Radical prostatectomy improves progression-free and cancer-specific survival in men with lymph node positive prostate cancer in the prostate-specific antigen era: a confirmatory study

Study Type – Therapy (outcomes research)
Level of Evidence 2b What’s known on the subject? and What does the study add? Historically, surgeons were reluctant to perform radical prostatectomy (RP) in LN positive disease. Nowadays, a shift towards multimodal treatment strategies in such patients, comprising RP with extended lymph node dissection followed by radiation and/or hormonal therapy can be detected. However, this change of paradigm is not supported by evidence derived from treatment guidelines. Retrospective studies on this topic, comprising small numbers of patients from the pre‐PSA era in the US suggest a survival advantage, if RP is performed. Our analyses of cancer control rates between patients with discontinued vs. completed prostatectomy revealed a superior clinical progression free‐ and cancer specific‐survival rate in those patients with completed prostatectomy. These results add knowledge on treatment outcome of a current patient population since previous retrospective studies include patients from the pre‐PSA era.

OBJECTIVE

? To assess the prognostic role of radical prostatectomy (RP) in lymph node (LN) positive patients with prostate cancer (PCa) in a contemporary RP cohort.

PATIENTS AND METHODS

? Between 1992 and 2004, 158 consecutive patients with clinically localized PCa and regional LN metastasis were identified. Fifty patients underwent LN dissection and discontinued RP, combined with early hormonal therapy (HT) (RP?), whereas, in 108 patients, RP was completed followed by adjunctive HT (RP+). ? Clinical progression‐free‐ (CPFS) and cancer‐specific survival (CSS) were studied using Kaplan–Meier analysis. ? Disease characteristics and the impact of RP on CPFS and CSS were further assessed using Cox proportional hazard models. ? A matched pair analysis between RP? and RP+ patients was performed based on clinical and pathological factors.

RESULTS

? Median follow‐up was 98 months (interquartile range, 88–113). Five‐ and 10‐year CPFS was 77% and 61% for RP+ patients vs 61% and 31%, for RP? patients (P= 0.005), respectively. ? A similar trend was observed for CSS (84% and 76% for RP+ vs 81% and 46% for RP?; P= 0.001). ? Type of treatment (RP? vs RP+) and number of positive LN were multivariate predictors of CPFS and CSS (all P≤ 0.05). ? In the matched pair analyses, RP+ patients showed superior CPFS and CSS (P < 0.005).

CONCLUSIONS

? RP had a beneficial impact, resulting in the superior survival of patients with LN positive PCa after controlling for LN tumour burden in a contemporary RP series. ? The findings obtained in the present study support the role of RP as an important component of multimodal strategies of LN positive PCa.     

Transperitoneal laparoscopic radical prostatectomy: The Tuen Mun Hospital experience

Background: The technique of laparoscopic radical prostatectomy was popularized after the report by a French group in 1998. The Tuen Mun Hospital started the program of laparoscopic radical prostatectomy since 2002 and the surgical technique has been evolving along a learning curve. Methods and results: We reviewed the transperitoneal approach of this procedure with emphasis on the variation of technique that the Tuen Mun Hospital has adopted. Conclusion: Although well described and standardized, the technique of transperitoneal laparoscopic radical prostatectomy is still evolving, as are many other surgical procedures. The exposure and development of different techniques allows the surgeons to be better equipped in catering for patients with different needs.     

The number of negative pelvic lymph nodes removed does not affect the risk of biochemical failure after radical prostatectomy

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVES

To assess patients who had radical prostatectomy (RP) and pelvic lymph node dissection (PLND) for pT2–4 N0M0 prostate cancer, to determine if LN yield affects the risk of biochemical failure (BCF), as the extent of PLND at the time of RP has become increasingly uncertain with the decreasing trend in tumour stage.

PATIENTS AND METHODS

We reviewed the Columbia University Urologic Oncology Database for patients with pT2–4 N0M0 prostate cancer treated with RP from 1990 to 2005. Exclusion criteria included <12 months of follow‐up, incomplete clinical and pathological data, and neoadjuvant androgen‐deprivation therapy (ADT) or immediate adjuvant ADT or external beam radiotherapy. Unadjusted and adjusted models were used to determine the ability of clinical and pathological variables to predict BCF.

RESULTS

The final dataset included 964 patients, with a mean age of 60.5 years and median preoperative prostate‐specific antigen (PSA) level of 6.2 ng/mL. The median (range) LN yield was 7 (1–42) and the median follow‐up 59 (12–190) months. In the unadjusted and adjusted models, preoperative PSA, pathological Gleason score, pathological stage, surgical margin status and year of surgery were significant predictors of BCF. The LN group was not a significant predictor of BCF in both the unadjusted and adjusted model (P = 0.759 and 0.408, respectively). When patients were stratified into high‐ and low‐risk groups, LN yield remained an insignificant predictor of BCF.

