Defining prostate cancer risk after radical prostatectomy

Prostate cancer encompasses a wide spectrum of tumor phenotypes with differing prognoses and a part of these patients are at risk of experiencing tumor recurrence after initial treatment. This review discusses the parameters that determine PCa risk for failure after radical prostatectomy and also focuses on the ability of currently available post-treatment nomograms to predict treatment outcomes, and probability of treatment failure. The use of predictive nomograms may be therefore helpful in the complex decision making process.     

机器人辅助在前列腺癌外科治疗的研究进展

前列腺癌发病率和死亡率逐年升高,开放性根治性前列腺切除术仍是局部晚期前列腺癌的治疗金标准。近年来,腹腔镜和机器人辅助前列腺切除术等微创技术已广泛应用,与传统开放性手术比较,其在肿瘤切缘控制、尿控能力和性功能等方面取得巨大进步。另外机器人辅助前列腺切除术在改善患者功能学方面更具优势。本综述就根治性前列腺切除术的发展、不同手术入路的选择、围手术期并发症、肿瘤学、功能学及学习曲线等方面阐述机器人运用在前列腺癌根治术中的进展。     

加速康复外科与传统围手术期管理模式在机器人辅助腹腔镜前列腺癌根治术的临床疗效对比分析

目的将加速康复外科(ERAS)围手术期管理模式应用于机器人辅助腹腔镜前列腺癌根治术(RARP),并对比传统围手术期管理模式与ERAS的临床实践效果差异。 方法回顾性分析2018年5月至2018年8月南京大学医学院附属鼓楼医院泌尿外科共110例行机器人辅助腹腔镜根治性前列腺切除术患者的临床资料,并按照筛选条件最终纳入共70例患者,采用RARP术,且均采用ERAS围手术期管理模式,为ERAS组。并按照纳入标准纳入既往于南京大学医学院附属鼓楼医院泌尿外科2017年5月至2018年4月行RARP但未行加速康复外科围手术期管理模式的70例患者为对照组。ERAS组与对照组患者在年龄、体质量指数、术前实验室检查如血清白蛋白及血红蛋白、前列腺体积、术前PSA、术前ECOG评分、EPIC评分、临床分期和Gleason评分的差异均无统计学意义(P>005)。 结果两组手术均顺利完成,围手术期未出现病死或严重并发症,患者均顺利出院。术中情况:ERAS组与对照组在手术时间、术中出血量、术中直肠损伤、闭孔神经损伤、大血管损伤、淋巴结清扫比率差异均无统计学意义(P>005)。术后情况:ERAS组与传统围手术管理组在回病房后至首次进食时间、首次活动时间、首次排气时间、术后6 h疼痛评分、住院天数差异均有统计学意义(P<005),术后Clavien Dindo并发症分级、切缘阳性情况、术后实验室指标差异及术后1周及术后1个月早期尿控恢复差异无统计学意义(P>005)。 结论将加速康复外科围手术期管理模式应用于机器人辅助腹腔镜前列腺癌根治术,较传统围手术期管理模式更能促进患者康复,缓解术后疼痛,缩短住院天数。     

Treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy for prostate cancer

Background The indications for and the efficacy of radiation therapy after radical operation for patients with prostate cancer are not clear. We analyzed the treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy. Methods Between September 1997 and November 2004, 57 patients received adjuvant radiotherapy or salvage radiotherapy after radical prostatectomy. Fifteen patients received radiation therapy because of positive margins and/or extracapsular invasion in surgical specimens (adjuvant group). Forty-two patients received radiation therapy because of rising prostate-specific antigen (PSA) during follow-up (salvage group). Radiation therapy was delivered to the fossa of the prostate ± seminal vesicles by a three-dimensional (3-D) conformal technique to a total dose of 60–66 Gy (median, 60 Gy). Biochemical control was defined as the maintenance of a PSA level of less than 0.2 ng/ml. Results The median follow-up period after radiation therapy was 33 months (range, 12–98 months). Three-year biochemical control rates were 87% for the adjuvant group and 61% for the salvage group. For patients in the salvage group treated without hormone therapy, the preradiation PSA value was the most significant factor for the biochemical control rate. The 3-year biochemical control rate was 93% in patients whose preradiation PSA was 0.5 ng/ml or less and 29% in patients whose preradiation PSA was more than 0.5 ng/ml. No severe adverse effects (equal to or more than grade 3) were seen in treated patients. Conclusion Radiation therapy after radical prostatectomy seemed to be effective for adjuvant therapy and for salvage therapy in patients with a preradiation PSA of 0.5 ng/ml or less. Also, radiation to the fossa of the prostate ± seminal vesicles, to a total dose of 60–66 Gy, using a three-dimensional (3-D) conformal technique, seemed to be safe.     

