Urinary incontinence after non-nerve-sparing radical prostatectomy with neoadjuvant androgen deprivation

OBJECTIVES: The impact of non-nerve-sparing retropubic radical prostatectomy (RRP) for prostate cancer combined with neoadjuvant androgen deprivation on urinary control is not well documented. We examined the incidence and severity of urinary incontinence after such therapy and determined the etiologic factors causing this complication. METHODS: We examined the postoperative continence status of 104 consecutive patients admitted to the National Cancer Center Hospital who underwent RRP with wide resection of the pelvic nerves after neoadjuvant androgen deprivation. Incontinence was scored according to the number of pads used daily by the patient for urinary leakage. The severity of incontinence was analyzed according to patient age, weight of resected specimen, status of cancer stage, duration of neoadjuvant androgen blockade therapy, preoperative length of membranous urethra, and duration of urethral catheterization after surgery. We also measured the configuration and diameter of the reconstructed bladder neck by retrograde cystourethrography. RESULTS: In 104 patients examined, the percentage of patients who became dry postoperatively was 22% at 1 month, 47% at 3 months, 69% at 6 months, and 78% at 1 year. Of 81 patients who became dry postoperatively at any interval, 22 (27%) became continent within 1 month of RRP, 49 (61 %) were continent within 3 months, 71 (88%) became continent by 6 months, and another 10 (12%) became continent between 6 and 12 months postoperatively. Of 48 patients who were followed up for more than 1 year and for whom continence status at 1 month after surgery was available, all patients who used 1 to 2 pads per day (13 of 13) at 1 month after surgery regained continence by 1 year after surgery. However, only 62% of patients (16 of 26) who required more than 3 pads per day at 1 month after surgery became dry by 1 year after surgery. Only age (older than 70 years) and large prostate size (weight of surgical specimen more than 40 g) temporarily influenced the recovery of urinary continence after surgery. Dilation of the bladder neck evaluated by retrograde cystourethrography was prominent in severely incontinent patients in the immediate postoperative period. CONCLUSIONS: Our experience in patients who undergo non-nerve-sparing RRP after neoadjuvant androgen deprivation closely matches published surveys of patient-reported complications. Postoperative incontinence is not a major contraindication for non-nerve-sparing RRP after neoadjuvant endocrine therapy. Dilation of the bladder neck affected the recovery from incontinence, highlighting the importance of adequate reconstruction of the bladder neck.     

Intermittent androgen deprivation: clinical experience and practical applications

Prostate cancer is more frequently being diagnosed at an earlier age, men are dying of prostate cancer at an older age, and men are now treated with androgen deprivation for biochemical relapse. As a result, the amount of time that patients are potentially subjected to androgen deprivation is increasing. Intermittent androgen deprivation (IAD) has been investigated as a potential alternative to continuous androgen deprivation (CAD) in order to improve quality of life and potentially delay the progression to androgen independence. Along with the increased use of primary hormonal therapy in clinically localized prostate cancer, IAD may supplant the traditional surgical or radiotherapy options, specifically in men who have underlying co-morbidities and decreased life expectancy. There are ongoing multi-institutional, randomized trials that will lend insight into the utility, efficacy, and feasibility of IAD versus CAD. This article discusses the theoretical benefits and rationale of IAD and reviews the completed and on-going IAD trials. Finally, the controversies, practical applications, and future directions of IAD are addressed.     

Treatment failure and clinical progression after salvage therapy in men with biochemical recurrence after radical prostatectomy: radiotherapy vs androgen deprivation

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

OBJECTIVE

To compare the outcomes between salvage radiotherapy (RT) and androgen‐deprivation therapy (ADT), to investigate factors determining clinical progression (CP) in men with prostate cancer.

PATIENTS AND METHODS

The study comprised 121 patients with biochemical recurrence while on follow‐up by prostate‐specific antigen (PSA) measurement, without adjuvant therapy after radical prostatectomy, received RT (45) or ADT (76). Failure after salvage therapy was defined as a PSA level of >0.2 ng/mL. Clinical, pathological and treatment factors were analysed.