CONCLUSION

A higher LN yield at the time of RP does not increase the chance of cure for patients with pT2–4N0M0 prostate cancer. This lack of a survival advantage holds true for patients with high‐risk disease.     

Pathological findings and prostate‐specific antigen outcomes after laparoscopic radical prostatectomy for high‐risk prostate cancer

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To review the biochemical recurrence‐free survival (RFS) rates of laparoscopic radical prostatectomy (LRP) in patients with a high risk of disease progression as defined by preoperative criteria of D’Amico et al.

PATIENTS AND METHODS

Between October 2000 and May 2008, 110 patients had extraperitoneal LRP and bilateral pelvic lymph node sampling for high‐risk prostate cancer in our department. High‐risk prostate cancer was defined as a prostate‐specific antigen (PSA) level of >20 ng/mL, and/or a biopsy Gleason score ≥8, and/or a clinical stage of T2c–T4 stage. The median follow‐up was 37.6 months. Risk factors for time to biochemical recurrence were tested using log‐rank survivorship analysis and Cox proportional hazards regression.

RESULTS

Prostate cancer was organ‐confined in 36% of patients; the Overall RFS was 79.4% and 69.8% at 1 and 3 years, respectively. The 3‐year RFS rates for organ‐confined cancer vs extracapsular extension were 100% and 54.3%, respectively (P < 0.001). The 3‐year RFS rates for tumour‐free seminal vesicle vs seminal vesicle invasion were 81.8% and 33.6%, respectively (P < 0.001). The 3‐year RFS rates for negative surgical margins vs positive were 85.2% and 47.3%, respectively (P = 0.001). Compared with men with any single pathological risk factor or any two risk factors, men with all three risk factors had a significantly shorter time to PSA failure after LRP (log‐rank test, P < 0.001).

CONCLUSION

Among patients at increased risk of disease progression as defined by preoperative criteria, a third of men with organ‐confined disease have a favourable prognosis. Men at high risk for early PSA failure could be better identified by pathological assessment of RP specimens, and selected for phase III randomized trials investigating adjuvant systemic treatment.     

Robot‐assisted radical prostatectomy in men aged ≥70 years

OBJECTIVES

To assess the outcomes of elderly men with prostate cancer treated with robot‐assisted radical prostatectomy (RARP), because more healthy elderly men will present with localized prostate cancer and many will seek surgical treatment as the population ages.

PATIENTS AND METHODS

Between 2005 and 2008, 203 men had RARP performed by one surgeon; patients were categorized into two groups based on their age (≥70 vs <70 years). All data were recorded prospectively in an institutional approved database.

RESULTS

Of the 203 men, 23 (11%) were aged ≥70 years; the older men had similar baseline characteristics as younger men, and had characteristics during and after surgery comparable to those in younger men. The pathological RARP Gleason grade was significantly greater in older men. Surgical complications were not significantly different between the groups. Continence rates were significantly lower in older men at 6 months after surgery, but returned to levels equivalent to those in younger men within 12 months after surgery. Older patients took significantly longer to be capable of driving after surgery.

CONCLUSIONS

The outcomes of RARP in elderly men are largely comparable to those in younger men, with the exception of higher pathological Gleason grade, a transient delay in return of continence, and taking longer to return to driving after surgery. Advanced chronological age should not be a contraindication for RARP in patients with clinically localized prostate cancer, but expectations should be managed preoperatively.     

Analysis of regional lymph nodes in periprostatic fat following robot-assisted radical prostatectomy

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? A few publications have reported on the presence of lymph nodes in the anterior prostate lymphofatty tissue. This is important as increasing emphasis is placed on extending the overall limits of lymph node dissection in prostate cancer. For a large group of patients treated with robotic prostatectomy we continue to routinely remove and examine this tissue in order to provide additional staging information for patients. In a comprehensive cancer centre, the long‐term oncologic ramifications of excising tumour containing lymph nodes will continue to be studied.

OBJECTIVE

? To determine the incidence and significance of lymph nodes in the anterior prostatovesicular lymphofatty tissue.

PATIENTS AND METHODS

? One hundred and twenty patients with clinically localized prostate cancer underwent robot‐assisted laparoscopic radical prostatectomy with excision of anterior prostatovesicular tissue at a single institution over a 6‐month period. ? Tissue was sent for pathological analysis. ? Separate pelvic lymph node dissection was carried out in moderate‐risk and high‐risk patients.

