HAVE COMPLICATION RATES DECREASED AFTER TREATMENT FOR LOCALIZED PROSTATE CANCER?

PURPOSE: The American Urological Association Prostate Cancer Clinical Guidelines Panel reviewed 12,501 publications on prostate cancer from 1955 to 1992 to determine whether the complication rates of external beam radiation therapy, interstitial radiotherapy and radical prostatectomy have decreased. MATERIALS AND METHODS: Complications reported in at least 6 series, study duration and sample sizes were extracted. Year specific study weighted mean patient ages and complication rates were computed. Regression analysis was performed of the study year on weighted mean patient age and complication rate. RESULTS: Study year had a significant effect on mean patient age and rate of the majority of complications examined. Data indicated a gradual increase in study patient age and a simultaneous decrease in complications from 1960 to 1990. CONCLUSIONS: Complication rates in the treatment of localized prostate cancer have decreased during the last 20 to 40 years. This decrease occurred despite evidence that the average age of treated patients had increased during the same period.     

DOES BODY MASS INDEX AFFECT SURVIVAL OF PATIENTS UNDERGOING RADICAL OR PARTIAL CYSTECTOMY FOR BLADDER CANCER?

PURPOSE: Obesity is estimated to account for up to 20% of all cancer deaths. We evaluated the effect of body mass index (BMI) on survival in patients undergoing radical or partial cystectomy for bladder cancer. MATERIALS AND METHODS: Pathological and medical records on 300 consecutive patients undergoing radical or partial cystectomy for invasive bladder cancer between January 1990 and December 1993 were reviewed. The standard WHO definition of BMI was used, that is normal weight-less than 25 kg/m, overweight-25 to 29.9 kg/m and obesity-30 kg/m or greater. Sufficient data were available on 288 of 300 patients (96%) with cystectomy (radical in 264 and partial in 24) for analysis. RESULTS: The BMI distribution was normal weight in 34% of patients, overweight in 41% and obesity in 25%. Mean followup was 53.4 months (median 39, range 1 to 168). Median overall survival was 43.0 months (95% CI 37.1 to 58.4), while median disease specific survival was 82.5 months (95% CI 50.0 to 127.5). Multivariate analysis revealed that age greater than 65 years, pathological stage, smoking history and soft tissue margin status as significant factors impacting overall survival (p <0.05). Pathological stage was organ confined (less than pT3a) in 51% of cases. BMI was not associated with disease specific survival as a continuous (p = 0.17) or categorical (p = 0.51) variable. Although it was insignificant, unadjusted analysis showed lower disease specific mortality in patients with a BMI of less than 25 mg/kg and organ confined disease (p = 0.08). CONCLUSIONS: There was no significant association between BMI and overall or disease specific survival, although there may be a trend toward better disease specific survival in normal weight (BMI less than 25 kg/m) patients with organ confined disease (p = 0.08).     

PROSTATE CANCER AND DIET: FOOD FOR THOUGHT?

? There is now increasing evidence that diet plays a major role in prostate cancer biology and tumorigenesis. ? In a health conscious society, it is becoming increasingly common for Urologists to be asked about the impact of diet on prostate cancer. ? In the present review, we explore the current evidence for the role of different dietary components and its' effect on prostate cancer prevention and progression. ? A literature search was conducted using PubMed? to identify key studies. ? There was some evidence to suggest that green tea, isoflavones, lycopenes, cruciferous vegetables and omega 3 polyunsaturated fatty acid intake to be beneficial in the prevention and/or progression of prostate cancer. ? There was also evidence to suggest that a high total fat, meat (especially well cooked) and multivitamin intake may be associated with an increased risk of developing prostate cancer. ? To date publications have been highly heterogeneous and variable in quality and design. More robust, high quality research trials are needed to help us understand the complex relationship between diet and prostate cancer.     

FAMILIAL PROSTATE CANCER: A DIFFERENT DISEASE?

Purpose

We analyzed the outcome after radical prostatectomy of patients with familial prostate cancer versus patients with sporadic prostate cancer.