RESULTS

The clinicopathological characteristics were similar between the RT and ADT groups except that men in the RT group were younger (61.4 vs 65.4 years). After ADT, salvage failed in 10 (13%) after a mean (sd ) of 18.5 (4.5) months of treatment, and 6.7 months after salvage failed all patients progressed clinically. After RT, salvage failed in 22 (49%) after 30.7 (5.2) months of response. Upon RT failure, all patients received ADT, after which in three (14%) patients the treatment failed again after 20.1 months of treatment and progressed to CP after 6.5 months, while in the remaining 19 (86%) patients the PSA level remained undetectable for 37.6 (7.7) months. On multivariate analysis, pathological stage (≥T3b) and Gleason grade 5 disease were independently prognostic of CP.

CONCLUSION

Salvage RT alone and combined with subsequent ADT provided PSA control in most patients, significantly increasing CP‐free survival compared with initial ADT. Patients with a short PSA doubling time (<3 months) are at high risk of failed salvage treatment after RT, and initial ADT might be considered. Regardless of salvage method, advanced pathological stage and Gleason grade 5 were factors prognostic of CP.     

根治术后即刻给予辅助内分泌治疗局部晚期高危前列腺癌

前列腺癌在欧美国家高发,尤其在美国和北欧[1],在全球范围内,前列腺癌位居男性恶性肿瘤发病率的第2位,仅次于肺癌之后。但前列腺癌的发病在不同种族和国家发病率相差较大。我国属于前列腺癌的低发国家,但随着人口老龄化及饮食结构的改变,近年来前列腺癌的发病率快速增加,尤其在一些经济较为发达的省份上升速度惊人。     

Radiotherapy for PSA recurrence after radical prostatectomy

OBJECTIVES: The treatment of patients presenting with an isolated PSA recurrence after radical prostatectomy (RP) remains controversial. The present study aims at assessing the results of salvage radiotherapy (RT), to define prognostic factors and to identify subgroups of patients most suitable for RT with curative intent. MATERIALS AND METHODS: A retrospective study was performed of 53 patients, diagnosed with a rising PSA after RP, and treated with RT to the prostate bed, between July 1992 and July 1998. RESULTS: On univariate analysis, significant determinants to obtain and maintain a nondetectable PSA (< 0.02 ng/ml) were Gleason grade (< or = III vs. < or = IV), pre-RT PSA, considered as categorical or continuous variable, and pathological stage, pT (2 vs. 3). Pre-RP PSA (< or = 10 vs. >10), time interval between surgery and moment of rising PSA and pathological section margin status were not significant. On multivariate analysis, only Gleason grade and pre-RT PSA remained significant. For the patient group with a Gleason grade < or = III the PSA-free survival at 3 years was 75% (+/- 11%) compared to 27% (+/- 9%) for the patients with a Gleason grade > or = IV (p = 0.002). Pre-RT PSA significantly influenced PSA-free survival in the first group, but not in the latter. CONCLUSION: From the group of RP patients with rising PSA following a postsurgery PSA-free period, subgroups can be defined with a distinctly different probability of obtaining and maintaining nondetectable PSA levels after salvage RT.     

Prostate specific antigen doubling time after radical prostatectomy: effect of neoadjuvant androgen deprivation therapy

PURPOSE: We determined the predictors of prostate specific antigen (PSA) doubling time in patients with relapse after radical prostatectomy as well as whether PSA doubling time is shorter in those treated versus not treated with neoadjuvant androgen deprivation therapy. MATERIALS AND METHODS: We calculated PSA doubling time in 204 patients with PSA relapse after radical prostatectomy who were or were not treated with neoadjuvant androgen deprivation therapy. Analysis of covariance was used to determine the effect of clinical and pathological parameters on PSA doubling time, and the proportion of variability explained by these parameters. RESULTS: Clinical stage, and combined clinical stage and margin status, clinical stage and androgen deprivation therapy status, androgen deprivation therapy status and time to PSA relapse, and androgen deprivation therapy status and pretreatment PSA were significant predictors of PSA doubling time. Any variable or combination of variables explained up to only 21% of PSA doubling time variability. When stratified by pretreatment PSA, clinical stage and biopsy grade, the difference in doubling times in patients treated with or without neoadjuvant androgen deprivation therapy was significant only for 4.1 to 10 ng./ml. PSA. In this group mean doubling time plus or minus standard deviation in patients receiving neoadjuvant androgen deprivation therapy and those treated only with radical prostatectomy was 7.6+/-1.0 and 15.4+/-2.6 months, respectively. CONCLUSIONS: Our study indicates that it is difficult to predict PSA doubling time in an individual. The small proportion of variability in PSA doubling time explained by the interaction of androgen deprivation therapy status and other variables indicates that these factors are not clinically significant.     

