Fracture risk in men with prostate cancer: a population-based study.

Fractures are increased among men with prostate cancer, especially those on androgen-deprivation therapy (ADT), but few data are available on men with localized prostate cancer. The purpose of this investigation was to estimate fracture risk among unselected community men with prostate cancer and systematically assess associations with ADT and other risk factors for fracture. In a population-based retrospective cohort study, 742 Olmsted County, MN, men with prostate cancer first diagnosed in 1990-1999 (mean age 68.2 ± 8.9 years) were followed for 6821 person-years. We estimated cumulative fracture incidence, assessed relative risk by standardized incidence ratios, and evaluated risk factors in time-to-fracture regression models. All together, 482 fractures were observed in 258 men (71 per 1000 person-years). Overall fracture risk was elevated 1.9-fold, with an absolute increase in risk of 9%. Relative to rates among community men generally, fracture risk was increased even among men not on ADT but was elevated a further 1.7-fold among ADT-treated compared with untreated men with prostate cancer. The increased risk following various forms of ADT was accounted for mainly by associations with pathologic fractures (14% of all fractures). Among men not on ADT (62% of the cohort), more traditional osteoporosis risk factors were implicated. In both groups, underlying clinical characteristics prompting different treatments (indication bias) may have been partially responsible for the associations seen with specific therapies. To the extent that advanced-stage disease and pathologic fractures account for the excess risk, the effectiveness of fracture prevention among men with prostate cancer may be limited.

Long-term outcome of ureterosigmoidostomy: an analysis of patients with >10 years of follow-up.

STUDY TYPE: Therapy (case series). LEVEL OF EVIDENCE: 4. OBJECTIVE: To examine our long-term experience with ureterosigmoidostomy (USS) to evaluate its potential applicability in the treatment of benign and malignant conditions of the urinary bladder, as USS has been largely disregarded recently, secondary to concerns of long-term complications, but has had a resurgence of interest due to its potential applicability to newer minimally invasive surgical techniques. PATIENTS AND METHODS: We identified 51 patients who had USS from 1956 to 2006 at our institution and with >10 years of follow-up. The patients were followed retrospectively by a chart review. Patient data were analysed in a multifaceted fashion, paying particular attention to metabolic abnormalities, early (< or =30 days) and late (>30 days) complication rates, continence rates, imaging changes, and the rate of repeat surgical intervention. RESULTS: The median (range) follow-up was 15.7 (10.0-45.4) years and the median age at surgery was 58.8 (0.4-79.0) years; 40 (79%) patients had the procedure for malignancy and 11 (22%) for benign disease. Six patients (12%) had at least one early complication, including one wound dehiscence and one pulmonary embolus. In all, 22 patients (43%) had at least one late complication, with anastomotic stricture being the most common (11/51, 22%). This was followed by recurrent pyelonephritis in eight patients (16%), stones in five (10%), chronic renal insufficiency in three (6%) and severe intractable acidosis in two (4%). A repeat surgical intervention was required in 19 (37%) patients. In all, 94% (48) reported complete continence. No patient developed colonic malignancy during the course of this study. CONCLUSIONS: USS is associated with long-term complications. While this complication rate might not be acceptable for all patients, some might be willing to undergo the procedure as the primary method of urinary diversion. When designing newer minimally invasive techniques for the treatment of benign and malignant conditions of the bladder, consideration could be given to USS as a form of urinary diversion in highly selected patients.

Locally recurrent prostate cancer after initial radiation therapy: a comparison of salvage radical prostatectomy versus cryotherapy.

