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Riina-Minna Väänänen,
Hans Lilja, Angel Cronin,
Leni Kauko,
Maria Rissanen,
Otto Kauko,
Henna Kekki,
Siina Vidbäck,
Martti Nurmi,
Kalle Alanen,
Kim Pettersson
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ABSTRACT: OBJECTIVES: The benefits of PSA (prostate specific antigen)-testing in prostate cancer remain controversial with a consequential need for validation of additional biomarkers. We used highly standardized reverse-transcription (RT)-PCR assays to compare transcript levels of 10 candidate cancer marker genes - BMP6, FGF-8b, KLK2, KLK3, KLK4, KLK15, MSMB, PCA3, PSCA and Trpm8 - in carefully ascertained non-cancerous versus cancerous prostate tissue from patients with clinically localized prostate cancer treated by radical prostatectomy. DESIGN AND METHODS: Total RNA was isolated from fresh frozen prostate tissue procured immediately after resection from two separate areas in each of 87 radical prostatectomy specimens. Subsequent histopathological assessment classified 86 samples as cancerous and 88 as histologically benign prostate tissue. Variation in total RNA recovery was accounted for by using external and internal standards and enabled us to measure transcript levels by RT-PCR in a highly quantitative manner. RESULTS: Of the ten genes, there were significantly higher levels only of one of the less abundant transcripts, PCA3, in cancerous versus non-cancerous prostate tissue whereas PSCA mRNA levels were significantly lower in cancerous versus histologically benign tissue. Advanced pathologic stage was associated with significantly higher expression of KLK15 and PCA3 mRNAs. Median transcript levels of the most abundantly expressed genes (i.e. MSMB, KLK3, KLK4 and KLK2) in prostate tissue were up to 10(5)-fold higher than those of other gene targets. CONCLUSIONS: PCA3 expression was associated with advanced pathological stage but the magnitude of overexpression of PCA3 in cancerous versus non-cancerous prostate tissue was modest compared to previously reported data.
Clinical biochemistry 02/2013; · 2.02 Impact Factor
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ABSTRACT: The types of surveillance recommended after radical cystectomy and the degree of patient compliance are not well characterized. We identified the pattern of post-cystectomy surveillance recommended in the oncologic community and assessed compliance to a predetermined schedule among a small group of urologists.
A survey was sent inquiring about the number of patients followed after cystectomy, physician specialty, type of practice, whether the followup schedule was stage dependent, the frequency of office visits and the type of tests. To assess noncompliance to a strict followup schedule we analyzed the records of 647 patients who underwent radical cystectomy.
The overall response rate to the survey was 37% (123 of 330). Of the respondents 96% were urologists, with 72% from United States academic centers, 13% from non-United States academic centers and 14% in private practice. In addition, 21% reported following yearly more than 100 patients after cystectomy, 29% between 51 and 100 patients, and 43% between 1 and 50. Of the respondents 60% tailored the followup schedule based on pathological stage. Computerized tomography of the abdomen and pelvis, chest x-ray and urine cytology were the most frequent tests used. Computerized tomography of the chest, magnetic resonance imaging and abdominal ultrasound were used occasionally.
There was significant deviation from a predetermined followup schedule. There was no uniformity among urological oncologists in post-cystectomy surveillance and there was lack of compliance to a predetermined followup schedule.
The Journal of urology 06/2011; 185(6):2091-6. · 4.02 Impact Factor
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ABSTRACT: We evaluated predictors of progression after starting active surveillance, especially the role of prostate specific antigen and immediate confirmatory prostate biopsy.
A total of 238 men with prostate cancer met active surveillance eligibility criteria and were analyzed for progression with time. Cox proportional hazards regression was used to evaluate predictors of progression. Progression was evaluated using 2 definitions, including no longer meeting 1) full and 2) modified criteria, excluding prostate specific antigen greater than 10 ng/ml as a criterion.