Predicting survival of men with recurrent prostate cancer after radical prostatectomy

IntroductionTo develop and externally validate a novel nomogram aimed at predicting cancer-specific mortality (CSM) after biochemical recurrence (BCR) among prostate cancer (PCa) patients treated with radical prostatectomy (RP) with or without adjuvant external beam radiotherapy (aRT) and/or hormonal therapy (aHT).Materials & methodsThe development cohort included 689 consecutive PCa patients treated with RP between 1987 and 2011 with subsequent BCR, defined as two subsequent prostate-specific antigen values >0.2 ng/ml. Multivariable competing-risks regression analyses tested the predictors of CSM after BCR for the purpose of 5-year CSM nomogram development. Validation (2000 bootstrap resamples) was internally tested. External validation was performed into a population of 6734 PCa patients with BCR after treatment with RP at the Mayo Clinic from 1987 to 2011. The predictive accuracy (PA) was quantified using the receiver operating characteristic-derived area under the curve and the calibration plot method.ResultsThe 5-year CSM-free survival rate was 83.6% (confidence interval [CI]: 79.6–87.2). In multivariable analyses, pathologic stage T3b or more (hazard ratio [HR]: 7.42; p = 0.008), pathologic Gleason score 8–10 (HR: 2.19; p = 0.003), lymph node invasion (HR: 3.57; p = 0.001), time to BCR (HR: 0.99; p = 0.03) and age at BCR (HR: 1.04; p = 0.04), were each significantly associated with the risk of CSM after BCR. The bootstrap-corrected PA was 87.4% (bootstrap 95% CI: 82.0–91.7%). External validation of our nomogram showed a good PA at 83.2%.ConclusionsWe developed and externally validated the first nomogram predicting 5-year CSM applicable to contemporary patients with BCR after RP with or without adjuvant treatment.     

寡转移性前列腺癌根治术的临床初步疗效观察及围手术期并发症分析

背景与目的：多项回顾性研究显示,寡转移性前列腺癌根治术可以提高肿瘤的局部控制率和患者的总生存受益,围手术期并发症是影响寡转移性前列腺癌患者行前列腺癌根治术的一个重要因素。该研究旨在探讨寡转移性前列腺癌患者行前列腺癌根治术的临床初步疗效及围手术期并发症发生率和严重程度。方法：收集2015年7月—2016年1月247例前列腺癌根治术患者数据,其中寡转移性前列腺癌患者25例,局限性前列腺癌患者222例。两组均采用Clavien-Dindo手术并发症分级标准对出现并发症的患者进行分级。观察前列腺特异性抗原(prostate specific antigen,PSA)下降比例并将并发症发生率与严重程度在寡转移组和非寡转移组间进行对比分析。结果：寡转移组术后3个月时21例(84.0%)出现下降PSA,下降比例低于局限组212例(95.5%),差异有统计学意义(P<0.05)。寡转移组共6例(24.0%)患者发生术后并发症,其中严重并发症(Ⅲ度及以上)1例(4.0%),局限组共49例(22.1%)患者发生术后并发症,其中严重并发症(Ⅲ度及以上)7例(3.2%),差异无统计学意义(P＞0.05)。结论：寡转移性前列腺癌患者行前列腺癌根治术治疗是安全、有效和可行的,并发症风险并非寡转移性前列腺癌患者行前列腺癌根治术的限制因素。     

Phase I-II study of intraoperative radiation therapy (IORT) after radical prostatectomy for prostate cancer

PURPOSE: Recent studies have suggested an alpha/beta ratio in prostate cancer of 1.5-3 Gy, which is lower than that assumed for late-responsive normal tissues. Therefore the administration of a single, intraoperative dose of irradiation should represent a convenient irradiation modality in prostate cancer. MATERIALS AND METHODS: Between February 2002 and June 2004, 34 patients with localized prostate cancer with only one risk factor (Gleason score > or =7, Clinical Stage [cT] > or =2c, or prostate-specific antigen [PSA] of 11-20 ng/mL) and without clinical evidence of lymph node metastases were treated with radical prostatectomy (RP) and intraoperative radiotherapy on the tumor bed. A dose-finding procedure based on the Fibonacci method was employed. Dose levels of 16, 18, and 20 Gy were selected, which are biologically equivalent to total doses of about 60-80 Gy administered with conventional fractionation, using an alpha/beta ratio value of 3. RESULTS: At a median follow-up of 41 months, 24 (71%) patients were alive with an undetectable PSA value. No patients died from disease, whereas 2 patients died from other malignancies. Locoregional failures were detected in 3 (9%) patients, 2 in the prostate bed and 1 in the common iliac node chain outside the radiation field. A PSA rise without local or distant disease was observed in 7 (21%) cases. The overall 3-year biochemical progression-free survival rate was 77.3%. CONCLUSIONS: Our dose-finding study demonstrated the feasibility of intraoperative radiotherapy in prostate cancer also at the highest administered dose.     