PURPOSE: We compared the treatment outcomes of salvage radical prostatectomy and salvage cryotherapy for patients with locally recurrent prostate cancer after initial radiation therapy. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who underwent salvage radical prostatectomy at the Mayo Clinic between 1990 and 1999, and those who underwent salvage cryotherapy at M. D. Anderson Cancer Center between 1992 and 1995. Eligibility criteria were prostate specific antigen less than 10 ng/ml, post-radiation therapy biopsy showing Gleason score 8 or less and prior radiation therapy alone without pre-salvage or post-salvage hormonal therapy. We assessed the rates of biochemical disease-free survival, disease specific survival and overall survival in each group. Biochemical failure was assessed using the 2 definitions of 1) prostate specific antigen greater than 0.4 ng/ml and 2) 2 increases above the nadir prostate specific antigen. RESULTS: Mean followup was 7.8 years for the salvage radical prostatectomy group and 5.5 years for the salvage cryotherapy group. Compared to salvage cryotherapy, salvage radical prostatectomy resulted in superior biochemical disease-free survival by both definitions of biochemical failure (prostate specific antigen greater than 0.4 ng/ml, salvage cryotherapy 21% vs salvage radical prostatectomy 61% at 5 years, p <0.001; 2 increases above nadir with salvage cryotherapy 42% vs salvage radical prostatectomy 66% at 5 years, p = 0.002) and in superior overall survival (at 5 years salvage cryotherapy 85% vs salvage radical prostatectomy 95%, p = 0.001). There was no significant difference in disease specific survival (at 5 years salvage cryotherapy 96% vs salvage radical prostatectomy 98%, p = 0.283). After adjusting for post-radiation therapy biopsy Gleason sum and pre-salvage treatment serum prostate specific antigen on multivariate analysis salvage radical prostatectomy remained superior to salvage cryotherapy for the end points of any increase in prostate specific antigen greater than 0.4 ng/ml (HR 0.24, p <0.0001), 2 increases in prostate specific antigen (HR 0.47, p = 0.02) and overall survival (HR 0.21, p = 0.01). CONCLUSIONS: Young, healthy patients with recurrent prostate cancer after radiation therapy should consider salvage radical prostatectomy as it offers superior biochemical disease-free survival and may potentially offer the best chance of cure.

How long is too long? The effect of the duration of anaesthesia on the incidence of non-urological complications after surgery.

OBJECTIVE: To examine the association between the duration of anaesthesia and non-urological complication (NUC) rates after surgery, as the increasing complexity of minimally invasive and laparoscopic procedures in urology has resulted in longer surgery and anaesthesia, and information on the effect of this on NUC rates is limited. PATIENTS AND METHODS: We identified 2196 patients who had open radical nephrectomy or nephron-sparing surgery at our institution between 1989 and 2002. Patients were subdivided into groups I, II, and III according to the duration of general anaesthesia (<4, 4-6 and > or =6 h, respectively). NUCs after surgery, and mortality during and after surgery, were evaluated. RESULTS: There were 1340, 723, and 133 patients in groups I, II and III, respectively. The incidences of any NUC were 3.1%, 5.8% and 13.5%, respectively. The odds ratios for the likelihood of a NUC were 1.91 (P = 0.004) and 4.84 (P < 0.001) for groups II and III, respectively. These differences remained significant even after adjusting for patient and tumour characteristics. Perioperative mortality was highest in group III, at 2.3%, vs 0.4% in groups I and II. CONCLUSIONS: Longer anaesthesia is associated with an increase in the incidence of perioperative complications and mortality, especially when the duration of anaesthesia is >6 h. This increase appears to be independent of patient's preoperative health status, tumour extent and blood loss.

Bladder cancer risk following primary and adjuvant external beam radiation for prostate cancer.

PURPOSE: Increased rates of secondary bladder malignancies have been reported after external beam radiation therapy (EBRT) for gynecological malignancies with relative risks of 2 to 4. This study was designed to determine if there was an increase in bladder cancer after EBRT for prostate cancer. MATERIALS AND METHODS: We retrospectively reviewed the Mayo Clinic Cancer Registry for patients who received EBRT for prostate cancer (1980 to 1998). Patients diagnosed with bladder cancer were identified. Comparative incidence rates were obtained from the national Surveillance, Epidemiology and End Results database. Subset analysis included patients treated with adjuvant radiation and those residing locally. Medical histories of patients with bladder cancer were reviewed. RESULTS: A total of 1,743 patients received EBRT for prostate cancer at our institution. In more than 12,353 man-years of followup no increase in bladder cancer risk was encountered. Subset analysis of men who received adjuvant radiation demonstrated that the relative risk of bladder cancer was increased but was not statistically significant. When the analysis was restricted to patients residing in the local area, the number of patients in whom subsequent bladder cancer developed was similar to Surveillance, Epidemiology and End Results rates. However, in the adjuvant radiation subset there was a statistically significant increase in subsequent bladder cancer. Patients in whom bladder cancer develops after EBRT often present with low grade disease but many have recurrence and progression. CONCLUSIONS: This retrospective review suggests there is not evidence of increased risk of bladder cancer after radiation therapy, assuming unbiased followup and complete ascertainment of cases. The natural history of bladder cancer in this population does not seem to be altered by a history of radiation.

