Prostate‐sparing cystectomy: long‐term oncological results

OBJECTIVE

To analyse the oncological outcome of prostate‐sparing cystectomy (PSC).

PATIENTS AND METHODS

Between 1994 and 2006, 63 men were treated with PSC after meeting the inclusion criteria (no tumour at the bladder neck, no prostate cancer). The results were compared with patients who had a standard cystoprostatectomy (SC) during the same study period, after matching for clinical and pathological characteristics.

RESULTS

The 3‐ and 5‐year disease‐specific survival rates were 77% and 66% in the PSC group, and 68% and 64% in the SC group (log‐rank, P = 0.6). The local recurrence rate was 7.9% and 16% for the PSC and the SC groups, respectively, and the respective distant recurrence rate was 29% and 33%. Subsequent prostate cancer was detected in 3% in the PSC group. None of these patients died from prostate cancer. In the SC group the final pathology showed that 18% had prostate cancer.

CONCLUSION

Local recurrences were not diagnosed more often in the PSC than the SC group. The outcomes of both procedures are comparable with contemporary cystoprostatectomy series. We consider this procedure oncologically safe and offer this to selected patients. However, selection is the key to success, and our results should further be corroborated by the experience of others.     

The incidence and relevance of prostate cancer in radical cystoprostatectomy specimens

Purpose

To review the incidence, histopathological features and clinical outcomes of patients with incidental prostate cancer (CaP) found in cystoprostatectomy specimens (CP) excised for bladder cancer and to determine whether these prostate cancers could affect the follow-up strategy.

Patients and methods

We retrospectively reviewed the records of 110 patients who underwent CP for bladder cancer (1998?C2011) at our institution. CaP grade, stage, volume and surgical margin status were recorded. Prostatic involvement by bladder tumour or carcinoma in situ (CIS) was studied. Pre-operative prostate assessment and follow-up in those diagnosed with incidental CaP were analysed.

Results

Incidental CaP was identified in 35 patients (32.5?%), 4 with prostatic PIN alone and 2 patients with diagnoses of CaP prior to cystectomy were excluded from study. Of the CaP cases, 28.5?% had clinically significant disease: 5 with Gleason score 7, 2 with Gleason score 9, who also had extracapsular invasion of tumour, and three with positive surgical margins. All patients were pN0 for CaP. Of the 108 patients, 16.5?% had prostatic urethral involvement with CIS or TCC. In the subgroup of patients with the incidentally diagnosed CaP who developed local recurrence of bladder tumour and/or metastatic disease, none originated from their CaP.

Conclusion

The majority of incidental CaP in CP specimens are organ confined and do not influence oncological outcome. The prognosis of such patients is primarily determined by bladder cancer. Our findings support previous reports and autopsy studies elsewhere.     

Outcomes of patients undergoing radical cystoprostatectomy for bladder cancer with prostatic involvement on final pathology

OBJECTIVE

To evaluate the impact of prostatic urothelial carcinoma (PUC) on survival of patients with bladder cancer undergoing radical cystoprostatectomy (RCP).

PATIENTS AND METHODS

From 1998 to 2005, 463 consecutive RCPs were performed for UC of the bladder. Patients with PUC at final pathology were grouped by route of prostatic invasion (bladder origin or prostatic urethral origin) and by depth of invasion (carcinoma in situ, ductal invasion, and stromal invasion). Univariate and multivariate survival analyses were performed.

RESULTS

In all, 35% (162/463) of patients had PUC. The 3‐year overall survival (OS) was 58.2% for patients who did not have PUC, 59.2%, 51.7%, and 16.8% in order of increasing depth of prostatic invasion for patients with PUC of urethral origin, and 6.7% for patients with bladder‐origin PUC. Survival differed significantly between stromal and non‐stromal PUC (P < 0.001). Patients with PUC of bladder origin had a higher rate of positive lymph nodes (LNs) than patients with stromal PUC of prostate origin (74.3% vs 27.8%, P < 0.001), but survival was similar (P = 0.619). On multivariate analysis, age (P = 0.035), increasing bladder stage (P = 0.003), stromal invasion (P = 0.002) and positive LNs (P < 0.001) were predictors of poor OS.

CONCLUSION

Depth of prostatic invasion correlates with outcome. While prostatic involvement originating in the bladder is associated with higher rates of positive LNs, survival is similar to patients with stromal involvement of urethral origin. Age, bladder tumour stage, prostatic stromal involvement and positive LNs predict adverse outcome. Our data support separate staging of the prostate in RCP specimens.     