Intermittent androgen deprivation (IAD) in patients with biochemical failure after radical retropubic prostatectomy (RRP) for clinically localized prostate cancer

We report a study in which our objective was to analyze the clinical response during IAD in patients with biochemical failure after RRP for clinically localized prostate cancer. Between February 1994 and May 1996, 34 patients who exhibited a primary postoperative decrease in PSA to below the detection limit after RRP and then showed PSA progression during follow-up were included as group 1 and 17 patients in whom PSA did not decrease after RRP were included as group 2. Patients were offered IAD when PSA progressed over 0.4 ng/ml in group 1 and over 4.0 ng/ml in group 2. Median follow-up is 184 weeks in group 1 and 206 weeks in group 2. The median time “off ” therapy increased from 25% (1st cycle) to 68.7% (5th cycle) of the entire cycle in group 1 and from 33.3% to 58.3% in group 2. Nine out of 12 cases with Gleason score ≥8 failed to respond to IAD and all developed metastatic and/or local failure. No case with Gleason score <7 failed to respond to IAD. Our conclusions suggest that IAD may be effective in patients with biochemical progression after RRP. In our experience, Gleason score seems to be an important variable.     

间断雄激素阻断治疗进展期前列腺癌之8年临床经验分析

目的:探讨间断雄激素阻断法(IAD)治疗进展期前列腺癌的安全性及用药周期特征。方法:178例进展期前列腺癌患者依据临床分期分为A(T3-4N0M0)、B(TXN1M0)和C(TXNXM1)3组。所有患者一经确诊即给予最大雄激素阻断治疗至少6个月,至PSA≤0.2μg/L后维持3个月后,暂停雄激素阻断治疗,进入间歇期(Off-Period);当PSA>4μg/L时,进入用药期(On-Period),直至PSA再次达到0.2μg/L以下停药。分别记录各组患者年龄、初始PSA值、Gleason评分以及治疗期间每个周期的用药期及停药期时间、PSA水平及肿瘤进展时间。结果:A、B、C 3组患者初始PSA水平分别为(27.5±14.6)、(43.4±21.8)、(62.8±44.6)μg/L(P<0.01);平均随访时间分别为(38.4±9.6)、(33.1±14.0)、(28.3±14.3)个月;开始治疗至出现肿瘤进展的平均时间为(37.4±6.6)、(27.4±10.2)、(16.6±4.4)个月。A组患者平均间歇期时间显著长于B组和C组,C组患者On/Off值显著大于A组,且完成的IAD周期数显著少于A组(P<0.01)。19例A组患者完成5个治疗周期。C组患者最多完成3个治疗周期即出现PSA及肿瘤进展。2例A组患者死于心血管事件;B组患者6例死亡,其中1例死于前列腺癌转移;C组36例死亡,其中21例死于转移性前列腺癌。结论:与存在远处转移的前列腺癌患者相比,局部进展性前列腺癌患者采用间断雄激素阻断治疗可有效缓解肿瘤进展,减少IAD治疗的相关不良反应,提高患者生活质量。     

Diffusion-weighted magnetic resonance imaging detects local recurrence after radical prostatectomy: initial experience

Current conventional cross-sectional imaging techniques, such as contrast-enhanced computed tomography and magnetic resonance imaging (MRI), are largely inaccurate in detecting local recurrence after radical prostatectomy. We report on five patients with biochemical recurrence after radical retropubic prostatectomy and pelvic lymph node dissection for whom local recurrence could only be detected with diffusion-weighted (DW) MRI. Prior to DW-MRI, all patients had negative digital rectal examinations, negative or equivocal conventional cross-sectional imaging, and negative bone scans. All suspicious lesions on DW-MRI imaging were histologically proved to be local recurrences of prostate cancer after either transrectal ultrasound-guided or transurethral biopsy. These results should encourage other centres to test our findings.     