Using full criteria 61 patients progressed during followup. The 2 and 5-year progression-free probability was 80% and 60%, respectively. With prostate specific antigen included in progression criteria prostate specific antigen at confirmatory biopsy (HR 1.29, 95% CI 1.14-1.46, p <0.0005) and positive confirmatory biopsy (HR 1.75, 95% CI 1.01-3.04, p = 0.047) were independent predictors of progression. Of the 61 cases 34 failed due to increased prostate specific antigen, including only 5 with subsequent progression by biopsy criteria. When prostate specific antigen was excluded from progression criteria, only 32 cases progressed, and 2 and 5-year progression-free probability was 91% and 76%, respectively. Using modified criteria as an end point positive confirmatory biopsy was the only independent predictor of progression (HR 3.16, 95% CI 1.41-7.09, p = 0.005).
Active surveillance is feasible in patients with low risk prostate cancer and most patients show little evidence of progression within 5 years. There is no clear justification for treating patients in whom prostate specific antigen increases above 10 ng/ml in the absence of other indications of tumor progression. Patients considering active surveillance should undergo confirmatory biopsy to better assess the risk of progression.
The Journal of urology 02/2011; 185(2):477-82. · 4.02 Impact Factor
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ABSTRACT: Abstract Background We have observed that the area under the receiver operating characteristic curve (AUC) is increasingly being used to evaluate whether a novel predictor should be incorporated in a multivariable model to predict risk of disease. Frequently, investigators will approach the issue in two distinct stages: first, by testing whether the new predictor variable is significant in a multivariable regression model; second, by testing differences between the AUC of models with and without the predictor using the same data from which the predictive models were derived. These two steps often lead to discordant conclusions. Discussion We conducted a simulation study in which two predictors, X and X*, were generated as standard normal variables with varying levels of predictive strength, represented by means that differed depending on the binary outcome Y. The data sets were analyzed using logistic regression, and likelihood ratio and Wald tests for the incremental contribution of X* were performed. The patient-specific predictors for each of the models were then used as data for a test comparing the two AUCs. Under the null, the size of the likelihood ratio and Wald tests were close to nominal, but the area test was extremely conservative, with test sizes less than 0.006 for all configurations studied. Where X* was associated with outcome, the area test had much lower power than the likelihood ratio and Wald tests. Summary Evaluation of the statistical significance of a new predictor when there are existing clinical predictors is most appropriately accomplished in the context of a regression model. Although comparison of AUCs is a conceptually equivalent approach to the likelihood ratio and Wald test, it has vastly inferior statistical properties. Use of both approaches will frequently lead to inconsistent conclusions. Nonetheless, comparison of receiver operating characteristic curves remains a useful descriptive tool for initial evaluation of whether a new predictor might be of clinical relevance.
BMC Medical Research Methodology. 01/2011;
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ABSTRACT: Our current lymph node involvement (LNI) nomogram was created using patients receiving both limited and standard lymph node dissection (LND). Over time, refinements in technique could affect the diagnostic yield from LND.
Our aim was to validate our existing LNI nomogram or develop a new nomogram with updated prediction coefficients that reflect the current standard LND template during radical prostatectomy (RP). We hypothesized that the existing nomogram would demonstrate good discrimination but poor calibration in a contemporary series of standard LND.
A retrospective analysis of 4176 consecutive primary RP patients was performed, including open procedures (3097 patients from 2000 to 2008) and laparoscopic procedures (1079 patients from 2005 to 2008). After excluding 127 patients (3%) with limited LND, 10 (0.2%) with pretreatment prostate-specific antigen (PSA) >50 ng/ml, and 318 (8%) with incomplete data, the final cohort totaled 3721 patients. The nomograms were evaluated using receiver operating characteristic analysis, calibration plots, and decision-curve analysis.
Patients received open or laparoscopic (conventional and robot-assisted) RP and standard LND in our center.
Assessments were obtained using preoperative PSA, biopsy Gleason score, and clinical stage.
The median number of nodes removed was 11, with ∼60% of patients having at least 10 nodes removed (n=2224). Overall, 5.2% of patients (n=194) had positive lymph nodes. The new nomogram had very high discriminative accuracy (area under the curve: 0.862). The decision-curve analysis showed that the new nomogram had the highest clinical net benefit for all reasonable threshold probabilities.
