8-month neoadjuvant hormonal therapy before radical prostatectomy for high-risk prostate cancer

PURPOSE: To evaluate the clinicopathological outcomes of 8 months of neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy for high-risk prostate cancer. PATIENTS AND METHODS: A multi-institutional prospective trial was performed between July 2000 and May 2003 involving high-risk prostate cancer patients without metastasis, including 21 who received 8 months of NHT before radical prostatectomy. High-risk group was defined as clinical stage > or =T2c and/or prostate-specific antigen (PSA) >20 ng/ml and/or Gleason score > or =8. PSA values were considered elevated (biochemical failure) if values of 0.1 ng/ml or greater were obtained. RESULTS: Median of initial PSA levels before prostate biopsy was 27.6 ng/ml (8.5-80.7 ng/ml), and median of pre-operative PSA levels after NHT was 0.28 ng/ml (0.02-4.2 ng/ml). There were 5 patients (23.8%) with lower limit of PSA detection (less than 0.02 ng/ml) in 8 months after NHT. The clinical T stage was T1c in 9 patients (42.9%), T2a-b in 8 patients (38.1%), T2c in 3 patients (14.3%), and T3a in 1 patient (4.8%). The median follow-up was 25 months (range 4 to 37). There were 2 patients (9.5%) in pT0, 5 patients (23.8%) with positive surgical margin, 5 patients (23.8%) with extracapsular extension (ECE) and 3 patients (14.3%) with seminal vesicle involvement (SVI). Biochemical failure was occurred in 9 of 21 (42.9%) including of one pT0. Range of time to postoperative biochemical failure was 2 to 25 months (median 6 months) and most of biochemical failure was found within 12 months after surgery. Biochemical failure rate was significantly higher in patient with positive SVI (p = 0.0308) and higher in patients with pre-operative PSA levels of more than 0.1 ng/ml (p = 0.0836), positive ECE (p = 0.0545) and positive surgical margin (p = 0.0545). CONCLUSION: Biochemical failure was frequent after this combined treatment, even in a pT0 case. Long-term follow-up of patients is needed to assess the impact of this therapy on mortality.     

Pathological effects of neoadjuvant hormonal therapy help predict progression of prostate cancer after radical prostatectomy

BACKGROUND: It is not clear whether pathological changes following neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy have any value as predictors of progression in prostate cancer. METHODS: We conducted a study of 100 patients with prostate cancer who underwent radical prostatectomy following NHT. We used the Japanese general rule as the criterion to assess the biochemical recurrence rate and pathological changes after NHT. RESULTS: In terms of preoperative risk factors, the probability of recurrence was significantly higher for patients with more than 20 ng/mL of pretreatment serum prostate-specific antigen (PSA) and/or a Gleason score of 7 or higher for biopsy specimens. We defined these pretreatment findings as high-risk factors. Among 65 patients with high-risk factors, patients with a post-NHT pathological effect of grade 3 according to the Japanese general rule showed no recurrence, whereas patients with a grade 0 had a poor prognosis. Patients with a PSA nadir 0.5 ng/mL or less tended to have a better prognosis. CONCLUSION: Despite preoperative high-risk factors, patients showing good pathological effects after NHT tend to have a favorable prognosis after radical prostatectomy. Therefore; assessment of the pathological effects of NHT using the Japanese general rule as the criterion proved to be useful for the prediction of biochemical recurrence.     

Pretreatment serum testosterone level as a predictive factor of pathological stage in localized prostate cancer patients treated with radical prostatectomy

OBJECTIVE: Pretreatment serum level of testosterone (T) is a potential prognostic factor for prostate cancer. The present study was conducted to evaluate the clinical significance of pretreatment serum T level in patients with clinically localized prostate cancer. MATERIALS AND METHODS: The subjects were 82 clinically localized prostate cancer patients treated with radical prostatectomy, whose pretreatment T levels were recorded. We investigated clinical and pathological factors such as pretreatment serum T level, age, pretreatment PSA or pathological Gleason score concerning the association with pathological stage and biochemical recurrence. RESULTS: The mean pretreatment T level was significantly lower in patients with non-organ-confined prostate cancer (pT3-T4, N1; 3.44+/-1.19 ng/ml) than in patients with organ-confined cancer (pT2; 4.33+/-1.42 ng/ml) (p=0.0078). Multivariate analysis demonstrated that pathological Gleason score, pretreatment serum T level and pretreatment PSA were significant predictors of extraprostatic disease. When the patients were divided into high and low T level groups according to the median value, pretreatment T levels were not significantly associated with PSA recurrence rates (p=0.7973). CONCLUSIONS: A lower pretreatment T level appears to be predictive of extraprostatic disease in patients with localized prostate cancer.     

