Biomedical subjects

Andrew J Vickers

Publications and source records attributed to Andrew J Vickers.

At least 19 recordsLinked to original sources

PubMed2006

Comparison of free and total forms of serum human kallikrein 2 and prostate-specific antigen for prediction of locally advanced and recurrent prostate cancer.

BACKGROUND: We evaluated the association of total and free forms of serum human kallikrein 2 (hK2) and prostate-specific antigen (PSA) with prostate cancers of unfavorable prognosis. METHODS: We retrospectively measured total PSA (tPSA), free PSA (fPSA), and total hK2 (thK2) in preoperative serum samples from 867 men [and assessed free hK2 (fhK2) measured in 577 of these men] treated with radical prostatectomy for clinically localized prostate cancer. Associations between biomarker concentrations and extracapsular extension, seminal vesicle invasion, and biochemical recurrence (BCR) were evaluated. A subset of patients with PSA < or =10 microg/L, the group most commonly seen in clinical practice in the US, was analyzed. RESULTS: thK2 was the strongest predictor of extracapsular extension and seminal vesicle invasion (areas under the ROC curve [AUC], 0.662 and 0.719, respectively), followed by tPSA (AUC, 0.654 and 0.663). All biomarkers were significant predictors of BCR. hK2 forms, but not PSA forms, remained highly significant for predicting BCR in the low-PSA group. Combining tPSA, fPSA, and thK2 in a multivariable model improved prediction compared with any biomarker used individually (AUC, 0.711, 0.755, and 0.752 for this combination predicting extracapsular extension, seminal vesicle invasion, and BCR, respectively; P <0.001 for all). CONCLUSIONS: Increased concentrations of hK2 in the blood are significantly associated with unfavorable features of prostate cancer, and thK2 is predictive of locally advanced and recurrent cancer in patients with PSA < or =10 microg/L. Independent of tPSA and fPSA, hK2 predicts unfavorable prognosis.

Aged↗

PubMed2006

Standardization of pelvic lymphadenectomy performed at radical cystectomy: can we establish a minimum number of lymph nodes that should be removed?

BACKGROUND: The number of lymph nodes (LNs) removed during radical cystectomy (RC) for transitional cell carcinoma (TCC) of the bladder affects overall and disease-specific survival, but no consensus exists regarding the minimum number of LNs that should be removed. The goal of the current study was to determine if a threshold number of nodes exists, above which taking additional LNs has no clinical benefit. METHODS: A total of 1121 patients were identified who underwent RC for clinically localized TCC of the bladder between January 1990 and April 2004. To determine the relation of LNs removal and overall survival, a Cox proportional hazards model was used with pathologic stage, age, and comorbidity as covariates. A dose-response curve, adjusted for covariates, was modeled to assess the impact of an increasing number of LNs removed on overall survival. RESULTS: A median of 9 LNs were removed (range, 0-53 LNs). In multivariable analysis, all covariates (number of LNs removed, age, stage of disease, and comorbidity) were found to be predictive of survival. The dose-response curve for number of LNs versus survival revealed that, when adjusted for covariates, the probability of survival did not plateau but instead continued to rise as the number of LNs removed increased. CONCLUSIONS: No evidence was found that a minimum number of LNs is sufficient for optimizing bladder cancer outcomes when a limited or extended pelvic LN dissection is performed during RC. Instead, the probability of survival continues to rise as the number of LNs removed increases. This study supports a more extended LN dissection at the time of RC, and highlights the challenges of interpreting retrospective LN dissection data.

Aged↗

PubMed2006

Selecting patients for randomized trials: a systematic approach based on risk group.

