Adverse event profile for immunotherapy agents compared with chemotherapy in solid organ tumors: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Immunotherapy agents are an innovative oncological treatment modality and as a result their use has expanded widely. Understanding the treatment-related adverse events (AEs) of these drugs compared with traditional chemotherapy is crucial for clinical practice. DESIGN: A systematic review of studies indexed in Medline (PubMed), Embase, Web of Science, and the Cochrane Databases from January 2000 to 14 February 2019 was conducted. Randomized clinical trials comparing immunotherapy [cytotoxic T-lymphocyte protein-4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed death-ligand 1 (PD-L1)] with standard-of-care chemotherapy in the treatment of advanced solid-organ neoplasms were included if AEs were reported as an outcome. Primary outcome was AEs ≥ grade 3 in severity. Secondary outcomes were proportion of overall AEs, treatment discontinuation due to AEs, deaths due to AEs, and specific AEs [fatigue, diarrhea, acute kidney injury (AKI), colitis, pneumonitis, and hypothyroidism]. Paule-Mandel pooling and a random effects model were used to produce odds ratios (ORs) for measures of effects. RESULTS: Among 10 598 abstracts screened, we included 22 studies involving 12 727 patients. In the immunotherapy group, 16.5% of patients developed an AE ≥ grade 3 in severity, compared with 41.09% in the chemotherapy arm [OR = 0.26, 95% confidence interval (CI) 0.19-0.35, I2 = 92%]. Patients receiving immunotherapy also had lower odds of developing an AE overall (OR = 0.35, 95% CI 0.28-0.44; I2 = 77%), terminating therapy due to an AE (OR = 0.55, 95% CI 0.39-0.78, I2 = 80%), or dying from a treatment-related AE (OR = 0.67, 95% CI 0.46-0.98, I2 = 0%). When treated with chemotherapy versus immunotherapy, patients more frequently experienced fatigue (25.10% versus 15.83%), diarrhea (14.97% versus 11.13%), and AKI (1.79% versus 1.31%). However, colitis (1.02% versus 0.26%), pneumonitis (3.36% versus 0.36%), and hypothyroidism (6.82% versus 0.37%) were more common in those treated with immunotherapy. CONCLUSIONS: Treatment of advanced solid-organ malignancies with immunotherapy compared with traditional chemotherapy is associated with a lower risk of AEs.

Complications following surgery with or without radiotherapy or radiotherapy alone for prostate cancer.

BACKGROUND: Men undergoing treatment of clinically localised prostate cancer may experience a number of treatment-related complications, which affect their quality of life. METHODS: On the basis of population-based retrospective cohort of men undergoing surgery, with or without subsequent radiotherapy, or radiotherapy alone for prostate cancer in Ontario, Canada, we measured the incidence of treatment-related complications using administrative and billing data. RESULTS: Of 36 984 patients, 15 870 (42.9%) underwent surgery alone, 4519 (12.2%) underwent surgery followed by radiotherapy, and 16 595 (44.9%) underwent radiotherapy alone. For all end points except urologic procedures, the 5-year cumulative incidence rates were lowest in the surgery only group and highest in the radiotherapy only group. Intermediary rates were seen in the surgery followed by radiotherapy group, except for urologic procedures where rates were the highest in this group. Although age and comorbidity were important predictors, radiotherapy as the primary treatment modality was associated with higher rates for all complications (adjusted hazard ratios 1.6-4.7, P=0.002 to <0.0001). CONCLUSIONS: In patients treated for prostate cancer, radiation after surgery increases the rate of complications compared with surgery alone, though these rates remain lower than patients treated with radiation alone. This information may inform patient and physician decision making in the treatment of prostate cancer.

The impact of a BRCA2 mutation on mortality from screen-detected prostate cancer.

BACKGROUND: Men with a BRCA2 mutation face an increased risk of prostate cancer. These cancers tend to have an aggressive nature and it has not yet been demonstrated that regular screening of BRCA2 carriers is associated with improved survival. METHODS: We identified 4187 men who underwent a prostate cancer biopsy for an elevated PSA or an abnormal digital rectal examination between 1998 and 2010. We screened the BRCA2 gene in its entirety for mutations and we followed the men for death from prostate cancer until December 2012. RESULTS: The 12-year prostate cancer-specific survival rate was 94.3% for men without a BRCA2 mutation and was 61.8% for men with a mutation (P<10(-4); log-rank test). CONCLUSIONS: The survival of men with screen-detected prostate cancer and a BRCA2 mutation is much poorer than expected.