Long-term results of neoadjuvant hormonal therapy prior to radical prostatectomy in patients with clinically localized prostate cancer: biochemical and pathological effects

The objective of this study was to evaluate the long-term biochemical and pathological effects induced by neoadjuvant hormonal therapy (NHT) in patients with clinically localized disease. Between March 1993 and May 1997, 24 patients with clinically localized prostate cancer received NHT for 3 to 11 months (median: 5 months) using luteinizing hormone-releasing hormone analogue prior to radical prostatectomy and pelvic lymphadenectomy. The clinical stage was T1 in 1 patient, T2 in 17 and T3 in 6, the pretreatment serum prostate-specific antigen (PSA) value was < or = 10 ng/ml in 5 patients, 10 to 20 ng/ml in 4 and > 20 ng/ml in 15 (mean: 34.7 micrograms/l), and the Gleason score was < or = 4 in 9 patients, 5 to 7 in 11 and > 8 in 3. The mean prostate specific antigen (PSA) value 3 months after NHT had reduced below 2 ng/ml in 18 of the 24 patients (67%), and finally decreased by an average of 95% (i.e., 1.9 ng/ml) prior to surgery. The pathological stage was pT0 in 2 patients, pT2 in 10 and pT3 in 12. The incidence of organ-confined disease (OCD) was significantly higher in patients with clinical stage T1 or T2a than with T2b or T3, with pretreatment PSA values < or = 10 ng/ml than with PSA values > 10 ng/ml, and with PSA values < or = 2 than with PSA values > 2 at 3 months after NHT; in contrast, the Gleason score had no significant impact on the rate of OCD. After a median follow-up of 49 months (range 34 to 85 months), 6 patients (25%) had a recurrence evidenced by rising PSA, and the 3-year recurrence-free survival rate was 79%. These results suggest that NHT appears not to be of significant additional benefit to patients who have a higher clinical T stage, higher pretreatment PSA values and/or in patients whose PSA values do not normalize early in the treatment process.     

Neoadjuvant Hormonal Therapy in Stage C Adenocarcinoma of the Prostate and Incidence of Biochemical Recurrence

This report describes the effects of neoadjuvant hormonal therapy (NHT) in 31 patients with clinical stage T3 adenocarcinoma of the prostate (CaP) who underwent radical prostatectomy (RP) and the incidence of biochemical recurrence, as evidenced by serum prostate specific antigen (PSA) >0.2 ng/mL after RP. Twenty-six patients received combined androgen blockade consisting of a gonadotropin-releasing hormone (GnRH) agonist (leuprolide) and an antiandrogen (flutamide), and the remaining five received flutamide alone. The mean Gleason score was 7.1 +/- 0.3. Five patients were found to have pathologic stage T(2c), 14 stage T(3a), 7 stage T(3b), and 4 stage T(3c) disease. One specimen had no evidence of adenocarcinoma in the whole-mount specimen. The mean PSA concentration decreased from 25.4 ng/mL (Hybritech method) to 1.18 ng/mL. The prostate volume decreased a mean of 47%, and pathologic effects of hormonal deprivation were observed in all patients. Approximately 39% of the patients (12/31) demonstrated evidence of biochemical recurrence, with the mean time to biochemical failure being 28.9 months after NHT. Follow-up ranged from 5 to 83 months with a mean of 52.7 months. Of the variables studied (pretreatment PSA, Gleason score, final pathologic stage, and nadir PSA before surgery), pretreatment PSA (p = 0.001, Fisher's exact test) and pathologic stage T(3c) (p = 0.012, Fisher's exact test) were found to have a statistically significant correlation with biochemical recurrence. Although there was a 39% biochemical recurrence rate in our study, we conclude that NHT offers an alternative mode of management for patients with stage T(3) CaP.     

Maximum tumor diameter is not an independent prognostic factor in high-risk localized prostate cancer