The new nomogram shows improved calibration when predicting lymph node invasion in a contemporary cohort of patients with prostate cancer exclusively treated with RP and standard LND. This nomogram will be used as the preferred predictive model for counseling patients and developing studies at our institution.
European urology 01/2011; 60(2):195-201. · 7.67 Impact Factor
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ABSTRACT: To determine if the location and number of positive surgical margins (PSMs) after radical prostatectomy (RP) are associated with recurrence after salvage external beam radiation therapy (sEBRT).
We retrospectively reviewed the medical records of 60 patients with PSMs who underwent three-dimensional conformal sEBRT for biochemical recurrence (BCR) or clinically detected local recurrence after RP between 1996 and 2007. PSMs were categorized as present or absent at three locations, and patients were classified as having either one or more than one PSM. BCR after RP was defined as a prostate-specific antigen (PSA) level of ≥ 0.1 ng/mL. BCR after sEBRT was defined as a serum PSA level of ≥ 0.1 ng/mL above the PSA nadir after sEBRT.
In all, 24 (40%) patients had more than one PSM. Overall, the most common location of a PSM was the posterior prostate with 40 (66%) patients having a positive posterior margin. The location of PSMs was not significantly associated with secondary BCR (global P= 0.8). There was a borderline result between the number of PSMs and BCR: men with more than one PSM were less likely to recur compared with those with only one PSM (hazard ratio 0.42; P= 0.067).
This is the first study to specifically analyse location and number of PSMs as prognostic factors for men who undergo sEBRT. There was no evidence to suggest that the location of a PSM predicted secondary BCR. Further research is needed to determine whether the number of PSMs is an important predictor of BCR after sEBRT.
BJU International 11/2010; 106(10):1454-7. · 2.84 Impact Factor
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ABSTRACT: Previous studies have shown that complications and biochemical recurrence rates after radical prostatectomy (RP) vary between different surgeons to a greater extent than might be expected by chance. Data on urinary and erectile outcomes, however, are lacking.
In this study, we examined whether between-surgeon variation, known as heterogeneity, exists for urinary and erectile outcomes after RP.
Our study consisted of 1910 RP patients who were treated by 1 of 11 surgeons between January 1999 and July 2007.
All patients underwent RP at Memorial Sloan-Kettering Cancer Center.
Patients were evaluated for functional outcome 1 yr after surgery. Multivariable random effects models were used to evaluate the heterogeneity in erectile or urinary outcome between surgeons, after adjustment for case mix (age, prostate-specific antigen, pathologic stage and grade, comorbidities) and year of surgery.
We found significant heterogeneity in functional outcomes after RP (p<0.001 for both urinary and erectile function). Four surgeons had adjusted rates of full continence <75%, whereas three had rates >85%. For erectile function, two surgeons in our series had adjusted rates <20%; another two had rates >45%. We found some evidence suggesting that surgeons' erectile and urinary outcomes were correlated. Contrary to the hypothesis that surgeons "trade off" functional outcomes and cancer control, better rates of functional preservation were associated with lower biochemical recurrence rates.
A patient's likelihood of recovering erectile and urinary function may differ depending on which of two surgeons performs his RP. Functional preservation does not appear to come at the expense of cancer control; rather, both are related to surgical quality.
European urology 11/2010; 59(3):317-22. · 7.67 Impact Factor
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ABSTRACT: • To report on the contemporary Memorial Sloan-Kettering Cancer Center experience with radical nephrectomy and vena caval thrombectomy.
• Patients who underwent radical nephrectomy and vena caval thrombectomy without the use of bypass techniques were retrospectively identified. • Data were collected on intraoperative and pathological findings as well as postoperative complications and oncological outcomes.
• In all, 78 patients underwent radical nephrectomy with off-bypass resection of vena caval thrombus between 1989 and 2009. • The median (interquartile range, IQR) operation duration was 293 (226-370) min, and median (IQR) blood loss was 1300 (750-2500) mL. In all, 10 patients (13%) were confirmed to have intra- or supra-hepatic tumour thrombus (level 3/4), eight of whom required supra-hepatic control of the inferior vena cava (IVC). • Major (grade 3-5) postoperative complications occurred in 14 (18%), with five postoperative deaths. Disease recurred in 27/62 patients who were considered completely resected at surgery and had adequate follow-up. • The overall 5-year survival (95% confidence interval) probability was 48% (35-60%).