BACKGROUND: A key aspect of randomized trial design is the choice of risk group. Some trials include patients from the entire at-risk population, others accrue only patients deemed to be at increased risk. We present a simple statistical approach for choosing between these approaches. The method is easily adapted to determine which of several competing definitions of high risk is optimal. METHOD: We treat eligibility criteria for a trial, such as a smoking history, as a prediction rule associated with a certain sensitivity (the number of patients who have the event and who are classified as high risk divided by the total number patients who have an event) and specificity (the number of patients who do not have an event and who do not meet criteria for high risk divided by the total number of patients who do not have an event). We then derive simple formulae to determine the proportion of patients receiving intervention, and the proportion who experience an event, where either all patients or only those at high risk are treated. We assume that the relative risk associated with intervention is the same over all choices of risk group. The proportion of events and interventions are combined using a net benefit approach and net benefit compared between strategies. RESULTS: We applied our method to design a trial of adjuvant therapy after prostatectomy. We were able to demonstrate that treating a high risk group was superior to treating all patients; choose the optimal definition of high risk; test the robustness of our results by sensitivity analysis. Our results had a ready clinical interpretation that could immediately aid trial design. CONCLUSION: The choice of risk group in randomized trials is usually based on rather informal methods. Our simple method demonstrates that this decision can be informed by simple statistical analyses.

Journal Article↗

PubMed2006

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

BACKGROUND: 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. METHODS: Patients who underwent radical cystectomy for urothelial cancer of the bladder with evidence of extravesical disease (> or =pT3 or any N+) were identified. Patients who received neoadjuvant chemotherapy were excluded. Serum creatinine immediately before and nadir serum creatinine after cystectomy were used to calculate creatinine clearance (CrCl) or glomerular filtration rate (GFR) using the Cockroft-Gault (CG), Jelliffe, and Modification of Diet in Renal Disease (MDRD) study formulas. A cutoff of CrCl <60 mL/min or GFR <60 mL/min/1.73 m2 was used to determine ineligibility for cisplatin-based chemotherapy. The proportion of patients ineligible by each formula was compared by univariate logistic regression. Univariate linear regression was performed to determine the effect of age on CrCl or GFR. RESULTS: : Most patients were pT3 or greater; 39% were lymph node-positive. The overall proportion of patients ineligible for cisplatin-based chemotherapy was 28% by the CG formula, 52% by Jelliffe, and 24% by MDRD. Concordance between formulas was low. With all formulas the probability of ineligibility increased with age: by the CG equation, >40% of patients age >70 years were ineligible. CONCLUSIONS: : The widespread use of cisplatin-based perioperative chemotherapy in patients with high-risk localized bladder cancer may be significantly limited by the high prevalence of baseline renal insufficiency in this population. This finding is most striking in the elderly. Better selection of patients who may safely receive cisplatin and more effective regimens devoid of cisplatin are required to optimize outcomes in this group of patients.

Age Factors↗

PubMed2006

Cancer-specific survival and predictors of prostate-specific antigen recurrence and survival in patients with seminal vesicle invasion after radical prostatectomy.

BACKGROUND: The objectives of the current study were to determine the long-term biochemical recurrence (BCR) and cancer-specific survival (CSS) rates for men with seminal vesicle invasion (SVI) and to identify risk factors for freedom from BCR and CSS in patients who received treatment in the prostate-specific antigen era and who had SVI identified at the time of radical prostatectomy (RP). METHODS: Prospective clinical, pathologic, and outcome data were collected for 5377 men who underwent RP between June 1983 and August 2004. There were 936 patients who were excluded because they received treatment before RP. Multivariable analysis was used to identify the factors that predicted BCR and CSS. RESULTS: Among 4441 eligible patients, 387 patients (8.7%) had SVI, and 91 of those 387 patients (24%) had lymph node involvement (LNI). In total, 210 patients experienced BCR. For patients without LNI, the 10-year and 15-year freedom from BCR rates were 36% and 32%, respectively, and the corresponding CSS rates were 89% and 81%, respectively. For the 91 men who had SVI and LNI, the 10-year BCR-free probability was 10%, but the 10-year CSS probability was 74%. By 10 years, patients with LNI were 3 times more likely to die from cancer than from other causes; nonetheless, 66% of patients were alive despite their advanced stage. The preoperative prostate-specific antigen level, extracapsular extension, LNI, and Gleason grade were associated independently with BCR. Gleason scores of 8 to 10 and LNI were significant predictors of CSS. CONCLUSIONS: SVI does not invariably signal BCR or death from cancer in patients who undergo RP and pelvic lymph node dissection. Fifteen years later, approximately 33% of men with SVI and negative lymph nodes are expected remain free of BCR, and CSS was surprisingly good.

