Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): 10-year results from a randomised, phase 3, factorial trial.

BACKGROUND: The optimal duration of androgen suppression for men with locally advanced prostate cancer receiving radiotherapy with curative intent is yet to be defined. Zoledronic acid is effective in preventing androgen suppression-induced bone loss, but its role in preventing castration-sensitive bone metastases in locally advanced prostate cancer is unclear. The RADAR trial assessed whether the addition of 12 months of adjuvant androgen suppression, 18 months of zoledronic acid, or both, can improve outcomes in men with locally advanced prostate cancer who receive 6 months of androgen suppression and prostatic radiotherapy. This report presents 10-year outcomes from this trial. METHODS: For this randomised, phase 3, 2 × 2 factorial trial, eligible men were 18 years or older with locally advanced prostate cancer (either T2b-4, N0 M0 tumours or T2a, N0 M0 tumours provided Gleason score was ≥7 and baseline prostate-specific antigen [PSA] concentration was ≥10 µg/L). We randomly allocated participants in a 2 × 2 factorial design by computer-generated randomisation (using the minimisation technique, and stratified by centre, baseline PSA concentration, clinical tumour stage, Gleason score, and use of a brachytherapy boost) in a 1:1:1:1 ratio to four treatment groups. Patients in the control group received 6 months of neoadjuvant androgen suppression with leuprorelin (22·5 mg every 3 months, intramuscularly) and radiotherapy alone (short-term androgen suppression [STAS]); this treatment was either followed by another 12 months of adjuvant androgen suppression with leuprorelin (22·5 mg every 3 months, intramuscularly; intermediate-term androgen suppression [ITAS]), or accompanied by 18 months of zoledronic acid (4 mg every 3 months, intravenously) starting at randomisation (STAS plus zoledronic acid), or both (ITAS plus zoledronic acid). All patients received radiotherapy to the prostate and seminal vesicles, starting from the end of the fifth month of androgen suppression; dosing options were 66, 70, and 74 Gy in 2-Gy fractions per day, or 46 Gy in 2-Gy fractions followed by a high-dose-rate brachytherapy boost dose of 19·5 Gy in 6·5-Gy fractions. Treatment allocation was open label. The primary endpoint was prostate cancer-specific mortality and was analysed according to intention-to-treat using competing-risks methods. The trial is closed to follow-up and this is the final report of the main endpoints. This trial is registered with ClinicalTrials.gov, number NCT00193856. FINDINGS: Between Oct 20, 2003, and Aug 15, 2007, 1071 men were enrolled and randomly assigned to STAS (n=268), ITAS (n=268), STAS plus zoledronic acid (n=268), and ITAS plus zoledronic acid (n=267). Median follow-up was 10·4 years (IQR 7·9-11·7). At this 10-year follow-up, no interactions were observed between androgen suppression and zoledronic acid so the treatment groups were collapsed to compare treatments according to duration of androgen suppression: 6 months of androgen suppression plus radiotherapy (6AS+RT) versus 18 months of androgen suppression plus radiotherapy (18AS+RT) and to compare treatments according to whether or not patients received zoledronic acid. The total number of deaths was 375 (200 men receiving 6AS+RT and 175 men receiving 18AS+RT), of which 143 (38%) were attributable to prostate cancer (81 men receiving 6AS+RT and 62 men receiving 18AS+RT). When analysed by duration of androgen suppression, the adjusted cumulative incidence of prostate cancer-specific mortality was 13·3% (95% CI 10·3-16·0) for 6AS+RT versus 9·7% (7·3-12·0) for 18AS+RT, representing an absolute difference of 3·7% (95% CI 0·3-7·1; sub-hazard ratio [sHR] 0·70 [95% CI 0·50-0·98], adjusted p=0·035). The addition of zoledronic acid did not affect prostate cancer-specific mortality; the adjusted cumulative incidence of prostate cancer-specific mortality was 11·2% (95% CI 8·7-13·7) with zoledronic acid vs 11·7% (9·2-14·1) without, representing an absolute difference of -0·5% (95% CI -3·8 to 2·9; sHR 0·95 [95% CI 0·69-1·32], adjusted p=0·78). Although safety analysis was not prespecified for this 10-year analysis, one new serious adverse event (osteonecrosis of the mandible, in a patient who received 18 months of androgen suppression plus zoledronic acid) occurred since our previous report, bringing the total number of cases of this serious adverse event to three (<1% out of 530 patients who received zoledronic acid evaluated for safety) and the total number of drug-related serious adverse events to 12 (1% out of all 1065 patients evaluable for safety). No treatment-related deaths occurred during the study. INTERPRETATION: 18 months of androgen suppression plus radiotherapy is a more effective treatment option for locally advanced prostate cancer than 6 months of androgen suppression plus radiotherapy, but the addition of zoledronic acid to this treatment regimen is not beneficial. Evidence from the RADAR and French Canadian Prostate Cancer Study IV trials suggests that 18 months of androgen suppression with moderate radiation dose escalation is an effective but more tolerable option than longer durations of androgen suppression for men with locally advanced prostate cancer including intermediate and high risk elements. FUNDING: National Health and Medical Research Council of Australia, Novartis Pharmaceuticals Australia, AbbVie Pharmaceuticals Australia, New Zealand Health Research Council, New Zealand Cancer Society, Cancer Standards Institute New Zealand, University of Newcastle (Australia), Hunter Medical Research Institute, Calvary Mater Newcastle Radiation Oncology Fund, and Maitland Cancer Appeal.