• Radical nephrectomy with vena caval thrombectomy is associated with acceptable postoperative morbidity and mortality, and long-term survival is possible in some patients. • Many level 3/4 thrombi could be safely approached without the use of bypass techniques.
BJU International 09/2010; 107(9):1386-93. · 2.84 Impact Factor
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ABSTRACT: We evaluated predictors of freedom from biochemical recurrence in patients with pelvic lymph node metastasis at radical prostatectomy.
Of 207 patients with lymph node metastasis treated with radical prostatectomy and bilateral pelvic lymph node dissection 45 received adjuvant androgen deprivation therapy and 162 did not. Cox proportional hazards regression models were used to investigate predictors of biochemical recurrence after radical prostatectomy. Recurrence probability was estimated using the Kaplan-Meier method.
A median of 13 lymph nodes were removed. Of the patients 122 had 1, 44 had 2 and 41 had 3 or greater positive lymph nodes. Of patients without androgen deprivation therapy 103 had 1, 35 had 2 and 24 had 3 or greater positive lymph nodes while 69 experienced biochemical recurrence. Median time to recurrence in patients with 1, 2 and 3 or greater lymph nodes was 59, 13 and 3 months, respectively. Only specimen Gleason score and the number of positive lymph nodes were independent predictors of biochemical recurrence. Recurrence-free probability 2 years after prostatectomy in men without androgen deprivation with 1 positive lymph node and a prostatectomy Gleason score of 7 or less was 79% vs 29% in those with Gleason score 8 or greater and 2 or more positive lymph nodes.
Prognosis in patients with lymph node metastasis depends on the number of positive lymph nodes and primary tumor Gleason grade. Of all patients with lymph node metastasis 80% had 1 or 2 positive nodes. A large subset of those patients had a favorable prognosis. Full bilateral pelvic lymph node dissection should be done in patients with intermediate and high risk cancer to identify those likely to benefit from metastatic node removal.
The Journal of urology 07/2010; 184(1):143-8. · 4.02 Impact Factor
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ABSTRACT: Surveillance, Epidemiology, and End Results data indicate only 19.7% of patients 80 years old or older with muscle invasive bladder cancer undergo radical cystectomy vs 49.4% of those with similar stage disease age 65 to 79 years, reflecting concern for perioperative morbidity. We evaluated the morbidity and survival outcomes of octogenarians treated with radical cystectomy at a tertiary cancer center.
We conducted a retrospective review of 1,142 patients entered prospectively into a hospital based complication database between 1995 and 2005 using a modified Clavien system. Complications were classified as minor or major based on the complexity of intervention required. Disease specific and competing risk survival curves for patients younger than 80 years vs 80 years old or older were created.
Octogenarians had a nonsignificantly higher rate of minor (55% vs 50%) and major complications (17% vs 13%) than younger patients, respectively (global p = 0.15). After adjusting for baseline characteristics the risk of any complication was roughly flat across all ages (p = 0.9). For major complications risk appeared to increase slightly up to age 65 years and then plateau (p = 0.16). After adjusting for deaths from other causes the cumulative incidence of death from bladder cancer in octogenarians was comparable to that in younger patients (5-year cumulative incidence of death from bladder cancer 26% vs 25%).
In our experience radical cystectomy in older patients with bladder cancer provides similar disease control and survival outcomes with risks of high grade perioperative morbidity comparable to those in younger patients, and remains an important treatment option.
The Journal of urology 06/2010; 183(6):2171-7. · 4.02 Impact Factor
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David G Pfister,
Barrie R Cassileth,
Gary E Deng,
K Simon Yeung,
Jennifer S Lee,
Donald Garrity, Angel Cronin,
Nancy Lee,
Dennis Kraus,
Ashok R Shaha,
Jatin Shah,
Andrew J Vickers
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ABSTRACT: To determine whether acupuncture reduces pain and dysfunction in patients with cancer with a history of neck dissection. The secondary objective is to determine whether acupuncture relieves dry mouth in this population.