OBJECTIVES: Previous studies suggest that maximum tumor diameter (MTD) is a predictor of recurrence in prostate cancer (PC). This study investigates the prognostic value of MTD for biochemical recurrence (BCR) in patients with PC, after radical prostatectomy (RP), with emphasis on high-risk localized prostate cancer. METHODS: RP specimens of 542 patients were evaluated with a median follow-up of 39.5 months (range 0.6-150 months). MTD was defined as the largest diameter of the largest tumor; high-risk as >or=T2c or PSA level>20 ng/ml or Gleason score>or=8 and BCR as two consecutive PSA levels>0.10 ng/ml. Proportional hazards multivariable regression models were composed to determine prognostic factors for BCR. RESULTS: Overall, 114 patients developed BCR after RP. The overall 5-year risk of BCR was 25% (95% CI=20.4-29.6), and median MTD was 24 mm (range 1-65). MTD in the total and high-risk group was associated with total tumor volume, volume of the largest tumor, pre-operative PSA levels, and Gleason score. In a univariable analyses, MTD was weakly associated with risk of BCR (HR=1.02 per mm increase, 95% CI=1.002-1.035, P=0.024) in the total group; in the high-risk group this association was lost (HR=1.01, 95%CI=0.99-1.03, P=0.18). Multivariable analyses indicated that positive surgical margins, higher Gleason score, advanced pathological stage, and multiple tumors were the main prognostic factors for BCR irrespective of the risk profile. MTD did not provide additional information. CONCLUSIONS: MTD is not an independent prognostic factor for BCR in patients treated with RP, irrespective of the risk profile.     

Predicting recurrence after radical prostatectomy for patients with high risk prostate cancer

PURPOSE: Previous studies have shown that patients with clinical stage T2c-T3 prostate cancer, serum prostate specific antigen (PSA) at diagnosis greater than 20 ng./ml. or a biopsy Gleason score of 8 to 10 are at high risk for disease recurrence after radical prostatectomy. We determined the most important pretreatment predictors of disease recurrence in this high risk population. MATERIALS AND METHODS: We identified 547 patients with high risk prostate cancer who underwent radical prostatectomy at University of California, San Francisco or as part of the Cancer of the Prostate Strategic Urological Research Endeavor data base, a longitudinal disease registry of patients with prostate cancer. High risk disease was defined as 1992 American Joint Committee on Cancer clinical stage T2c-T3 disease in 411 patients, serum PSA at diagnosis greater than 20 ng./ml. in 124 and/or biopsy Gleason score 8 to 10 in 114. Disease recurrence was defined as PSA 0.2 ng./ml. or greater on 2 consecutive occasions after radical prostatectomy or second cancer treatment more than 6 months after surgery. The Cox proportional hazards analysis was performed to determine significant independent predictors of disease recurrence. The likelihood of disease recurrence for clinically relevant patient groups was determined using the Kaplan-Meier method and compared using the log rank test. RESULTS: Median followup after surgery was 3.1 years. Disease recurred in 177 patients (32%). Multivariate analysis demonstrated that serum PSA at diagnosis, biopsy Gleason score, ethnicity and the percent of positive prostate biopsies were significant independent predictors of disease recurrence, while patient age and clinical tumor stage were not. Patients with a Gleason score 8 to 10 tumor and a serum PSA of 10 ng./ml. or less had a significantly higher likelihood of remaining disease-free 5 years after surgery than those with PSA greater than 10 ng./ml. (47% versus 19%, p <0.05). Patients with a serum PSA at diagnosis of greater than 20 ng./ml. and a Gleason score of less than 8 had a significantly higher likelihood of remaining disease-free 5 years after surgery than similar patients with a Gleason score of 8 or greater (45% versus 0%, p <0.05). CONCLUSIONS: PSA, Gleason score, ethnicity and the percent of positive prostate biopsies appear to be the most important pretreatment predictors of disease recurrence in men with high risk prostate cancer. Patients with high grade disease may continue to be appropriate candidates for local therapy if PSA is less than 10 ng./ml. at diagnosis or there are fewer than 66% positive prostate biopsies.     

Percentage of positive biopsy cores, preoperative prostate-specific antigen (PSA) level, pT and Gleason score as predictors of PSA recurrence after radical prostatectomy: a multi-institutional outcome study in Japan

OBJECTIVE: To evaluate the clinical outcome of radical prostatectomy (RP) in Japan, by retrospectively analysing the clinicopathological data in patients with clinical T1-T2 prostate cancer treated by RP, as there can be prostate-specific antigen (PSA) recurrence after RP in substantially many patients, and its character can differ according to ethnic group and/or country. PATIENTS AND METHODS: We reviewed 1192 patients who had a RP from 1993 to 2002 with no neoadjuvant/adjuvant therapy and whose PSA level after RP decreased at least once to undetectable levels (<0.2 ng/mL). PSA recurrence was defined as > or = 0.20 ng/mL. The patient data were collected from the Urological Oncology Study Group, a subgroup of Japan Clinical Oncology Group. RESULTS: The patients' median (range) age was 67 (47-83) years and their PSA level before RP was 8.7 (1.0-153) ng/mL. During the median follow-up of 45.6 months, 302 of the 1192 patients (25.3%) developed PSA recurrence. The median time to recurrence was 369 (61-2128) days after RP. A log-rank test showed that five significant clinicopathological factors were associated with PSA recurrence after RP: the percentage of prostate needle-biopsy cores with cancer, the biopsy Gleason score, PSA level before RP, pathological stage, and the Gleason score of the RP specimen (P < 0.001 for all). In multivariate analyses, the percentage of positive biopsy cores, PSA level before RP, pT and the Gleason score of the RP specimen were all independent significant predictors of PSA recurrence after RP in Japanese men. CONCLUSIONS: The frequency of PSA recurrence after RP was 25.3% in Japan and the percentage of positive biopsy cores, PSA level before RP, pT and the Gleason score of the RP specimen were independent significant factors for PSA recurrence.     