Aged↗

PubMed2006

Whose data set is it anyway? Sharing raw data from randomized trials.

BACKGROUND: Sharing of raw research data is common in many areas of medical research, genomics being perhaps the most well-known example. In the clinical trial community investigators routinely refuse to share raw data from a randomized trial without giving a reason. DISCUSSION: Data sharing benefits numerous research-related activities: reproducing analyses; testing secondary hypotheses; developing and evaluating novel statistical methods; teaching; aiding design of future trials; meta-analysis; and, possibly, preventing error, fraud and selective reporting. Clinical trialists, however, sometimes appear overly concerned with being scooped and with misrepresentation of their work. Both possibilities can be avoided with simple measures such as inclusion of the original trialists as co-authors on any publication resulting from data sharing. Moreover, if we treat any data set as belonging to the patients who comprise it, rather than the investigators, such concerns fall away. CONCLUSION: Technological developments, particularly the Internet, have made data sharing generally a trivial logistical problem. Data sharing should come to be seen as an inherent part of conducting a randomized trial, similar to the way in which we consider ethical review and publication of study results. Journals and funding bodies should insist that trialists make raw data available, for example, by publishing data on the Web. If the clinical trial community continues to fail with respect to data sharing, we will only strengthen the public perception that we do clinical trials to benefit ourselves, not our patients.

Editorial↗

PubMed2006

FCGR2A polymorphism is correlated with clinical outcome after immunotherapy of neuroblastoma with anti-GD2 antibody and granulocyte macrophage colony-stimulating factor.

PURPOSE: Anti-GD2 murine IgG3 antibody 3F8 kills neuroblastoma cells by antibody-dependent cell-mediated cytotoxicity (ADCC). Granulocyte macrophage colony-stimulating factor (GM-CSF) enhances phagocyte-mediated ADCC. The differential affinity of the human FCGR polymorphic alleles for 3F8 may influence the effectiveness of antibody immunotherapy. PATIENTS AND METHODS: The entire cohort of high risk neuroblastoma patients (N = 136) treated on protocol using 3F8 and GM-CSF were the subjects of this analysis. Tumor response was measured by standard clinical tools plus sensitive molecular monitoring using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Polymorphic alleles of FCGR2A and FCGR3A were determined by PCR plus direct sequencing using genomic DNA samples obtained from marrow or blood of patients. RESULTS: FCGR2A (R/R) genotype correlated with progression-free survival for the entire cohort (P = .049) and for the subset of patients with no history of prior relapse (P = .023). FCGR2A (R/R) also correlated with marrow remission 2.5 months after treatment initiation: by histology (P = .021 and P = .036, for the entire cohort and the subset, respectively) and by qRT-PCR (P = .052 and P = .033, respectively). CONCLUSION: The favorable outcome associated with FCGR2A (R/R) genotype is consistent with the proposed role of FCGR2A and phagocyte-mediated ADCC in 3F8 plus GM-CSF immunotherapy.

Antibodies, Monoclonal↗

PubMed2006

Acupuncture is a feasible treatment for post-thoracotomy pain: results of a prospective pilot trial.

BACKGROUND: Thoracotomy is associated with severe pain that may persist for years. Acupuncture is a complementary therapy with a proven role in pain control. A randomized trial showed that acupuncture was effective in controlling pain after abdominal surgery, but the efficacy of this technique for the treatment of thoracotomy pain has not been established. We developed a novel technique for convenient application of acupuncture to patients undergoing thoracotomy, and in a Phase II trial evaluated the safety of this intervention and the feasibility of doing a randomized trial. METHODS: Adult patients scheduled for unilateral thoracotomy with preoperative epidural catheter placement received acupuncture immediately prior to surgery. Eighteen semi-permanent intradermal needles were inserted on either side of the spine, and four were inserted in the legs and auricles. Needles were removed after four weeks. Using a numerical rating scale, pain was measured on the first five postoperative days. After discharge, pain was assessed using the Brief Pain Inventory at 7, 30, 60 and 90 days. RESULTS: Thirty-six patients were treated with acupuncture. Of these, 25, 23, and 22 patients provided data at 30, 60, and 90 days, respectively. The intervention was well tolerated by patients with only one minor and transient adverse event of skin ulceration. CONCLUSION: The rate of data completion met our predefined criterion for determining a randomized trial to be feasible (at least 75% of patients tolerated the intervention and provided evaluable data). This novel intervention is acceptable to patients undergoing thoracotomy and does not interfere with standard preoperative care. There was no evidence of important adverse events. We are now testing the hypothesis that acupuncture significantly adds to standard perioperative pain management in a randomized trial.

