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.
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.
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).
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.
prostate; prostatic neoplasms; lymph nodes; lymph node excision; neoplasm recurrence; local
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.
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).
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.
Neo-adjuvant hormonal therapy; radical retropubic prostatectomy; single surgeon study
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.
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).
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.
Prostatic neoplasms; Proto-oncogene proteins; B-cell leukemia/lymphoma 2; Recurrence; Prostatectomy
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
prostate cancer; PSA nadir; radical retropubic prostatectomy
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.
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).
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.
Prostatic neoplasms; Clodronic acid; Osteoporosis; Androgen antagonists; Zoledronic acid; Hormone antagonists
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.
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).
Patients can be expected to recover erectile function more quickly after RALP than after ORP, especially in cases of a small prostate volume.
Erectile dysfunction; Prostatectomy; Prostatic neoplasms; Robotics; Urinary incontinence
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.
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.
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.
Prostatectomy; Prostatic neoplasms
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.
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.
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.
prostate; prostatic neoplasms; prostatectomy; mortality; biopsy
Often, a diagnosis of pT3 is made on the basis of radical retropubic prostatectomy specimens, despite a Gleason score of 6 on the preoperative prostate biopsy. Thus, we investigated the preoperative variables in patients displaying these characteristics.
Materials and Methods
Study subjects comprised patients at our institute from 1996 to July 2010 who had exhibited a Gleason score of 6 on their prostate biopsies and had undergone a radical retropubic prostatectomy. Through univariate and multivariate analysis, we investigated pT3 predictive factors including age, preoperative prostate-specific antigen (PSA) levels, transrectal ultrasonography (TRUS)-weighted prostate volume, digital rectal examination findings, bilaterality via prostate biopsy, prostatic cancer in prostate base cores via prostate biopsy, maximum length and percent of prostatic cancer, and number of cores detected in prostatic cancer via prostate biopsy.
In the univariate logistic regression mode, a PSA value of 7.4 ng/ml or higher, TRUS-weighted PSA density of 0.2 ng/ml/cc or higher, prostate cancer detected in the basal core, and prostate cancer detected in 2 or more cores out of 12 were predictive factors for extraprostatic extension. Independent predictive factors for stage pT3 were a PSA of 7.4 ng/ml or higher and prostate cancer detected in 2 or more cores out of 12.
In the case of patients with the foregoing risk factors, it is advisable not to perform nerve-sparing surgery but to prepare for the possibility of a pT3 stage.
Prostatectomy; Prostate-specific antigen; Prostatic neoplasms
We assessed the role of urinary prostate-specific antigen (uPSA) in the follow-up of prostate cancer after retropubic radical prostatectomy (RRP) for the early detection of local recurrences.
We recruited 50 patients previously treated for prostate cancer with RRP and who had not experienced a prostate-specific antigen (PSA) recurrence within their first postoperative year into a cross-sectional laboratory assessment and prospective 6-year longitudinal follow-up study. We defined biochemical failure as a serum PSA (sPSA) of 0.3 μg/L or greater. Patients provided blood samples and a 50-mL sample of first-voided urine. We performed Wilcoxon rank-sum and Fisher exact tests for statistical analysis.
The median sPSA was 0.13 μg/L. The median uPSA was 0.8 μg/L, and was not significantly different when comparing Gleason scores or pathological stages. Of the 50 patients, 27 initially had a nondetectable sPSA but a detectable uPSA, and 11 patients experienced sPSA failure after 6 years. Six patients had detectable sPSA and uPSA initially. Fifteen patients were negative for both sPSA and uPSA, and 13 remained sPSA-free after 6 years. The odds ratio (OR) of having sPSA failure given a positive uPSA test was 4.5 if sPSA was undetectable, but was reduced to 2.6 if sPSA was detectable. The pooled Mantel–Haenszel OR of 4.2 suggested that a detectable uPSA quadrupled the risk of recurrence, independent of whether sPSA was elevated or not. The sensitivity of uPSA for detecting future sPSA recurrences was 81% and specificity was 45%.
Urinary PSA could contribute to an early detection of local recurrences of prostate cancer after a radical prostatectomy.
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.
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).
These results suggest that there were no clinical benefits to the administration of NHT before RRP from the viewpoint of biochemical recurrence.
Neoadjuvant therapy; Prostatectomy; Prostatic neoplasms
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.