Biodistribution and Efficacy of Low Temperature-Sensitive Liposome Encapsulated Docetaxel Combined with Mild Hyperthermia in a Mouse Model of Prostate Cancer.

PURPOSE: Low temperature sensitive liposome (LTSL) encapsulated docetaxel were combined with mild hyperthermia (40-42°C) to investigate in vivo biodistribution and efficacy against a castrate resistant prostate cancer. METHOD: Female athymic nude mice with human prostate PC-3 M-luciferase cells grown subcutaneously into the right hind leg were randomized into six groups: saline (+/- heat), free docetaxel (+/- heat), and LTSL docetaxel (+/- heat). Treatment (15 mg docetaxel/kg) was administered via tail vein once tumors reached a size of 200-300 mm(3). Mice tumor volumes and body weights were recorded for up to 60 days. Docetaxel concentrations of harvested tumor and organ/tissue homogenates were determined by LC-MS. Histological evaluation (Mean vessel density, Ki67 proliferation, Caspase-3 apoptosis) of saline, free Docetaxel and LTSL docetaxel (+/- heat n = 3-5) was performed to determine molecular mechanism responsible for tumor cell killing. RESULT: LTSL/heat resulted in significantly higher tumor docetaxel concentrations (4.7-fold greater compared to free docetaxel). Adding heat to LTSL Docetaxel or free docetaxel treatment resulted in significantly greater survival and growth delay compared to other treatments (p < 0.05). Differences in body weight between all Docetaxel treatments were not reduced by >10% and were not statistically different from each other. Molecular markers such as caspase-3 were upregulated, and Ki67 expression was significantly decreased in the chemo-hyperthermia group. Vessel density was similar post treatment, but the heated group had reduced vessel area, suggesting thermal enhancement in efficacy by reduction in functional perfusion. CONCLUSION: This technique of hyperthermia sensitization and enhanced docetaxel delivery has potential for clinical translation for prostate cancer treatment.

Reporting combined outcomes with Trifecta and survival, continence, and potency (SCP) classification in 337 patients with prostate cancer treated with image-guided hypofractionated radiotherapy.