Risk assessment of prostatic pathology in patients undergoing radical cystoprostatectomy

Objectives

To determine the incidence and location of prostate adenocarcinoma (PCa) and prostatic urothelial carcinoma (PUC) for patients undergoing radical cystoprostatectomy (RCP) for bladder cancer and to ascertain what preoperative information may be useful in predicting PUC or PCa in patients who may be candidates for prostate-sparing cystectomy.

Methods

Between 2001 and 2004, 235 consecutive patients underwent RCP and had whole-mount sections of the prostate. We reviewed our prospective radical cystectomy database for preoperative clinicopathological information associated with each patient. The bladder and whole-mount prostate sections were re-reviewed to determine the location and depth of the bladder tumor as well as the presence of any associated PCa and PUC.

Results

We identified 113 of 235 (48%) and 77 of 235 (33%) men with PCa and PUC, respectively. Among patients with PCa, 33 (29%) had Gleason score of ≥ 7, 25 (22%) had PCa tumor volume > 0.5 cc, and 15 (13%) had extracapsular extension. On multivariable analysis, only increasing age was significantly associated with PCa (odds ratio = 1.3, p = 0.046). Of the 77 with PUC, 28 (36%) had in situ disease only, while 49 (64%) had prostatic stromal invasion. Bladder tumor location in the trigone/bladder neck (p < 0.001) and bladder carcinoma in situ (p < 0.001) was strongly associated with PUC in the final specimen. Overall, 158 (67%) had either PCa or PUC in the prostate.

Conclusions

PCa and/or PUC is present in a majority of RCP specimens. Current preoperative staging and tumor characteristics are not adequate for determining who can safely be selected for prostate-sparing cystectomy.     

Evaluation of the prostate peripheral zone/capsule in patients undergoing radical cystoprostatectomy: defining risk with prostate capsule sparing cystectomy

OBJECTIVES: Prostate capsule sparing cystectomy has been performed in conjunction with orthotopic diversion to preserve sexual function and improve urinary control. Because concerns remain regarding incomplete surgical resection, we evaluated the risk of urothelial and prostate cancer in a series of patients undergoing radical cystoprostatectomy. METHODS: A total of 35 men undergoing radical cystoprostatectomy (August 2003-August 2005) had separate submission of the prostate peripheral zone/capsule from the prostate adenoma and bladder after surgery. These specimens were evaluated for bladder and prostate cancer grade, stage, and largest diameter of prostate cancer. Patient records were reviewed for demographic and medical information. Clinical variables were compared between patients with and without carcinoma involving the prostate using standard statistical software. RESULTS: Of patients, 57% had cancer involving the prostate at radical cystoprostatectomy. There were 9 patients (26%) who had urothelial carcinoma involving the prostate; only prostatic urethral biopsy identified these patients before radical cystoprostatectomy. Prostate adenocarcinoma was evident in 16 of 35 (47%) patients, with a majority involving the prostate peripheral zone/capsule (43%). There were 4 patients (11%) who had clinically significant prostate cancer (Gleason sum >6 or tumor volume >0.5 cm(3)). Patients with prostate cancer were significantly older than patients without prostate cancer (P = 0.01). CONCLUSIONS: No clinical variable can confidently predict patients with prostate cancer involving the prostate. Because a majority of patients undergoing radical cystoprostatectomy have cancer involving their prostate, preoperative evaluation with prostatic urethral and prostate biopsy may be useful to guide patient selection for prostate capsule sparing cystectomy.     

Pathologic pattern of invasive bladder carcinoma: Impact of bilharziasis

Objective

To describe the pathologic pattern of invasive bladder carcinoma in cystectomy specimens in relation to bilharziasis.

Patients and Methods

Between April 2002 and October 2006, 148 consecutive patients with invasive bladder cancer were subjected to radical cystectomy and orthotopic sigmoid bladder substitution at Al-Azhar Urology Department, Cairo, Egypt. A retrospective computerized database analysis of the pathologic features of the cystectomy specimens was done focusing on the impact of bilharziasis on the pathology of bladder carcinoma. The tumor cell type, stage, grade and gross features in addition to lymph node involvement were particularly noted.

Results

Bilharzial bladder pathology (lesions or ova) was present in 105 (70.9%) of 148 cystectomy specimens. Tumor histology included transitional cell carcinoma (TCC) in 84 (56.7%), squamous cell carcinoma (SCC) in 51 (34.5%), adenocarcinoma in 9 (6.1%) and anaplastic tumor in 4 (2.7%) of these specimens. Most tumors associated with bilharziasis were bulky and appeared fungating or ulcerative. The pathologic tumor stage was pT2 in 23%, pT3 in 70.9% and pT4a involving the prostate or seminal vesicles in 6.1%. None of these pT4a tumors were SCC. The tumor grade was described as low grade in 72 (48.6%) and high grade in 76 (51.4%) specimens. Regional lymph node involvement was detected in 31 (20.9%) specimens irrespective of bilharzial infestation.