The clinical potential of pretreatment serum testosterone level to improve the efficiency of prostate cancer screening

OBJECTIVES: The aim of the present study was to evaluate the clinical value of the pretreatment serum testosterone (T) level as a potential predictor of prostate cancer risk in screening for prostate cancer. MATERIALS AND METHODS: The subjects were 420 patients suspected of having prostate cancer who underwent prostate biopsy, and whose pretreatment T levels were recorded. We checked for association between the presence of prostate cancer and the following clinical factors: pretreatment serum T level, age, pretreatment prostate-specific antigen (PSA) level, digital rectal examination findings, ratio of free to total PSA, prostate volume, and PSA density (PSAD). RESULTS: Overall, there was no significant difference in mean pretreatment T level between patients diagnosed with cancer (3.9+/-2.4 ng/ml) and patients diagnosed with benign prostate disease (BPD; 3.7+/-1.7 ng/ml); diagnosis was based on prostate biopsy. However, among patients with PSA <10 ng/ml, the pretreatment T level was significantly higher in patients diagnosed with prostate cancer (4.2+/-2.6 ng/ml) than in patients diagnosed with BPD (3.6+/-1.4 ng/ml) (p=0.007); a similar trend was observed among patients with PSAD <0.15 ng/ml/cc. Multivariate analysis indicated that pretreatment T level was an independent significant predictor of positive prostate biopsy (p=0.020). Additionally, the serum T level was significantly lower in patients with a Gleason score >or=7 (3.7+/-2.1 ng/ml) versus a score <7 (4.2+/-1.7 ng/ml) (p=0.030). Also, serum T levels were significantly higher in well-differentiated prostate cancer (4.8+/-2.1 ng/ml) versus moderately differentiated (3.8+/-1.3 ng/ml) or poorly differentiated (3.7+/-1.4 ng/ml) (p<0.01). CONCLUSIONS: Among relatively low-risk patients, serum T level was an independent significant predictor of positive prostate biopsy, suggesting that the efficiency of prostate cancer screening can be improved by including measurement of serum T level.     

Pathological results and rates of treatment failure in high‐risk prostate cancer patients after radical prostatectomy

Study Type – Therapy (outcomes research) Level of Evidence 2b What’s known on the subject? and What does the study add? In the current literature, cT3 stage, biopsy Gleason > 8, PSA > 20 ng/ml, and D’Amico high‐risk category are frequently used definitions of high‐risk prostate cancer. Patients with clinically localized high‐risk prostate cancer do not have a uniformly poor prognosis after surgery. The rates of favourable pathological characteristics and biochemical‐recurrence free survival vary depending on the definition used for high‐risk prostate cancer.

OBJECTIVE

? To investigate the pathological characteristics and the rates of biochemical recurrence (BCR) ‐free survival after radical prostatectomy (RP) in men with high‐risk prostate cancer.

METHODS

? Of 4760 patients treated with RP for prostate cancer at three institutions, 293 patients (6.2%) had clinical stage T3, 269 (5.7%) had a biopsy Gleason sum ≥ 8, 370 (7.8%) had preoperative PSA ≥ 20 ng/mL and 887 (18.6%) were considered high‐risk according to the D’Amico classification (clinical stage ≥ T2c or prostate‐specific antigen (PSA) ≥ 20 ng/mL or biopsy Gleason sum ≥ 8). ? Actuarial BCR‐free survival probabilities after RP and the rate of favourable pathology (organ‐confined cancer, negative surgical margin and Gleason ≤ 7) were assessed.