Materials and Methods

The study included 720 patients with prostate carcinoma who were treated with prostatectomy between 1987 and 1996. Patients were excluded from the study if they had received adjuvant or neoadjuvant treatment, or had no available pretreatment prostatic specific antigen (PSA) level, no available biopsy Gleason score, incomplete pathological information or no available followup PSA levels. The analysis was performed on 529 cases. Patients were considered to have a positive family history for prostate cancer when the index patient confirmed the diagnosis of prostate cancer in a first degree relative (brother or father). The outcomes of interest were biochemical relapse-free survival, local failure and distant metastases. Proportional hazards were used to analyze the effect of family history and confounding variables (that is age, stage, biopsy Gleason score, initial PSA levels, surgical specimen Gleason score, extracapsular extension, lymph node metastasis, seminal vesicle invasion and surgical margin involvement) on treatment outcome.

Results

Median followup was 30 months. Of all cases 12% had a positive family history. Younger age was the only factor associated with positive family history, with 18% of patients younger than 65 years having a positive family history versus 6% of older patients (chi-square p <0.001). The 5-year biochemical relapse-free survival rate for the entire group was 64%. The 5-year biochemical relapse-free survival rates for patients with negative family history versus positive history were 66% and 46%, respectively (p = 0.001). A multivariate time-to-failure analysis using the proportional hazards model was performed based on family history, age (less than 65 versus 65 to 69 versus 70 or greater, initial PSA (10 or less versus greater than 10), biopsy Gleason score (6 or less versus 7 or greater), clinical T stage (T1-T2 versus T2B-C), prostatectomy specimen Gleason score (6 or less versus 7 or greater), extracapsular extension, seminal vesicle involvement, surgical margin involvement and lymph node involvement. After adjusting for the potential confounding factors, positive family history remained strongly associated with biochemical failure. The clinical failure rate for the entire group was 14%. The 5-year local failure rate was 7%, with positive surgical margins being the only independent predictor of local failure. The 5-year distant metastasis rate was 8%, with family history and initial PSA levels being independent predictors of distant relapse.

Conclusions

Our study suggests that patients with a familial prostate cancer have a higher likelihood of biochemical failure after radical prostatectomy than patients with sporadic cancer. This effect is independent of pretreatment or pathological factors. Our results suggest that the higher failure rates associated with familial prostate cancer are mainly secondary to higher distant relapse rates, and that familial prostate cancer may be more biologically aggressive than sporadic cancers.     

CANCER SPECIFIC SURVIVAL FOR PATIENTS WITH pT3 RENAL CELL CARCINOMA—CAN THE 2002 PRIMARY TUMOR CLASSIFICATION BE IMPROVED?

PURPOSE: The 2002 primary tumor classification for renal cell carcinoma (RCC) does not distinguish between patients with tumor thrombus involving the renal vein only and those with inferior vena cava tumor thrombus below the diaphragm. We evaluated the association of tumor thrombus level and fat invasion with outcome to determine if further subclassification would improve the prognostic accuracy of the current classification. MATERIALS AND METHODS: We studied 675 patients treated with radical nephrectomy or nephron sparing surgery for pT3a (206, 30.5%), pT3b (422, 62.5%), pT3c (19, 2.8%) or pT4 (28, 4.2%) RCC at the Mayo Clinic between 1970 and 2000. Associations with outcome were evaluated using Cox proportional hazards regression. RESULTS: There were 531 deaths from RCC at a median of 1.5 years following nephrectomy. Patients with pT3b RCC and level I, II or III tumor thrombus were significantly more likely to die of RCC compared to patients with pT3b RCC and level 0 tumor thrombus (risk ratio 1.62, p <0.001). Patients with peripheral perinephric or renal sinus fat invasion were also more likely to die of RCC compared to patients without fat invasion (risk ratio 1.87, p <0.001). Therefore, patients with pT3 RCC were reclassified into 4 groups as thrombus level 0 without fat invasion, fat invasion only, thrombus level 0 with fat invasion or thrombus level I, II or III without fat invasion, and thrombus level I, II or III with fat invasion or thrombus level IV. This reclassification significantly improved prediction of death from RCC compared with the current classification (c indexes of 0.61 versus 0.55, respectively). CONCLUSIONS: Further subclassification of the primary tumor classification for patients with pT3 RCC improved prognostic accuracy.     

