blood loss (ORP vs. RALP: 910 mL vs. 640 mL, p<0.001) but a longer operation time (150 minutes vs. 220 minutes, p<0.001) than was ORP. No statistically significant differences were found between the two groups for oncological outcomes, such as positive surgical margin (40% vs. 39%, p=0.911) or biochemical recurrence (12% vs. 7%, p=0.155). The overall functional outcomes showed no statistically significant differences at 2 years of follow-up (continence: 97% vs. 94%, p=0.103; potency: 51% vs. 56%, p=0.614). In the results of an inter-subgroup analysis, potency recovery was more rapid in patients who underwent RALP in a small-volume prostate than in those who underwent ORP in a small-volume prostate (3 months: 24% vs. 0%, p=0.005; 6 months: 36% vs. 10%, p=0.024). However, patients who underwent RALP in a large-volume prostate were less likely to recover continence than were patients who underwent ORP in a large-volume prostate (97% vs. 88%, p=0.025).
Conclusions
Patients can be expected to recover erectile function more quickly after RALP than after ORP, especially in cases of a small prostate volume.
doi:10.4111/kju.2013.54.1.15
PMCID: PMC3556547  PMID: 23362442
Erectile dysfunction; Prostatectomy; Prostatic neoplasms; Robotics; Urinary incontinence
20.  Do Positive Surgical Margins Predict Biochemical Recurrence in All Patients Without Adjuvant Therapy After Radical Prostatectomy? 
Korean Journal of Urology  2013;54(8):510-515.
Purpose
The objective was to study whether positive surgical margins (PSMs) predict biochemical recurrence (BCR) in all patients without adjuvant therapy after radical prostatectomy (RP).
Materials and Methods
We retrospectively reviewed the medical records of patients who underwent RP for prostate cancer at Veterans Health Service Medical Center from 2005 to 2011. BCR was defined by a prostate-specific antigen (PSA) value ≥0.2 ng/mL. The clinicopathological factors of the PSM group were compared with those of the negative surgical margin (NSM) group, and the predictive impact of a PSM for BCR-free survival were evaluated. In addition, we analyzed the prognostic difference for BCR-free survival between solitary and multiple PSMs.
Results
A PSM was noted in 167 patients (45.5%). BCR was reported in 101 men in total (27.5%). The BCR-free survival rate of the PSM group was lower than that of the NSM group (p<0.001). In a multivariate analysis for the total patients, PSM was significantly associated with BCR-free survival (p<0.001). After stratification by pathological T stage, Gleason score (GS), and preoperative PSA value, PSM was significantly predictive for BCR-free survival in men with pT2 and/or GS ≤6 or 7 and/or a PSA value <10 or 10-20 ng/mL (all p<0.05). Multiple PSMs were more predictive of BCR-free survival than was a solitary PSM (p=0.001).
Conclusions
A PSM is a significant predictor of postoperative BCR in patients with pT2 and/or GS ≤7 and/or preoperative PSA <20 ng/mL. Multiple PSMs are considered a stronger prognostic factor for prediction of BCR than is a solitary PSM.
doi:10.4111/kju.2013.54.8.510
PMCID: PMC3742902  PMID: 23956825
Prostatectomy; Prostatic neoplasms; Recurrence
21.  Epidural Analgesia during Open Radical Prostatectomy Does Not Improve Long-Term Cancer-Related Outcome: A Retrospective Study in Patients with Advanced Prostate Cancer 
PLoS ONE  2013;8(8):e72873.
Background
A beneficial effect of regional anesthesia on cancer related outcome in various solid tumors has been proposed. The data on prostate cancer is conflicting and reports on long-term cancer specific survival are lacking.
Methods
In a retrospective, single-center study, outcomes of 148 consecutive patients with locally advanced prostate cancer pT3/4 who underwent retropubic radical prostatectomy (RRP) with general anesthesia combined with intra- and postoperative epidural analgesia (n=67) or with postoperative ketorolac-morphine analgesia (n=81) were reviewed. The median observation time was 14.00 years (range 10.87-17.75 yrs). Biochemical recurrence (BCR)-free, local and distant recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier technique. Multivariate Cox proportional-hazards regression models were used to analyze clinicopathologic variables associated with disease progression and death.