Clinicopathological features of prostate cancer in Japanese men diagnosed on repeat transrectal ultrasound-guided biopsy

Background The objective of this study was to analyze the clinicopathological features of prostate cancer detected on repeat transrectal ultrasound-guided random biopsy in comparison with those detected on initial biopsy.Methods Between January 1999 and March 2004, 132 Japanese men underwent radical retropubic prostatectomy without neoadjuvant therapy at our institution. In 109 patients (group A) prostate cancer was detected on initial biopsy, while in the remaining 23 (group B), it was diagnosed on repeat biopsy. We retrospectively characterized differences in clinicopathological features between these two groups.Results There were no significant differences in age, serum prostate specific antigen (PSA) value, or biopsy Gleason score between groups A and B. However, prostate volume in group A was significantly smaller than that in group B, while PSA density, the percentage of positive biopsy cores, and the percentage of cancers in the biopsy set in group A were significantly higher than those in group B. Pathological examination of the radical prostatectomy specimens showed that there were no significant differences in the distribution of pathological T stage or in the Gleason score; or in the incidences of lymphatic invasion, vascular invasion, and perineural invasion between groups A and B. Despite there being a significantly larger tumor volume in the radical prostatectomy specimens in group A compared to that in group B, there was no significant difference in the incidence of insignificant disease between these two groups.Conclusion These findings suggest that missing the cancer on the initial needle biopsy may be due to a small cancer focus in a large prostate; however, there were no significant differences in the final pathological features of prostate cancers detected on the initial and repeat biopsies, suggesting similar biological behaviors. Thus performance of a repeat biopsy in cases negative for malignancy on the initial biopsy is advocated.Missing prostate cancer on the initial biopsy may be due to a small cancer focus in a large prostate; however prostate cancers detected on initial and repeat biopsies may have similar biological behavior.     

Oncological and functional outcomes of elderly men treated with HIFU vs. minimally invasive radical prostatectomy: A propensity score analysis

Aim

To assess outcomes of whole gland high-intensity focused ultrasound (HIFU) as compared with minimally-invasive radical prostatectomy (MIRP) in elderly patients.

Adjuvant radiotherapy following radical prostatectomy for pathologic T3 or margin-positive prostate cancer: A systematic review and meta-analysis

BACKGROUND AND PURPOSE: Results following radical prostatectomy (RP) are suboptimal in patients found to have cancer extending beyond the prostatic capsule (pT3) or present at the resection margins (R1). The optimal postoperative management of such patients is undefined. Therapeutic alternatives include adjuvant radiotherapy (RT) or active surveillance. METHODS: Randomized controlled trials (RCTs) were eligible for inclusion in this systematic review if they compared adjuvant RT in the immediate period after RP to active surveillance - with therapies held in reserve for salvage - in prostate cancer patients with pT3 or R1 disease or both. The primary outcome of interest was overall survival. RESULTS: Three RCTs representing 1,743 patients satisfied the eligibility criteria. Two trials reported data on overall survival; a meta-analysis of the data showed no significant improvement associated with adjuvant RT (hazard ratio=0.91, 95% CI 0.67-1.22, p=0.52). All trials reported data on biochemical progression-free survival (bPFS). On meta-analysis, adjuvant RT significantly improved bPFS (hazard ratio=0.47, 95% CI 0.40-0.56, p<0.00001). One trial provided comparative graded toxicity data; there were no significant differences between arms in severe (grade 3) gastrointestinal or genitourinary toxicity at five years. CONCLUSIONS: To date, adjuvant RT has not been shown to improve overall survival compared with active surveillance. Longer follow-up from completed RCTs is required to accurately assess this outcome. Adjuvant RT does, however, significantly improve bPFS and is not associated with excess severe late toxicity.     

Minimum incision endoscopic radical prostatectomy: Clinical and oncological outcomes at a single institute

Aims

The objective of this study was to investigate the clinical and oncological outcomes of prostatectomy patients undergoing minimum incision endoscopic radical prostatectomy (MIE-RP).