RESULTS

? A total of 20 out of 120 patients (16.7%) had lymph nodes in the anterior lymphofatty tissue. ? Average lymph node number when present was 1.5 (one to three). ? Pathological assessment of the lymph nodes revealed metastatic prostate cancer in 3 out of 120 (2.5%) patients, each of whom had adverse pathological features. ? Patients with metastatic lymph nodes in the anterior tissue did not have cancer involvement of the pelvic lymph nodes. ? Patients with lymph nodes found in the anterior lymphofatty tissue were slightly younger but were otherwise similar with respect to other demographics, prostate‐specific antigen, biopsy Gleason score, clinical stage, pathological stage, pathological Gleason score, seminal vesicle invasion, and margin status.

CONCLUSIONS

? Anterior lymphofatty tissue overlying the prostate occasionally contains lymph nodes that can harbour malignant disease and routine excision may eradicate regional tumour burden. ? Of patients with nodes, 15% were found to have malignant involvement. ? The long‐term impact on progression‐free and overall survival requires further study.     

Photodynamic diagnosis of positive margin during radical prostatectomy: Preliminary experience with 5‐aminolevulinic acid

Objectives: To investigate the feasibility of intraoperative photodynamic diagnosis (PDD) by 5‐aminolevulinic acid (ALA) for the identification of positive surgical margins (PSM) during retropubic radical prostatectomy (RRP) in patients with prostate cancer (PCa). Methods: Intraoperative PDD was carried out in 16 patients with pathologically confirmed PCa by biopsy of the apex, or carrying >25% of probability of extraprostatic extension as defined by Japan PC Table. Before operation, 1.0 g of ALA was given orally. During open RRP, the resection margins inside the body were examined by PDD system with a fluorescence laparoscope. After their removal, 12 harvested prostates were divided and also investigated by PDD. Red fluorescent‐positive lesions were biopsied and compared with the pathological result. Results: All 16 patients were fluorescence‐negative inside the body, and negative margins were pathologically confirmed during PDD. Among the 43 specimens of 12 cases obtained by biopsy under PDD, 11 specimens (25.6%) were pathologically diagnosed as malignant tissue (adenocarcinoma, 10 specimens; high grade prostatic intraepithelial neoplasia, 1 specimen) and 19 specimens (44.2%) were evaluated as positive fluorescence by PDD with a sensitivity of 81.8%, a specificity of 68.8% and a predictive accuracy of 72.1%. No side‐effects were observed and the procedures were well tolerated. Conclusions: PDD mediated by ALA during RRP might be a feasible and safe modality for detection of surgical margins. Further prospective randomized studies with larger populations are required.     

Is a limited lymphadenectomy targeting obturator nodes alone an adequate procedure for Japanese men undergoing radical prostatectomy?

BACKGROUND: The objective of the present study was to investigate the significance of pelvic lymphadenectomy during radical prostatectomy in Japanese men with prostate cancer. METHODS: A total of 178 consecutive patients who underwent radical prostatectomy and standard pelvic lymphadenectomy targeting the external iliac nodes and obturator fossa for clinically localized prostate cancer were studied. The median observation period of this series was 18 months (range: 3-36 months). RESULTS: Lymph node metastases were detected in 13 patients; that is, positive nodes were located in the external iliac nodes alone in seven patients, the obturator fossa alone in four patients, and both external iliac nodes and obturator fossa in two patients. Of these 13 patients, all of the seven with more than one positive node demonstrated biochemical recurrence, whereas five of the six with single node involvement remained without signs of biochemical recurrence. Furthermore, a single positive node was located in the external iliac region in five of the six patients. When a group at high-risk for lymph node metastasis was defined as those meeting more than two of the following three criteria: (i) pretreatment serum prostate specific antigen value > or = 20 ng/mL; (ii) biopsy Gleason sum > or = 8; or (iii) percentage of positive biopsy core > or = 50%, the incidence of lymph node metastasis was 24.5% in the high-risk group and 0.8% in the low-risk group. CONCLUSIONS: These findings suggest that limited dissection of the obturator node alone may not be sufficient for Japanese men undergoing radical prostatectomy; therefore, we recommend performing standard pelvic lymphadenectomy targeting both the external iliac nodes and the obturator fossa for patients at high-risk of lymph node involvement.     