CAN DIET IN CONJUNCTION WITH STRESS REDUCTION AFFECT THE RATE OF INCREASE IN PROSTATE SPECIFIC ANTIGEN AFTER BIOCHEMICAL RECURRENCE OF PROSTATE CANCER?

PURPOSE: Epidemiological and laboratory evidence indicates that a Western diet is associated with an increased incidence of prostate cancer. Specific components of the diet, such as high saturated fat, low fiber and high meat content, may have greatest clinical significance in the later stages of tumor promotion and progression. However, departure from the conventional diet is difficult to initiate and maintain. Therefore, we combined the well-known Mindfulness-Based Stress Reduction (MBSR) program with a low saturated fat, high-fiber, plant-based diet to determine the effect on the rate of change in prostate specific antigen (PSA) in patients with biochemical recurrence after prostatectomy. MATERIALS AND METHODS: We enrolled 10 men and their partners in a 4-month group-based diet and MBSR intervention. A pre-study post-study design in which each subject served as his own control was used to compare the rate of increase in and doubling time of PSA before and after intervention. RESULTS: The rate of PSA increase decreased in 8 of 10 men, while 3 had a decrease in absolute PSA. Results of the signed rank test indicated a significant decrease in the rate of increase in the intervention period (p = 0.01). Estimated median doubling time increased from 6.5 months (95% confidence interval 3.7 to 10.1) before to 17.7 months (95% confidence interval 7.8 to infinity) after the intervention. CONCLUSIONS: Our small study provides evidence that a plant-based diet delivered in the context of MBSR decreases the rate of PSA increase and may slow the rate of tumor progression in cases of biochemically recurrent prostate cancer. Larger-scale randomized studies are warranted to explore further the preventive and therapeutic potential of diet and lifestyle modification in men with prostate cancer.     

FOCAL THERAPY FOR LOCALISED PROSTATE CANCER: ARE WE ASKING THE CORRECT RESEARCH QUESTIONS?

The goals of focal therapy are laudable, namely reducing morbidity of treatment while ensuring at least equivalent oncological outcomes when compared with established interventions for localised prostate cancer, e.g. RP and external beam radiotherapy. While progress has been made towards better identifying the index lesion in these patients, there is much yet to be done to establish the validity of the index lesion theory as the metastatic focus and to establish that current targeting and ablative platforms are adequate to deliver the goals outlined above. The correct research questions have not yet been asked to establish either of these key principles underpinning focal therapy for localised prostate cancer.     

BLADDER TUMOURS: TIME FOR A PARADIGM SHIFT?

The results for many types of cancers have improved during later decades but not so for bladder cancer. Most patients with muscle-invasive tumors will still succumb to the disease and a high recurrence rate characterises non-muscle invasive tumors.The objective is to critically review the present model of bladder cancer based on newly acquired biological data. The definition of bladder cancer has extended with the introduction of the WHO classification. The corresponding loss of distinction between benign tumor and cancer has not been rewarding and should be reintroduced to facilitate exploration of new molecular findings. The common endpoints recurrence and progression should be redefined or replaced by more appropriate endpoints. The concept of surgery only for locally advanced cancers has proven unsuccessful and has to be complemented with early administered systemic treatment.     

DOES FIBRIN SEALANT DECREASE IMMEDIATE URINARY LEAKAGE FOLLOWING RADICAL RETROPUBIC PROSTATECTOMY?

PURPOSE: We determined the effectiveness of fibrin sealant in decreasing postoperative urinary leakage following radical retropubic prostatectomy performed by 1 surgeon at Washington Hospital Center. MATERIALS AND METHODS: Between April and November 2003 our group treated 32 consecutive patients with prostate cancer with radical retropubic prostatectomy. The first 16 patients (control) underwent the Walsh described technique and the second group of 16 patients had an additional application of fibrin sealant around the urethro vesical anastomosis. Postoperative drain output was measured every 8 hours. The results of the 2 groups were compared. RESULTS: The Blake drain was removed after 4 nursing shifts (times 1 through 4) in 81% (13 of 16) of the control group and in 100% (16 of 16) of the fibrin sealant group. The fibrin sealant group had significantly less drainage output overall compared with the control group (p = 0.005). The drainage output from each group decreased with time at a significant rate independent of each other (p <0.001), and there was a larger difference (p = 0.04) in output between groups at times 1 and 2 compared with times 3 and 4. There was no relationship between the amount of urinary drainage and drain output. There was no immediate morbidity associated with the use of fibrin sealant. CONCLUSIONS: The application of fibrin sealant to the urethro vesical anastomosis during radical retropubic prostatectomy does decrease postoperative drain output. With earlier drain removal, patients would benefit from less discomfort and from skilled nursing requirements. In select patients early drain removal could accelerate discharge home.     