Conclusion

Invasive bladder carcinoma associated with bilharzial pathology is mainly stage pT3, low-grade SCC and commonly appears as an ulcerative, bulky, fungating or verrucous mass. On the other hand, bladder carcinoma not associated with bilharziasis is mainly high-grade TCC and commonly appears as nodular or fungating lesions. Positive surgical margin and lymph node involvement are unrelated to bilharzial infestation.     

Risk factors for urothelial carcinoma of the prostate in patients undergoing radical cystoprostatectomy for bladder cancer

OBJECTIVE

To examine the risk factors for urothelial carcinoma (UC) involvement of the prostate in patients undergoing radical cystoprostatectomy (RCP) for bladder cancer, as such involvement has both prognostic and therapeutic implications.

PATIENTS AND METHODS

We examined 308 consecutive men from 1998 to 2005 who had RCP for UC of the bladder, with whole‐mount processing of their prostate. Prostatic involvement was categorized by site of origin (the bladder or the prostatic urethra) and, in the case of prostatic urethral origin, by depth of invasion, i.e. dysplasia/carcinoma in situ (CIS), involving the prostatic urethra, prostatic ductal invasion or prostatic stromal invasion. The impact of pathological characteristics was evaluated.

RESULTS

In all, 121 (39.3%) patients had some form of urothelial involvement of the prostate, of whom 59 (48.8%) had dysplasia/CIS of the prostatic urethra, 20 (16.5%) had ductal involvement and 32 (26.4%) had stromal involvement. Multivariate analysis showed that bladder CIS (odds ratio 2.0, 95% confidence interval, 1.2–3.6, P = 0.012) and trigonal involvement of bladder tumours (2.0, 1.1–3.7, P = 0.028) were independent risk factors for urothelial involvement of the prostate.

CONCLUSION

There was prostatic involvement with UC in nearly 40% of patients undergoing RCP. In this study CIS and trigonal involvement were independent predictors of risk, but were not adequate enough to accurately identify most patients who have UC within their prostate; further prospective studies are needed to more accurately predict risk factors and depth of invasion.     

Value of routine frozen section analysis of urethral margin in male patients undergoing radical cystectomy in predicting prostatic involvement

Purpose

To prospectively investigate diagnostic value of routine frozen section analysis (FSA) of urethral margin for male patients undergoing cystectomy for bladder cancer.

Materials and methods

One hundred consecutive male patients were subjected to radical cystectomy for bladder cancer with routine FSA obtained from distal prostatic urethral margin. Definitive pathological condition of the specimens was reviewed to diagnose urethral?±?prostatic malignant involvement. The diagnostic value of FSA was identified and compared with different clinical and pathological predictors. Patients with false-negative results were followed for 5?years.

Results

Six patients showed evidence of malignancy by FSA of the prostatic urethral margin (one patient was false positive), and all were managed by urethrectomy. Prostatic?±?urethral involvement was diagnosed in 15 patients by definitive histopathology (15?%). Sensitivity and specificity of urethral margin frozen section were 33.3 and 98.8?%, respectively, with overall accuracy of 89?% while positive and negative predictive values were 83.3 and 89.4?%, respectively. There was no significant correlation identified between tumor site or morphology, clinical staging, clinically suspicious prostate, cystoscopic involvement of bladder neck, tumor grade, and associated carcinoma in situ or nodal involvement with prostatic malignant involvement. Positive intraoperative FSA was the only predictor significantly associated with malignant urothelial involvement of the prostate. None of the 10 patients with false-negative results developed late urethral recurrence at 5?years.

Conclusion

Intraoperative urethral frozen section shows high predictive diagnostic value of malignant prostatic involvement. Nevertheless, its impact in preventing late urethral recurrence is doubtful.     

Extracting data from electronic medical records: validation of a natural language processing program to assess prostate biopsy results

Objective

The extraction of specific data from electronic medical records (EMR) remains tedious and is often performed manually. Natural language processing (NLP) programs have been developed to identify and extract information within clinical narrative text. We performed a study to assess the validity of an NLP program to accurately identify patients with prostate cancer and to retrieve pertinent pathologic information from their EMR.

