Radical exenteration surgery is curative in locally advance mucinous prostatic adenocarcinoma involving bladder and rectum.

The management of mucinous prostatic adenocarcinoma include hormonal treatment, radiotherapy and radical prostatectomy with variable long-term outcome. We report a 59 year old man with advanced mucinous prostatic adenocarcinoma involving almost the entire bladder and had failed treatment with hormonal and radiotherapy, but subsequently underwent radical pelvic exenteration surgery that resulted in long-term cure. He remains alive, his PSA remains undetectable and his surveillance CT scans did not show any evidence of recurrence after 11 years post-surgery. The favourable outcome of radical surgery suggests that radical surgery should be considered, especially in cases with failed initial treatments.

Associations between timing of exposure to ultraviolet radiation, T-stage and survival in prostate cancer.

BACKGROUND: Exposure to ultraviolet radiation (UVR) has been inversely associated with prostate cancer risk. We determined if skin type and UVR exposure are linked with parameters of prostate cancer outcome. METHODS: We used a questionnaire to determine UVR exposure parameters and skin type in 553 men with prostate cancer and, using logistic regression and survival analysis, studied their association with T-stage, Gleason score, and survival after starting hormone manipulation therapy. RESULTS: UVR exposures 10, 20, and 30 years before diagnosis were inversely associated with T-stage. The odds ratio (OR) for UVR exposure 10 years before diagnosis was lowest (OR=0.69, 95% CI=0.56-0.86). ORs were lower in men with skin types I/II than III/IV. Skin types I/II were associated with longer survival after commencing hormone therapy (hazard ratio=0.62, 95% CI=0.40-0.95). CONCLUSIONS: Our finding that UVR exposure is beneficial is compatible with accumulating data showing sunlight has a protective effect on disease phenotype.

Prostate cancer susceptibility is mediated by interactions between exposure to ultraviolet radiation and polymorphisms in the 5' haplotype block of the vitamin D receptor gene.

Vitamin D receptor (VDR) polymorphisms are prostate cancer risk candidates. We determined if SNPs in haplotype block sub-regions C2 (SNPs C2-1, G/C(3436), C2-2, A/G(3944)) or C1 (C1-1, C/T(20965), C1-2, C/T(30056)) are associated with risk in an ultraviolet radiation (UVR)-dependent manner. In men with very low exposure, SNPs in both sub-regions were associated with risk. Various haplotypes in haplotype block C including G(3436)-A(3944)-C(20965)-C(30056), (G or C)-A-C-C and G-A-(C or T)-C were significantly associated with increased risk (odds ratios between 1.95 and 2.37). These findings suggest various block C SNPs are associated with prostate cancer risk via a mechanism involving exposure to sunlight.

Associations between G/A1229, A/G3944, T/C30875, C/T48200 and C/T65013 genotypes and haplotypes in the vitamin D receptor gene, ultraviolet radiation and susceptibility to prostate cancer.

Ultraviolet radiation (UVR) may protect against prostate cancer via a mechanism involving vitamin D. Thus, the vitamin D receptor (VDR) gene is a susceptibility candidate, though published data are discrepant. We studied the association of prostate cancer risk with five VDR single nucleotide polymorphisms (SNPs): G/A(1229) (SNP 1), A/G(3944) (SNP 2), T/C(30875) (SNP 3), C/T(48200) (SNP 4) and C/T(65013) (SNP 5), in 430 cancer and 310 benign prostatic hypertrophy (BPH) patients. The SNP 2 GG genotype frequency was lower in cancer than BPH patients (odds ratio = 0.63, 95% CI = 0.41-0.98, p = 0.039). SNPs 1 and 2, and SNPs 4 and 5, were in linkage disequilibrium. Two copies of haplotypes comprising SNPs 1-2, G-G (odds ratio = 0.63, p = 0.039), SNPs 2-3 G-C (odds ratio = 0.45, p = 0.008) and SNPs 1-2-3 G-G-C (odds ratio = 0.44, p = 0.006), but not SNPs 1-3, G-C (odds ratio = 0.81, p = 0.34), were associated with reduced risk (reference, no copies of the haplotypes). These associations were observed after stratification of subjects by extent of UVR exposure. These data show that SNP 2 GG genotype mediates prostate cancer risk, complementing studies reporting this allele is protective in malignant melanoma pathogenesis. They further suggest that published associations of risk with SNP 1 may result from linkage disequilibrium with SNP 2.

Polymorphisms in the vitamin D receptor gene, ultraviolet radiation, and susceptibility to prostate cancer.