DOES THE MANAGEMENT OF BLADDER PERFORATION DURING TRANSURETHRAL RESECTION OF SUPERFICIAL BLADDER TUMORS PREDISPOSE TO EXTRAVESICAL TUMOR RECURRENCE?

PURPOSE: We evaluated the impact of a bladder perforation during transurethral resection of superficial bladder tumor on extravesical tumor recurrence and patient prognosis. We also defined potential risk factors for extravesical recurrence prospectively giving emphasis to the management of the perforation. MATERIALS AND METHODS: The medical records of 3,410 patients were reviewed. Parameters recorded included patient age and sex, tumor stage, grade, number, size and location at the time of perforation, the type of bladder perforation (extraperitoneal vs intraperitoneal) and the way the perforation was managed (open surgical repair vs conservative treatment). Logistic regression analysis was used to identify risk factors for extravesical recurrence. Cox regression analysis was used to compare cancer specific survival. RESULTS: A total of 34 cases of bladder perforation were recorded, 4 patients were treated with open surgery and 30 treated conservatively. The 4 patients who underwent open surgery presented with extravesical recurrence after a mean followup of 7.5 months. The remaining 30 patients had no evidence of extravesical recurrence after a mean followup of 60 months (p <0.001). Of the patients with extravesical relapse 3 died of disease. The surgical management of bladder perforation was the best predictor of extravesical recurrence (p <0.001, r = 1.13), followed by an intraperitoneal localization of the perforation (p =0.0003, r = 0.67) and tumor size (p =0.01, r = 0.42). CONCLUSIONS: Surgical repair of a bladder perforation during transurethral resection of bladder tumor increases the risk of extravesical tumor cell recurrence and negatively affects patient prognosis.     

EXTENDING THE INDICATIONS AND ANATOMICAL LIMITS OF PELVIC LYMPH NODE DISSECTION FOR PROSTATE CANCER: IMPROVED STAGING OR INCREASED MORBIDITY?

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

OBJECTIVE

• ? To assess, in a risk/benefit analysis, the additional risk for complications and benefits of extending the indications and anatomical limits of pelvic lymph node dissection (PLND).

PATIENTS AND METHODS

• ? In total, 971 consecutive patients with clinically localized prostate cancer underwent laparoscopic radical prostatectomy from 2003–2007.
• ? Before 1 February 2005, patients with a nomogram probability of lymph node invasion (LNI) <2% did not undergo PLND (No PLND group), whereas those with a LNI ≥2% had a PLND limited to the external iliac nodal group (limited PLND group).
• ? After 1 February 2005, all patients underwent a standard PLND including the external iliac, hypogastric and obturator fossa nodal groups (standard PLND group).
• ? The risk parameters were PLND‐related complications and operating time. Complications were graded using a modified Clavien classification. The benefit was the detection of nodal metastases.

RESULTS

• ? In the subgroup of patients with a LNI ≥2%, standard PLND was a superior operation than the limited PLND in detecting nodal metastases (14.3% vs 4.5%, respectively; P = 0.003).
• ? The risk/benefit of standard vs limited PLND would be one additional grade 3 complication per 20 additional patients with nodal metastases. In the subgroup of patients with LNI <2%, three patients (1.0%) had positive nodes after a standard PLND.
• ? The risk/benefit of standard PLND vs no PLND would be one additional grade 3 complication per three or four additional patients with nodal metastasis. The no PLND group was associated with the lowest risk of grade 1, 2 and 3 complications compared to either the limited or standard PLND groups (P < 0.001).

CONCLUSIONS

• ? In patients with LNI ≥2%, standard PLND detects more nodal metastasis. PLND is associated with higher but non‐prohibitive complications rate.
• ? The present study found no evidence that the incidence of complications would be reduced by a limited PLND.