Materials and methods

A retrospective review was performed of a prospectively collected database including patients from the Southern California Kaiser Permanente Medical Region that underwent prostate biopsies during a 2-week period. A NLP program was used to identify patients with prostate biopsies that were positive for prostatic adenocarcinoma from all pathology reports within this period. The application then processed 100 consecutive patients with prostate adenocarcinoma to extract 10 variables from their pathology reports. The extraction and retrieval of information by NLP was then compared to a blinded manual review.

Results

A consecutive series of 18,453 pathology reports were evaluated. NLP correctly detected 117 out of 118 patients (99.1 %) with prostatic adenocarcinoma after TRUS-guided prostate biopsy. NLP had a positive predictive value of 99.1 % with a 99.1 % sensitivity and a 99.9 % specificity to correctly identify patients with prostatic adenocarcinoma after biopsy. The overall ability of the NLP application to accurately extract variables from the pathology reports was 97.6 %.

Conclusions

Natural language processing is a reliable and accurate method to identify select patients and to extract relevant data from an existing EMR in order to establish a prospective clinical database.     

Does perineural invasion on prostate biopsy predict adverse prostatectomy outcomes?

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

OBJECTIVE

To determine the relationship between perineural invasion (PNI) on prostate biopsy and radical prostatectomy (RP) outcomes in a contemporary RP series, as there is conflicting evidence on the prognostic significance of PNI in prostate needle biopsy specimens.

PATIENTS AND METHODS

From 2002 to 2007, 1256 men had RP by one surgeon. Multivariable logistic regression and Cox proportional hazards models were used to examine the relationship of PNI with pathological tumour features and biochemical progression, respectively, after adjusting for prostate‐specific antigen level, clinical stage and biopsy Gleason score. Additional Cox models were used to examine the relationship between nerve‐sparing and biochemical progression among men with PNI.

RESULTS

PNI was found in 188 (15%) patients, and was significantly associated with aggressive pathology and biochemical progression. On multivariate analysis, PNI was significantly associated with extraprostatic extension and seminal vesicle invasion (P < 0.001). Biochemical progression occurred in 10.5% of patients with PNI, vs 3.5% of those without PNI (unadjusted hazard ratio 3.12, 95% confidence interval 1.77–5.52, P < 0.001). However, PNI was not a significant independent predictor of biochemical progression on multivariate analysis. Finally, nerve‐sparing did not adversely affect biochemical progression even among men with PNI.

CONCLUSION

PNI is an independent risk factor for aggressive pathology features and a non‐independent risk factor for biochemical progression after RP. However, bilateral nerve‐sparing surgery did not compromise the oncological outcomes for patients with PNI on biopsy.     

The results of concurrent chemo‐radiotherapy for recurrence after treatment with bacillus Calmette‐Guérin for non‐muscle‐invasive bladder cancer: is immediate cystectomy always necessary?

OBJECTIVES

To report our original experience in patients in whom bacille Calmette‐Guérin (BCG) therapy has failed for T1 bladder cancer with subsequent progression to T2 disease treated with chemo‐radiotherapy, as the management of recurrent high‐grade T1 bladder cancer after failed BCG therapy is challenging, and radical cystectomy is the standard treatment because there are no well established second‐line bladder‐preserving therapies.

PATIENTS AND METHODS

From 1988 to 2002, 18 patients with T2 recurrence after failure of BCG therapy for T1 bladder cancer were treated with chemo‐radiotherapy at the authors’ institution. Patients received a visibly complete transurethral resection of the bladder tumour (TURBT) and concurrent chemo‐radiotherapy with a mid‐treatment evaluation after 40 Gy. Patients with less than a complete response had a prompt cystectomy; the others completed radiotherapy to 64–65 Gy. The primary treatment outcome was freedom from cystectomy due to recurrence not treatable by conservative measures; secondary outcomes included disease‐specific (DSS) and overall survival (OS).

RESULTS

With a median follow‐up of 7.0 years, only one patient had persistent tumour at re‐staging TURBT and had an immediate cystectomy. Of the remaining 17 patients, 10 (59%) were free of any bladder recurrence. The actuarial 7‐year DSS and OS were 70% and 58%, respectively. At 7 years, 54% of patients were alive with intact bladders and free of invasive recurrence.

CONCLUSIONS

In this study we specifically evaluated patients with apparently small muscle‐invasive recurrences after BCG treatment for T1 bladder cancer. Selective bladder preservation with chemo‐radiotherapy is possible, with low morbidity and a high chance of long‐term bladder control. If successful in treating T2 recurrences after BCG therapy, it now seems timely to critically evaluate chemo‐radiotherapy as an alternative to immediate cystectomy in the management of patients with T1 recurrences after BCG.     

