Uncommon Manifestation of Oligometastatic Prostate Cancer: Sister Mary Joseph Nodule.

ABSTRACT: A 76-year-old man with a history of prostate cancer diagnosed in 2008 developed biochemical recurrence in 2010 and started intermittent androgen deprivation therapy. In 2021, due to rising prostate-specific antigen, an 18 F-piflufolastat PSMA PET/CT was performed. It showed a radiotracer-avid sclerotic lesion in the right iliac bone and an indeterminate radiotracer-avid nodule in the umbilical region, demonstrating progressive enlargement and increased uptake on subsequent imaging. Pathologic analysis of the umbilical nodule revealed metastatic prostate cancer-a finding eponymically referred to as a Sister Mary Joseph nodule.

Safety and efficacy of nivolumab plus ipilimumab in patients with advanced non-clear cell renal cell carcinoma: results from the phase 3b/4 CheckMate 920 trial.

BACKGROUND: CheckMate 920 (NCT02982954) is a multicohort, phase 3b/4 clinical trial of nivolumab plus ipilimumab treatment in predominantly US community-based patients with previously untreated advanced renal cell carcinoma (RCC) and clinical features mostly excluded from phase 3 trials. We report safety and efficacy results from the advanced non-clear cell RCC (nccRCC) cohort of CheckMate 920. METHODS: Patients with previously untreated advanced/metastatic nccRCC, Karnofsky performance status ≥70%, and any International Metastatic Renal Cell Carcinoma Database Consortium risk received up to four doses of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks followed by nivolumab 480 mg every 4 weeks for ≤2 years or until disease progression/unacceptable toxicity. The primary endpoint was incidence of grade ≥3 immune-mediated adverse events (AEs) within 100 days of last dose of study drug. Key secondary endpoints included objective response rate (ORR), progression-free survival (PFS; both investigator-assessed), time to response (TTR), and duration of response (DOR), all using RECIST V.1.1. Overall survival (OS) was exploratory. RESULTS: Fifty-two patients with nccRCC (unclassified histology, 42.3%; papillary, 34.6%; chromophobe, 13.5%; translocation-associated, 3.8%; collecting duct, 3.8%; renal medullary, 1.9%) received treatment. With 24.1 months minimum study follow-up, median duration of therapy (range) was 3.5 (0.0-25.8) months for nivolumab and 2.1 (0.0-3.9) months for ipilimumab. Median (range) number of doses received was 4.5 (1-28) for nivolumab and 4.0 (1-4) for ipilimumab. Grade 3-4 immune-mediated AEs were diarrhea/colitis (7.7%), rash (5.8%), nephritis and renal dysfunction (3.8%), hepatitis (1.9%), adrenal insufficiency (1.9%), and hypophysitis (1.9%). No grade 5 immune-mediated AEs occurred. ORR (n=46) was 19.6% (95% CI 9.4 to 33.9). Two patients achieved complete response (papillary, n=1; unclassified, n=1), seven achieved partial response (papillary, n=4; unclassified, n=3), and 17 had stable disease. Median TTR was 2.8 (range 2.1-14.8) months. Median DOR was not reached (range 0.0+-27.8+); eight of nine responders remain without reported progression. Median PFS (n=52) was 3.7 (95% CI 2.7 to 4.6) months. Median OS (n=52) was 21.2 (95% CI 16.6 to not estimable) months. CONCLUSIONS: Nivolumab plus ipilimumab for previously untreated advanced nccRCC showed no new safety signals and encouraging antitumor activity. TRIAL REGISTRATION NUMBER: NCT02982954.

Role of DNA Methylation in Cabazitaxel Resistance in Prostate Cancer.

BACKGROUND/AIM: Cabazitaxel is an approved second-line treatment for docetaxel-refractory metastatic castration-resistant prostate cancer. However, the median time to progression on cabazitaxel is 2.8 months. We aimed to determine whether DNA methylation plays a role in cabazitaxel resistance. MATERIALS AND METHODS: DU145 cells, resistant to docetaxel and cabaxitaxel (DU145 10DRCR), were generated from cells resistant to 10 nM docetaxel (DU145 10DR). The effect of pre-treatment with 5-azacytidine was determined with regards to cabazitaxel sensitivity. Gene expression profiling was carried-out on DU145 10DR, DU145 10DRCR and DU145 10DRCR treated with 5-azacytidine. RESULTS: Pre-treatment of cells with 5-azacytidine resulted in enhanced sensitivity to cabazitaxel. Gene expression profiling identified a subset of genes that may be regulated by DNA methylation. CONCLUSION: Our results indicate that DNA methylation of pro-apoptotic and cell-cycle regulatory genes may contribute to cabazitaxel resistance and pre-treatment with 5-azacytidine may restore sensitivity to cabazitaxel in prostate cancer cells.