MicroRNAs in prostate cancer: from biomarkers to molecularly-based therapeutics.

MicroRNAs (miRNAs) are effective regulators of gene expression that have a significant role in the pathogenesis of prostate and various other cancers. The high prevalence of aberrant miRNA expression in prostate cancer, and miRNAs' distinctive properties, give much hope that they can be used as biomarkers and next generation of molecular anticancer therapeutics. Herein, we review the literature on miRNA involvement in prostate cancer pathogenesis and the current understanding of their role as oncogenes, tumor suppressors and metastasis-regulators. We also review the latest research on miRNAs in prostate cancer preclinical studies and clinical trials, and highlight the advantages and challenges of possible miRNA-based therapies. The emerging information regarding the biology of miRNAs in prostate cancer is promising, and may lead to a role(s) for these molecules as diagnostic/prognostic markers and effective therapeutic tools for better molecularly targeted treatment of prostate cancer.

Prostate cancer genes associated with TMPRSS2-ERG gene fusion and prognostic of biochemical recurrence in multiple cohorts.

BACKGROUND: Recent studies have indicated that prostate cancer patients with the TMPRSS2-ERG gene fusion have a higher risk of recurrence. To identify markers associated with TMPRSS2-ERG fusion and prognostic of biochemical recurrence, we analysed a cohort of 139 men with prostate cancer for 502 molecular markers. METHODS: RNA from radical prostatectomy tumour specimens was analysed using cDNA-mediated, annealing, selection, extension and ligation (DASL) to determine mRNAs associated with TMPRSS2-ERG T1/E4 fusion and prognostic of biochemical recurrence. Differentially expressed mRNAs in T1/E4-positive tumours were determined using significance analysis of microarrays (false discovery rate (FDR) <5%). Univariate and multivariate Cox regression determined genes, gene signatures and clinical factors prognostic of recurrence (P-value <0.05, log-rank test). Analysis of two prostate microarray studies (GSE1065 and GSE8402) validated the findings. RESULTS: In the 139 patients from this study and from a 455-patient Swedish cohort, 15 genes in common were differentially regulated in T1/E4 fusion-positive tumours (FDR <0.05). The most significant mRNAs in both cohorts coded ERG. Nine genes were found prognostic of recurrence in this study and in a 596-patient Minnesota cohort. A molecular recurrence score was significant in prognosticating recurrence (P-value 0.000167) and remained significant in multivariate analysis of a mixed clinical model considering Gleason score and TMPRSS2-ERG fusion status. CONCLUSIONS: TMPRSS2-ERG T1/E4 fusion-positive tumours had differentially regulated mRNAs observed in multiple studies, the most significant one coded for ERG. Several mRNAs were consistently associated with biochemical recurrence and have potential clinical utility but will require further validation for successful translation.

Fusion in the ETS gene family and prostate cancer.

It has recently been shown that the majority of prostate cancers harbour a chromosomal rearrangement that fuses the gene for an androgen-regulated prostate-specific serine protease, TMPRSS2, with a member of the ETS family of transcription factors, most commonly ERG. These are among the most common genetic alterations in any human solid tumour. This knowledge may provide us with clues to prostate carcinogenesis, and may lead to the development of important molecular-based biomarkers for patients with localised prostate cancer. The most common variant is fusion between the 5'-untranslated region of TMPRSS2 and the 3' region of ERG. However, over 20 other fusion variants have now been described (involving over 10 different genes) and the number of variants continues to grow. Fusion products can be identified by several techniques, including FISH, RT-PCR, and expression profiling using exon arrays. The protein products associated with the fusion transcripts have not been characterised, and the phenotypic expression of the various products of gene fusion on prostate cancer histology, or on the clinical course of cancer, are not yet understood. Several early cohort studies suggest that the presence of the TMPRSS2:ERG fusion product is associated with relatively poor cancer-specific survival. Studies that examine how individual variants and their associated phenotypes affect prostate cancer presentation and progression are required.

Rapid progression of prostate cancer in men with a BRCA2 mutation.