RESULTS

? Median follow up was 2.4 years and 1179 (24.8%) patients had follow up beyond 5 years. ? The rate of favourable pathology increased in the following order: clinical stage T3 (13.7%), biopsy Gleason ≥ 8 (16.4%), the D’Amico high‐risk group (21.4%) and PSA ≥ 20 ng/mL (21.6%). ? The 5‐year BCR‐free survival probabilities were 35.4% for Gleason ≥ 8, 39.8% for PSA ≥ 20 ng/mL, 47.4% for D’Amico high‐risk group and 51.6% for clinical stage T3. ? Patients with only one risk factor had the most favourable 5‐year BCR‐free survival (50.3%), relative to patients with two or more risk factors (27.5%)

CONCLUSIONS

? Men with clinically localized high‐risk prostate cancer do not have a uniformly poor prognosis after RP. ? The rate of favourable pathology and of BCR‐free survival may vary substantially, depending on the definition used. ? RP should be considered a valid treatment modality for high‐risk prostate cancer patients, as many can be surgically down‐staged.     

Oncologic control obtained after radical prostatectomy in men with a pathological Gleason score ≥ 8: A single-center experience

ObjectiveTo assess the oncologic control afforded by radical prostatectomy (RP) in high-risk prostate cancers with a Gleason score ≥ 8.Materials and methodsWe performed a retrospective review of prostate cancer patients who underwent RP between 1995 and 2005 for prostate cancer and who had a pathologic Gleason score ≥ 8. Biochemical recurrence was defined as a single rise in PSA levels over 0.2 ng/ml after surgery.ResultsOverall, 64 patients were included and followed for a median time of 84.3 months. The mean age was 63 ± 5.2 years. The mean preoperative PSA was 11.9 ± 7.3 ng/ml (1.9–31), and 29 patients (46%) had a PSA > 10 ng/ml. The biopsy Gleason score was ≤7 for 49 patients (76.6%). After pathologic analysis, there were 25 (39%) stage pT2, 37 (58%) stage pT3, and 2 (3%) stage pT4 patients. Nine patients had lymph node involvement (14%). The surgical margins were positive in 25 patients (39%). In 51 patients, (80%) the Gleason score was underestimated by biopsies: 40 patients with a definitive score of Gleason 8 had a Gleason score of 6 or 7 on biopsies, while 11 patients with a Gleason score of 9 initially, had a Gleason score of 7 or 8. Twenty-seven patients underwent adjuvant treatment: external radiation therapy (n = 19), HRT (n = 3), or both (n = 5). During follow-up, 41 patients (64%) presented with a biochemical recurrence, and 11 (17%) died. The PSA-free survival rate at five year was 44%.ConclusionRP remains a possible therapeutic option in certain cases of the high-risk cohort of patients with a Gleason score ≥ 8. However, patients should be warned that surgery might only be the first step of a multi-modal treatment approach. The modalities of adjuvant treatments and the right schedule to deliver it following RP still need to be defined.     

Neoadjuvant Hormonal Therapy Improves the Outcomes of Patients Undergoing Radioactive Seed Implantation for Localized Prostate Cancer

Neoadjuvant hormonal therapy (NHT) has been extensively studied in patients undergoing radical prostatectomy and external-beam irradiation for prostate cancer. While there are a few reports in the literature on its use in men undergoing brachytherapy, little information exists about its beneficial effects in such patients. In this report, we describe the effects of NHT on prostate volume (PV) prior to seed implantation and on the prostate specific antigen (PSA) and postimplant biopsy outcomes of patients who presented with high-risk features. Hormone therapy (leuprolide and flutamide 750 mg/day) was given to 145 patients for 3 months prior to and for 3 months after permanent iodine-125 (160 Gy) or palladium-103 (115 Gy) seed implantation. Of these, 28 (19%) received NHT because of a preimplant PV >50 cc, and 117 patients received NHT because they had a PSA >10 ng/mL, Gleason score >/=7, or clinical stage >/=T(2b). All patients underwent implantation using the real-time intraoperative method, and no patients received external-beam irradiation. Of the 145 patients treated, 67 (46%) had a PSA >10 ng/mL (range 1.9-57 ng/mL; mean 12.2 ng/mL), 50 (35%) had Gleason score >/=7, and 80 (55%) had stage >/=T(2b) disease. Prostate volume was measured in 106 patients prior to NHT and 3 months later immediately prior to the seed implant. The mean PV was 50.4 cc (range 17-150 cc), whereas the mean PV after NHT was 31 cc (range 11.7-73.7 cc). The mean PV reduction was 35% (range 2%-62%). Volume reduction was compared in those patients who presented with a PV <40 cc (N = 51) and those with a PV >/=40 cc (N = 56). The mean reduction for the smaller glands was 29% (range 2%-54%) compared with 41% (range 7%-62%) for the larger glands (P < 0.05). Patients were followed for a minimum of 1 year (range 1.0-6.4; mean 2.2 years). The 4-year actuarial rate of freedom from PSA failure (PSA >1.0 ng/mL with two consecutive elevations) was 85%. There was no difference in rates of freedom from PSA failure for those with initial Gleason 2-4 (96%), 5-6 (78%), 7 (80%), or 8-9 (83%; P = 0.5). Control rates were 85% for patients with PSA 20 ng/mL (P = 0.8). There was a trend to decreased control rates with higher-stage disease (98% for T(1)-T(2a) v 68% for T(2c)), but these differences were likewise not significant (P = 0.12). The control rates for the 28 low-risk patients with enlarged prostate glands were compared with those of the 117 with high-risk features and were not different (100% v 82%; P = 0.1). There were 62 patients who agreed to eight-core prostate biopsies 2 years after implantation, and 60 (97%) were negative for tumor. This trial shows that NHT can reduce PV an average of 35% prior to seed implantation with the greatest reduction found in patients with larger prostates (41%). Hormonal therapy also appears to improve biochemical (PSA) control and local control (prostate biopsy) in patients with high-risk disease, yielding results similar to those in men with low-risk prostate cancer.     