Prognostic significance of cystoscopy findings following neoadjuvant chemotherapy for muscle-invasive bladder cancer.

INTRODUCTION: To evaluate the potential significance of cystoscopy findings following neoadjuvant chemotherapy (NAC) as prognostic indicator in patients undergoing radical cystectomy for muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: Patients who received NAC prior to radical cystectomy for MIBC were analyzed. Patients were divided into two groups according to cystoscopy performed after two cycles of NAC: responders and non-responders. Univariate analysis was performed to analyze associations between observed response to chemotherapy and pT stage, pN stage and tumor downstaging. Logistic regression modeling was fitted to evaluate predictors for extravesical disease and pathologic downstaging. Kaplan-Meier analysis was used to evaluate disease specific survival. RESULTS: We identified 101 patients who received neoadjuvant chemotherapy prior to radical cystectomy. According to the cystoscopy findings, 60 patients (59%) were identified as responders to NAC. Stage pT0 at cystectomy was confirmed in 22 patients (36.5%) in the responder group versus only 1 patient (2.5%) in the non-responder group. Univariate analysis showed statistically significant association between response to chemotherapy observed on cystoscopy and pT stage as well as tumor downstaging. Multivariate regression modeling revealed that cystoscopy findings were an independent predictor of extravesical disease and pathologic downstaging. There was a distinct survival benefit in NAC responder group (p < 0.001). Cox proportional hazard model identified cystoscopy findings as an independent predictor of survival (OR 0.38, 95% CI 0.20-0.74, p = 0.004). CONCLUSIONS: Observed response to NAC on follow up cystoscopy is associated with favorable pathological outcomes and is a significant predictor of survival in patients undergoing radical cystectomy for MIBC.

Phase I/II study of azacitidine, docetaxel, and prednisone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel-based therapy.

INTRODUCTION: Methylation-mediated silencing of genes contributes to docetaxel resistance in prostate cancer. We propose that azacitidine, a demethylating agent, can reverse docetaxel resistance. PATIENTS AND METHODS: Metastatic castration-resistant prostate cancer (mCRPC) patients, who progressed during or within 6 months of docetaxel chemotherapy, were eligible. Fifteen and 7 patients were treated in phase I and II, respectively. In phase I, azacitidine and docetaxel were alternately escalated in a standard 3 + 3 design. All patients received prednisone 5 mg twice daily continuously. Patients were evaluated for toxicity and efficacy. Growth arrest and DNA damage-inducible alpha (GADD45A) methylation was measured before and after azacitidine treatment in the first cycle in phase I patients. RESULTS: In phase I, no dose-limiting toxicity was observed. At the highest dose (azacitidine 150 mg/m(2) daily for 5 days followed by docetaxel 75 mg/m(2) on day 6), Grade 4 neutropenia was frequent, but infrequent with growth factor. Six patients in the phase II study received the highest dose including growth factor support. The sixth phase II patient died because of neutropenic sepsis. After data and safety monitoring board review, the phase II dose was reduced to azacitidine 75 mg/m(2) daily for 5 days followed by docetaxel 75 mg/m(2) on day 6 with growth factor support. Prostate-specific antigen response was seen in 10 of 19 evaluable patients and objective response was observed in 3 of 10 evaluable patients. Significant demethylation of GADD45A was observed with azacitidine treatment. CONCLUSION: The combination of azacitidine, docetaxel, and prednisone with growth factor support is active in mCRPC patients.

Free circulating DNA as a biomarker of prostate cancer: comparison of quantitation methods.