Salvage radiotherapy for biochemical recurrence after radical prostatectomy

OBJECTIVE: To evaluate the clinical outcome of salvage radiotherapy (RT) for biochemical recurrence after radical prostatectomy (RP) at our institution. PATIENTS AND METHODS: Between March 1999 and January 2004, 37 patients had salvage RT for prostate-specific antigen (PSA) failure after RP, including eight who had had neoadjuvant hormone therapy. After surgery, PSA was measured with ultrasensitive immunoassays. In all patients RT was delivered to the prostatic bed at a total dose of 60 Gy with a four-field box technique. RESULTS: The median (range) PSA level before salvage RT was 0.146 (0.06-3.216) ng/mL and RT was started at a PSA level of <0.5 ng/mL in 34 of the 37 patients (92%). With a median follow-up of 31.9 (0-69.8), months, 11 patients (30%) had disease progression after RT and the 3- and 5-year progression-free probability was 74% and 54%, respectively. Univariate analysis showed that clinical and pathological tumour stages and PSA level before RT (>0.15 vs < or = 0.15 ng/mL) were significant predictors of disease progression. There were no late adverse events related to RT. CONCLUSION: Salvage RT for biochemical failure after RP at a low PSA level, using ultrasensitive immunoassays for monitoring, is a reasonably effective treatment. A relatively low radiation dose (60 Gy) seems to be effective.     

Local recurrence after radical prostatectomy for prostatic cancer

The local recurrence rate after radical prostatectomy for prostate cancer has varied across studies but seems sufficiently high (20 to 40%) to warrant a reappraisal of the oncological usefulness of this procedure performed in isolation using current techniques. Local recurrence can be either biological or clinical. In biological recurrences, the only abnormality is recurrent PSA elevation. It has been suggested that this event, even in the absence of ultrasound changes or histological documentation, should lead to additional therapy, usually in the form of local radiation therapy, and that the efficacy criterion for this treatment should be a fall in PSA to undetectable levels. However, differences in the "ultrasensitive" assays used to detect PSA pose a serious obstacle to comparisons of published studies. Furthermore, in most publications, the pathological stage is more severe than the clinical stage, and this clinical underestimation of disease severity complicates the evaluation of recurrence rates. In clinical recurrences, rectal digital examination or endorectal ultrasonography show abnormalities and, more importantly, examination of a biopsy specimen establishes that these abnormalities are due to malignant disease. Symptoms may or may not be present. Many authors, particularly in Europe, feel that only clinical recurrences warrant additional treatment, usually in the form of radiation therapy. However, as a preliminary, all available imaging techniques should be used to confirm that the absence of metastases. A valuable tool in this situation is the study of PSA kinetics (elevation rate or postoperative doubling time). If the recurrence seems local, radiation therapy alone is the best initial option, since concomitant hormone therapy leads to a decrease in PSA levels even in the presence of metastatic disease, thus depriving the patient and physician of a valuable therapeutic test. Success rates after radiation therapy for recurrences have varied widely across studies. Some authors consider that this treatment approach is ineffective or provides only transient benefits. Follow-ups were often short, particularly given the considerable variability of the natural history of prostate cancer. The enthusiasm initially generated by radical prostatectomy should be tempered, at least regarding the possibility of a complete cure.     