Disease progression and survival in patients with prostate carcinoma and positive lymph nodes after radical retropubic prostatectomy

OBJECTIVE: To determine disease progression and survival in patients with lymph node-positive prostate carcinoma after ascending radical retropubic prostatectomy (RP) and pelvic lymphadenectomy with different forms of postoperative adjuvant treatment. PATIENTS AND METHODS: We analysed 82 patients with lymph node metastases at the time of surgery and who had a RP between 1993 and 2002. Data from clinical records and follow-up questionnaires were used. Overall survival, time to clinical disease progression and time to biochemical progression were used as endpoints to assess the outcome. Clinical progression was defined as documented local recurrence or distant metastases, and biochemical as an increase in prostate-specific antigen (PSA) of > or = 0.4 ng/mL. Variables analysed included PSA level, Gleason score before and after RP, clinical and pathological stage, number of positive lymph nodes and hormone therapy after RP. The statistical assessment included univariate regression analysis, and to analyse the distribution of clinical findings in different groups, Mantel-Haenszel statistics were used to test for differences in the numbers of patients. Survival and progression-free interval were assessed by Kaplan-Meier estimates and differences between groups calculated by log-rank statistics and Cox regression models. RESULTS: The median (range) follow-up was 55 (10-125) months. Adjuvant hormonal treatment was used in 77 patients, five of whom had immediate adjuvant radiotherapy, and nine delayed radiotherapy because of local progression or symptomatic bone metastases; five had no additional treatment. The rates for 5- and 10-year overall survival, clinical progression-free survival and biochemical progression-free survival were 84% and 79%, 83% and 77%, and 70% and 60%, respectively. Ten patients died (12%), eight (10%) of them from the cancer; bone metastases were detected in nine (11%). Local recurrences developed in three (4%) patients, 10 (12%) had a PSA increase of > or = 0.4 ng/mL alone and 58 (71%) had no signs of progression, but two died from other causes. CONCLUSIONS: Most patients with prostate cancer who had RP and pelvic lymphadenectomy followed by adjuvant hormone therapy, and who had lymph node metastases at the time of surgery, had excellent overall and progression-free survival in the long term.     

前列腺癌盆腔各解剖区域淋巴结转移特点及其临床意义

目的：探讨前列腺癌盆腔各解剖区域淋巴结转移特点及其临床意义。方法：收集因前列腺癌而行前列腺根治切除＋分区盆腔淋巴结清扫术93例患者的临床病理资料,将盆腔淋巴结分为9区5组,明确盆腔各解剖区域淋巴结转移的频率和分布,比较各组淋巴结转移率和转移度。结果：全组有25例发生淋巴结转移,转移率为26．9％（25／93）。低、中、高危组前列腺癌的淋巴结转移率分别为2．6％（1／39）、30．0％（9／30）、62．5％（15／24）。各组转移率由高到低排列为髂内、闭孔、髂外、骶前和髂总,分别为16．4％（11／67）,15．1％（14／93）,11．8％（11／93）,2．3％（1／44）和0（0／67）,差异有统计学意义（P〈0．01）。转移淋巴结（阳性）53枚,转移度为3．2％（53／1643）。各组转移度由高到低排列为闭孔、髂内、髂外、骶前和髂总分别为4．9％（23／468）,4．0％（16／401）,3．2％（12／378）,0．9％（2／222）和0（0／174）,差异有统计学意义（P〈0．01）。结论：①对低危组的患者可不实施盆腔淋巴结清扫;对中一高危组患者,必须实施淋巴结清扫。②清扫范围：髂外、髂内和闭孔组为必须清扫的最小区域范围;髂总和骶前组不必进行常规清扫;③可根据术中闭孔、骶前组淋巴结快速冰冻病理检查,明确有无转移,来决定盆腔淋巴结清扫最适个体化清扫范围。     

Knotless “three‐U‐stitches” technique for urethrovesical anastomosis during laparoscopic radical prostatectomy

We describe a new technique for urethrovesical anastomosis that consists of placing three “U” stitches of Monocryl 2‐0 to connect the bladder neck and urethral stump together. The margins are united by a double passage of the suture, without tying any knots. The sutures are tied on the bladder's surface using Lapra‐Ty clips fixed at a certain distance from where to two mucosal margins have been joined. We carried out this technique on 90 patients who underwent laparoscopic extraperitoneal radical prostatectomy. The good joining of the margins, the absence of knots and the minimum trauma to the urethral wall together enable to create an anastomosis that is both “sealed” and “tension free”, allowing a quick “welding” of the margins and an early catheter removal. Regarding urinary continence, 56.6% (51) of patients were continent at catheter removal, 87.6% (78) were continent 3 months later and 98.9% (89) were continent after 6 months. In nine patients (10%), an episode of acute urinary retention occurred within 24 h after the removal of the catheter. We did not encounter any cases of vesicourethral anastomosis stenosis.