AIM: To identify a simpler method of free circulating DNA (fcDNA) quantitation that may improve the specificity of the prostate cancer prostate-specific antigen (PSA) screening test. MATERIALS AND METHODS: The patient group consisted of 241 men with elevated PSA/abnormal digital rectal exam (DRE), undergoing prostate biopsy. Serum fcDNA levels were measured by UV absorbance and PicoGreen. Results were compared to previously published quantitative polymerase chain reaction (qPCR) data. RESULTS: We found that levels of fcDNA measured by PicoGreen correlated well with those measured by qPCR (r=0.8552). In the patient group with PSA >4 to 10 ng/ml, those with fcDNA (PicoGreen) >53.1 ng/ml were at increased risk for prostate cancer compared to those with fcDNA ≤ 53.1 ng/ml. Moreover, we found that measuring fcDNA levels by PicoGreen does not compromise the negative predictive value, accuracy or specificity of the qPCR fcDNA test. CONCLUSION: If validated in larger studies, PicoGreen quantitation of fcDNA could serve as a simple method to aid in prostate cancer diagnosis.

Resolution of thrombocytopenia secondary to disseminated intravascular coagulation with docetaxel chemotherapy in prostate cancer.

Patients with metastatic hormone-refractory prostate carcinoma may have dramatic and life-threatening coagulation complications from their disease. They are at risk for either clotting or bleeding events. We report the case of a man with metastatic castration-resistant prostate cancer with disseminated intravascular coagulation who had both clotting and bleeding in addition to thrombocytopenia. The patient did not respond to supportive therapy and was treated with docetaxel despite a platelet count of 46/mm³. The treatment resulted in resolution of disseminated intravascular coagulation, normalization of the platelet count, and resolution of hematuria. We review disseminated intravascular coagulation in prostate cancer and different possible treatments.

Neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer: The likelihood of initiation and completion.

INTRODUCTION: Chemotherapy was shown to improve survival in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). The initiation and completion rates for perioperative chemotherapy are variable. Our aim is to compare the likelihood of initiating and completing neoadjuvant (NAC) and adjuvant chemotherapy (AC) in patients who underwent of RC for MIBC. MATERIALS AND METHODS: We performed a retrospective analysis of patients who underwent RC between 1992 and 2011. NAC was advised for patients with clinical stage ≥T2, hydronephrosis, extensive lymphovascular invasion (LVI), or prostatic stromal invasion. Patients with ≥pT3 or lymph node metastases were considered for AC. RESULTS: A total of 363 patients were considered for perioperative chemotherapy. Among the 141 patients who were offered NAC, 125 (88.6%) initiated NAC. A total of 222 were considered for AC, and 151 (68.0%) initiated AC (P < 0.001). In the NAC group, 118 (83.5%) completed planned number of cycles of chemotherapy and 7 (5.6%) did not complete the planned chemotherapy. In the AC group, 79 (35.5%) completed at least four cycles and 72 (47.3%) could not complete the planned cycles (P < 0.001). CONCLUSIONS: Patients with MIBC are more likely to initiate and complete NAC than AC.

Epigenetics in prostate cancer.

Prostate cancer (PC) is the most commonly diagnosed nonskin malignancy and the second most common cause of cancer death among men in the United States. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequences. Two common epigenetic mechanisms, DNA methylation and histone modification, have demonstrated critical roles in prostate cancer growth and metastasis. DNA hypermethylation of cytosine-guanine (CpG) rich sequence islands within gene promoter regions is widespread during neoplastic transformation of prostate cells, suggesting that treatment-induced restoration of a "normal" epigenome could be clinically beneficial. Histone modification leads to altered tumor gene function by changing chromosome structure and the level of gene transcription. The reversibility of epigenetic aberrations and restoration of tumor suppression gene function have made them attractive targets for prostate cancer treatment with modulators that demethylate DNA and inhibit histone deacetylases.

5-azacytidine reverses drug resistance in bladder cancer cells.

BACKGROUND: Patients with metastatic and muscle-invasive bladder cancer are commonly treated with cisplatin. A significant proportion of patients develop disease progression after an initial response to chemotherapy. Presently there is no standard of care for such patients. We examined whether pretreatment with an epigenetic agent would result in reversal of drug resistance. MATERIALS AND METHODS: Methylation of proapoptotic and cell cycle genes in bladder cancer cells was examined. Cisplatin- and docetaxel-resistant cells were generated. The effect of target of methylation-induced silencing (TMS1) expression and pretreatment of wild-type and drug-resistant cells with 5-azacytidine on chemosensitivity was determined. RESULTS: Unidirectional crossresistance of cisplatin-resistant UMUC3 cells to docetaxel was observed. Recombinant expression of TMS1 or pre-treatment of wild-type and drug-resistant cells with 5-azacytidine resulted in enhanced sensitivity to cisplatin and docetaxel. CONCLUSION: Our results indicate that epigenetic therapy may restore sensitivity to chemotherapeutic agents in bladder cancer cells.