Characterization of biochemical recurrence after radical prostatectomy

BACKGROUND: This study sought to characterize the variables that predict postoperative prostate-specific antigen doubling time (PSADT) and biochemical recurrence time (RT) in patients who have failed radical prostatectomy (RP). METHODS: A total of 477 patients underwent RP at our institution for clinically localized prostate cancer. Of these patients, 64 (13.4%) demonstrated evidence of postoperative biochemical failure. PSADT and biochemical RT were calculated for all patients. PSADT and RT were correlated with clinical variables including preoperative PSA level, patient age, race, prostate weight and with pathologic characteristics of the operative specimen using uni- and multivariate analyses. In addition, PSADT and RT were also correlated with each other and with the time to postoperative adjuvant therapy. RESULTS: Median postoperative PSADT for patients who recurred after radical prostatectomy was 9.7 months. Postoperative PSADT was predicted by lymph node involvement (p < 0.001) and Gleason grade (p = 0.06). Rapid PSADT also correlated with institution of postoperative adjuvant therapy (p = 0.003). Median biochemical RT for all patients was 6.7 months. Gleason grade and pathologic stage were found to be predictors of RT (p < 0.002). Postoperative PSADT did not correlate with RT (r = 0.08; p = 0.53). PSADT and RT were not different between Caucasian- versus African-Americans. CONCLUSIONS: These results serve to better characterize our cohort of patients who have evidence of biochemical recurrence after radical prostatectomy. Aggressiveness of recurrent disease (i.e. PSADT) seems to be predicted by lymph node involvement and higher pathologic grade. Furthermore, the lack of correlation of RT and PSADT suggests that early recurrences are not necessarily aggressive tumors: conversely, aggressive recurrences may occur at any point in the postoperative period. This information may aid in the postoperative treatment of recurrent disease and help to better define those patients who are at higher risk for developing clinical recurrence and who would benefit from greater vigilance during the postoperative period.     

Diagnosis of local recurrence after radical prostatectomy

In the long-term there is biochemical evidence of recurrent prostate carcinoma in approximately 40% of patients after radical prostatectomy (RP). Detecting the site of recurrence (local vs distant) is critical for defining the optimum treatment. Pathological and clinical variables, e.g. Gleason score, involvement of seminal vesicles or lymph nodes, margin status at surgery, and especially the timing and pattern of prostate-specific antigen (PSA) recurrence, may help to predict the site of relapse. Transrectal ultrasonography (TRUS) of the prostatic fossa in association with TRUS-guided needle biopsy is considered more sensitive than a digital rectal examination for detecting local recurrence, especially if PSA levels are low. Although it cannot detect minimal tumour mass at very low PSA levels (< 1 ng/mL) TRUS biopsy is presently the most sensitive method for detecting local recurrence. Nevertheless, the conclusive role of biopsy of the vesico-urethral anastomosis remains unclear. However, 111In-capromab pendetide scintigraphy and [11C]-choline tomography (which are better than conventional imaging for detecting metastatic tumour), have low detection rates for local disease and are considered complementary to TRUS in this setting. Patients with a high PSA after RP may be managed with external beam salvage radiotherapy. An initial PSA of < 1 ng/mL, Gleason score < 8 and radiation dose of 66-70 Gy seem to be key factors in determining success. Although a positive TRUS anastomotic biopsy may predict a better outcome after radiation therapy, the need to take a biopsy in the event of PSA failure remains under investigation. The value of salvage radiation to the prostatic bed for PSA-only progression after RP remains in question.     

Clinical outcome of patients with lymph node positive prostate cancer after radical prostatectomy versus androgen deprivation

OBJECTIVE(S): To compare the outcome of patients with stage D1 (TxN+M0) prostate cancer undergoing radical prostatectomy or androgen deprivation alone. PATIENTS AND METHODS: Eighty-two patients treated for lymph node positive prostate cancer were retrospectively analyzed for time to progression, tumor-specific and overall survival. Furthermore, subsequent tumor and treatment related morbidity requiring intervention including frequency and duration of associated hospital stays was recorded. RESULTS: The extent of lymph node metastasis was significantly lower in 50 patients undergoing radical prostatectomy (+/- early androgen deprivation) compared to 32 receiving androgen deprivation only. The treatment groups, however, did not differ with regard to other characteristics including age, comorbidity, stage, grade and preoperative PSA. Mean actuarial progression-free, and tumor-specific survival was significantly longer for the radical prostatectomy patients (36% and 47%, respectively at 10 years) compared to androgen deprivation (15% and 32%, respectively). The latter group required more secondary interventions resulting in more frequent and overall longer hospital stays. CONCLUSIONS: Patients undergoing radical prostatectomy for stage D1 prostate cancer possibly benefit with regard to the necessity for secondary interventions and, at least for limited (solitary) nodal disease, in terms of progression-free and tumor-specific survival. However, the latter observation may be biased by a larger extent of lymph node metastasis in the androgen deprivation group.