Angel M. Serio

Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study

BACKGROUND Chronic kidney disease is a graded and independent risk factor for substantial comorbidity and death. We aimed to examine new onset of chronic kidney disease in patients with small, renal cortical tumours undergoing radical or partial nephrectomy. METHODS We did a retrospective cohort study of 662 patients with a normal concentration of serum creatinine and two healthy kidneys undergoing elective partial or radical nephrectomy for a solitary, renal cortical tumour (</=4 cm) between 1989 and 2005 at a referral cancer centre. Glomerular filtration rate (GFR) was estimated with the abbreviated Modification in Diet and Renal Disease Study equation. Separate analysis was undertaken, with chronic kidney disease defined as GFR lower than 60 mL/min per 1.73 m(2) and GFR lower than 45 mL/min per 1.73 m(2). FINDINGS 171 (26%) patients had pre-existing chronic kidney disease before surgery. After surgery, the 3-year probability of freedom from new onset of GFR lower than 60 mL/min per 1.73 m(2) was 80% (95% CI 73-85) after partial nephrectomy and 35% (28-43; p<0.0001) after radical nephrectomy; corresponding values for GFRs lower than 45 mL/min per 1.73 m(2) were 95% (91-98) and 64% (56-70; p<0.0001), respectively. Multivariable analysis showed that radical nephrectomy remained an independent risk factor for patients developing new onset of GFR lower than 60 mL/min per 1.73 m(2) (hazard ratio 3.82 [95% CI 2.75-5.32]) and 45 mL/min per 1.73 m(2) (11.8 [6.24-22.4]; both p<0.0001). INTERPRETATION Because the baseline kidney function of patients with renal cortical tumours is lower than previously thought, accurate assessment of kidney function is essential before surgery. Radical nephrectomy is a significant risk factor for the development of chronic kidney disease and might no longer be regarded as the gold standard treatment for small, renal cortical tumours.

B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome

B7-H3 and B7x are recently discovered members of the B7-CD28 family thought to dampen peripheral immune responses via negative costimulation. We evaluated their potential expression in human prostate cancer using a large cohort of patients with 7 years of follow-up. We identified 823 patients with tissue available treated with radical prostatectomy between 1985 and 2003. Immunohistochemistry was performed on tissue microarray sections using anti-B7-H3 and -B7x. The percentage and intensity of immunoreactivity by tumor cells were blindly evaluated by two urological pathologists, and outcome analyses were conducted. Both B7-H3 and B7x were highly expressed; 93% and 99% of tumors had aberrant expression, respectively. The median percentage of tumor cells staining positive was 80% for each molecule. Strong intensity for B7-H3 and B7x was noted in 212 (26%) and 120 (15%) patients, respectively. Patients with strong intensity for B7-H3 and B7x were significantly more likely to have disease spread at time of surgery (P < 0.001 and P = 0.005, respectively). Additionally, patients with strong intensity for B7-H3 and B7x were at significantly increased risk of clinical cancer recurrence (P < 0.001 and P = 0.005) and cancer-specific death (P = 0.004 and P = 0.04, respectively). To our knowledge, we present the largest investigation of B7 family molecules in a human malignancy and a previously undescribed evaluation of B7x in prostate cancer. B7-H3 and B7x are abundantly expressed in prostate cancer and associated with disease spread and poor outcome. Given the proposed immune-inhibitory mechanisms of B7-H3 and B7x, these molecules represent attractive targets for therapeutic manipulation in prostate cancer.

Impact of renal impairment on eligibility for adjuvant cisplatin-based chemotherapy in patients with urothelial carcinoma of the bladder

Perioperative cisplatin‐based chemotherapy has shown benefit in patients with high‐risk localized urothelial bladder cancer, but it is not widely used. Renal impairment may be a major factor limiting its use. The current study was designed to determine the proportion of patients ineligible to receive adjuvant cisplatin‐based chemotherapy based on inadequate renal function alone.

Long-Term Prediction of Prostate Cancer Up to 25 Years Before Diagnosis of Prostate Cancer Using Prostate Kallikreins Measured at Age 44 to 50 Years

PURPOSE We examined whether prostate-specific antigen (PSA) forms and human kallikrein 2 (hK2) measured at age 44 to 50 years predict long-term risk of incident prostate cancer. METHODS From 1974 to 1986, 21,277 men age 50 years in Malmö, Sweden, enrolled onto a cardiovascular study (74% participation). The rate of PSA screening in this population is low. According to the Swedish Cancer Registry, 498 were later diagnosed with prostate cancer. We measured hK2, free PSA, and total PSA (tPSA) in archived blood plasma from 462 participants later diagnosed with prostate cancer and from 1,222 matched controls. Conditional logistic regression was used to test for association of prostate cancer with hK2 and PSA forms measured at baseline. RESULTS Median delay between venipuncture and prostate cancer diagnosis was 18 years. hK2 and all PSA forms were strongly associated with prostate cancer (all P < .0005). None of the 90 anthropometric, lifestyle, biochemical, and medical history variables measured at baseline was importantly predictive. A tPSA increase of 1 ng/mL was associated with an increase in odds of cancer of 3.69 (95% CI, 2.99 to 4.56); addition of other PSA forms or hK2 did not add to the predictive value of tPSA. tPSA remained predictive for men diagnosed > or = 20 years after venipuncture, and the predictive value remained unchanged in an analysis restricted to palpable disease. CONCLUSION A single PSA test at age 44 to 50 years predicts subsequent clinically diagnosed prostate cancer. This raises the possibility of risk stratification for prostate cancer screening programs.