After radical retropubic prostatectomy 'insignificant' prostate cancer has a risk of progression similar to low-risk 'significant' cancer.

OBJECTIVE: To assess progression and survival among patients with small-volume, well-differentiated, organ-confined prostate cancer found at radical retropubic prostatectomy (RRP), often defined as being 'insignificant', thus testing whether they are indeed 'insignificant'. PATIENTS AND METHODS: We identified 6496 men treated for prostate cancer by RRP between 1990 and 1999, and defined 'insignificant' tumours as those in men having a prostate-specific antigen (PSA) level of < 10 ng/mL before RRP, a cancer volume of < or = 0.5 mL, a specimen Gleason of score < or = 6 and stage < or = pT2. Survival was assessed using the Kaplan-Meier method and compared using the two-sided log-rank test. RESULTS: 'Insignificant' tumours were found in 354 (5.5%) men, of whom only one had metastatic progression and none died from prostate cancer, with a median (range) follow-up of 9.2 (0.8-15.6) years. Biochemical progression-free survival (87% vs 85%, respectively, at 10 years, P = 0.5), systemic progression-free survival (100% vs 99%, P = 0.3), overall survival (91% vs 88%, P = 0.16) and cancer-specific survival (100% in each group, P = 0.32) were each similar among men with 'insignificant' prostate cancer and men with low-risk (defined by Gleason score, preoperative PSA level, seminal vesicle and surgical margin status) 'significant' cancer. Clinical stage, biopsy Gleason score and preoperative PSA doubling time were multivariably predictive of 'insignificant' tumours at RRP. CONCLUSIONS: 'Insignificant' prostate cancer at RRP is associated with a comparable risk of biochemical progression as low-risk 'significant' cancer. Although clinical predictors for 'insignificant' pathology can be identified, it remains to be established whether such patients can be safely managed conservatively.

Predictors of survival from urachal cancer: a Mayo Clinic study of 49 cases.

BACKGROUND: Outcome results of a long-term analysis of urachal cancer using a new staging system are presented. METHODS: The authors analyzed clinical outcomes from 49 patients with the diagnosis of urachal cancer who were seen at the Mayo Clinic, Rochester, Minnesota from 1950 to 2003. The TNM staging system was used to predict outcome after surgical resection. RESULTS: Among 49 study patients, 33 were men, 16 were women, and their median age at presentation was 57.5 years. The vast majority of tumors were adenocarcinomas (89%), 4% were sarcomas and transitional cell carcinomas, and the rest were high-grade mixed neoplasms. Among the adenocarcinomas, 63.6% were mucin-producing tumors. Partial cystectomy with or without pelvic lymph node dissection and removal of the urachus was performed in 41 (83%) cases. Overall survival for all stages was 62 months with 17 (34%) patients still alive more than 5 years after treatment. Applying the TNM staging system, the authors demonstrated a median survival time for stage I/II patients of 10.8 years (95% CI, 6.9 years to 12.0 years) compared with a median survival of 1.3 years (95% CI, 1.1 years to 1.9 years; log-rank P<.0001) for patients with advanced disease (stages III and IV). CONCLUSIONS: Stage at presentation by the TNM staging system proved to be the main predictor of outcome after surgery for urachal cancer. Better systemic modality treatments are needed for advanced stages of this disease.

Treatment of prostate cancer local recurrence after radical retropubic prostatectomy with 17-gauge interstitial transperineal cryoablation: initial experience.