Journal Article↗

PubMed2006

Clinical characteristics of bladder cancer in patients previously treated with radiation for prostate cancer.

OBJECTIVE: To determine if bladder cancer diagnosed after prostatic radiation therapy (RT) differs in behaviour from bladder cancer diagnosed after prostate cancer not treated with RT, as such bladder cancer is thought to be more aggressive than de novo bladder cancer, and epidemiological studies show a higher rate of bladder cancer in patients after irradiation. PATIENTS AND METHODS: We reviewed our records to identify patients who had a diagnosis of bladder cancer with a previous diagnosis of prostate cancer. Patient age, date of diagnosis of prostate cancer, date of diagnosis of bladder cancer, symptoms, clinical stage, initial pathology, definitive therapy, definitive pathological stage, and disease status were recorded. RESULTS: In all, 100 patients were identified who had a diagnosis of bladder cancer after a diagnosis of prostate cancer between January 1992 and August 2003; 58 had had RT for prostate cancer. The mean time between a diagnosis of bladder cancer and prostate cancer was 62 months in the RT group and 34 months in the unirradiated group (P = 0.002) At diagnosis of bladder cancer, 56 (97%) of the patients who received RT had high-grade urothelial carcinoma, vs 27 (64%) of those not irradiated (P < 0.001). Thirty (52%) of the patients with RT had muscle-invasive bladder cancer, vs 17 (40%) of those not irradiated (P = 0.3). The survival rate was similar for both groups. CONCLUSIONS: Bladder cancer is diagnosed later, and is of higher grade, in patients who are irradiated for prostate cancer than in those treated with other methods. Patients with prostate cancer who are treated with RT should be monitored closely for the presence of bladder cancer.

Aged↗

PubMed2006

Risk assessment for biochemical recurrence prior to radical prostatectomy: significant enhancement contributed by human glandular kallikrein 2 (hK2) and free prostate specific antigen (PSA) in men with moderate PSA-elevation in serum.

Most models to predict biochemical recurrence (BCR) of prostate cancer use pretreatment serum prostate-specific antigen (PSA), clinical stage and prostate biopsy Gleason grade. We investigated whether human glandular kallikrein 2 (hK2) and free prostate-specific antigen (fPSA) measured in pretreatment serum enhance prediction. We retrospectively measured total PSA (tPSA), fPSA and hK2 in preoperative serum samples from 461 men with localized prostate cancer treated with radical prostatectomy between 1999 and 2001. We developed a regression model to predict BCR using preoperative tPSA, clinical stage and biopsy Gleason grade. We then compared the predictive accuracy of this "base" model with a model with fPSA and hK2 as additional predictors. BCR was observed in 90 patients (20%), including 48 patients with a pretreatment tPSA < or = 14 ng/ml (13%), and 28 patients (10%) with a pretreatment tPSA < or = 10 ng/ml. Overall, the predictive accuracy of the base model (bootstrap-corrected concordance index of 0.813) was not improved after the addition of fPSA or hK2 (0.818). However, for men with moderate tPSA-elevation (tPSA < or = 10 ng/ml), addition of fPSA and hK2 data increased predictive accuracy (from a base model concordance index of 0.756-0.815, p = 0.005). The improvement in accuracy was not sensitive to the threshold for "moderately elevated" PSA. For patients with a moderate tPSA-elevation (tPSA < or = 10 ng/ml), which closely corresponds to concurrent disease demographics, BCR-prediction was enhanced when fPSA and hK2 were added to the conventional model. Measurements of fPSA and hK2 improve on our ability to counsel patients prior to treatment as to their risk of BCR.