Patients at a tertiary cancer center with chronic pain or dysfunction attributed to neck dissection were randomly assigned to weekly acupuncture versus usual care (eg, physical therapy, analgesia, and/or anti-inflammatory drugs, per patient preference or physician recommendation) for 4 weeks. The Constant-Murley score, a composite measure of pain, function, and activities of daily living, was the primary outcome measure. Xerostomia, a secondary end point, was assessed using the Xerostomia Inventory.
Fifty-eight evaluable patients were accrued and randomly assigned from 2004 to 2007 (28 and 30 patients on acupuncture and control arms, respectively). Constant-Murley scores improved more in the acupuncture group (adjusted difference between groups = 11.2; 95% CI, 3.0 to 19.3; P = .008). Acupuncture produced greater improvement in reported xerostomia (adjusted difference in Xerostomia Inventory = -5.8; 95% CI, -0.9 to -10.7; P = .02).
Significant reductions in pain, dysfunction, and xerostomia were observed in patients receiving acupuncture versus usual care. Although further study is needed, these data support the potential role of acupuncture in addressing post-neck dissection pain and dysfunction, as well as xerostomia.
Journal of Clinical Oncology 05/2010; 28(15):2565-70. · 18.37 Impact Factor
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ABSTRACT: We previously reported that a panel of four kallikrein forms in blood-total, free, and intact prostate-specific antigen (PSA) and kallikrein-related peptidase 2 (hK2)-can reduce unnecessary biopsy in previously unscreened men with elevated total PSA. We aimed to replicate our findings in a large, independent, representative, population-based cohort.
The study cohort included 2,914 previously unscreened men undergoing biopsy as a result of elevated PSA (> or = 3 ng/mL) in the European Randomized Study of Screening for Prostate Cancer, Rotterdam, with 807 prostate cancers (28%) detected. The cohort was randomly divided 1:3 into a training and validation set. Levels of kallikrein markers were compared with biopsy outcome.
Addition of free PSA, intact PSA, and hK2 to a model containing total PSA and age improved the area under the curve from 0.64 to 0.76 and 0.70 to 0.78 for models without and with digital rectal examination results, respectively (P < .001 for both). Application of the panel to 1,000 men with elevated PSA would reduce the number of biopsies by 513 and miss 54 of 177 low-grade cancers and 12 of 100 high-grade cancers. Findings were robust to sensitivity analysis.
We have replicated our previously published finding that a panel of four kallikreins can predict the result of biopsy for prostate cancer in men with elevated PSA. Use of this panel would dramatically reduce biopsy rates. A small number of men with cancer would be advised against immediate biopsy, but these men would have predominately low-stage, low-grade disease.
Journal of Clinical Oncology 05/2010; 28(15):2493-8. · 18.37 Impact Factor
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ABSTRACT: To report the heterogeneity in the treatment of patients with cT1 urothelial carcinoma by different surgeons, and to report outcomes in patients with and without bacillus Calmette-Guérin (BCG) treatment.
We retrospectively reviewed 396 patients who had undergone a re-staging transurethral resection (TUR) for cT1 bladder cancer. We assessed both differences in the treatment by surgeon, and the association of early treatment with BCG with recurrence, progression and bladder cancer-specific death.
Muscle was captured in the re-staging TUR specimen in a median of 76% of patients (range 50-94 when stratified by surgeon). On multivariable analysis there was significant heterogeneity among surgeons in the use of early cystectomy (P < 0.001), deferred cystectomy (P < 0.001), and BCG (P= 0.014). However, there was no significant heterogeneity between surgeons in clinical outcome for recurrence (P= 0.9) and overall survival (P= 0.3). Among 288 patients placed on surveillance, the 5-year probability (95% confidence interval) of freedom from recurrence was 45 (36-54)% for those receiving and 54 (44-62)% for those not receiving early BCG. On multivariable analysis, early BCG was not significantly associated with recurrence (P= 0.14). The cumulative incidence of progression was ≈10% for both groups, and the cumulative incidence of bladder cancer-specific death was ≈7% for both groups. The cumulative incidence of deferred cystectomy before progression was 14% for those receiving and 15% for those not receiving early BCG.
