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BACKGROUND To the authors' knowledge, the literature to date lacks studies examining lifetime costs and quality-adjusted life-years (QALYs) of prostate cancer (PCa) management strategies that integrate localized and advanced disease. The objective of the current study was to assess lifetime costs and QALYs associated with contemporary PCa management strategies across risk groups by integrating localized and advanced disease. METHODS The authors' validated Markov chain Monte Carlo model was used to predict lifetime direct costs and QALYs. The health states modeled were active surveillance, initial treatments (radical prostatectomy or radiotherapy), PCa recurrence, PCa recurrence free, metastatic castration-resistant prostate cancer, and death (cause specific/other causes). Data regarding treatment distribution, state transition probabilities, adverse effects of management options, costs, utilities, and disutilities were derived from the published literature. RESULTS The total cost per patient for the overall cohort increased from $18,503 at 5 years to $28,032 and $39,143, respectively, at 10 years and 15 years. Furthermore, the results indicated the influence of risk group on total cost, with the high-risk group accruing the maximum per patient cost followed by the intermediate-risk and low-risk groups. Active surveillance was found to confer the most QALYs (12.5 years) and was the least costly strategy ($18,452) for individuals at low risk. For all risk groups, radical prostatectomy was less costly and conferred modestly more QALYs compared with intensity-modulated radiotherapy modalities. CONCLUSIONS Public health care systems in Canada and elsewhere are operating under budget constraints to allocate finite resources. The findings of the current study might inform discussions concerning budget planning to provide health care services. Cancer 2016;122:1085–1096. © 2016 American Cancer Society

BACKGROUND: Sequential bacillus Calmette-Guerin (BCG) and electromotive mitomycin (sequential therapy) have been shown in a randomized prospective trial to be superior to therapy with BCG alone in patients with high-risk non–muscle-invasive bladder cancer. The objective of the current study was to compare the costs and benefits of these 2 treatment strategies by performing a 5-year and 10-year cost-effectiveness study. METHODS: A Markov model was developed to estimate the incremental cost-effectiveness ratio over a 5-year and 10-year period. Estimates of disease progression, death, and treatment efficacy were obtained from what to the authors’ knowledge is the only randomized trial comparing the 2 therapies. Costs included: 1) medical costs (physician fees); 2) drug costs (preparation and instillation); and 3) hospital costs (procedure fees, admission fees, and tests and procedures done during surveillance). Patients were allowed a second course of induction therapy. RESULTS: Sequential therapy was found to be associated with a higher initial material cost for induction and maintenance. The average effectiveness for the patients treated with therapy with BCG alone was 4.39 years with a mean cost of $9236 (95% confidence interval, $9118-$9345) per patient. The sequential group resulted in an average effectiveness of 4.65 years, with a mean cost of $16,468 (95% confidence interval, $16,371-$16,527). The 5-year incremental cost-effectiveness ratio of sequential versus BCG-alone therapy was $27,815 per life-year gained. The corresponding figure over a 10year period was $8618 per life-year gained. CONCLUSIONS: The results of the current study suggest that sequential therapy is a cost-effective treatment for patients with high-risk non–muscle-invasive bladder cancer. Cancer 2014;000:000-000. V C 2014 American Cancer Society.

BACKGROUND. Active surveillance (AS) with deferred treatment is an established management option for patients with prostate cancer and favorable clinical parameters. The impact of repeat biopsy after diagnosis was examined in a cohort of men with prostate cancer on AS. METHODS. In all, 186 men with prostate cancer with favorable parameters or who refused treatment were conservatively managed by AS. Of these, 92 patients had at least 1 biopsy after diagnosis. Patients were followed every 3 to 6 months with prostate-specific antigen (PSA) and physical examination and were offered rebiopsy annually or if there were any changes on physical examination or in the PSA value. Disease progression while on AS was defined as having ≥1 of the following: ≥cT2b disease, ≥3 positive cores, >50% of cancer in at least 1 core, or a predominant Gleason pattern of 4 in rebiopsies. RESULTS. The median age of the patients at the time of diagnosis was 67 years (range, 49–78 years). The median follow-up was 76 months (range, 20–169 months). Of the 92 patients who underwent repeat biopsies, 42 patients, 25 patients, 13 patients, 10 patients, and 2 patients had 1, 2, 3, 4, and 5 rebiopsies, respectively. A total of 34 patients (36%) demonstrated disease progression on rebiopsy. The first rebiopsy was positive for cancer in 48 patients (52.2%) and negative in 44 patients (47.8%). The 5-year actuarial progression-free probability was 82% for patients with a negative first repeat biopsy compared with 50% for patients with a positive first rebiopsy (P = .02). A PSA doubling time