Ultraviolet radiation (UVR) exposure may protect against prostate cancer development via a mechanism involving vitamin D. The vitamin D receptor (VDR) gene is therefore a candidate susceptibility factor for prostate cancer. This possibility has been previously investigated with conflicting results. We examined the association of VDR genotypes (variants at the CDX-2, Fok1, and Taq1 sites), haplotypes, and genotype combinations with risk by studying 368 prostate cancer and 243 benign prostatic hypertrophy (BPH) patients. CDX-2, Fok1, and Taq1 genotype and haplotype frequencies were not significantly different in cancer and BPH patients. As the impact of VDR polymorphisms may depend on UVR exposure, we studied associations of variants with risk in men stratified into low (below median) and high (above median) cumulative exposure/year groups. In men with UVR exposure above the median (1,100 hr/year), CDX-2 GA and AA (odds ratios [OR] = 2.11 and 2.02, respectively) and Fok1 ff (OR = 2.91) were associated with increased prostate cancer risk. No associations were observed for Taq1 genotypes. Of the genotype combinations, relative to all other CDX-2 and Taq1 and combinations, GGTT (P = 0.022, OR = 0.30), and relative to all other Fok1 and Taq1 combinations, FFTT (P = 0.026, OR = 0.35) were associated with reduced prostate cancer risk in the presence of the main effects. None of the other two- or three-genotype combinations was associated with risk. These data indicate that VDR variants influence prostate cancer risk and that this association is dependent on the extent of UVR exposure.

Associations between prostate cancer susceptibility and parameters of exposure to ultraviolet radiation.

Low sunlight exposure confers increased prostate cancer risk. In a study conducted in northern England, we investigated how combinations of exposure measures affect this risk. Recursive partitioning was used to identify combinations of exposure parameters that distinguished 453 prostate cancers from 312 benign hypertrophy patients. Sunbathing score most significantly defined cancer patients; 78.7% men with low scores (8.0) had cancer. These subgroups were stratified by childhood sunburning, holidays in a hot climate and skin type such that subgroups with a 13.0-fold increased risk of cancer were identified.

Susceptibility to prostate cancer: studies on interactions between UVR exposure and skin type.

Recent studies have proposed that exposure to ultraviolet radiation (UVR) protects against development of some internal cancers including that in prostate. This effect may be mediated by UVR-induced cutaneous synthesis of vitamin D. It is also proposed that ability to pigment in response to UVR will influence susceptibility to prostate cancer through its effects on vitamin D synthesis. We wished to determine first, whether ability to pigment, as assessed by skin type, influences the extent of exposure to UVR, secondly, whether skin type is associated with prostate cancer susceptibility and thirdly, whether such an effect is mediated by the extent of UVR exposure. We studied 453 prostatic adenocarcinoma and 312 benign prostatic hypertrophy (BPH) patients using a validated questionnaire to assess two parameters of exposure; months of cumulative exposure per year and adult sunbathing score. We used analysis of variance to show that cancer cases with sun-sensitive skin (skin type 1) had lower cumulative exposure per year (P = 0.014) and sunbathing scores (P < 0.0001) than those with type 4, possibly because of a tendency to avoid exposure. Further, cumulative exposure per year and sunbathing score were significantly lower in cancer compared with BPH patients (P < 0.001 and P < 0.001, respectively). While the proportion of subjects with skin types 1 and 2 was lower in cancer than BPH patients, these were not significantly different (logistic regression analysis, skin type 1 versus type 4; P = 0.11). We used recursive partitioning to determine if skin type influenced susceptibility to prostate cancer in subgroups stratified by exposure. Analysis of the data showed that in men with low sunbathing scores, skin type 1 conferred protection compared with skin types 2-4 (OR = 4.78, 95% CI 3.01-8.25, P < 0.0009). These findings indicate that susceptibility to prostate cancer is in part determined by extent of exposure to UVR and that ability to pigment mediates this effect.

Glutathione S-transferase GSTP1 genotypes are associated with response to androgen ablation therapy in advanced prostate cancer.

We determined whether the glutathione S-transferase GSTP1 Ile105 --> Val105 substitution is associated with response to androgen ablation therapy in patients with advanced prostate cancer. As response may be associated with tumor grade, Gleason score, clinical T stage and presence of metastases we also determined if GSTP1 genotypes were associated with these prognostic parameters. We speculated that GSTP1 Ile105/Ile105 would be linked with good response to androgen ablation therapy and, low/moderate tumor grade, 1/2 clinical T-stage, Gleason score < 6 and, no metastases. Genotype frequencies in cases and controls were not significantly different (P = 0.70) indicating that allelism in GSTP1 is not associated with susceptibility. There was no association between GSTP1 (Ile105/Ile105 versus Ile105/Val105 and Val105/Val105) and grade (P = 0.28, OR = 0.92), Gleason score (P = 0.84, OR = 0.94) or metastatic state (P = 0.68, OR = 0.88) though the frequency of GSTP1 Ile105/Ile105 was higher in cases with stage 1/2 tumors than those with stage 3/4 tumors (P = 0.03, OR = 1.89). GSTP1 Val105/Val105 was also associated with response to hormone ablation therapy. Thus, the GSTP1 Ile105/Ile105 frequency was significantly higher in 86/118 patients who demonstrated a good response than in those with poor response (P = 0.03, OR = 2.70). We speculate that the association of GSTP1 with response results from an effect of the gene product early in carcinogenesis.