Hypomethylating agents for urologic cancers.

Silencing of tumor suppressor genes by promoter-region methylation as an epigenetic mechanism of gene regulation is increasingly recognized as beneficial in cancer. Initially developed as cytotoxic high-dose therapies, azacitidine and decitabine are now being reinvestigated in lower-dose cancer treatment regimens with a different paradigm - hypomethylation. Recent evidence for benefit in myelodysplastic syndromes and acute myeloid leukemias has renewed interest in hypomethylation as a therapeutic option in epithelial cancers. In this article, we describe the mechanistic aspects of DNA methylation, which alters gene expression, and review the evidence for hypomethylation as a therapeutic option in urologic cancers. Potential correlative studies that may assist in developing tailored therapy with hypomethylating agents are reviewed. Given that the population with urologic cancers is typically elderly with multiple comorbidities, the excellent tolerability of lower-dose hypomethylating agents provides a high therapeutic index and rational development is warranted, bearing in mind that the cytostatic and delayed activity present challenges in the choice of appropriate trial end points.

Methylation-mediated silencing of TMS1 in pancreatic cancer and its potential contribution to chemosensitivity.

BACKGROUND: Resistance to chemotherapeutic agents, resulting in part from epigenetic silencing of pro-apoptotic genes, is one of the causes of treatment failure of pancreatic cancer. We examined whether epigenetic silencing of target of methylation induced silencing 1 (TMS1) contributes to resistance to chemotherapy in pancreatic cancer. MATERIALS AND METHODS: Methylation analysis was performed by methylation-specific PCR (MS-PCR) and gene expression was analyzed by quantitative reverse transcriptase PCR (qRT-PCR). MIA PaCa-2 cells were transfected with pCMV6-XL5/TMS1 plasmid and the effect of TMS1 expression on sensitivity to gemcitabine and docetaxel was determined. Cell viability was measured using Cell Titer Blue assay. RESULTS: TMS1 expression was repressed in MIA PaCa-2 cells by DNA methylation. Up-regulation of TMS1 by recombinant gene expression in MIA PaCa-2 cells or by pre-treatment of these cells with 5-azacytidine resulted in enhanced sensitivity to gemcitabine and docetaxel. CONCLUSION: Our results suggest that TMS1 is a potential therapeutic target in pancreatic cancer.

Serum free circulating DNA is a useful biomarker to distinguish benign versus malignant prostate disease.

BACKGROUND: Free circulating DNA (fcDNA) has been shown to be elevated in serum of prostate cancer patients compared with benign controls. However, studies evaluating the role of fcDNA as a biomarker in a "representative" patient group who have undergone prostate cancer screening are lacking. Our study examined the use of serum fcDNA levels as a biomarker of prostate cancer in such a setting. METHODS: The study included 252 men, with prostate-specific antigen (PSA) levels >4 ng/mL and/or abnormal digital rectal exam. fcDNA levels in serum before prostate biopsy were quantitated by real-time PCR amplification of the glutathione S-transferase, pi, gene. RESULTS: Patients with PSA < or = 10 ng/mL with fcDNA > 180 ng/mL were at increased risk for prostate cancer compared with those with fcDNA < or =180 ng/mL (odds ratio, 4.27; 95% confidence interval, 2.05-8.88; P < 0.001; area under the curve, 0.742). The multivariate model including age, race, PSA, fcDNA, and interaction between fcDNA and PSA yielded a high negative predictive value of 93.1% and increased specificity of 33.1% compared with negative predictive value of 73.3% and specificity of 6.7% in the model excluding fcDNA. CONCLUSIONS: Our results indicate that fcDNA may improve the specificity of prostate cancer screening. IMPACT: Our study shows that adding fcDNA to prostate cancer screening can reduce the number of unnecessary prostate biopsies.

Methylation mediated silencing of TMS1 in breast cancer and its potential contribution to docetaxel cytotoxicity.