Men with BRCA2 mutations have been found to be at increased risk of developing prostate cancer. There is a recent report that BRCA2 carriers with prostate cancer have poorer survival than noncarrier prostate cancer patients. In this study, we compared survival of men with a BRCA2 mutation and prostate cancer with that of men with a BRCA1 mutation and prostate cancer. We obtained the age at diagnosis, age at death or current age from 182 men with prostate cancer from families with a BRCA2 mutation and from 119 men with prostate cancer from families with a BRCA1 mutation. The median survival from diagnosis was 4.0 years for men with a BRCA2 mutation vs 8.0 years for men with a BRCA1 mutation, and the difference was highly significant (P<0.01). It may be important to develop targeted chemotherapies to treat prostate cancer in men with a BRCA2 mutation.

A genome-wide association screen identifies regions on chromosomes 1q25 and 7p21 as risk loci for sporadic prostate cancer.

We conducted a genome-wide association study of 3090 sporadic prostate cancer patients and controls using the Affymetrix 10 000 SNP GeneChip. Initial screening of 40 prostate cancer cases and 40 non-cancer controls revealed 237 SNPs to be associated with prostate cancer (P<0.05). Among these SNPs, 33 were selected for further association analysis of 2069 men who had undergone a cancer-screening prostate biopsy. Results identified five loci as being significantly associated with increased prostate cancer risk in this larger sample (rs 1930293, OR=1.7, P=0.03; rs 717809-2p12, OR=1.3, P=0.03; rs 494770-4q34, OR=1.3, P=0.01; rs 2348763-7p21, OR=1.5, P=0.01; rs 1552895-9p22, OR=1.5, P=0.002). To validate these association data, 61 additional HapMap tagSNPs spanning the latter five loci were genotyped in this subject cohort and an additional 1021 men (total subject number=3090). This analysis revealed tag SNP rs 4568789 (chromosome 1q25) and tag SNP rs 13225697 (chromosome 7p21) to be significantly associated with prostate cancer (P-values 0.009 and 0.008, respectively). Haplotype analysis revealed significant associations of prostate cancer with two allele risk haplotypes on both chromosome 1q25 (adjusted OR of 2.7 for prostate cancer, P=0.0003) and chromosome 7p21 (adjusted OR of 1.3, P=0.0004). As linkage data have identified a putative prostate cancer gene on chromosome 1q25 (HPC1), and microarray data have revealed the ETV1 oncogene to be overexpressed in prostate cancer tissue, it appears that chromosome 1q25 and 7p21 may be sites of gene variants conferring risk for sporadic and inherited forms of prostate cancer.

Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer.

The prostate-specific gene, TMPRSS2 is fused with the gene for the transcription factor ERG in a large proportion of human prostate cancers. The prognostic significance of the presence of the TMPRSS2:ERG gene fusion product remains controversial. We examined prostate cancer specimens from 165 patients who underwent surgery for clinically localised prostate cancer between 1998 and 2006. We tested for the presence of TMPRSS2:ERG gene fusion product, using RT-PCR and direct sequencing. We conducted a survival analysis to determine the prognostic significance of the presence of the TMPRSS2:ERG fusion gene on the risk of prostate cancer recurrence, adjusting for the established prognostic factors. We discovered that the fusion gene was expressed within the prostate cancer cells in 81 of 165 (49.1%) patients. Of the 165 patients, 43 (26.1%) developed prostate-specific antigen (PSA) relapse after a mean follow-up of 28 months. The subgroup of patients with the fusion protein had a significantly higher risk of recurrence (58.4% at 5 years) than did patients who lacked the fusion protein (8.1%, P<0.0001). In a multivariable analysis, the presence of gene fusion was the single most important prognostic factor; the adjusted hazard ratio for disease recurrence for patients with the fusion protein was 8.6 (95% CI=3.6-20.6, P<0.0001) compared to patients without the fusion protein. Among prostate cancer patients treated with surgery, the expression of TMPRSS2:ERG fusion gene is a strong prognostic factor and is independent of grade, stage and PSA level.

Permanent flank bulge is a consequence of flank incision for radical nephrectomy in one half of patients.