Aged↗

PubMed2006

Does a delay between diagnosis and radical prostatectomy increase the risk of disease recurrence?

BACKGROUND: Men diagnosed with clinically localized prostate carcinoma have several treatment options. The investigation of these options may delay the initiation of definitive therapy. In the current study, the authors evaluated whether time from biopsy to radical prostatectomy (RP) was predictive of postoperative biochemical disease recurrence (BCR). METHODS: A total of 3149 consecutive patients who underwent RP as their initial treatment for prostate carcinoma within a year of diagnosis were identified. The time between diagnosis and RP was entered as a predictor in a multivariate logistic regression model predicting BCR at 3 years, 5 years, 8 years, and 10 years. The year surgery was performed and the nomogram-predicted probability of recurrence, which incorporates stage of disease, Gleason grade, and prostate-specific antigen (PSA) level, were used as covariates. RESULTS: The authors found no clear evidence of a significant effect of delay to diagnosis on BCR. For those patients treated within 6 months (96% of the total sample) the odds ratio for each additional month of delay was 1.04, 1.07, 1.08, and 1.02, respectively, for 3-year, 5-year, 8-year, and 10-year BCR-free survival (P>0.2 for all analyses). However, the 95% confidence intervals were wide and included the possibility that even a minor delay in surgery might have a large impact on the probability of BCR. CONCLUSIONS: The time between biopsy and surgery does not appear to have a large effect on the risk of disease recurrence. Counseling patients on the importance of avoiding undue delay to surgery must be based on clinical judgment, particularly with respect to modifying advice based on the patient's risk.

Aged↗

PubMed2006

Unconventional anticancer agents: a systematic review of clinical trials.

PURPOSE: A substantial number of cancer patients turn to treatments other than those recommended by mainstream oncologists in an effort to sustain tumor remission or halt the spread of cancer. These unconventional approaches include botanicals, high-dose nutritional supplementation, off-label pharmaceuticals, and animal products. The objective of this study was to review systematically the methodologies applied in clinical trials of unconventional treatments specifically for cancer. METHODS: MEDLINE 1966 to 2005 was searched using approximately 200 different medical subject heading terms (eg, alternative medicine) and free text words (eg, laetrile). We sought prospective clinical trials of unconventional treatments in cancer patients, excluding studies with only symptom control or nonclinical (eg, immune) end points. Trial data were extracted by two reviewers using a standardized protocol. RESULTS: We identified 14,735 articles, of which 214, describing 198 different clinical trials, were included. Twenty trials were phase I, three were phase I and II, 70 were phase II, and 105 were phase III. Approximately half of the trials investigated fungal products, 20% investigated other botanicals, 10% investigated vitamins and supplements, and 10% investigated off-label pharmaceuticals. Only eight of the phase I trials were dose-finding trials, and a mere 20% of phase II trials reported a statistical design. Of the 27 different agents tested in phase III, only one agent had a prior dose-finding trial, and only for three agents was the definitive study initiated after the publication of phase II data. CONCLUSION: Unconventional cancer treatments have not been subject to appropriate early-phase trial development. Future research on unconventional therapies should involve dose-finding and phase II studies to determine the suitability of definitive trials.

Antineoplastic Agents↗

PubMed2006

Poorly differentiated prostate cancer treated with radical prostatectomy: long-term outcome and incidence of pathological downgrading.