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.
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.
CAPRA; staging; prostate cancer; prostatectomy; biochemical recurrence
Postoperative PSA doubling time (PSADT) may be used as a surrogate for prostate cancer (PCa)-specific mortality in patients with biochemical recurrence after radical prostatectomy. Less is known about the utility of preoperative PSA doubling time (PSADT) for the initial prediction of prostatectomy outcomes.
Materials and Methods
Preoperative PSADT was calculated in 1208 men from a large PCa screening study who were treated with radical prostatectomy. We then examined the relationship between PSADT with tumor features and biochemical progression-free survival (PFS).
Overall, PSADT was associated with non-organ-confined disease (OR 0.996, 95% CI 0.992–0.999, p=0.013), but not with biochemical progression (HR 1.000, 95% CI 0.998–1.001, p=0.66). Using previously published thresholds for PSADT of 18 months and 36 months, respectively, there was no significant relationship between PSADT with specific adverse pathology features or biochemical progression. Using the concordance index, PSADT did not enhance the prediction of biochemical progression beyond that achieved with a model with PSA, clinical stage and biopsy Gleason score.
In our series of men with newly diagnosed clinically localized PCa, shorter preoperative PSADT was associated with non-organ confined disease, but not with biochemical progression following radical prostatectomy. All PSA kinetics calculations may not be equivalent, and caution should be exercised in using PSADT in the pretreatment setting.
prostate-specific antigen; PSA kinetics; doubling time; biochemical progression; radical prostatectomy
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.
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.
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).
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.
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.
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.
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.
metastasis-free survival; natural history; prostate cancer; PSA recurrence
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.
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.
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.
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.
prostate cancer; surgeon experience; recurrence; predictive value; nomogram
The authors evaluated the long-term outcomes of men with prostate cancer and very high (≥50 ng/mL) preoperative serum prostate-specific antigen (PSA) values that were treated with radical prostatectomy.
This study included 236 men with preoperative serum PSA values ≥50 ng/mL who underwent radical retropubic prostatectomy between 1987 and 2004. For comparison, the study cohort was divided into 2 groups: patients with PSA levels between 50 and 99 ng/mL and patients with PSA levels ≥100 ng/mL. Biochemical recurrence was defined as a single postoperative serum PSA value of 0.4 ng/mL or greater. Systemic disease progression was defined as the development of a local recurrence or systemic metastases, and any death resulting from prostate cancer or its treatment was defined as a cancer-specific mortality.
Biochemical recurrence-free survival rates in the groups of patients with a PSA level 50 to 99 ng/mL and ≥100 ng/mL were 43% and 36% at 10 years, respectively. Systemic progression-free survival rates in the PSA 50 to 99 ng/mL and PSA ≥100 ng/mL groups were 83% and 74% at 10 years, respectively. Estimated overall cancer-specific survival was 87% at 10 years.
Patients with prostate cancer and a serum PSA level ≥50 ng/mL have very high-risk prostate cancer that carries a high likelihood of being pathologically advanced. Although the probability of realizing long-term survival in these high-risk patients is less than in patients with more favorable disease, 10-year survival outcomes remain excellent and argue for aggressive management of these cases.
androgen deprivation therapy; external beam radiotherapy; prostate cancer; prostate-specific antigen; radical prostatectomy
Short prostate specific antigen doubling time following recurrence after radical prostatectomy portends a poor prognosis in men with prostate cancer. We determined which demographic and clinicopathological variables were predictive of a short prostate specific antigen doubling time in a cohort of men with clinically localized prostate cancer treated with radical prostatectomy.
Materials and Methods
Data on 856 men from the Shared Equal Access Regional Cancer Hospital database who underwent radical prostatectomy for node negative prostate cancer between 1988 and 2003 were included in the analysis. We used logistic regression analysis to determine the independent factors associated with a short prostate specific antigen doubling time of less than 9 months vs a longer doubling time of 9 months or greater, or no recurrence. The variables analyzed were patient age, race, logarithmically transformed preoperative prostate specific antigen, body mass index, year of surgery, pathological Gleason sum, extraprostatic extension, surgical margin status and seminal vesicle invasion.