The objective of the study was to determine the incidence and predictors of post operative pain and flank bulging in patients undergoing nephrectomy for a renal tumor through a flank or thoracoabdominal incision. Only one previous retrospective study (1974) has directly addressed this issue in urologic patients. This reported a 3% incidence of flank bulging. This was at variance with our own experience. To determine the incidence of pain and post-operative flank bulge after flank or thoraco-abdominal incision, a cross sectional survey among in 70 patients, who had a nephrectomy for a renal tumor between 1996 and 2000, was assessed by telephone interview. Four surgeons contributed patients to the study. Thirty-four of seventy (49%) patients complained of a flank bulge persisting more than 1 yr after surgery. Durable flank pain was experienced by 24%. This was severe in 3% of patients. Median pain magnitude was 5/10. There was no difference in bulge incidence between surgeons (P = 0.49). Flank bulging occurred more frequently in left sided nephrectomy (P = 0.054) than right. Other parameters including gender, age, and tumor size had no correlation with the rate of either complication. In all patients who described a flank bulge, the deformity was durable; there were no cases of spontaneous resolution. Patients described a significant impact on QOL, particularly in those under 60 yrs. The overall rate of postoperative flank bulging is considerably higher than has been previously reported. This deformity affects quality of life. The observation that almost 50% of patients experience a flank bulge following a flank incision supports the shift towards laparoscopic nephrectomy, and should be incorporated into decision making regarding the optimal surgical approach. This may be particularly relevant in the choice between open partial nephrectomy and laparoscopic radical nephrectomy in a patient with a normal contralateral kidney.

Long-term followup of a randomized trial of 0 versus 3 months of neoadjuvant androgen ablation before radical prostatectomy.

PURPOSE: In 1992 we initiated a national randomized prospective trial of 3 months of cyproterone acetate before radical prostatectomy compared to prostatectomy alone. Initial results indicated a 50% decrease in the rate of positive surgical margins. This decrease did not translate into a difference in prostate specific antigen (PSA) progression at 3 years. This report is on the long-term outcome (median followup 6 years) of this cohort. MATERIALS AND METHODS: This prospective, randomized, open label trial compared 100 mg cyproterone acetate 3 times daily for 3 months before surgery to surgery alone. Randomization occurred between January 1993 and April 1994. Patients were stratified according to clinical stage, baseline serum PSA and Gleason sum. A total of 213 patients were accrued. Biochemical progression was defined as 2 consecutive detectable PSAs (greater than 0.2 ng/ml) at least 4 weeks apart, re-treatment or death from prostate cancer. RESULTS: A total of 34 (33.6%) patients undergoing surgery only and 42 (37.5%) patients given neoadjuvant hormone therapy (NHT) had biochemical recurrence during the median followup of 6 years. Despite the significant pathological down staging in this study, there was no significant difference in number of patients with no evidence of biochemical disease (bNED) survival (p = 0.732). A bNED survival benefit favoring NHT was seen in men with a baseline PSA greater than 20 (p = 0.015). CONCLUSIONS: After 6 years of followup there was no overall benefit with 3 months of NHT. Improved bNED survival was seen in the highest risk PSA group (PSA greater than 20). The possibility that high risk patients may benefit from NHT warrants further investigation.

HPC2 variants and screen-detected prostate cancer.

Two studies have reported significant associations between susceptibility to prostate cancer and two common missense variants of the HPC2/ELAC2 gene, with estimated relative risks in the range of two- to threefold. We investigated whether these polymorphisms could be informative in the prediction of the presence of prostate cancer in men undergoing prostatic biopsy for the evaluation of an elevated serum-PSA level (> or = 4.0 ng/ml). We genotyped 944 men who underwent a prostate biopsy at our institution, as well as a control population of 922 healthy, unselected women from the same population. The prevalence of the HPC2 Ala541Thr allele was similar in men with prostate cancer (6.3%), men with other prostatic conditions (6.8%), and healthy women (6.3%) (P = .83). We conclude that HPC2 genotyping is unlikely to be a useful adjunct to PSA in the prediction of the presence of biopsy-detected prostate cancer in asymptomatic men.

Levels of insulin-like growth factor I (IGF-I) and IGF binding proteins 2 and 3 in serial postoperative serum samples and risk of prostate cancer recurrence.