PURPOSE: Patients with high grade (Gleason score 8 to 10) prostate cancer on biopsy are at high risk for cancer recurrence after local treatment, such as radiation therapy and radical prostatectomy. We examined long-term outcomes in patients with high grade prostate cancer on biopsy who were treated with radical prostatectomy alone. We also investigated the impact on outcomes of changes in the radical prostatectomy Gleason score. MATERIALS AND METHODS: Of 5,662 patients who underwent radical prostatectomy during 20 years 238 had a biopsy Gleason score of 8 to 10. We analyzed the rate of biochemical recurrence in this subgroup according to the Gleason grade of cancer in the radical prostatectomy specimen. RESULTS: Ten-year biochemical recurrence-free probability in the cohort was 39%. However, 45% of patients (95% CI 38 to 51%) with Gleason score 8 to 10 cancer on biopsy had a Gleason score of 7 or less in the radical prostatectomy specimen. These patients had a 10-year biochemical recurrence-free probability of 56% compared to 27% in those with a final Gleason score that remained 8 to 10 (p = 0.0004). On multivariate analysis neither prostate specific antigen nor biopsy features, including total number of cores, number of cores with cancer and percent of cancer in the cores, was a significant predictor of downgrading. However, clinical stage and biopsy Gleason score were significant with 58% of cT1c and 51% of biopsy Gleason score 8 cancers downgraded. Almost 65% of cT1c Gleason score 8 cancers were downgraded compared to 11% of cT3 Gleason score 9 cancers. CONCLUSIONS: Patients diagnosed with poorly differentiated prostate cancer (Gleason score 8 to 10) on biopsy do not uniformly have a poor prognosis. Of the patients 39% remain free of cancer recurrence 10 years after radical prostatectomy. Of these cancers 45% have a lower Gleason score in the radical prostatectomy specimen and a correspondingly more favorable long-term outcome. Predictors of downgrading are lower clinical stage (cT1c) and Gleason score 8 in the biopsy specimen.

Cell Differentiation↗

PubMed2006

Temporary renal ischemia during nephron sparing surgery is associated with short-term but not long-term impairment in renal function.

PURPOSE: The emergence of laparoscopic nephron sparing surgery has rekindled interest in the impact of warm renal ischemia on renal function. To provide data with which warm renal ischemia can be compared we analyzed short-term and long-term changes in the glomerular filtration rate after temporary cold renal ischemia. MATERIALS AND METHODS: In patients undergoing open nephron sparing surgery the estimated glomerular filtration rate was assessed preoperatively, early in the postoperative hospital stay, and 1 and 12 months after surgery using the abbreviated Modification of Diet in Renal Disease Study equation. We separately analyzed 70 patients with a solitary kidney and 592 with 2 functioning kidneys. The end point was the percent change from the baseline glomerular filtration rate. A linear regression model was used to test the association between the glomerular filtration rate change, and ischemia time, patient age, tumor size, estimated blood loss and intraoperative fluid administration. RESULTS: Median cold ischemia time was 31 minutes in patients with a solitary kidney and 35 minutes in those with 2 kidneys. Compared to patients with 2 kidneys those with a solitary kidney had a significantly lower preoperative estimated glomerular filtration rate (p < 0.001), which decreased a median of 30% during the early postoperative period, and 15% and 32% 1 and 12 months after surgery, respectively. In patients with 2 kidneys the corresponding glomerular filtration rate decreases were 16%, 13% and 14%, respectively. On multivariate analyses in each group cold ischemia duration and intraoperative blood loss were significantly associated with early glomerular filtration rate changes. However, 12 months after surgery age was the only independent predictor of a glomerular filtration rate decrease in patients with 2 kidneys. CONCLUSIONS: Cold renal ischemia during nephron sparing surgery is a significant determinant of the short-term postoperative glomerular filtration rate. Longer clamping time is particularly detrimental in patients with a solitary kidney but it does not appear to influence long-term renal function. Patients of advanced age may be less likely to recover from acute ischemic renal injury.

Aged↗

PubMed2006

The association between total and positive lymph node counts, and disease progression in clinically localized prostate cancer.