Evaluation of an orthotopic rat bladder urothelial cell carcinoma model by cystoscopy

OBJECTIVES

To enable preclinical testing of intravesical therapies against non‐muscle‐invasive bladder cancer (NMIBC) in an orthotopic rat bladder tumour model, augmented by the use of serial cystoscopy for in vivo tumour assessment and follow‐up.

MATERIALS AND METHODS

Fischer F344 rats had a 16‐G transurethral cannula placed. The bladder mucosa was conditioned with an acid rinse, followed by a 1‐h instillation of 1.5 × 10⁶ AY‐27 rat bladder urothelial cell carcinoma (UCC) cells (day 0). Cystoscopy (1 mm) was done on day 0 (control) and at 3, 4, 5, 6, 7, 10, 13 and 17 days. At the scheduled times the rats were killed after cystectomy (four at each time) for histopathological examination of the bladder.

RESULTS

Overall, tumour establishment was >80%, with predominantly carcinoma in situ preceding or concomitant with invasive tumour growth. All tumours were formed at 3–5 days, and remained non‐muscle‐invasive up to 5 days. From 6 days, tumours progressed to muscle‐invasive disease in 40% of the rats. Visibility at cystoscopy was excellent and tumours were apparent in >90% of rats from 5 days on, with a specificity and sensitivity of >90%. Cystoscopy could not distinguish NMIBC from muscle‐invasive disease.

CONCLUSIONS

This is a reliable model of orthotopic rat bladder UCC, with early high‐grade NMIBC growth, immediately followed by muscle‐invasive growth, i.e. the recommended time to start intravesical therapy would be 5 days after tumour cell inoculation. Tumour growth can easily be monitored by cystoscopy, but cannot be used to distinguish NMIBC from muscle‐invasive bladder cancer.     

Selective bladder-sparing protocol consisting of induction low-dose chemoradiotherapy plus partial cystectomy with pelvic lymph node dissection against muscle-invasive bladder cancer: oncological outcomes of the initial 46 patients

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? TURBT plus full‐dose chemoradiotherapy (CRT) against MIBC allow more than 40% of patients to spare the bladder while maintaining survival outcomes comparable to those of radical cystectomy (RC) series, contributing to improvement of the patients’ quality of life. Limitations of these protocols, however, include 1) MIBC recurrence in the preserved bladder mainly due to subclinical residual disease in the original MIBC site, 2) potential lack of curative intervention to regional lymph nodes and 3) increased mortality of salvage RC due to previous high‐dose pelvic irradiation. We propose a novel selective bladder‐sparing protocol consisting of induction low‐dose CRT plus consolidative partial cystectomy with pelvic lymph node dissection, which potentially contributes to overcoming the limitations of the conventional bladder‐sparing protocols.

OBJECTIVE

• ? To evaluate oncological outcomes of muscle‐invasive bladder cancer (MIBC) patients who were treated with a selective bladder‐sparing protocol consisting of induction low‐dose chemoradiotherapy (LCRT) plus partial cystectomy (PC) with pelvic lymph node dissection.

PATIENTS AND METHODS

• ? From 1997–2010, 183 consecutive patients with cT2–4aN0M0 bladder cancer (median age 70 years, women/men = 46/137, T2/3/4a = 100/69/14) underwent debulking transurethral resection followed by LCRT (radiation at 40 Gy to the small pelvis concurrently with two cycles of i.v. cisplatin at 20 mg/day for 5 days).
• ? Criteria for PC include: (i) essentially solitary MIBC or intravesically circumscribed tumours (≈25% or less of the bladder in area, excluding the bladder neck and trigone); (ii) no involvement of bladder neck or trigone; and (iii) clinically, no residual disease or minimal amounts of non‐invasive disease in the original MIBC site after LCRT; otherwise, radical cystectomy (RC) is recommended.
• ? Primary and secondary endpoints were cancer‐specific survival (CSS) and intravesical MIBC recurrence‐free survival (MRFS) for bladder‐preserved patients, respectively.

RESULTS

• ? Of the 183 patients, 87 (48%) achieved a clinical complete response after LCRT and 65 (36%) met the PC criteria; 46 (25%) patients actually underwent PC, 86 (47%) had RC, and the remaining 51 (28%) had neither PC, nor RC.
• ? Histological examination of the 46 PC specimens showed residual muscle‐invasive disease in three (7%).
• ? Overall, 5‐year overall survival and CSS rates were 64% and 71%, respectively (median follow‐up for survivors of 45 months).
• ? In the 46 PC patients, neither MIBC, nor pelvic recurrence was observed; 5‐year CSS and MRFS rates were both 100%.
• ? In 13 non‐PC patients who achieved a complete response after LCRT and who met PC criteria but declined PC, 5‐year CSS and MRFS rates were 74% and 81%, respectively; CSS and MRFS were significantly better in the PC group than in the non‐PC group (P= 0.025 and 0.002, respectively).