Identification of factors predicting response to adjuvant radiation therapy in patients with positive margins after radical prostatectomy

PURPOSE: Radical prostatectomy (RP) is a highly effective treatment for patients with prostate cancer. However, patients with positive surgical margins after radical prostatectomy have less than ideal outcomes with 5-year progression rates between 36% and 50%. Postoperative radiation therapy (RT) is often advocated for improving these outcomes. We identified predictors of response to adjuvant RT given for positive margins after RP. MATERIALS AND METHODS: We retrospectively reviewed the clinical records of men who underwent RP between 1987 and 1999 at our institution and who received adjuvant RT for positive surgical margins. Only patients in whom prostate specific antigen (PSA) was undetectable after RP as well as before the initiation of RT were included. Numerous clinicopathological variables, including pre-RP PSA, pathological stage, margin length and location, and extracapsular extension or seminal vesicle involvement, were assessed for their adverse effect on the biochemical recurrence rate after adjuvant RT. RESULTS: A total of 62 men met our inclusion criteria. Median age at surgery was 60.7 +/- 6.1 years and median PSA at presentation was 9.0 ng/ml (range 1.4 to 64.9). The median RT dose was 60.0 +/- 3.6 Gy. RT was started a median of 5.0 +/- 3.6 months after RP. The 5 and 10-year biochemical disease-free survival rates for the whole group were 90.2% and 87.9%, respectively. Of all parameters tested only Gleason score 4 + 3 or greater (p = 0.037) and pre-RP PSA greater than 10.9 ng/ml (p = 0.040) were predictive of biochemical recurrence after adjuvant RT on univariate analysis. On multivariate analysis only pre-RP PSA greater than 10.9 ng/ml remained an independent predictor (p = 0.031). CONCLUSIONS: In the setting of true adjuvant RT in patients with positive margins after RP and undetectable PSA those with predominant Gleason grade 4 or greater, or PSA greater than 10.9 ng/ml at presentation are at increased risk for recurrence after adjuvant RT.     

新辅助内分泌治疗对临床局限性前列腺癌手术病理和生化复发的影响

目的 了解新辅助内分泌治疗(NHT)对临床局限性前列腺癌手术病理和生化复发的影响.方法 经直肠前列腺穿刺活检确诊的52例临床局限性前列腺癌患者,分为联合治疗组(NHT之后行手术治疗,26例)和单纯手术组(26例),均由同一医师行开放性经耻骨后根治性前列腺切除术.统计2组手术时间、出血量、术后住院时间、PSA水平、穿刺组织和手术标本的Gleason评分、临床分期和病理分期及无生化复发生存率.用独立样本t检验比较2组手术时间、出血量、术后住院时间及PSA水平.用秩和检验比较2组穿刺和术后病理的Gleason评分、临床分期和病理分期.用配对t检验比较联合治疗组NHT治疗前后PSA水平的变化.用配对秩和检验比较穿刺组织和手术标本分期和Gleason评分的变化.用Fisher精确概率法比较2组Gleason评分和分期变化的比例.用Kaplan-Meier法分析术后无生化复发生存率.结果 联合治疗组和单纯手术组平均手术时间分别为184.3、183.2 min,平均出血量分别为1275.0、1411.5 ml,平均术后住院时间分别为10.1、13.2 d,2组比较差异均无统计学意义(P＞0.05).就诊时的平均PSA水平分别为28.11、18.40ng/ml(P＞0.05),联合治疗组患者经平均6.58个月NHT治疗后.平均PSA水平降至0.53 ng/ml(P＜0.01).联合治疗组穿刺组织和手术标本平均Gleason评分分别为7.46和7.62(P＞0.05),单纯手术组分别为6.46和7.31(P＜0.01).联合治疗组穿刺Gleason评分高于单纯手术组(P＜0.05),而2组手术标本Glesaon评分比较差异无统计学意义(P＞0.05).联合治疗组临床分期为T2 12例(46%)、T3 14例(54%),单纯手术组T1 1例(4%)、T2 21例(81%)、T3 4例(15%),2组比较差异有统计学意义(P＜0.01).联合治疗组病理分期T2 19例(73%),T3 7例(27%),单纯手术组T2 19例(73%)、T3 7例(27%),2组比较差异无统计学意义(P＞0.05).联合治疗组病理分期低于临床分期(P＜0.01),单纯手术组的病理分期和临床分期差异无统计学意义(P＞0.05).随访2～81个月,2组分别平均随访时间29.4、31.4个月.2组的1年无生化复发率分别为71%(10/14)和80%(16/20,P＞0.05),2年无生化复发率为56%(5/9)和60%(9/15,P＞0.05).结论 NHT治疗不会增加临床局限性前列腺癌患者的手术风险.对患者术后病理分期与Gleason评分有一定改善,对术后无生化复发生存率可能有积极影响.     

Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study

We report a multicenter trial with transrectal high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. A total of 72 consecutive patients with stage T1c-2NOM0 prostate cancer were treated using the Sonablate 500TM HIFU device (Focus Surgery, Indianapolis, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and prostate specific antigen (PSA) level were 72 years and 8.10 ng/ml, respectively. The median follow-up period for all patients was 14.0 months. Biochemical disease-free survival rates in all patients at 1 and 2 years were 78% and 76%, respectively. Biochemical disease-free survival rates in patients with stage T1c, T2a and T2b groups at 2 years were 89, 67% and 40% (p = 0.0817). Biochemical disease-free survival rates in patients with Gleason scores of 2-4, 5-7 and 8-10 at 2 years were 88, 72% and 80% (p = 0.6539). Biochemical disease-free survival rates in patients with serum PSA of less than 10 ng/ml and 10-20 ng/ml were 75% and 78% (p = 0.6152). No viable tumor cells were noted in 68% of patients by postoperative prostate needle biopsy. Prostatic volume was decreased from 24.2 ml to 14.0 ml at 6 months after HIFU (p < 0.01). No statistically significant differences were noted in International Prostate Symptom Score, maximum urinary flow rate and quality of life analysis with Functional Assessment of Cancer Therapy. HIFU therapy appears to be minimally invasive, efficacious and safe for patients with localized prostate cancer with pretreatment PSA levels less than 20 ng/ml.     

Percentages of positive cores, cancer length and Gleason grade 4/5 cancer in systematic sextant biopsy are all predictive of adverse pathology and biochemical failure after radical prostatectomy

AIM: We investigated whether the quantitative parameters of systematic sextant biopsies were predictive of either adverse pathological findings or disease recurrence after radical prostatectomy (RP). METHODS: We retrospectively evaluated a total of 117 men with untreated prostate cancer whose needle biopsies were matched with RP specimens. The pretreatment parameters of the serum prostate-specific antigen (PSA), the PSA density, the percentage of positive biopsy cores, the percentage of cancer length and the percentage of Gleason grade 4/5 cancer in the biopsy were determined and compared with the pathological features of prostate cancer in RP specimens. These pretreatment parameters and pathological factors in the RP specimens, including the cancer volume, the percentage of Gleason grade 4/5 cancer, the positive surgical margin and the seminal vesicle invasion were evaluated for their ability to predict the disease recurrence. RESULTS: The percentages of positive biopsy cores, the Gleason grade 4/5 cancer in the biopsy and the cancer length in the biopsy had a weak correlation with the cancer volume in RP specimens (r = 0.373, 0.345, 0.408, respectively). All quantitative biopsy parameters were strongly predictive of the non-organ-confined status, the positive surgical margin and the seminal vesicle invasion in the logistic regression analysis. The percentage of positive biopsy cores and the percentage of Gleason grade 4/5 cancer in the biopsy predicted biochemical failure after RP. CONCLUSION: These results indicate that quantitative biopsy parameters are independent predictors of the adverse pathology of prostate cancers and disease recurrence after RP.     