There is a significant variability among surgeons in the management of patients with T1 disease. The similar outcome for the BCG-treated and -untreated patients in our study is most likely confounded by patient selection.
BJU International 03/2010; 106(10):1502-7. · 2.84 Impact Factor
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ABSTRACT: Surgical margin status is commonly used as an end point for surgical learning. We examined the surgical margin learning curve and investigated whether surgical margins are a good marker for oncological outcome.
The study cohort included 7,765 patients with prostate cancer treated with radical prostatectomy by 1 of 72 surgeons at a total of 4 major American academic medical centers. We calculated the learning curve for surgical margins and a concordance probability between the surgeon rates of positive surgical margins and 5-year biochemical recurrence.
A positive surgical margin was identified in 2,059 patients (27%). On multivariate analysis surgeon experience was strongly associated with surgical margin status (p = 0.017). The probability of a positive surgical margin was 40% for a surgeon with 10 prior cases, which decreased to 25% for a surgeon with 250 (absolute difference 15%, 95% CI 11 to 18). Learning curves differed dramatically among surgeons. For surgeon pairs the surgeon with the superior positive surgical margin rate also had the better biochemical recurrence rate only 58% of the time.
We noted a learning curve for surgical margins after open radical prostatectomy. The poor concordance between surgeon margin and recurrence rates suggests that while margins clearly matter and efforts should be made to decrease positive margin rates, surgical margin status is not a strong surrogate for cancer control. These results have implications for using the margin rate to evaluate changes in surgical technique and as surgeon feedback.
The Journal of urology 02/2010; 183(4):1360-5. · 4.02 Impact Factor
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ABSTRACT: We have previously shown that a panel of kallikrein markers--total prostate-specific antigen (PSA), free PSA, intact PSA and human kallikrein-related peptidase 2 (hK2)--can predict the outcome of prostate biopsy in men with elevated PSA. Here we investigate the properties of our panel in men subject to clinical work-up before biopsy.
We applied a previously published predictive model based on the kallikrein panel to 262 men undergoing prostate biopsy following an elevated PSA (≥ 3 ng/ml) and further clinical work-up during the European Randomized Study of Prostate Cancer screening, France. The predictive accuracy of the model was compared to a "base" model of PSA, age and digital rectal exam (DRE).
83 (32%) men had prostate cancer on biopsy of whom 45 (54%) had high grade disease (Gleason score 7 or higher). Our model had significantly higher accuracy than the base model in predicting cancer (area-under-the-curve [AUC] improved from 0.63 to 0.78) or high-grade cancer (AUC increased from 0.77 to 0.87). Using a decision rule to biopsy those with a 20% or higher risk of cancer from the model would reduce the number of biopsies by nearly half. For every 1000 men with elevated PSA and clinical indication for biopsy, the model would recommend against biopsy in 61 men with cancer, the majority (≈80%) of whom would have low stage and low grade disease at diagnosis.
In this independent validation study, the model was highly predictive of prostate cancer in men for whom the decision to biopsy is based on both elevated PSA and clinical work-up. Use of this model would reduce a large number of biopsies while missing few cancers.