Background. Prostate adenocarcinoma is predominantly a disease of older men. Males younger than 50 years account for 1% of all patients with prostate cancer. The authors retrospectively examined cases of prostate adenocarcinoma in patients younger than 50 years of age to determine the natural history and prognosis of this malignancy in the younger population. Methods. The medical records of 151 patients were reviewed, with particular attention to age and year at diagnosis, race, symptoms at presentation, family history of prostate cancer, histologic grade, clinical and pathologic stage, treatment modality, and clinical outcome. Results. Univariate analyses demonstrated a significant correlation between higher disease stage (P = 0.0001), higher tumor grade (P = 0.0001), earlier year of diagnosis (P = 0.01), symptoms at presentation (P = 0.0001), and race (P = 0.01) with shorter disease-specific survival. However, multivariate analysis revealed that only stage and grade were statistically significant predictors for poor prognosis after controlling for other variables. With a one-unit increase of stage or grade, the risk of death from disease increases 2.2 or 1.9 times, respectively. Conclusion. These data suggest that patients younger than 50 years with prostate cancer present with similar symptomatology, histologic grade, and disease stage as the older population. Patients with disease confined to the prostate have a relatively good disease-specific survival but remain at risk for death even 15 years after diagnosis When carcinoma escapes the confines of the prostate, the prognosis is uniformly poor.

Background. Although hormonal manipulation is standard therapy for patients with metastatic prostatic cancer, its use in localized disease in combination with surgical extirpation of the gland has not been investigated thoroughly and systematically. Methods. The authors report their initial pilot studies using preoperative neoad2j1uvant endocrine therapy. Results. Although marked reduction in serum prostate-specific antigen (PSA) levels occurred in all patients, the PSA level after endocrine manipulation did not predict the pathologic stage

BACKGROUND. The objective of the current study was to evaluate the outcome of a surveillance strategy in patients with renal masses. METHODS. The medical records of patients with renal masses diagnosed between January 1992 and May 2006 were reviewed retrospectively. In all, 45 patients with renal masses under observation were identified. Of these, 35 patients with 44 renal masses measuring

BACKGROUND Late-stage prostate cancer patients are refractory to hormone therapy and exhibit a high propensity to develop skeletal metastasis. In this regard, the role of a novel cytokine system belonging to the tumor necrosis factor (TNF) family that is critical for osteoclastic osteolysis and that consists of receptor activator of NF-κB ligand (RANKL), its receptor (RANK), and decoy receptor osteoprotegerin (OPG) is of potential interest. METHODS Reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemical analysis was used to examine the expression of RANKL, RANK, and OPG in human prostate cancer cell lines and in 89 archival samples of primary and metastatic (lymph nodes, skeleton) prostate cancer patients. Expression of these proteins was correlated with clinicopathogic parameters of the prostate cancer. RESULTS Expression of RANKL/RANK/OPG was low in normal but markedly higher in prostate cancer cell lines. Analysis of surgical biopsy specimens showed the expression of RANKL (31%), RANK (38%), and OPG (19%) in primary carcinoma. The expression frequency was significantly higher (RANKL [44%], RANK [49%], and OPG [73%]) in metastatic prostate cancer. OPG (83%) production was more common in skeletal as compared with lymph node metastases (46%), whereas the expression of RANKL expression was less discordant in bone (47%) and lymph node metastases (36%). The increased expression of RANKL/RANK/OPG observed correlated with Gleason score, TNM stage, androgen status, and serum prostate-specific antigen (PSA) levels in the prostate cancer patients. CONCLUSIONS Expression of RANKL/RANK/OPG correlates with more aggressive, advanced, metastatic prostate carcinoma to suggest their role as diagnostic, prognostic, and therapeutic targets for prostate cancer. Cancer 2006. © 2006 American Cancer Society.

BACKGROUND Wnt-1 and β-catenin expression levels play an important role in several malignancies. The authors determined the level of production of Wnt-1 and β-catenin in normal and malignant human prostate carcinoma cell lines. Surgical pathology specimens from primary prostatic adenocarcinoma, lymph node metastases, and skeletal metastases were used to establish a correlation between the level of Wnt-1/β-catenin expression, Gleason score, serum prostate-specific antigen (PSA) status, and androgen receptor (AR) status. METHODS Immunohistochemical analysis was used to investigate the expression of Wnt-1 and β-catenin in human prostate carcinoma cell lines and in paraffin embedded sections of archival samples from 67 patients with prostate carcinoma. Comparison was made with the expression of tumoral AR and lymph node and skeletal metastases. These results were used to establish a correlation with the clinicopathologic status of patients with prostate carcinoma. RESULTS Levels of both Wnt-1 and β-catenin were low in normal prostate cells and were expressed highly in human prostate carcinoma cell lines. Wnt-1 and cytoplasmic/nuclear β-catenin expression was observed in 52% and 34%, respectively, of primary prostate carcinoma specimens. High levels of expression of Wnt-1 and β-catenin were seen in 77% of lymph node metastases and in 85% of skeletal metastases. These increased levels of expression were related directly to the Gleason score and to serum PSA levels in these patients. Maximum levels of Wnt-1 and β-catenin production were observed in skeletal metastases, whereas normal prostatic tissue failed to exhibit any detectable nuclear staining for β-catenin. CONCLUSIONS High levels of Wnt-1 and β-catenin expression were associated with advanced, metastatic, hormone-refractory prostate carcinoma, in which they can serve as markers of disease progression. Cancer 2004. © 2004 American Cancer Society.