On multivariate analysis higher preoperative prostate specific antigen (OR 2.20, 95% CI 1.52–3.19, p <0.001), pathological Gleason sum 8–10 (OR 4.70, 95% CI 2.11–10.43, p <0.001) and 7 (OR 2.11, 95% CI 1.09–4.08, p = 0.026), tumors with extraprostatic extension and/or positive surgical margins (OR 2.08, 95% CI 1.48–3.91, p = 0.023), and seminal vesicle invasion (OR 3.26, 95% CI 1.48–7.21, p = 0.003) were independent predictors of a short prostate specific antigen doubling time. Based on these risk factors we developed a table to estimate the risk of recurrence with a prostate specific antigen doubling time of less than 9 months.
The factors that are invariably used to predict overall biochemical recurrence following radical prostatectomy, including high prostate specific antigen, high grade and adverse pathological findings, also predict aggressive recurrence.
prostate; prostatic neoplasms; prostate-specific antigen; neoplasm recurrence; local; tumor markers; biological
To evaluate the impact of primary Gleason grade in Gleason score (GS) 7 prostate cancer on biochemical recurrence (BCR) after radical prostatectomy in Korean men.
Materials and Methods
We retrospectively reviewed records of 1,026 patients who underwent radical prostatectomy at Seoul National University Bundang Hospital between November 2003 and June 2009. We excluded patients who had received neoadjuvant therapy and had positive resection margins. Finally, 295 and 113 patients with GS 3+4 and GS 4+3, respectively, were included in this study. All patients were followed for at least 2 years.
Of the 408 GS 7 patients, 295 (72.3%) were 3+4 and 113 (27.7%) were 4+3. Mean serum prostate specific antigen level in primary Gleason 3 was 8.99 ng/ml and primary Gleason 4 was 11.11 ng/ml. Patients with GS 4+3 were more likely to have extracapsular extension (30.1% vs. 17.6%, p<0.010) and lymphatic invasion (16.8% vs. 7.1%, p<0.005). After 2 years follow up BCR was detected in a total of 40 patients. In GS 7 with primary Gleason 3, BCR occurred in 15 (5.08%) patients while 20 (17.70%) showed BCR in GS 7 with primary Gleason 4.
In this study of a large, single center cohort of Korean men with GS 7 prostate cancer a noticeable difference in BCR was seen. Primary Gleason grade 4 have a higher risk of BCR compared to primary Gleason grade 3. This information may be useful when counseling patients on their prognosis and further management options.
Biopsy; Prostate; Prostatectomy
We assessed the factors predictive of continence recovery after radical retropubic prostatectomy performed by use a single operative technique by a single surgeon.
Materials and Methods
Preoperative factors, including age, body mass index (BMI), prostate volume, prostate-specific antigen level, and anatomical information from preoperative magnetic resonance imaging (MRI), such as membranous urethral length, thickness of the levator ani muscle, and urogenital diaphragm, were evaluated in 94 consecutive patients who underwent radical retropubic prostatectomy between April 2005 and October 2010. Patients were also categorized into four different groups according to the overlying pattern of the prostatic apex and the membranous urethra. Continence status was evaluated by direct patient questioning at 12 months after the operation.
The overall continence rate at 12 months after the operation was 79.8%. In the age- and BMI-adjusted logistic regression analysis, the membranous urethral length and the overlying pattern of the prostatic apex were significant predictive factors of the continence rate at 12 months after the operation (p=0.006 and p=0.007, respectively). Other predictive factors were not contributory. Patients with no overlapping observed between the prostatic apex and membranous urethra had longer membranous urethral lengths (14.24±2.73 mm) and higher rates of recovery of continence compared with other groups.
Membranous urethral length and shape of the prostatic apex as assessed by preoperative MRI are significantly associated with recovery of urinary continence after radical retropubic prostatectomy.
Prostate neoplasms; Prostatectomy; Urinary incontinence
Clinical decision for primary treatment for prostate cancer is dictated by variables with insufficient specificity. Early detection of prostate cancer likely to develop rapid recurrence could support neo-adjuvant therapeutics and adjuvant options prior to frank biochemical recurrence. This study compared markers in serum and urine of patients with rapidly recurrent prostate cancer to recurrence-free patients after radical prostatectomy. Based on previous identification of urinary sarcosine as a metastatic marker, we tested whether methionine metabolites in urine and serum could serve as pre-surgical markers for aggressive disease.