CONCLUSIONS

• ? In the current selective bladder‐sparing protocol, one‐third of MIBC patients met the PC criteria; when patients from this group underwent PC with pelvic lymph node dissection, their oncological outcomes were excellent.
• ? Consolidative PC potentially reduces MIBC recurrence in the preserved bladder, eventually improving survival in properly selected MIBC patients.

     

Ureteral frozen sections at the time of radical cystectomy: reliability and clinical implications

Background:

We hypothesized that the incidence of ureteral abnormalities on frozen section analysis (FS) at the time of radical cystectomy is much lower than historical values and that FS has minimal impact on outcomes. We also sought to determine the accuracy of FS and the associated costs.

Methods:

We reviewed the records of 301 patients who underwent a radical cystectomy for urothelial carcinoma of the bladder (UC) between March 2000 and January 2007. The ureteral margins were sent for FS and subsequent permanent hematoxyllin and eosin (H&E) sections and results were compared. Analyses were performed to determine the costs of FS and if any association was present with the pathological stage of the primary bladder tumour and regional lymph nodes, the presence of urothelial carcinoma in situ of the bladder (CIS) and survival outcomes with the FS.

Results:

We identified 602 ureters for this study. The incidence of CIS or solid urothelial carcinoma in the ureter was 2.8%. The presence of CIS of the bladder and prostatic urethra was significantly associated with a positive FS (p = 0.02). The FS were not associated with survival outcomes. The cost to pick up 1 patient with any abnormality on FS was $2080. The cost to pick up 1 patient with CIS or solid urothelial carcinoma of the ureter on FS was $6471.

Conclusion:

The incidence of CIS and tumour on FS during radical cystectomy for UC is low. The costs associated with FS are substantial. Frozen section analysis should only be performed in select patients undergoing radical cystectomy.     

A contemporary standard for morbidity and outcome after radical cystectomy

OBJECTIVE

To report the temporal changes in peri‐operative outcome over an extended period in patients undergoing radical cystectomy (RC) for all causes, irrespective of the previous treatment or pathology; and to establish a current standard of peri‐operative outcome for RC by analysis of contemporary operative mortality rates (2000–5) factored for risk factors that might predict outcome.

PATIENTS AND METHODS

All patients undergoing RC between 1970 and 2005 were analysed; this was an unselected single‐centre series and included patients previously treated by definitive radiotherapy, chemotherapy, and cases of RC where the primary tumour involved the bladder but was not of bladder origin.

RESULTS

In all, 846 patients had a RC, of whom 647 had a bladder primary tumour and 199 a primary tumour elsewhere (gynaecological, colorectal and others). There was a progressive reduction in 30‐ and 60‐day mortality rates, such that the current peri‐operative mortality (1999–2005) was 0.4% and 2.6%, respectively. There was a significant reduction in the re‐operation rate over the decades (P = 0.01), which is currently 4.7%. Patient age was a significant factor in 30‐ and 60‐day mortality rates (P < 0.001 for both) but there was no significant association between either American Society of Anesthesiologists grade or T stage with complication rates (P = 0.61 and 0.12, respectively).

CONCLUSION

There has been a progressive reduction in mortality related to RC, associated with both cases of RC and pelvic exenteration. The contemporary standard for 30‐and 60‐day mortality rates for these operations is 0.4% and 2.6%, respectively.     

Incidental prostate cancer at radical cystoprostatectomy: implications for apex‐sparing surgery

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

OBJECTIVE

To analyse retrospectively the clinicopathological features of incidental prostate cancer in patients undergoing radical cystoprostatovesiculectomy (RCP) for invasive bladder cancer, as recent studies suggest that prostatic apex‐sparing surgery in patients undergoing RCP improves urinary continence and erectile function after surgery, but in those with incidental prostate cancer, leaving the apical region endangers the oncological outcome.

PATIENTS AND METHODS

From 2004 to 2007, at our institution, 95 men had RCP for invasive bladder cancer. We reviewed their clinicopathological variables, especially apical involvement, and the course of prostate‐specific antigen (PSA) levels before and after surgery. We compared clinically significant and insignificant prostate cancers.