OBJECTIVES: Interstitial transperineal cryoablation with 17-gauge cryoprobes is an accepted treatment modality for localized prostate cancer. The effectiveness of cryoablation in the treatment of local prostate cancer recurrence after radical retropubic prostatectomy (RRP) is unknown. METHODS: We reviewed the outcome of cryoablative treatment in 15 patients for biopsy-proven locally recurrent prostate cancer after RRP. The follow-up data included prostate-specific antigen (PSA) level, imaging findings, side effects, and an assessment of voiding habits. RESULTS: The mean follow-up time for the entire group was 20 months (range 4 to 32). Of the 15 patients, 6 (40%) had sustained declines in the PSA level (cryoablation success group) and 9 (60%) had disease progression (cryoablation failure group), defined as a PSA increase greater than 0.1 ng/mL from the PSA nadir, or the addition of external beam radiotherapy or androgen deprivation therapy. The pre-RRP PSA level and pre-cryoablation PSA level were similar for both groups. The pre-RRP biopsy Gleason scores (P = 0.03), RRP Gleason scores (P = 0.03), and lesion size on magnetic resonance imaging (P = 0.001) were lower in the success group than in the failure group. All patients who were recurrence free after cryotherapy had a biopsy and Gleason score of 6 or less. Of the 15 patients, 3 (20%) developed worsening of post-RRP incontinence. CONCLUSIONS: Our preliminary results suggest that salvage cryoablation can be an effective and safe treatment modality and a possible alternative to external beam radiotherapy for targeted control of confirmed local recurrences after RRP, especially in those with favorable biopsy or pathologic Gleason scores before cryotherapy. Larger cohorts and longer follow-up are needed to assess the viability of this treatment.

Endoscopic management of upper tract urothelial carcinoma in patients with a history of bladder urothelial carcinoma.

PURPOSE: Endoscopic management of renal pelvis and ureteral urothelial carcinoma is gaining acceptance as a conservative treatment modality. Patients with a history of bladder urothelial carcinoma are at high risk for upper tract recurrence. We evaluate the role of endoscopic management of upper tract urothelial carcinoma in patients with a history of primary bladder urothelial carcinoma. MATERIALS AND METHODS: We retrospectively reviewed 90 patients with a history of primary bladder urothelial carcinoma who underwent endoscopic treatment of localized upper tract urothelial carcinoma between 1983 and 2004. RESULTS: Median patient age at diagnosis was 73 years (range 50 to 90). A total of 13 (14.4%) patients previously underwent cystectomy. With a median followup of 4.3 years (range 0.1 to 17), 105 upper tract urothelial carcinoma recurrences developed in 55 patients at a mean of 0.6 years (range 22 days to 5.9 years). Of these recurrences 76 were amenable to endoscopic management while 29 required nephroureterectomy. In 38 patients there were 91 bladder recurrences. At last followup 48 patients died, 17 of urothelial carcinoma at a median of 3.4 years (range 1 to 10). Cancer specific survival at 5 years for this cohort was 71.2%. Risk of death from urothelial carcinoma was significantly associated with stage (RR 3.23) and grade (RR 4.05) of upper tract urothelial carcinoma, imperative indication (RR 4.30), and treatment of bladder urothelial carcinoma with cystectomy (RR 3.34). CONCLUSIONS: Endoscopic management of upper tract urothelial carcinoma in patients with primary bladder urothelial carcinoma demonstrates a significant local recurrence rate. Furthermore, 5-year cancer specific survival is low. These patients represent a high risk cohort requiring strict ureteroscopic followup after endoscopic management is instituted.

Stratification of patient risk based on prostate-specific antigen doubling time after radical retropubic prostatectomy.