Age‐adjusted Charlson comorbidity score is associated with treatment decisions and clinical outcomes for patients undergoing radical cystectomy for bladder cancer

By using the age‐adjusted Charlson comorbidity index (ACCI), the authors characterized the impact of age and comorbidity on disease progression and overall survival after radical cystectomy (RC) for transitional cell carcinoma of the bladder. Also evaluated was whether ACCI was associated with clinicopathologic and treatment characteristics.

Comprehensive Prospective Comparative Analysis of Outcomes Between Open and Laparoscopic Radical Prostatectomy Conducted in 2003 to 2005

PURPOSE In a nonrandomized prospective fashion we compared the oncological, functional and morbidity outcomes after laparoscopic and retropubic radical prostatectomy. MATERIALS AND METHODS Between January 2003 and December 2005 a total of 1,430 consecutive men with clinically localized prostate cancer underwent radical prostatectomy, laparoscopic in 612 and retropubic in 818. The surgical approach was selected by the patient. Preoperative staging, respective surgical techniques, pathological examination and followup were uniform. Functional outcome was measured by patient completed health related quality of life questionnaire. RESULTS Positive surgical margin rates (11%) and freedom from progression (median followup 18 months) were comparable between laparoscopic and retropubic radical prostatectomy (HR 0.99 for laparoscopic vs retropubic radical prostatectomy, p = 0.9). We found no significant association between operation type and time to postoperative potency (HR 1.04 for laparoscopic vs retropubic radical prostatectomy; 95% CI 0.74, 1.46; p = 0.8). Patients who underwent laparoscopic radical prostatectomy were less likely to become continent than those treated with retropubic radical prostatectomy (HR 0.56 for laparoscopic vs retropubic radical prostatectomy; 95% CI 0.44, 0.70; p <0.0005). Laparoscopic radical prostatectomy was associated with less blood loss (mean ml +/- SD 315 +/- 186 vs 1,267 +/- 660) and lower overall transfusion rate (3% vs 49%). No significant difference was noted in cardiovascular, thromboembolic and urinary complications. Emergency room visits and readmissions were higher after laparoscopic radical prostatectomy (15% vs 11% and 4.6% vs 1.2%, respectively). CONCLUSIONS At our institution and during the study period laparoscopic radical prostatectomy and retropubic radical prostatectomy provided comparable oncological efficacy. Laparoscopic radical prostatectomy was associated with less blood loss and a lower transfusion rate, and higher postoperative hospital visits and readmission rate. While the recovery of potency was equivalent, that of continence was superior after retropubic radical prostatectomy.

Surgeon experience is strongly associated with biochemical recurrence after radical prostatectomy for all preoperative risk categories.

PURPOSE We have previously reported that there is a learning curve for open radical prostatectomy. In the current study we determined whether the effects of the learning curve are modified by patient risk, as defined by preoperative tumor characteristics. MATERIALS AND METHODS The study included 7,683 eligible patients with prostate cancer treated with open radical prostatectomy by 1 of 72 surgeons. Surgeon experience was coded as the total prior number of radical prostatectomies done by the surgeon before a patient surgery. Multivariate survival time regression models were used to evaluate the association between surgeon experience and biochemical recurrence separately in each preoperative risk group. RESULTS We saw no evidence that patient risk affected the learning curve. There was a statistically significant association between biochemical recurrence and surgeon experience on all analyses. The absolute risk difference in a patient receiving treatment from a surgeon with 10 vs 250 prior radical prostatectomies was 6.6% (95% CI 3.4-10.3), 12.0% (95% CI 6.9-18.2) and 9.7% (95% CI 1.2-18.2) in patients at low, medium and high preoperative risk. Recurrence-free probability in patients with low risk disease approached 100% for the most experienced surgeons. CONCLUSIONS Cancer control after radical prostatectomy improves with increasing surgeon experience irrespective of patient risk. Excellent rates of cancer control in patients with low risk disease treated by the most experienced surgeons suggest that the primary reason that recurrence develops in such patients is inadequate surgical technique. The results have significant implications for clinical care.