BMC Cancer 01/2010; 10:635. · 3.01 Impact Factor
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ABSTRACT: Abstract Background The purpose of clinical trials of acupuncture is to help clinicians and patients make decisions about treatment. Yet this is not straightforward: some trials report acupuncture to be superior to sham (placebo) acupuncture while others show evidence that acupuncture is superior to usual care but not sham, and still others conclude that acupuncture is no better than usual care. Meta-analyses of these trials tend to come to somewhat indeterminate conclusions. This appears to be because, until recently, acupuncture research was dominated by small trials of questionable quality. The Acupuncture Trialists' Collaboration, a group of trialists, statisticians and other researchers, was established to synthesize patient-level data from several recently published large, high-quality trials. Methods There are three distinct phases to the Acupuncture Trialists Collaboration: a systematic review to identify eligible studies; collation and harmonization of raw data; statistical analysis. To be eligible, trials must have unambiguous allocation concealment. Eligible pain conditions are osteoarthritis; chronic headache (tension or migraine headache); shoulder pain; and non-specific back or neck pain. Once received, patient-level data will undergo quality checks and the results of prior publications will be replicated. The primary analysis will be to determine the effect size of acupuncture. Each trial will be evaluated by analysis of covariance with the principal endpoint as the dependent variable and, as covariates, the baseline score for the principal endpoint and the variables used to stratify randomization. The effect size for acupuncture from each trial - that is, the coefficient and standard error from the analysis of covariance - will then be entered into a meta-analysis. We will compute effect sizes separately for comparisons of acupuncture with sham acupuncture, and acupuncture with no acupuncture control for each pain condition. Other analyses will investigate the impact of different sham techniques, styles of acupuncture or frequency and duration of treatment sessions. Discussion Individual patient data meta-analysis of high-quality trials will provide the most reliable basis for treatment decisions about acupuncture. Above all, however, we hope that our approach can serve as a model for future studies in acupuncture and other complementary therapies.
Trials. 01/2010;
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ABSTRACT: Despite the clear demonstration that different histological subtypes of renal cell carcinoma show distinct pathogenesis and genetic alterations, the impact of histology on prognosis remains controversial. We evaluated our experience with tumor histology in patients with localized renal cell carcinoma.
We identified 1,863 patients with localized clear cell, papillary or chromophobe renal cell carcinoma who were treated surgically between 1989 and 2006 at our tertiary care center. Cox proportional hazards regression models were used to evaluate the relationship between tumor histology and outcome, defined as metastasis or death from disease, adjusting for age, sex, operation type, American Society of Anesthesiologists score, TNM stage and tumor size.
Of 1,863 patients 1,333 (72%) had clear cell histology, and 310 (17%) and 220 (12%) had papillary and chromophobe renal cell carcinoma, respectively. Median followup in patients without an event was 3.4 years. On univariate analysis patients with clear cell histology had a worse clinical outcome. Five-year probability of freedom from metastasis or death from disease was 86% (95% CI 84, 88), 95% (95% CI 91, 97) and 92% (95% CI 85, 96) in patients with clear cell, papillary and chromophobe histology, respectively (p <0.001). On multivariate analysis chromophobe (HR 0.40; 95% CI 0.20, 0.80) and papillary (HR 0.62; 95% CI 0.34, 1.14) histology was also significantly associated with better outcome (p = 0.014).
Clear cell histology seems to be independently associated with worse outcomes in patients who undergo surgery for renal cell carcinoma even after controlling for widely accepted factors influencing prognosis.
The Journal of urology 09/2009; 182(5):2132-6. · 4.02 Impact Factor
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ABSTRACT: To evaluate the indications for early and deferred cystectomy and to report the impact of this tailored approach on survival.
We retrospectively studied 523 patients seen at our institution who were initially diagnosed with T1 disease between 1990 and 2007.
Variables analyzed included age, gender, multifocality, multifocal T1 disease, carcinoma in situ, grade, recurrence rate, and restaging status. End points were overall and disease-specific survival.
A restaging transurethral resection (TUR) was performed in 523 patients. Of the patients who underwent restaging, 106 (20%) were upstaged to muscle-invasive disease and 417 patients were considered true clinical T1 (cT1); 84 of the latter group underwent immediate cystectomy. The median follow-up for survivors was 4.3 yr. The cumulative incidence of disease-specific death at 5 yr was 8% (95% confidence interval [CI], 5-13%), 10% (95% CI, 5-17%), and 44% (95% CI, 35-56%) for those restaged with lower than T1, T1, and T2 disease, respectively. Immediate cystectomy was more likely in patients with cT1 disease at restaging than in those with disease lower than cT1, but there were no other obvious differences in clinical characteristics between those with and without immediate cystectomy. Survival was not statistically different for patients who underwent an immediate cystectomy versus those who were maintained on surveillance with deferred cystectomy if deemed appropriate. Of 333 patients who did not undergo immediate cystectomy, 59 had a deferred cystectomy, and the likelihood of deferred cystectomy was greater in those with T1 disease on restaging TUR (hazard ratio: 2.40; 95% CI, 1.43-4.01; p=0.001).