OBJECTIVE: To assess the risk of local recurrence, systemic progression, and death from cancer among patients who experience biochemical relapse after radical retropubic prostatectomy and to stratify those patients by prostate-specific antigen (PSA) doubling time (DT). PATIENTS AND METHODS: We identified patients who experienced biochemical recurrence (defined as a PSA level < or =0.4 ng/mL) after radical prostatectomy from January 1, 1990, to December 31, 1999, for prostate adenocarcinoma. The PSA-DT was calculated by log linear regression using all PSA values within 2 years of biochemical recurrence. Local recurrence- and systemic progression- free survival and cancer-specific survival were estimated using the Kaplan-Meier method and analyzed by the log-rank test and Cox models. RESULTS: Biochemical recurrence was noted in 1521 (27%) of 5533 men during the follow-up period. Of the 1064 patients with a calculable PSA-DT, 322 (30%) had a PSA-DT of less than 1 year, 357 (34%) had a PSA-DT of 1 to 9.9 years, and 385 (36%) had a PSA-DT of 10 years or more. Patients with a PSA-DT of 10 years or more were less likely to have a higher preoperative PSA level, Gleason score, advanced pathologic stage, and seminal vesicle invasion. Patients with a PSA-DT of 10 years or more were at low risk of local recurrence (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.06-0.14; compared with patients with a PSA-DT of <1 year), systemic progression (HR, 0.05; 95% CI, 0.02-0.13), or death from cancer (HR, 0.15; 95% CI, 0.05-0.43). CONCLUSIONS: Prostate-specific antigen DT is an independent predictor of clinical disease recurrence and mortality after surgical biochemical failure. Risk stratification into high-, intermediate-, and low-risk categories based on the PSA-DT provides helpful clinical information and assists in the development of salvage therapy trials.

The impact of ischemia time during open nephron sparing surgery on solitary kidneys: a multi-institutional study.

PURPOSE: The safe duration of ischemia during nephron sparing surgery remains controversial. We performed a multi-institutional study to evaluate the renal effects of vascular clamping in patients with solitary kidneys. MATERIALS AND METHODS: Using the Cleveland Clinic and Mayo Clinic databases, we identified 537 patients with solitary kidneys who underwent open nephron sparing surgery. Renal complications were compared among patients who did not require vascular clamping (85), and those who had warm ischemia (174) and cold ischemia (278). RESULTS: Median patient age (63, 65, 64 years) and preoperative creatinine (1.4, 1.3, 1.4 mg/dl) were similar among patients with no ischemia, warm ischemia and cold ischemia, respectively. Median tumor size was smaller in patients with no ischemia (2.5 cm), compared to patients with warm (3.5 cm) and cold (4.0 cm) ischemia (p <0.001). Warm and cold ischemia was associated with a significantly increased risk of urine leak (p = 0.006), acute (p <0.001) and chronic (p = 0.027) renal failure, and temporary dialysis (p = 0.028) compared to patients with no ischemia. Warm ischemia longer than 20 minutes and cold ischemia longer than 35 minutes were associated with a higher incidence of acute renal failure (p = 0.002 and p = 0.003, respectively). Additionally, warm ischemia more than 20 minutes was associated with an increased risk of chronic renal insufficiency (41% vs 19%, p = 0.008), increase in creatinine greater than 0.5 (42% vs 15%, p <0.001) and permanent dialysis (10% vs 4%, p = 0.145). CONCLUSIONS: Vascular clamping during open nephron sparing surgery is associated with a higher incidence of renal complications. Attempts to limit warm ischemia to 20 minutes and cold ischemia to 35 minutes should be used when vascular clamping is necessary.

Dynamic outcome prediction in patients with clear cell renal cell carcinoma treated with radical nephrectomy: the D-SSIGN score.

PURPOSE: To date all prediction models for patients with renal cell carcinoma have estimated outcome in static fashion starting from the date of surgery only. We created a dynamic outcome prediction model for continual surveillance that accounts for the disease-free interval following surgery. MATERIALS AND METHODS: We identified 1,560 patients treated with radical nephrectomy for pM0 clear cell renal cell carcinoma between 1970 and 1999. The previously published stage, size, grade and necrosis score was used to stratify patients according to the risk of death from renal cell carcinoma. Cancer specific survival rates were calculated using the Kaplan-Meier method at surgery and at various disease-free intervals following surgery. RESULTS: At last followup 461 of the 1,560 patients had died of renal cell carcinoma at a median of 3.1 years following surgery. Median followup in patients still alive was 11.2 years. Patient outcome improved as the disease-free interval following surgery increased. For example, patients with a stage, size, grade and necrosis score of 5 had an estimated 5-year cancer specific survival rate of 69.6% at surgery. However, those who survived without disease for 1, 2 and 3 years following surgery had adjusted estimated 5-year cancer specific survival rates of 81.9%, 91.9% and 93.2%, respectively. Patients with a stage, size, grade and necrosis score of 7 had a 5-year cancer specific survival rate of 44.9% at surgery, which increased to 63.3%, 71.0% and 72.8% after 1 to 3 years of disease-free followup, respectively. CONCLUSIONS: Within each stage, size, grade and necrosis score cancer specific survival rates increase as the disease-free interval following surgery increases. We present a dynamic outcome prediction model that allows clinicians to continually adjust surveillance as the disease-free interval increases.