RESULTS

Of the 95 patients, 26 had incidental prostate cancer (mean age 68 years, range 53–80) on definitive histological examination. The mean (sd , range) preoperative PSA level in all 26 men was 3.6 (0.8, 0.2–14) ng/mL, but six of the 26 patients had preoperative PSA levels of >4 ng/mL and one other had suspicious findings on a digital rectal examination. Involvement of the apex was histologically confirmed in seven of the 26 patients (27%), including four with significant prostate cancer (P = 0.039). Preoperative PSA levels did not differ significantly between the seven patients with significant and 19 with insignificant prostate cancer, but seven patients with apical involvement had significantly higher PSA levels before RCP than the 19 who did not (P < 0.04). PSA levels after RCP remained below the limit of detection in all patients over a mean (range) follow‐up 14.3 (3–32) months.

CONCLUSION

In our series, preserving the apex of the prostate to decrease morbidity after RCP carried a 7.3% risk (seven of 95 patients) of leaving significant cancer in the residual prostatic tissue. No preoperative clinical value could exclude apical involvement. Therefore, our findings stress the oncological need for a careful and complete excision of the prostate during RCP.     

Precursor of prostate‐specific antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 90 cases

OBJECTIVE

To assess the expression of the precursor of prostate‐specific antigen (pro‐PSA), a distinct molecular form of serum‐free PSA that includes native and truncated forms, in benign epithelium, high‐grade prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma.

MATERIALS AND METHODS

We immunohistochemically evaluated 90 formalin‐fixed, paraffin‐embedded prostate needle biopsies using monoclonal antibodies against [?2] pro‐PSA, native [?5/?7] pro‐PSA, prostate‐specific membrane antigen (PSMA), PSA and racemase. Staining intensity was recorded using a scale of 0–3 (0, no staining; 3, highest staining). The percentage of immunoreactive cells in benign epithelium, high‐grade PIN and adenocarcinoma was estimated in increments of 10%.

RESULTS

All cases had [?5/?7] pro‐PSA immunoreactivity. There was weak focal perinuclear cytoplasmic immunoreactivity for [?5/?7] pro‐PSA in 62% (range 0–90%) of benign epithelial cells, whereas there was strong diffuse cytoplasmic staining in 83% (range 10–90%) of high‐grade PIN and 87% (range 40–90%) of cancer cells. Almost all (99%) cases were immunoreactive for [?2] pro‐PSA. The median (range) proportion of cells expressing [?2] pro‐PSA was lower in benign epithelium, at 17 (0–80)%, than in high‐grade PIN, at 55 (0–90)% (P < 0.001) and adenocarcinoma, at 55 (0–100)% (P < 0.001). The intensity of immunoreactivity for both isoforms increased from benign to neoplastic (high‐grade PIN and adenocarcinoma) epithelium. A total of 31% of high‐grade PIN and 11% of cancer cases with negative racemase staining showed strong staining for [?5/?7] pro‐PSA.

CONCLUSION

The expression of [?5/?7] pro‐PSA in benign and neoplastic cells might be used in combination with high molecular weight keratin, p63, and racemase to distinguish benign epithelium from high‐grade PIN and adenocarcinoma, particularly when racemase staining is negative. Both isoforms are sensitive markers for prostatic epithelium, making them possible candidates for investigating carcinoma with an unknown primary, particularly in cases in which PSA staining is negative and the level of suspicion is high.     

Prospective study of transitional cell carcinoma in the prostatic urethra and prostate in the cystoprostatectomy specimen. Incidence, characteristics and preoperative detection

OBJECTIVES: To prospectively evaluate the incidence of transitional cell carcinoma (TCC) in the prostatic urethra and prostate in the cystoprostatectomy specimen, investigate characteristics of bladder tumours in relation to the risk of involvement of the prostatic urethra and prostate and examine the sensitivity of preoperative loop biopsies from the prostatic urethra. MATERIAL AND METHODS: Preoperatively, patients were investigated with cold cup biopsies from the bladder and transurethral loop biopsies from the bladder neck to the verumontanum. The prostate and bladder neck were submitted to sagittal whole-mount pathological analysis. RESULTS: The incidence of TCC in the prostatic urethra and prostate in the cystoprostatectomy specimen was 29% (50/175 patients). Age, previous bacillus Calmette-Guérin treatment, carcinoma in situ (Cis) in the cold cup mapping biopsies and tumour grade were not associated with the risk of TCC in the prostatic urethra/prostate. Cis, multifocal Cis (> or = 2 locations) and tumour location in the trigone were significantly more common in cystectomy specimens with TCC in the prostatic urethra and prostate: 21/50 (42%) vs 32/125 (26%), p=0.045; 20/50 (40%) vs 27/125 (22%), p=0.023; and 20/50 (40%) vs 26/125 (21%), p=0.01, respectively. Preoperative resectional biopsies from the prostatic urethra in the 154 patients analysed identified 31/47 (66%) of patients with TCC in the prostatic urethra/prostate, with a specificity of 89%. The detection of stromal-invasive and non-stromal involvement was similar: 66% and 65%, respectively. CONCLUSIONS: The incidence of TCC in the prostatic urethra and prostate was 29% (50/175) in the cystoprostatectomy specimen. Preoperative biopsies from the prostatic urethra identified 66% of patients with such tumour growth. Our findings suggest that preoperative cold cup mapping biopsies of the bladder for detection of Cis add little extra information with regard to the risk of TCC in the prostatic urethra and prostate.     