PURPOSE: We examined the association between the number of LNs removed, the number of positive LNs and disease progression in patients undergoing pelvic lymph node dissection and radical retropubic prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: We analyzed 5,038 consecutive patients who underwent radical retropubic prostatectomy between 1983 and 2003. Clinicopathological parameters, including the administration of neoadjuvant hormonal therapy, preoperative prostate specific antigen, specimen Gleason score, surgeon and pathological stage, were collected prospectively in our prostate cancer database. We excluded men treated with radiation or chemotherapy before surgery. BCR was defined as 2 postoperative prostate specific antigen increases greater than 0.2 ng/ml. Cox models were used to determine whether the number of nodes removed or the number of positive nodes predicted freedom from BCR after adjustment for prognostic covariates. RESULTS: The 4,611 eligible patients had a median of 9 LNs (IQR 5 to 13) removed. Positive nodes were found in 175 patients (3.8%). Overall the number of LNs removed did not predict freedom from BCR (HR per additional 10 nodes removed 1.02, 95% CI 0.92 to 1.13, p = 0.7). Results were similar in patients receiving and not receiving neoadjuvant hormonal therapy. Finding any LN involvement was associated with a BCR HR of 5.2 (95% CI 4.2 to 6.4, p <0.0005). However, in men without nodal involvement an increased number of nodes removed correlated significantly with freedom from BCR (p = 0.01). CONCLUSIONS: Nodal disease increased the risk of progression. Extensive lymphadenectomy enhances the accuracy of surgical staging. However, we were unable to determine that removing more nodes improves freedom from BCR uniformly. Since the proportion of patients with prostate cancer with positive nodes is low, the value of extensive lymphadenectomy requires a multi-institutional, randomized clinical trial.

Aged↗

PubMed2006

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.

Adult↗

PubMed2006

Primer: using decision analysis to improve clinical decision making in urology.

Many clinical decisions in urology involve uncertainty about the course of disease or the effectiveness of treatment. Many decisions also involve trade-offs; for example, an improvement in patient survival at the cost of an increased risk of treatment-related adverse effects. Decision analysis is a formal, quantitative method for systematically comparing the benefits and harms of alternative clinical strategies under circumstances of uncertainty. The basic steps in performing a decision analysis are to define the clinical scenario or problem, identify the clinical strategies to be considered in the decision, enumerate all of the important sequelae of each strategy and their associated probabilities, define the outcome of interest, and assign a value to each possible outcome. Health outcomes can be defined in a number of ways, including quality-adjusted survival. A key aspect of decision analysis is allowing the values of particular health outcomes to vary from patient to patient, depending on individual preferences. Decision analysis has already been used to assess a variety of prevention, screening and treatment decisions in urology, and there is much potential for its future application. Greater incorporation of decision-analytic techniques into urology research and clinical practice might improve decision making, and thereby improve patient outcomes.

Decision Making↗

PubMed2006

Comparison of outcomes in elective partial vs radical nephrectomy for clear cell renal cell carcinoma of 4-7 cm.

OBJECTIVE: To compare the outcomes of patients who had a elective partial nephrectomy (PN) or radical nephrectomy (RN) for clear cell renal cell carcinoma (RCC) of 4-7 cm. PATIENTS AND METHODS: From March 1998 to July 2004, 45 and 151 patients underwent PN and RN, respectively, for clear cell RCC. A multivariate Cox model was constructed for disease-free survival with adjustment for markers of disease severity, and a propensity-score approach used as a confirmatory analysis. RESULTS: In the PN and RN cohorts the treatment failed in one and 20 patients, respectively; the median follow-up was 21 months. The hazard ratio (95% confidence interval) for PN after adjusting for disease severity was 0.36 (0.05-2.82; P = 0.3). Using planned PN as a predictor (intent-to-treat analysis) the hazard ratio was 1.06 (0.32-3.53; P = 0.9). In the propensity-score model, planned PN was associated with a hazard ratio of 1.75 (0.50-6.14; P = 0.4). The serum creatinine level 3 months after surgery was significantly lower in patients who had PN, with a difference between the means of 0.36 (0.23-0.48; P < 0.001). CONCLUSIONS: Renal function was preserved after PN for 4-7 cm clear cell RCC tumours. When comparing the outcomes of PN and RN it is important to consider the intended operation as an independent variable. There was no clear evidence that PN was associated with worse cancer control, although a continued follow-up of this and other cohorts is warranted.

Carcinoma, Renal Cell↗