Results
The survival estimates for BCR-free, local and distant recurrence-free, cancer-specific survival and overall survival did not differ between the two groups (P=0.64, P=0.75, P=0.18, P=0.32 and P=0.07). For both groups, higher preoperative PSA (hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.01-1.02, P<0.0001), increased specimen Gleason score (HR 1.24, 95% CI 1.06-1.46, P=0.007) and positive nodal status (HR 1.66, 95% CI 1.03-2.67, P=0.04) were associated with higher risk of BCR. Increased specimen Gleason score predicted death from prostate cancer (HR 2.46, 95% CI 1.65-3.68, P<0.0001).
Conclusions
General anaesthesia combined with epidural analgesia did not reduce the risk of cancer progression or improve survival after RRP for prostate cancer in this group of patients at high risk for disease progression with a median observation time of 14.00 yrs.
doi:10.1371/journal.pone.0072873
PMCID: PMC3747085  PMID: 23977366
22.  Undetectable ultrasensitive PSA after radical prostatectomy for prostate cancer predicts relapse-free survival 
British Journal of Cancer  2000;83(11):1432-1436.
Radical retropubic prostatectomy is considered by many centres to be the treatment of choice for men aged less than 70 years with localized prostate cancer. A rise in serum prostate-specific antigen after radical prostatectomy occurs in 10–40% of cases. This study evaluates the usefulness of novel ultrasensitive PSA assays in the early detection of biochemical relapse. 200 patients of mean age 61.2 years underwent radical retropubic prostatectomy. Levels ≤ 0.01 ng ml–1 were considered undetectable. Mean pre-operative prostate-specific antigen was 13.3 ng ml–1. Biochemical relapse was defined as 3 consecutive rises. The 2-year biochemical disease-free survival for the 134 patients with evaluable prostate-specific antigen nadir data was 61.1% (95% CI: 51.6–70.6%). Only 2 patients with an undetectable prostate-specific antigen after radical retropubic prostatectomy biochemically relapsed (3%), compared to 47 relapses out of 61 patients (75%) who did not reach this level. Cox multivariate analysis confirms prostate-specific antigen nadir ≤ 0.01 ng ml–1 to be a superb independent variable predicting a favourable biochemical disease-free survival (P < 0.0001). Early diagnosis of biochemical relapse is feasible with sensitive prostate-specific antigen assays. These assays more accurately measure the prostate-specific antigen nadir, which is an excellent predictor of biochemical disease-free survival. Thus, sensitive prostate-specific antigen assays offer accurate prognostic information and expedite decision-making regarding the use of salvage prostate-bed radiotherapy or hormone therapy. © 2000 Cancer Research Campaign http://www.bjcancer.com
doi:10.1054/bjoc.2000.1474
PMCID: PMC2363433  PMID: 11076649
prostate cancer; PSA nadir; radical retropubic prostatectomy
23.  Inguinal hernia developed after radical retropubic surgery for prostate cancer 
Purpose
In this retrospective study, we aimed to compare the clinical characteristics of inguinal hernia developed after radical retropubic surgery for prostate cancer to the hernia without previous radical prostatectomy.
Methods
Twenty-three patients (group A) who had radical retropubic surgery for prostate cancer underwent laparoscopic or open tension-free inguinal hernia repair from March 2007 to February 2011. Nine hundred and forty patients (group B) without previous radical retropubic surgery received laparoscopic or tension-free open hernia operation.
Results
Group A was older than group B (mean ± standard deviation, 69.6 ± 7.2 vs. 54.1 ± 16.1; P < 0.001). Right side (73.9%) and indirect type (91.3%) in group A were more prevalent than in group B (51.5% and 69.4%, respectively) with statistic significance (P = 0.020 and P = 0.023). The rate of laparoscopic surgery in group B (n = 862, 91.7%) was higher than in group A (n = 14, 64.3%, P < 0.001). In comparing perioperative variables between the two groups, operative time (49.4 ± 23.5 minutes) and hospital stay (1.9 ± 0.7 days) in group A were longer than in group B (38.9 ± 16.9, 1.1 ± 0.2; P = 0.046 and P < 0.001, respectively) and pain score at 7 days in group A was higher than in group B (3.1 ± 0.7 vs. 2.3 ± 1.0, P < 0.001). Postoperative recurrence rate was not significantly different between the two groups.