Impact of tumor size on the predictive ability of the pT3a primary tumor classification for renal cell carcinoma.

PURPOSE: The accuracy of the pT3a primary tumor classification for renal cell carcinoma has been questioned recently. We investigated the association of perinephric and renal sinus fat invasion with death from renal cell carcinoma independent of tumor size. MATERIALS AND METHODS: We identified 2,165 patients treated with open radical nephrectomy or nephron sparing surgery for clinically localized, sporadic pT1a, pT1b, pT2 or pT3a renal cell carcinoma between 1970 and 2002. Patients with pT3a disease were then subdivided into 3 groups according to tumor size to match the size definitions for the pT1a, pT1b and pT2 tumor classifications. RESULTS: There were 834 patients with pT1a RCC, 674 with pT1b, 494 with pT2 and 163 with pT3a RCC. At last followup 317 patients died of RCC at a median of 3.8 years following surgery. The median followup among the 1,087 patients still alive at last followup was 7.8 years (range 0 to 34). The risk ratios (95% CI) for the association between fat invasion and death from RCC among patients with tumors 4 cm or smaller, 4 to 7 cm and more than 7 cm were 6.15 (1.84-20.50, p = 0.003), 4.12 (2.50-6.78, p <0.001) and 2.13 (1.53-2.97, p <0.001), respectively. These associations remained statistically significant in a multivariate analysis that included nuclear grade and histological coagulative tumor necrosis. CONCLUSIONS: Peripheral perinephric and renal sinus fat invasion was associated with death from RCC independent of tumor size. Our data contradict reports suggesting that pT3a tumors should be reclassified according to tumor size only.

The role of nephron sparing surgery for metastatic (pM1) renal cell carcinoma.

PURPOSE: Studies have demonstrated increased time to progression when cytoreductive nephrectomy is performed for metastatic renal cell carcinoma. We evaluated the role of nephron sparing surgery in these patients. MATERIALS AND METHODS: We selected all patients with pM1 renal cell carcinoma treated with nephron sparing surgery or radical nephrectomy, and all patients with pM0 renal cell carcinoma undergoing nephron sparing surgery for solitary kidney from 1970 to 2002 from the Mayo Clinic Nephrectomy Registry. RESULTS: We identified 16 patients who underwent nephron sparing surgery for pM1 renal cell carcinoma. Solitary kidney was present in 12, 3 had bilateral synchronous disease and 1 had elective nephron sparing surgery. Cancer specific survival rates at 1, 3 and 5 years were 81%, 49% and 49%, respectively. We identified 404 patients who underwent radical nephrectomy for pM1 renal cell carcinoma. Cancer specific survival rates at 1, 3 and 5 years were 51%, 21% and 13%, respectively. The pM1 nephron sparing surgery for solitary kidney cases were more likely to have early (33% vs 10%, p = 0.009) or late (50% vs 19%, p = 0.018) complications compared with pM1 radical nephrectomy cases. There were no significant differences in early (p = 0.475) or late (p = 0.350) complications between pM1 nephron sparing surgery cases and 139 pM0 nephron sparing surgery cases. CONCLUSIONS: Cancer specific survival rates in pM1 nephron sparing surgery cases were comparable to pM1 radical nephrectomy cases. Although there were differences in early and late complications between the pM1 nephron sparing surgery and pM1 radical nephrectomy groups, there were no differences when compared with imperative pM0 nephron sparing surgery cases. This study demonstrates that nephron sparing surgery can achieve adequate cytoreductive therapy while preserving renal function, with postoperative complication rates similar to those of pM0 nephron sparing surgery cases.

Outcomes of Gleason score 10 prostate carcinoma treated by radical prostatectomy.