Prognostic indicators for long term outcome following radical retropubic prostatectomy for prostate cancer involving the seminal vesicles

Seminal vesicle involvement at the time of radical prostatectomy (RP) for prostate cancer has been equated with metastatic disease. We review our biochemical freedom from disease results following RP in patients with seminal vesicle involvement with particular attention to identifying variables that may be predictive of disease recurrence. We retrospectively reviewed our surgical database and identified patients with pT3b (2002 AJCC) prostate cancer at RP [corrected]. There were 70 cases without lymph node involvement and with available clinical follow-up identified. Any patient receiving androgen deprivation therapy, radiation therapy, or with a sustained PSA elevation greater than 0.2 ng/mL was considered a biochemical failure. Results were calculated using the Kaplan-Meier method. Mean age was 63.4 (range 45.7-79.5) years, mean preoperative PSA was 11.3 ng/mL (range 2-60), mean biopsy Gleason score was 7.2 (range 4-9), mean RP Gleason score was 7.5 (range 5-9), and median follow-up time was 61.5 months (range 2.3-160.6). Overall, 33/70 (47%) patients were without evidence of disease without further therapy. For patients with pT3bN0Mx prostate cancer, margin status, capsular invasion, and PSA were not statistically significant risk factors for disease progression. Gleason score and major Gleason grade were the only statistically significant variables that predicted disease progression. A specimen Gleason score of greater than 7 and major Gleason grades greater than 3 were associated with an increased rate of disease progression in this patient group.     

Preoperative neural network using combined magnetic resonance imaging variables, prostate specific antigen, and Gleason score to predict prostate cancer recurrence after radical prostatectomy

OBJECTIVE: An artificial neural network analysis (ANNA) was developed to predict the biochemical recurrence more effectively than regression models based on the combined use of pelvic coil magnetic resonance imaging (pMRI), prostate specific antigen (PSA) and biopsy Gleason score in patients with clinically organ-confined prostate cancer after radical prostatectomy (RP). METHODS: Two-hundred-and-ten patients undergoing retropubic RP with pelvic lymphadenectomy were evaluated. Predictive study variables included clinical TNM classification, preoperative serum PSA, biopsy Gleason score, transrectal ultrasound (TRUS) findings, and pMRI findings. The predicted result was a biochemical failure (PSA >or=0.1 ng/ml). Using a five-way cross-validation method, the predicted ability of ANNA for a validation set of 200 randomly selected patients was compared with those of Cox regression analysis and "Kattan nomogram" by area under the receiver operating characteristic curve (AUC) analysis. RESULTS: Seventy-three patients (35%) failed at median follow-up of 61 (mean: 60, range: 2-94) months. Using similar input variables, the AUC of ANNA (0.765, 95% Confidence Interval [CI]: 0.704-0.825) was comparable (p > 0.05) to those for Cox regression (0.738, 95%CI: 0.691-0.819) and Kattan nomogram (0.728, 95%CI: 0.644-0.819). Contrarily, adding the pMRI findings, the ANNA is significantly (p < 0.05) superior to any other predictive model (0.897, 95%CI: 0.841-0.977). The Gleason score represented the most influential predictor (relative weight: 2.4) of PSA recurrence, followed by pMRI (2.2), and PSA (2.0). CONCLUSION: ANNA is superior to regression models to predict accurately biochemical recurrence. The relative importance of pMRI and the utility of ANNA to predict the PSA failure in patients referred for RP must be confirmed in further trials.     

Extended 12-core prostate biopsy increases both the detection of prostate cancer and the accuracy of Gleason score

OBJECTIVE: To evaluate the effect of extended 12-core prostate biopsy in improving the detection rate of prostate cancer and increasing the accuracy of Gleason score. METHODS: This study included 113 patients who underwent TRUS-guided lateral sextant biopsy (group I) and 176 patients who underwent extended 12-core biopsy (group II). Inclusion criteria for prostate biopsy were elevated serum PSA levels (>3.0 ng/ml) and/or suspicious digital rectal examination (DRE). RESULTS: Clinical characteristics were similar in both groups. Cancer was detected in 28 (24.8%) and 64 (36.4%) patients in group I and II respectively, chi2=4.26, p=0.039. Among patients with cancer in group I, 14 were treated by radical prostatectomy (RP). The median Gleason sum was 6 (range 3-8) and 7 (range 5-9) for needle and prostatectomy specimens respectively. There was an agreement between the biopsy and prostatectomy Gleason sum in 7 (50%) patients while the biopsy Gleason sum was lower in 7 (50%) cases. Among patients with cancer in group II, 27 were treated by RP. The median and the range of Gleason sum was the same for needle and prostatectomy specimen (median 6, range 4-9). There was an agreement between the biopsy and prostatectomy specimen in 23 (85.2%) patients while the biopsy sum was lower than prostatectomy in 4 (14.8%) patients. The agreement between the biopsy and prostatectomy specimen was significantly higher in group II (82.5%) than group I (50%), Fisher's Exact Test, p=0.026. CONCLUSION: Extended 12-core prostate biopsy significantly increases both the detection rate of prostate cancer and the accuracy of biopsy Gleason score.