Methods

Between September 2005 and May 2010, 541 patients underwent MIE-RP with bilateral lymphadenectomy for clinically localized prostate cancer at Hirosaki University Hospital. The present retrospective study enrolled 375 patients who had not received neoadjuvant or adjuvant therapy. MIE-RP was performed through a 6-cm suprapubic midline incision. A 30° laparoscope was conveniently positioned on the head side of the patient for precise observation and monitoring.

Results

The median operating time was 119 min, and the estimated blood loss was 900 ml. The most frequent perioperative complication was leakage from the vesicourethral anastomosis (6.7%), and rectal injury occurred in 1.0%. Overall, 31.2% of the patients had a positive surgical margin, including 11.1% with pT2, 52.9% with pT3 and 100% with pT4 diseases. The post-operative median follow-up period was 40.5 months (range, 2-56.5 months). The 5-year PSA-free survival rate was 71.6%. In multivariate analysis, high-risk patients (according to the D’Amico risk criteria), pathological T stage and positive surgical margins were identified as independent predictors of PSA-free survival. The limitations of this study included a retrospective study, relatively short follow-up period and single-institution nature of the study.

Conclusions

MIE-RP is a safe and minimally invasive procedure that may represent a reliable alternative to laparoscopic and robotic-assisted RP.     

根治性前列腺切除术后病理大切片与常规切片的对比分析

背景与目的：在根治性前列腺切除术(radical prostatectomy,RP)组织标本中,应用病理大切片技术可以全面观察组织,其在病理诊断、形态学研究方面拥有独特的优势。但是由于制作技术、设备限制、工作量较大等原因,目前在临床上尚未常规开展。本研究通过比较RP后行常规切片及病理大切片患者的临床及病理变量,评价RP后病理大切片技术在前列腺癌诊断中的意义。方法：选择2012年12月-2014年2月在复旦大学附属肿瘤医院行RP后做病理大切片的229例前列腺癌患者作为研究组,同时选取2010年1月-2012年6月行RP后做常规病理切片的393例前列腺癌患者作为对照组,对比分析包括两组患者年龄,术前PSA值,术前是否接受新辅助内分泌治疗,前列腺癌确诊方式,确诊时Gleason评分、临床分期,RP后Gleason评分、病理分期、手术切缘、前列腺包膜外侵犯、精囊侵犯、术后盆腔淋巴结转移等变量。结果：两组患者术前临床及病理变量：RP后病理Gleason评分、病理分期、前列腺包膜外侵犯情况、术后盆腔淋巴结转移差异均无统计学意义(P>0.05),但是研究组患者手术切缘及精囊侵犯的阳性率明显高于对照组,差异有统计学意义(26.2% vs 17.6%,P=0.010;23.1% vs 17.0%,P=0.025)。结论：应用病理大切片技术可明显提高前列腺标本切缘阳性及精囊侵犯的阳性检出率,因此病理大切片技术值得在前列腺癌病理诊断中推广。     

The trifecta outcome in 300 consecutive cases of robotic-assisted laparoscopic radical prostatectomy according to D'Amico risk criteria

Background

To analyze the trifecta outcome (continence, potency, and cancer control) in 300 cases of robotic-assisted laparoscopic radical prostatectomy (RARP).

Methods

A prospective assessment of outcomes in 300 consecutive patients that underwent a RARP performed by a single surgeon. Patients were grouped according to D'Amico risk criteria: Group I consisted of ‘low-risk’ cases (n = 64), Group II consisted of ‘intermediate-risk’ cases (n = 88), and Group III consisted of ‘high-risk’ cases (n = 148). Patients were evaluated for perioperative complications and the trifecta outcome.

Results

The operation time, blood loss, post-operative stay, duration of urethral catheterization, and perioperative complication rate were similar among all groups. The incidence of bilateral neurovascular bundle (NVB) preservation was significantly decreased with the increasing risk of cases (P < 0.001). The continence rates at the 1-week, 1-month, 3-month, 6-month, and 12-month follow-ups did not differ significantly between groups. The potency rates at the 12-month follow-up were not significantly different. The positive surgical margin and positive lymph node metastasis rate increased with the increasing risk of cases (P < 0.001). The biochemical recurrence rate (BCR, PSA >0.2 ng/mL) was 3.1, 11.36, and 19.59% in Groups I, II and III, respectively (P = 0.004). The trifecta outcome for RARP with bilateral NVB preservation showed no significant differences among groups.

Conclusions

Undergoing a RARP is safe and feasible in high-risk prostate cancer patients. Compared to low-risk and intermediate-risk groups, the high-risk group had a significant higher incidence of positive surgical margin, positive lymph node metastasis, and BCR rate.     