OBJECTIVES: To evaluate the outcome of radical prostatectomy for the rarest and most poorly differentiated prostate tumors of all: those with Gleason score 10. Controversy exists as to which form of therapy is most effective for high-grade prostate cancer (PCa). METHODS: We retrospectively reviewed the charts of all patients with pathologic Gleason score 10 PCa treated at our institution with radical prostatectomy from 1977 to 1999. All pathology specimens were reviewed by a urologic pathologist, and 13 cases with true Gleason score 10 PCa were identified. The preoperative covariables (prostate-specific antigen level, biopsy Gleason score, and clinical stage), perioperative covariables (pathologic stage, margin status, and tumor ploidy), and postoperative covariables (prostate-specific antigen level and adjuvant and salvage treatments) were assessed with respect to the oncologic outcomes. RESULTS: The median follow-up was 4.2 years. Preoperatively, only 4 of the 13 cases were correctly identified at biopsy, and the median preoperative prostate-specific antigen level was 4.5 ng/mL (interquartile range 0.3 to 12.5). Pathologic examination showed a small cell component in 7 cases, seminal vesicle invasion in 11, and positive lymph nodes in 3. Six patients developed recurrent PCa: three local, two systemic, and one biochemical recurrence. The biochemical recurrence-free and cancer-specific survival rate at 5 years was 53.8% and 76.9%, respectively. CONCLUSIONS: Gleason score 10 PCa is a highly aggressive disease that is usually lethal if managed conservatively. The results of the present study have provided some evidence that radical prostatectomy may be of benefit to patients with Gleason score 10 PCa.

Second primary malignancies associated with renal cell carcinoma histological subtypes.

PURPOSE: Renal cell carcinoma has been linked to numerous secondary malignancies. We evaluated the risk of secondary malignancies by renal cell carcinoma histological subtype in patients with clear cell, papillary and chromophobe renal cell carcinoma. MATERIALS AND METHODS: We studied 2,722 patients who underwent nephrectomy for sporadic renal cell carcinoma at our institution between 1970 and 2000. All specimens were reviewed by a single urological pathologist for histological subtype. Associations of second primary malignancies by histological subtype were evaluated using the chi-square and Fisher exact tests. RESULTS: Of the patients studied 2,188 (80.4%) had clear cell, 378 (13.9%) had papillary and 128 (4.7%) had chromophobe renal cell carcinoma. Patients with papillary renal cell carcinoma were significantly more likely to have colon cancer (p = 0.041), prostate cancer (p = 0.003), any second malignancy (p <0.001) and multiple malignancies (p <0.001) compared with patients with clear cell renal cell carcinoma. In addition, patients with chromophobe renal cell carcinoma were significantly more likely to have colon cancer than patients with clear cell renal cell carcinoma (p = 0.020). Although patients with papillary renal cell carcinoma were more likely to have bladder cancer, the incidence did not differ significantly compared with that in patients harboring clear cell and chromophobe renal cell carcinoma (p = 0.193). We did not find a significant difference in the incidence of breast cancer, lung cancer, rectal cancer or lymphoma among histological subtypes. CONCLUSIONS: Our data indicate that patients with papillary renal cell carcinoma are more likely to harbor secondary malignancies, including colon and prostate cancer, than patients with clear cell renal cell carcinoma. These results may have important implications for patient education and followup evaluation, and they should prompt mechanistic investigations.

Impact of familial and hereditary prostate cancer on cancer specific survival after radical retropubic prostatectomy.

PURPOSE: Men with a family history of prostate cancer are at higher risk for prostate cancer. There are conflicting data regarding the impact of hereditary forms of prostate cancer on long-term outcomes after radical prostatectomy. We examined the impact of familial and hereditary prostate cancer treatment in the prostate specific antigen era. MATERIALS AND METHODS: Patients who underwent radical prostatectomy for prostate cancer from 1987 to 1997 were surveyed (3,560 responders) to determine the family history of prostate cancer. Patients were categorized as having familial prostate cancer if they had at least 1 first-degree relative with prostate cancer. Hereditary prostate cancer was defined as nuclear families with 3 cases of prostate cancer, families with prostate cancer in each of 3 generations and families with 2 men diagnosed before age 55 years. Sporadic prostate cancer was defined as patients with no family history. Clinical and pathological features, and long-term outcome measures, including biochemical recurrence-free, systemic progression-free and cancer specific survival, were compared among patients with familial, hereditary and sporadic prostate cancer. RESULTS: A total of 865 and 133 patients were categorized as having familial prostate cancer and hereditary prostate cancer, respectively. Preoperatively prostate specific antigen was higher in patients with hereditary prostate cancer than in the other 2 groups (p = 0.04). Ten-year biochemical progression-free, systemic progression-free and cancer specific survival were equivalent. CONCLUSIONS: Except for preoperative prostate specific antigen, clinicopathological features and long-term oncological outcomes are equivalent after radical prostatectomy in patients with familial, hereditary and sporadic prostate cancer.