OBJECTIVES: To determine changes of insulin-like growth factor I (IGF-I), IGF binding protein-2 (IGFBP-2), and IGFBP-3 levels in serial postoperative serum samples from prostate cancer patients with and without relapse and to evaluate the prognostic value of these molecules in the recurrence of prostate cancer. METHODS: From a group of patients with prostate cancer who had been followed for disease recurrence for almost 5 years after radical prostatectomy, we selected 38 patients (cases) who developed recurrent disease and 40 patients (controls) who were in remission. Of these patients, 70 had 4 and 8 had 3 serial postoperative serum samples collected. The median times for serum collection after surgery were 1.5 years for the first serial samples, 2.6 years for the second, 3.5 years for the third, and 4.5 years for the fourth. Serum levels of IGFBP-2, IGFBP-3, and IGF-I were measured, using commercial immunoassay kits. RESULTS: The study showed lower serum levels of IGFBP-2 and IGFBP-3 in the cases than in controls(P <0.05) but no difference in IGF-I levels between the two groups (P = 0.277). In the sequential samples, IGFBP-2 levels increased over time in the controls (P = 0.014) but did not change in the cases (P = 0.528). There were no increasing or decreasing trends for IGF-I and IGFBP-3 in either case or control group(P >0.05). CONCLUSIONS: The study suggests that IGFBP-2 may play a role in the progression of prostate cancer, but serum levels of IGFBP-2 as well as IGF-I and IGFBP-3 have no predictive values in the prognosis of prostate cancer.

V89L polymorphism of type-2, 5-alpha reductase enzyme gene predicts prostate cancer presence and progression.

OBJECTIVES: The valine (V) to leucine (L) polymorphism of the SRD5A2 gene is associated with 5-alpha reductase-2 activity; patients with the V allele have high activity and patients with the L allele have low activity. We examined whether this polymorphism predicts the presence of prostate cancer in 320 men without cancer who underwent biopsy and cancer progression in 318 men who underwent radical prostatectomy. METHODS: The effect of the SRD5A2 gene in predicting the presence of prostate cancer was examined using logistic regression analysis, controlling for established risk factors. The effect of the SRD5A2 gene in predicting prostate cancer progression was examined using a nested, matched, case-control design. Most of the participants were white. RESULTS: Of the 320 men, 158 (49.4%) were found on biopsy to have prostate cancer. The overall distribution of the V/V, V/L, and L/L genotypes was 47.5%, 42.5%, and 10.0%, respectively. The adjusted odds ratio for having prostate cancer for patients with at least one V allele was 2.53 compared with patients with the L/L genotype (P = 0.03). Of the 318 patients with cancer, 80 had biochemically detected recurrence and 238 had no evidence of recurrence. The odds ratio for progression for patients with at least one V allele was 3.32 (95% confidence interval 1.67 to 6.62, P = 0.0006) compared with patients with the L/L genotype. CONCLUSIONS: Men who have the V allele of the SRD5A2 gene have a twofold increase in the risk of prostate cancer development and an additional twofold increase in the risk of progression compared with men with the L/L genotype.

Influence of initial semen quality on the integrity of human sperm DNA following semen processing.

OBJECTIVE: To examine and compare the effects of density-gradient centrifugation on the integrity of sperm DNA from the semen of both fertile and infertile men. DESIGN: Prospective, observational study. SETTING: University infertility clinic. PATIENTS: Forty-four nonazoospermic, infertile men and nine fertile controls. INTERVENTIONS: Semen samples were processed by density-gradient centrifugation. Sperm motility and sperm chromatin structure (evaluated by flow cytometry analysis of acridine orange-treated spermatozoa) were monitored before and after semen was processed. MAIN OUTCOME MEASURES: Sperm motility and DNA integrity. RESULTS: Following density-gradient centrifugation, mean sperm motility (+/-SEM) improved significantly compared to whole semen in samples from fertile and infertile men, respectively (71 +/- 6 vs. 49 +/- 7% and 56 +/- 3 vs. 44 +/- 3%, P<0.05). However, the percentage of sperm with denatured DNA increased compared to whole semen after processing of samples from infertile (25 +/- 3 vs. 15 +/- 2%, P<0. 01) but not fertile men (9 +/- 3 vs. 8 +/- 2%, P>0.05). CONCLUSIONS: Our data indicate that the potential detrimental effect of density-gradient centrifugation on sperm DNA integrity is related to the initial semen quality. These data urge us to examine our current sperm-processing techniques to minimize sperm DNA damage.

Significance of the CAG repeat polymorphism of the androgen receptor gene in prostate cancer progression.