BACKGROUND: The tumor suppressor gene TMS1 (target of methylation-induced silencing) has been described in the literature as a pro-apoptotic gene. This study examined the methylation status of TMS1 in breast cancer cells and its potential role in sensitivity to docetaxel chemotherapy. MATERIALS AND METHODS: Methylation of the TMS1 promoter was examined by methylation-specific PCR (MS-PCR) and gene expression was analyzed by reverse transcriptase PCR (RT-PCR). Apoptosis was evaluated by annexin V/propidium iodide staining followed by flow cytometric analysis. RESULTS AND CONCLUSION: The TMS1 promoter was unmethylated in ZR75-1, MB-231 and MCF7 cells which expressed the gene and partially methylated in SKBR3 and Hs578t cells in which TMS1 expression was down-regulated. Treatment of SKBR3 and Hs578t cells with demethylating agents resulted in reactivation of the TMS1 gene. Pretreatment with 5-azacytidine increased sensitivity to docetaxel treatment in SKBR3 and Hs578t cells, indicating that TMS1 reactivation in these cells may contribute to docetaxel sensitivity.

Outcome after radical cystectomy in patients with clinical T2 bladder cancer in whom neoadjuvant chemotherapy has failed.

OBJECTIVE: To analyse the outcome after radical cystectomy (RC) in patients with clinical T2 bladder cancer not responding to neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: In a retrospective analysis, study patients received NAC for clinical T2 disease before RC and a control group had RC for clinical T2 disease with no NAC. Patients treated with NAC were further grouped based on the pathological response; failure to respond was defined as 'no change in T stage or a higher T stage in the RC specimen (>or=pT2)', and the relevant clinical and pathological data were analysed. RESULTS: In all, 53 patients satisfied the inclusion criteria for the study group and 200 for the control group. In the study group 18 (34%) responded to NAC (group 1) of whom 11 (61%) were pT0 and seven (39%) pT1, and among the non-responders (group 2) 19 (54%) were pT3/pT4 and 16 (46%) were pT2; 16 (46%) patients in group 2 had lymph node metastasis. The mean follow-up was 26 months. In group 2, local recurrence occurred in six (17%) vs none in group 1. Seven patients (20%) in group 2 developed metastases, vs one (5%) in group 1 (P = 0.01). The 5-year disease-free survival was significantly lower for group 2 (40%) than group 1 (91%, P = 0.007) and the control group (67%, P = 0.04). There were 14 deaths from bladder cancer in group 2, vs one in group I (P = 0.01). The 5-year disease-specific survival was significantly lower for group 2 (52%) than group 1 (83%, P = 0.008) and the control group (70%, P = 0.001). CONCLUSION: A lack of response to NAC is associated with a significantly higher local and distant recurrence, and with lower survival.

Methylation-mediated repression of GADD45alpha in prostate cancer and its role as a potential therapeutic target.

Defects in apoptotic pathway contribute to uncontrolled proliferation of cancer cells and confer resistance to chemotherapy. Growth arrest and DNA damage inducible, alpha (GADD45alpha) is up-regulated on docetaxel treatment and may contribute to docetaxel-mediated cytotoxicity. We examined the mechanism of regulation of GADD45alpha in prostate cancer cells and the effect of its up-regulation on sensitivity to docetaxel chemotherapy. Expression of GADD45alpha in PC3 cells was higher than that in Du145 and LNCaP cells (17- and 12-fold, respectively; P < 0.05). Although the proximal promoter region was unmethylated in all three cell lines, methylation of a 4 CpG region upstream of the proximal promoter correlated inversely with gene expression levels. Methylation was reversed by treatment of Du145 and LNCaP cells with DNA methyltransferase inhibitors, leading to reactivation of GADD45alpha expression in these cells. The 5' 4 CpG region was also frequently methylated in prostate cancer tissues. Methylation of this region correlated inversely with gene expression in prostate cancer and benign prostate tissues. The methyl binding protein MeCP2 was associated with the methylated 4 CpGs in Du145 cells, and knockdown of MeCP2 in these cells (Du145 MeCP2(-)) led to a significantly increased expression of GADD45alpha (3-fold; P = 0.035) without affecting the methylation status of the gene. Enhanced sensitivity to docetaxel was observed by up-regulation of GADD45alpha in Du145 cells by recombinant expression of GADD45alpha or pretreatment with 5-azacytidine. Our results show that GADD45alpha is epigenetically repressed and is a potential target for treatment of prostate cancer.