Conclusion
Inguinal hernia following radical retropubic surgery for prostate cancer was predominantly right side and indirect type with statistic significance compared to hernias without previous radical prostatectomy.
doi:10.4174/jkss.2013.85.4.175
PMCID: PMC3791360  PMID: 24106684
Prostate neoplasms; Prostatectomy; Inguinal hernia; Recurrence
24.  Preoperative and Postoperative Nomograms Incorporating Surgeon Experience for Clinically Localized Prostate Cancer 
Cancer  2009;115(5):1005-1010.
BACKGROUND
Accurate preoperative and postoperative risk assessment has been critical for counseling patients regarding radical prostatectomy for clinically localized prostate cancer. In addition to other treatment modalities, neoadjuvant or adjuvant therapies have been considered. The growing literature suggested that the experience of the surgeon may affect the risk of prostate cancer recurrence. The purpose of this study was to develop and internally validate nomograms to predict the probability of recurrence, both preoperatively and postoperatively, with adjustment for standard parameters plus surgeon experience.
METHODS
The study cohort included 7724 eligible prostate cancer patients treated with radical prostatectomy by 1 of 72 surgeons. For each patient, surgeon experience was coded as the total number of cases conducted by the surgeon before the patient’s operation. Multivariable Cox proportional hazards regression models were developed to predict recurrence. Discrimination and calibration of the models was assessed following bootstrapping methods, and the models were presented as nomograms.
RESULTS
In this combined series, the 10-year probability of recurrence was 23.9%. The nomograms were quite discriminating (preoperative concordance index, 0.767; postoperative concordance index, 0.812). Calibration appeared to be very good for each. Surgeon experience seemed to have a quite modest effect, especially postoperatively.
CONCLUSIONS
Nomograms have been developed that consider the surgeon’s experience as a predictor. The tools appeared to predict reasonably well but were somewhat little improved with the addition of surgeon experience as a predictor variable.
doi:10.1002/cncr.24083
PMCID: PMC3391599  PMID: 19156928
prostate cancer; surgeon experience; recurrence; predictive value; nomogram
25.  Oncologic outcomes following radical prostatectomy in the active surveillance era 
Objective:
In this study, we examine the oncologic outcomes of men with low, intermediate and high preoperative risk for prostate cancer treated with radical prostatectomy prior to and during the active surveillance era.
Methods:
We analyzed records from patients who underwent radical prostatectomy at our Canadian tertiary care facility from 2000 to 2012. Patients were stratified by D’Amico preoperative risk category and by year of treatment. Biochemical recurrence-free survival was estimated using the Kaplan-Meier method.
Results:
We included 2643 consecutive patients in our analysis. The proportion of men with low-risk disease undergoing radical prostatectomy decreased from 2007 onwards coincident with the implementation of an active surveillance strategy in our institution. Men with low-risk and high-risk disease showed significantly worse biochemical outcomes from 2007 to 2012 compared to 2000 to 2006 (p < 0.05), while men with intermediate-risk prostate cancer showed no significant differences (p = 0.27). Within the low-risk cohort, the later treatment group displayed significantly lower age, pre-treatment prostate specific antigen and tumour volume and significantly higher testosterone and body mass index.
Conclusions:
The time period corresponding with the implementation of active surveillance at our institution corresponded with significant deterioration of biochemical outcomes in the low- and high-risk groups. This suggests that the men with most favourable disease deferred treatment, whereas men with worse preoperative disease characteristics were increasingly treated with radical prostatectomy in the past 6 years perhaps to their benefit.
doi:10.5489/cuaj.1404
PMCID: PMC3713145  PMID: 23914263

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