PURPOSE: The CAG repeat polymorphism of the androgen receptor gene has been associated with an increased prostate cancer risk, and the repeat length correlated with cancer stage and grade at presentation. Men with an allele length of 18 CAG repeats, controlling for grade, stage and serum PSA level at diagnosis using Cox proportional hazard modeling. RESULTS: Overall, the CAG repeat allele was not predictive of recurrence; tumor grade, stage and PSA level at diagnosis were the only predictors of recurrence in a multivariate analysis. However, for patients at low risk for recurrence (Gleason score 2 to 6, stage pT2, and PSA 18 CAG repeats. In contrast, for patients at high risk of recurrence (Gleason score >/= 7, stage pT3/4, or PSA >10 ng./ml.), the relative risk associated with the 18 CAG repeat allele. CONCLUSIONS: The length of the CAG repeat polymorphism of the androgen receptor gene may be important for prostate cancer recurrence among patients who are otherwise at low risk for recurrence after radical prostatectomy. These findings have potential implications for patient selection for adjuvant treatment, and for the development of novel treatments.

Serum human glandular kallikrein-2 protease levels predict the presence of prostate cancer among men with elevated prostate-specific antigen.

PURPOSE: We hypothesize that serum human glandular kallikrein-2 (hK2) levels predict the presence of prostate cancer among men prescreened by prostate-specific antigen (PSA). PATIENTS AND METHODS: We conducted a cross-sectional study of 324 men who had no history of prostate cancer and who were referred for prostate biopsy. PSA and hK2 levels were measured using specific nonisotopic immunometric techniques. Cases were patients who were diagnosed with adenocarcinoma of the prostate from biopsy, and controls were patients who had no evidence of cancer from biopsy. The odds ratio for detection of prostate cancer was determined for hK2 measurements, controlling for age, total-PSA level, digital rectal examination, and symptoms of urinary obstruction. RESULTS: Of 324 men, 159 (49.1%) had cancer. Mean hK2 levels and hK2:free-PSA ratios were significantly higher in cases than in controls (1.18 v 0.53 ng/mL, respectively, for hK2, P =.0001; 1.17 v 0.62 for hK2:free-PSA ratio, P =.0001). The crude odds ratio for prostate cancer detection for patients in the highest quartile of hK2 level was 5.83 (95% confidence interval [CI], 2.8 to 12.1; P =.0001) compared with patients in the lowest quartile. The adjusted odds ratio was 6.72 (95% CI, 2.9 to 15.6; P =.0001). Similarly, the crude and adjusted odds ratios for prostate cancer detection using the hK2:free-PSA ratio were 7.36 (95% CI, 3.6 to 15.1; P =.0001) and 8.06 (95% CI, 3. 7 to 17.4; P =.0001), respectively. These odds ratios were higher than that observed for prostate cancer detection by total-PSA level (2.73; P =.03). CONCLUSION: Among men prescreened with PSA for prostate cancer, patients with high hK2 measurements have a five- to eight-fold increase in risk for prostate cancer, adjusting for PSA level and other established risk factors. hK2 measurements may be a useful adjunct to PSA in improving patient selection for prostate biopsy.

Comparison of molecular and conventional strategies for followup of superficial bladder cancer using decision analysis.

PURPOSE: Patients with superficial bladder cancer require long-term surveillance for recurrence. We compared the cost of cystoscopy and cytology (standard care) to that of urinary markers (modified care) for patients with a history of superficial bladder cancer. MATERIALS AND METHODS: We constructed a decision analysis model that compared the 2 strategies for a hypothetical followup interval of 3 years. Probabilities required for the decision tree were based on a cohort of 361 patients diagnosed with superficial bladder cancer from 1987 to 1997. Sensitivity analyses were used to determine whether test sensitivity and specificity would affect cost thresholds. Costs for each strategy were then applied to actual practice patterns. RESULTS: The cost of modified care ranged from $158 to $228 for each followup visit when using a urinary marker with a sensitivity and specificity of 95% and 77%, respectively. The cost of standard care was $240 for each followup visit. Based on sensitivity analyses the probability of disease recurrence and urinary marker accuracy were important determinants of expected costs. Mean number of followup assessments for patients followed more than 3 years was 4.3, 2.2 and 1.5 for years 1, 2 and 3, respectively. Cumulative costs of modified care were lower than those of standard care. CONCLUSIONS: Urinary marker testing for followup of patients with superficial bladder cancer is less expensive than the standard method of cystoscopy and urinary cytology based on our model. Future studies will be required to consider other factors that could affect the cost advantage of urinary markers, including indirect costs, the psychosocial impact of testing and different surveillance frequencies.