Restaging TUR should be performed in patients diagnosed with cT1 bladder cancer to improve staging accuracy. Patients with T1 disease on restaging are at higher risk of progression and should be considered for early cystectomy.
European urology 08/2009; 56(6):903-10. · 7.67 Impact Factor
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R Houston Thompson,
Jennifer R Hill,
Yuriy Babayev, Angel Cronin,
Matt Kaag,
Shilajit Kundu,
Melanie Bernstein,
Jonathan Coleman,
Guido Dalbagni,
Karim Touijer,
Paul Russo
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ABSTRACT: Recent evidence suggests significantly discordant findings regarding tumor size and the metastasis risk in renal cell carcinoma cases. We present our experience with renal cell carcinoma. We evaluated the association between tumor size and the metastasis risk in a large patient cohort.
Using our prospectively maintained nephrectomy database we identified 2,691 patients who were treated surgically for a sporadic renal cortical tumor between 1989 and 2008. Associations between tumor size and synchronous metastasis at presentation (M1 renal cell carcinoma) were evaluated with logistic regression models. Metastasis-free survival after surgery was estimated using the Kaplan-Meier method in 2,367 patients who did not present with M1 renal cell carcinoma and were followed postoperatively.
Of the 2,691 patients 162 presented with metastatic renal cell carcinoma. Only 1 of 781 patients with a tumor less than 3 cm had M1 renal cell carcinoma at presentation and tumor size was significantly associated with metastasis at presentation (for each 1 cm increase OR 1.25, p <0.001). Of the 2,367 patients who did not present with metastasis metastatic disease developed in 171 during a median 2.8-year followup. In this group only 1 of the 720 patients with renal cell carcinoma less than 3 cm showed de novo metastasis during followup. Metastasis-free survival was significantly associated with tumor size (for each 1 cm increase HR 1.24, p <0.001).
In our experience tumor size is significantly associated with synchronous and asynchronous metastases after nephrectomy. Our results suggest that the risk of metastatic disease is negligible in patients with tumors less than 3 cm.
The Journal of urology 06/2009; 182(1):41-5. · 4.02 Impact Factor
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ABSTRACT: A publication on behalf of the European Society of Urological Oncology questioned the need for removing the seminal vesicles during radical prostatectomy in patients with prostate specific antigen less than 10 ng/ml except when biopsy Gleason score is greater than 6 or there are greater than 50% positive biopsy cores. We applied the European Society of Urological Oncology algorithm to an independent data set to determine its predictive value.
Data on 1,406 men who underwent radical prostatectomy and seminal vesicle removal between 1998 and 2004 were analyzed. Patients with and without seminal vesicle invasion were classified as positive or negative according to the European Society of Urological Oncology algorithm.
Of 90 cases with seminal vesicle invasion 81 (6.4%) were positive for 90% sensitivity, while 656 of 1,316 without seminal vesicle invasion were negative for 50% specificity. The negative predictive value was 98.6%. In decision analytic terms if the loss in health when seminal vesicles are invaded and not completely removed is considered at least 75 times greater than when removing them unnecessarily, the algorithm proposed by the European Society of Urological Oncology should not be used.
Whether to use the European Society of Urological Oncology algorithm depends not only on its accuracy, but also on the relative clinical consequences of false-positive and false-negative results. Our threshold of 75 is an intermediate value that is difficult to interpret, given uncertainties about the benefit of seminal vesicle sparing and harm associated with untreated seminal vesicle invasion. We recommend more formal decision analysis to determine the clinical value of the European Society of Urological Oncology algorithm.
The Journal of urology 01/2009; 181(2):609-13; discussion 614. · 4.02 Impact Factor