Recovery of Urinary Continence after Radical Prostatectomy: Association with Urethral Length and Urethral Fibrosis Measured by Preoperative and Postoperative Endorectal Magnetic Resonance Imaging

BACKGROUND Limited data on endorectal magnetic resonance imaging (MRI) features and urinary continence after radical prostatectomy (RP) are available. OBJECTIVE To assess whether recovery of urinary continence after RP is associated with endorectal MRI findings regarding preoperative and postoperative membranous urethral length (MUL), percent change in MUL, and postoperative urethral and periurethral fibrosis. DESIGN, SETTING, AND PARTICIPANTS Sixty-four patients who received an MRI scan before and after RP for localized prostate cancer were evaluated in a retrospective study at a single institution. INTERVENTION All patients underwent RP. MEASUREMENTS The postoperative scan was performed to detect local recurrence in patients with rising levels of prostate-specific antigen. Urinary continence was graded on a five-point scale. MUL was measured on T2-weighted images. Urethral and periurethral fibrosis was graded from 0 to III based on axial T2-weighted images. Univariate Cox proportional hazards regression was performed to assess variables associated with continence. RESULTS AND LIMITATIONS Forty-eight patients regained continence following surgery. The median follow-up for patient who were incontinent at their last assessment was 7 mo. The median interval from RP to postoperative endorectal MRI was 10 mo. A longer preoperative or postoperative MUL was associated with superior continence (both p<0.01). The MUL loss ratio was significantly associated with postoperative continence (p=0.02). Patients with a high grade of postoperative periurethral fibrosis tended to have worse postoperative continence; nevertheless a statistical correlation was not reached (hazard ratio: 0.64, p=0.16). This is a retrospective study. CONCLUSIONS Preoperative and postoperative MUL and the MUL loss ratio are related to the recovery time and level of urinary continence after RP. Therefore, preservation of urethral length during surgery is recommended. Periurethral fibrosis might impede the recovery of continence after RP by altering the elasticity of the external sphincter.

Long-Term Prediction of Prostate Cancer: Prostate-Specific Antigen (PSA) Velocity Is Predictive but Does Not Improve the Predictive Accuracy of a Single PSA Measurement 15 Years or More Before Cancer Diagnosis in a Large, Representative, Unscreened Population

PURPOSE We tested whether total prostate-specific antigen velocity (tPSAv) improves accuracy of a model using PSA level to predict long-term risk of prostate cancer diagnosis. METHODS During 1974 to 1986 in a preventive medicine study in Sweden, 5,722 men aged <or= 50 gave two blood samples about 6 years apart. We measured free (fPSA) and total PSA (tPSA) in archived plasma samples from 4,907 participants. Prostate cancer was subsequently diagnosed in 443 (9%) men. Cox proportional hazards regression was used to evaluate tPSA and tPSAv as predictors of prostate cancer. Predictive accuracy was assessed by the concordance index. RESULTS The median time from second blood draw to cancer diagnosis was 16 years; median follow-up for men without prostate cancer was 21 years. In univariate models, tPSA level at second assessment and tPSAv between first and second assessments were associated with prostate cancer (both P < .001). tPSAv was highly correlated with tPSA level (r = 0.93). Twenty-year probabilities of cancer for men at 50th, 90th, and 95th percentile of tPSA and tPSAv were 10.6%, 17.1%, and 21.2% for tPSA, and 9.1%, 11.8%, and 14.1% for tPSAv, respectively. The concordance index for tPSA level was 0.771. Adding tPSAv, fPSA, %fPSA or velocities of fPSA and %fPSA did not importantly increase accuracy of tPSA to predict prostate cancer. Results were unchanged if the analysis was restricted to patients with advanced cancer at diagnosis. CONCLUSION Although PSA velocity is significantly increased in men with prostate cancer up to two decades before diagnosis, it does not aid long-term prediction of prostate cancer.

Association of cysteine-rich secretory protein 3 and beta-microseminoprotein with outcome after radical prostatectomy.

Purpose: It has been suggested that cysteine-rich secretory protein 3 (CRISP-3) and β-microseminoprotein (MSP) are associated with outcome in prostate cancer. We investigated whether these markers are related to biochemical recurrence and whether addition of the markers improves prediction of recurring disease. Experimental Design: Tissue microarrays of radical prostatectomy specimens were analyzed for CRISP-3 and MSP by immunohistochemistry. Associations between marker positivity and postprostatectomy biochemical recurrence [prostate-specific antigen (PSA) >0.2 ng/mL with a confirmatory level] were evaluated by univariate and multivariable Cox proportional hazards regression. Multivariable analyses controlled for preoperative PSA and pathologic stage and grade. Results: Among 945 patients, 224 had recurrence. Median follow-up for survivors was 6.0 years. Patients positive for CRISP-3 had smaller recurrence-free probabilities, whereas MSP-positive patients had larger recurrence-free probabilities. On univariate analysis, the hazard ratio for patients positive versus negative for CRISP-3 was 1.53 (P = 0.010) and for MSP was 0.63 (P = 0.004). On multivariable analysis, both CRISP-3 (P = 0.007) and MSP (P = 0.002) were associated with recurrence. The hazard ratio among CRISP-3–positive/MSP-negative patients compared with CRISP-3–negative/MSP-positive patients was 2.38. Adding CRISP-3 to a base model that included PSA and pathologic stage and grade did not enhance the prediction of recurrence, but adding MSP increased the concordance index minimally from 0.778 to 0.781. Conclusion: We report evidence that CRISP-3 and MSP are independent predictors of recurrence after radical prostatectomy for localized prostate cancer. However, addition of the markers does not importantly improve the performance of existing predictive models. Further research should aim to elucidate the functions of CRISP-3 and MSP in prostate cancer cells.