Efficacy and tolerance of salvage radiotherapy after radical prostatectomy, with emphasis on high-risk patients suited for adjuvant radiotherapy

Background and purpose

Goals of this study are to report the outcomes and tolerance of salvage radiotherapy (SRT) after prostatectomy, to identify risk factors for failure after SRT and to evaluate how these results compare with published results of immediate post-operative adjuvant radiotherapy (ART).

Material and methods

Men receiving SRT for elevated PSA levels after radical prostatectomy (RP) were included. Biochemical progression-free survival (bPFS), overall survival (OS) and disease-specific survival (DSS) were estimated. Risk factors for biochemical failure and death were evaluated. Late toxicity and quality of life were evaluated. Secondary bPFS (defined as bPFS from prostatectomy until progression after radiotherapy) was calculated for high-risk patients (pT3 and/or positive surgical margins) in order to compare SRT outcomes with ART.

Results

197 Men were included. Five-year bPFS after SRT was 59% (95% CI 49-69%). Five-year OS and DSS were 90% (85-96%) and 97% (93-100%), respectively. Capsular perforation (pT ? T3), negative surgical margins and serum PSA > 1 ng/ml at the start of RT were significant predictors of lower bPFS. Patients without any negative factors had a 5-year bPFS of 89%. No severe late toxicity was reported. Five-year secondary bPFS for SRT in high-risk patients was 78% and comparable with published results for ART.

Conclusions

Salvage radiotherapy for patients with organ-confined prostate cancer was effective and well tolerated. SRT outcomes were comparable with published ART results for high-risk patients. Initially monitoring serum PSA and considering early SRT for these patients are not harmful and might be a valuable alternative for immediate ART.     

Open, laparoscopic and robotic radical prostatectomy: Optimizing the surgical approach

As advances in the understanding of prostatic anatomy led to improvements in functional and oncologic outcomes after prostatectomy of the past few decades, advances in technology and surgical technique have made minimally-invasive prostate surgery a reality. Today patients diagnosed with clinically localized prostate cancer have more surgical treatment options than in the past including open, laparoscopic and robot-assisted laparoscopic radical prostatectomy. Advantages and disadvantages exist for each modality and lead to subtle differences in the technical execution of the procedure. Evidence from centers of excellence and from experienced surgeons demonstrates that both laparoscopic and robotic-assisted laparoscopic radical prostatectomy appear to be comparable to outcomes achieved with open radical retropubic prostatectomy series. Individual surgeon skill, experience and clinical judgment are likely the stronger predictors of outcome rather than the technique chosen. However, learning curves, oncologic outcomes and cost-efficacy remain important considerations in the dissemination of minimally-invasive prostate surgery. A greater appreciation of the periprostatic anatomy and further modification of surgical technique will result in continued improvement in functional outcomes and oncological control for patients undergoing radical prostatectomy, whether by open or minimally-invasive surgery.     

The impact of robot-assisted radical prostatectomy on the use and extent of pelvic lymph node dissection in the “post-dissemination” period

Introduction

Previous series during the dissemination era of minimally invasive techniques for treatment of prostate cancer (PCa) showed a declining use of pelvic lymph node dissection (PLND). The aim of our study was to re-assess the impact of robot-assisted radical prostatectomy (RARP) on the utilization rate of PLND and its extent in the post-dissemination period.

Methods

Relying on the Surveillance Epidemiology and End Results (SEER) Medicare-linked database, 5804 patients with non-metastatic PCa undergoing open radical prostatectomy (ORP) or RARP between years 2008 and 2009 were identified. Uni- and multivariable logistic regression analyses tested the relationship between surgical approach (RARP vs. ORP) and: 1 – the rate of PLND (pNx vs. pN0-1); and 2 – the extent of PLND (limited vs. extended).

Results

Overall, 3357 (57.8%) patients underwent a PLND. The proportion of patients treated with PLND was significantly higher among ORP vs. RARP patients: 71.2 vs. 48.6%, respectively (P < 0.001). In addition, the median number of lymph nodes removed was significantly higher for patients treated with ORP vs. RARP: 5 vs. 4, respectively (P < 0.001). In multivariable analyses, ORP was associated with 2.7- and 1.3-fold higher odds of undergoing PLND and of receiving an extended PLND compared to RARP, respectively (both P ≤ 0.001). Stratified analyses according to disease risk classifications revealed similar trends.

Conclusions

In the post-dissemination era, RARP remains associated with a decreased use of PLND and suboptimum extent. Efforts should be made to improve guideline adherence in performing a PLND whenever indicated according to tumor aggressiveness, despite surgical approach.