Soluble CD44 is a potential marker for the early detection of head and neck cancer.

INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) is a devastating and deadly disease, largely because it is diagnosed in late stage. Cure rates, currently at 50%, could increase to >80% with early detection. In this study, we evaluate soluble CD44 (solCD44) as an early detection tool for HNSCC by determining whether it reliably distinguishes HNSCC from benign disease of the upper aerodigestive tract. METHODS: We carried out the solCD44 ELISA on oral rinses from 102 patients with HNSCC and 69 control patients with benign diseases of upper aerodigestive tract to determine the sensitivity and specificity of the test for differentiating HNSCC from benign disease. Furthermore, we did a pilot study using methylation-specific PCR primers on oral rinses from 11 HNSCC patients with low solCD44 levels and 10 benign disease controls. RESULTS: Mean salivary solCD44 levels were 24.4 +/- 32.0 ng/mL for HNSCC patients (range, 0.99-201 ng/mL) and 9.9 +/- 16.1 ng/mL (range, 0.73-124 ng/mL) for the patients with benign disease (P < 0.0001). Depending on cutoff point and HNSCC site, sensitivity ranged from 62% to 70% and specificity ranged from 75% to 88%. Nine of 11 HNSCC and 0 of 10 controls with low solCD44 levels showed hypermethylation of the CD44 promoter. CONCLUSIONS: SolCD44 is elevated in the majority of HNSCC and distinguishes cancer from benign disease with high specificity. Whereas the solCD44 test lacks sensitivity by itself, methylation status of the CD44 gene seems to complement the solCD44 test. Our pilot data indicate that, together, these markers will detect HNSCC with very high sensitivity and specificity.

EGFR targeting of solid tumors.

BACKGROUND: Recent clinical trials suggest that epidermal growth factor receptor (EGFR)-targeted agents could benefit many patients with cancer. METHODS: We review the current status of several EGFR-targeted therapies in cancer patients and address the efficacy of theses drugs as monotherapy or in combination with other drugs and/or treatments. RESULTS: Cetuximab is the most widely studied anti-EGFR monoclonal antibody. Other monoclonal antibody agents under investigation are panitumumab, matuzumab, MDX-447, nimutozumab, and mAb806. Extensive research has also evaluated the efficacy of EGFR tyrosine kinase inhibitors such as erlotinib, gefitinib, EKB-569, lapatinib (GW572016), PKI-166, and canertinib (CI-1033). All of these agents have been studied for the treatment of colorectal, lung, breast, pancreatic, renal, head and neck, gynecologic, and prostate cancer. Currently, cetuximab and panitumumab are FDA approved for the treatment of metastatic colorectal cancer. Additionally, cetuximab is approved for head and neck cancer. Erlotinib is FDA approved for advanced/metastatic lung cancer. Erlotinib in combination with gemcitabine is approved for advanced/metastatic pancreatic cancer treatment. CONCLUSIONS: EGFR-targeted agents have already shown utility in different scenarios. Researchers are continuously investigating additional cancer types and combined treatment modalities that could also benefit from the use of EGFR-targeted agents. Careful patient selection through the identification of specific biologic markers, such as gene expression, genomic polymorphism, and posttranslational modifications of EGFR downstream effectors, most likely will contribute to the successful use of these agents.

The emerging role of epigenetics in urological cancers.

DNA methylation and histone modifications constitute the common epigenetic modifications in vertebrate genomes. The epigenetic changes are early event in the cancer development and are reversible. Over the last decade, the field of epigenetics has made considerable progress both in the diagnosis and treatment of variety of malignancies. Novel epigenetic markers are being studied, which have the potential as sensitive diagnostic and prognostic markers. DNA methylation has been identified as a powerful diagnostic tool in classification, detection and risk assessment of cancers. As DNA methylation is reversible, inhibitors of DNA methyl transferases and histone deacteylases have been designed for use in treatment of a variety of urological malignancies. Variety of drugs targeting epigenetic changes are being studied, which can be effective individually or in combination with other conventional drugs used in cancer therapy. The emerging area of epigenetic therapy holds great promise for novel chemotherapeutic and chemoprevention approaches against cancer.