Urine and serum samples (n = 54 and 58, respectively), collected at the time of prostatectomy were divided into subjects who developed biochemical recurrence within 2 years and those who remained recurrence-free after 5 years. Multiple methionine metabolites were measured in urine and serum by GC-MS. The role of serum metabolites and clinical variables (biopsy Gleason grade, clinical stage, serum prostate specific antigen [PSA]) on biochemical recurrence prediction were evaluated. Urinary sarcosine and cysteine levels were significantly higher (p = 0.03 and p = 0.007 respectively) in the recurrent group. However, in serum, concentrations of homocysteine (p = 0.003), cystathionine (p = 0.007) and cysteine (p<0.001) were more abundant in the recurrent population. The inclusion of serum cysteine to a model with PSA and biopsy Gleason grade improved prediction over the clinical variables alone (p<0.001).
Higher serum homocysteine, cystathionine, and cysteine concentrations independently predicted risk of early biochemical recurrence and aggressiveness of disease in a nested case control study. The methionine metabolites further supplemented known clinical variables to provide superior sensitivity and specificity in multivariable prediction models for rapid biochemical recurrence following prostatectomy.
Neoadjuvant hormone therapy (NHT) prior to radical prostatectomy results in pathologic downstaging, but generally no reduction in biochemical recurrence (BCR) on early followup. In an institutional randomized prospective trial of radical prostatectomy with or without a 3-month course of NHT, we observed no reduction in BCR at 3 years. We report our long-term followup of this cohort.
Patients and Methods
From December 1992 to June 1996, 148 patients with clinically localized prostate cancer were randomized to radical prostatectomy only or 3 months of goserelin acetate and flutamide before radical prostatectomy. BCR was defined as a detectable serum prostate specific antigen (greater than 0.1 ng/mL) at least 6 weeks after surgery with a confirmatory rise.
The median followup for recurrence-free patients was 8 years. There was no significant difference in recurrence-free probabilities between groups (p = 0.7). The BCR-free probability at 7 years was 78% for patients undergoing RP only and 80% for patients undergoing NHT and RP (difference of 2%; 95% CI, 12%–16%). A Cox regression showed no significant relationship between NHT and BCR (HR 1.16; 95% CI, 0.56 – 2.39, p = 0.7). Overall, 2 patients had local recurrence and 6 patients developed metastases, and were evenly split among the RP only and NHT groups.
Although our study was not originally powered to detect differences in BCR, we did not demonstrate an overall benefit in BCR-free probability, local recurrence or metastasis with 3 months of NHT at 8 years of followup. Pending evidence of improvement in patient outcomes, NHT before radical prostatectomy appears unjustified outside of clinical trials.
prostate; prostatic neoplasms; prostatectomy; neoadjuvant therapy; hormones
The survival benefits of adjuvant androgen-deprivation therapy (ADT) in prostate cancer and lymph node metastasis remain unclear. We assessed the role of ADT in disease progression after radical prostatectomy (RP).
Materials and Methods
Of 937 patients who underwent RP, we identified 40 (4.2%) who had lymph node metastasis. A total of 18 received adjuvant ADT (ADT group) and 22 were observed (observation group). Clinical progression-free survival (PFS), cancer- specific survival (CSS), and overall survival (OS) were compared in the 2 groups. Prognostic factors for clinical progression and biochemical recurrence (BCR) were analyzed.
The 5-year PFS, CSS, and OS of the entire cohort were 75.0%, 85.0%, and 72.5%, respectively. In the ADT group, 6 patients (33.3%) showed clinical progression at a median 42.7 months. The 5-year PFS, CSS, and OS rates of this group were 72.2%, 83.3%, and 72.2%, respectively. In the observation group, 14 patients (63.6%) received salvage therapy owing to BCR. Nine patients (40.9%) with BCR in the observation group showed clinical progression at a median 43.4 months after RP. The 5-year PFS, CSS, and OS rates of this group were 77.2%, 86.4%, and 72.8%, respectively. In the observation group, the BCR rate was lower in patients with pT3a or less disease than in those with pT3b disease.
Adjuvant ADT in node-positive prostate cancer did not reduce or delay disease progression or improve survival. Because a substantial number of untreated patients with pT3a or less disease did not experience recurrence, administration of ADT should be initiated carefully. However, in patients with pT3b disease, adjuvant ADT and radiotherapy could be considered.
Androgens; Lymph nodes; Prostatectomy