Seminal sparing cystectomy and ileocapsuloplasty: long-term followup results

PURPOSE: The efficacy of nerve sparing techniques to save potency in cystoprostatectomy is about 50%. This radical surgery may be proposed to young men with normal sexual function. We report the results of a 13-year experience with our innovative seminal sparing cystectomy and bladder replacement to maintain sexual function in such patients. MATERIALS AND METHODS: Seminal sparing cystectomy is a modification of standard radical cystectomy in which the posterior bladder dissection is anterior to the seminal vesicle plane to preserve the vasa deferens, seminal vesicles, prostatic capsule and neurovascular bundles. Ablation of the whole bladder and the prostatic urothelium with surrounding hypertrophic tissue is guaranteed, and injury to the pelvic nerve plexus that provides autonomic innervation to the corpora cavernosa is avoided. From April 1990 to December 2002 we performed 68 procedures in 63 patients (7 of whom were lost to followup) with superficial bladder cancer resistant to conservative therapies (18 patients with stage T1G2 disease, 13 TaG2, 11 T1G3 and 14 TaG3) and in 5 patients with invasive bladder cancer (T2G3) which was monofocal and away from the bladder neck. All patients had normal sexual function. A complete clinical evaluation (with prostate specific antigen [PSA], digital rectal examination and transrectal ultrasound) to exclude concomitant prostate cancer was performed. Average patient age was 49 years and mean followup was 68 months. RESULTS: Normal erectile function was preserved in 58 patients (95%). Complete daytime continence was reached in 58 patients (95%) and nighttime continence was reached in 19 patients (31%). The early postoperative complication rate was 18% and the delayed complication rate was 26.2%. A total of 55 patients (90.2%) are alive and 6 patients (9.8%) died, 5 of cancer progression. High grade prostatic intraepithelial neoplasia was noticed in prostatic specimens in 3 patients and prostatic cancer was noted in 1 patient. These patients had a normal PSA before operation and a serum PSA less than 0.2 ng/ml at a mean followup of 19 months. No positive margins were identified on permanent histological analysis of the specimens, nor were local pelvic recurrences observed. CONCLUSIONS: Our innovative technique is safe, effective and easy to perform. The oncological and functional results obtained with a long followup justify seminal sparing cystectomy as an excellent surgical procedure which can be proposed to some oncological and nononcological cases.     

Syndecan‐1 expression in prostate cancer and its value as biomarker for disease progression

OBJECTIVE

To evaluate the association between syndecan‐1 (CD138) expression and prostate cancer.

PATIENTS AND METHODS

We evaluated syndecan‐1 expression using a recently constructed tissue microarray of prostatic samples taken from 243 patients, corresponding to 1400 cores, with 69.8%, 5.6%, 17.6% and 7% of the cores representing localized prostate cancer, high‐grade prostatic intraepithelial neoplasia, benign prostate tissue and hormone refractory/metastatic disease, respectively.

RESULTS

Metastatic cases had the highest frequency and membranous staining intensity for syndecan‐1 overexpression, followed by hormone refractory and localized disease (83.3% vs 34.8% and 25.7%, respectively). There was no significant difference in the frequency of membranous syndecan‐1 expression between localized prostate cancer and benign glands (25.7% vs 24.7% of cases, respectively). However, benign glands showed significantly higher intensity staining than localized prostate cancer. We found no significant association between syndecan‐1 expression and any of the following: Gleason score, pathological stage, surgical margin status and biochemical recurrence.

CONCLUSION

The current available evidence, from the present and previous studies, show that syndecan‐1 is not an independent predictor of recurrence or tumour‐specific survival, diminishing its significance as a clinical marker.