Detectable prostate specific antigen between 60 and 120 days following radical prostatectomy for prostate cancer: natural history and prognostic significance.

PURPOSE: Following radical retropubic prostatectomy for prostate cancer, if the serum prostate specific antigen fails to become undetectable, occult micrometastatic disease is suspected. We assessed the natural history of disease progression, and predictors of recurrence and survival in this group of patients. MATERIALS AND METHODS: We identified 303 men treated with radical retropubic prostatectomy for prostate cancer between 1990 and 1999, who had a detectable prostate specific antigen between 60 and 120 days postoperatively. Systemic recurrence-free and cancer specific survival were estimated using the Kaplan-Meier method, and analyzed using Cox proportional hazards models. RESULTS: Clinical and pathological features were more adverse among men whose postoperative prostate specific antigen was detectable. These men had poorer systemic recurrence-free survival and cancer specific survival compared to men with an undetectable postoperative prostate specific antigen, and even men whose prostate specific antigen subsequently became detectable. These differences persisted after multivariate adjustment for preoperative prostate specific antigen, specimen Gleason score, seminal vesicle and margin status. With a median followup of 8.5 years, 50 systemic recurrences and 26 deaths from cancer were observed. Gleason score and the prostate specific antigen doubling time were multivariate predictors of systemic recurrence, while Gleason score, margin status and seminal vesicle invasion were predictors of death from cancer. CONCLUSIONS: A detectable prostate specific antigen immediately following radical retropubic prostatectomy confers an increased risk of progression and death, but only in a subset of patients, who may be identified on the basis of pathological features and prostate specific antigen doubling time. In future such patients may be suitable for trials of systemic therapy.

Conventional assessment of needle biopsy specimens is more useful than digital image analysis of proliferation and DNA ploidy in prediction of positive surgical margins at radical prostatectomy.

OBJECTIVES: The preoperative prediction of the likelihood of positive surgical margins (+SMs) at radical retropubic prostatectomy (RRP) may be useful for counseling and determining the surgical approach. The aim of this study was to assess the additional value of digital image analysis (DIA) of ploidy and proliferation on needle biopsies, in addition to the known preoperative predictors of +SMs at RRP. METHODS: We identified 454 patients treated by RRP at our institution from 1995 to 1998 for prostate cancer verified by transrectal ultrasound-guided biopsy, with a specimen adequate for DIA. Patients receiving preoperative hormonal therapy were excluded. The clinical features, transrectal ultrasound-guided biopsy findings, and DIA evaluation of MIB-I immunostaining and DNA ploidy were assessed in a multivariate logistic regression model to predict for +SMs at RRP. RESULTS: The mean +/- SD age at treatment was 64.5 +/- 6.5 years, the percentage of positive cores was 40.4% +/- 24.3%, the median prostate-specific antigen level was 6.3 ng/mL (range 0.6 to 112.0), median biopsy Gleason score was 6 (range 4 to 9), and median percentage of diploid nuclei was 67% (range 0% to 100%). Of the 454 patients, 185 (40.7%) had +SMs; this finding was time dependent (1995 to 1996, 45% and 1997 to 1998, 31%; P = 0.004). Univariately, preoperative prostate-specific antigen, biopsy Gleason score, extent of cancer on biopsy, MIB-1 expression, percentage of diploid or nondiploid nuclei, and year of surgery were predictive for +SMs. On multivariate analysis, the preoperative prostate-specific antigen level, biopsy Gleason score, percentage of positive cores, and year of surgery remained significant. CONCLUSIONS: The results of our study have shown that the likelihood of +SMs at RRP is best predicted on the basis of conventional prognostic factors. The DIA features of needle biopsies did not provide additional predictive power.