OBJECTIVE: To report the image-guided hypofractionated radiotherapy (hypo-IGRT) outcome for patients with localised prostate cancer according to the new outcome models Trifecta (cancer control, urinary continence, and sexual potency) and SCP (failure-free survival, continence and potency). PATIENTS AND METHODS: Between August 2006 and January 2011, 337 patients with cT1-T2N0M0 prostate cancer (median age 73 years) were eligible for a prospective longitudinal study on hypo-IGRT (70.2 Gy/26 fractions) in our Department. Patients completed four questionnaires before treatment, and during follow-up: the International Index of Erectile Function-5 (IIEF-5), the International Prostate Symptom Score (IPSS), and the European Organization for Research and Treatment of Cancer prostate-cancer-specific Quality of Life Questionnaires (QLQ) QLQ-PR25 and QLQ-C30. Baseline and follow-up patient data were analysed according to the Trifecta and SCP outcome models. Cancer control, continence and potency were defined respectively as no evidence of disease, score 1 or 2 for item 36 of the QLQ-PR25 questionnaire, and total score of >16 on the IIEF-5 questionnaire. Patients receiving androgen-deprivation therapy (ADT) at any time were excluded. RESULTS: Trifecta criteria at baseline were met in 72 patients (42% of all ADT-free patients with completed questionnaires). Both at 12 and 24 months after hypo-IGRT, 57% of the Trifecta patients at baseline were still meeting the Trifecta criteria (both oncological and functional success according to the SCP model). The main reason for failing the Trifecta criteria during follow-up was erectile dysfunction: in 18 patients after 6 months follow-up, in 12 patients after 12 months follow-up, and in eight patients after 24 months. Actuarial 2-year Trifecta failure-free survival rate was 44% (95% confidence interval 27-60%). In multivariate analysis no predictors of Trifecta failure were identified. Missing questionnaires was the main limitation of the study. CONCLUSION: The Trifecta and SCP classifications can be used as tools to report RT outcome.

Abiraterone Acetate for Metastatic Prostate Cancer in Patients With Suboptimal Biochemical Response to Hormone Induction.

IMPORTANCE: Men with metastatic prostate cancer who have a poor response to initial androgen-deprivation therapy (ADT), as reflected by a prostate-specific antigen (PSA) level higher than 4.0 ng/mL after 7 months of ADT, have a poor prognosis, based on historical controls. OBJECTIVE: To determine the efficacy of abiraterone acetate with prednisone in these high-risk patients with a suboptimal response to hormonal induction. DESIGN, SETTING, AND PARTICIPANTS: A phase 2 single-arm study was conducted through the National Clinical Trials Network-Southwest Oncology Group. Eligible patients had metastatic prostate cancer and a PSA level higher than 4.0 ng/mL between 6 and 12 months after starting ADT. The PSA level could be rising or falling at the time of enrollment, but had to be higher than 4.0 ng/mL. No previous chemotherapy or secondary hormonal therapies were allowed, except in patients receiving a standard, first-generation antiandrogen agent with a falling PSA level at the time of enrollment; this therapy was continued in this cohort. Abiraterone acetate, 1000 mg, once daily with prednisone, 5 mg, twice daily was administered to all participants. A total of 41 men were enrolled between the trial's activation on August 9, 2011, and closure on August 1, 2013. Data analysis was conducted from March 21 to November 29, 2016. INTERVENTIONS: Abiraterone acetate, 1000 mg, once daily by mouth with prednisone, 5 mg, by mouth twice daily. MAIN OUTCOMES AND MEASURES: The primary end point was a PSA level of 0.2 ng/mL or lower within 12 months of starting abiraterone acetate plus prednisone. A partial response (PR) was a secondary end point, defined as a PSA level reduction to lower than 4.0 ng/mL but higher than 0.2 ng/mL. RESULTS: Of the 41 men enrolled, 1 did not receive any protocol treatment and was excluded from analysis. The median (range) age of the 40 participants was 66 (39-85) years. Five (13%) patients achieved a PSA level of 0.2 ng/mL or lower (95% CI, 4%-27%). Thirteen (33%) additional patients achieved a partial response, with a reduction in the PSA level to lower than 4.0 ng/mL but higher than 0.2 ng/mL. Sixteen (40%) patients had no PSA response and 6 (15%) were not assessable and assumed to be nonresponders. The median progression-free survival was 17.5 months (95% CI, 8.6-25.0 months) and the median overall survival was 25.8 months (95% CI, 15.7-25.8 months). There was 1 incident each of grade 4 adverse events of alanine aminotransferase level elevation and rectal hemorrhage. Eleven patients reported grade 3 adverse events. CONCLUSIONS AND RELEVANCE: This study did not reach its prescribed level of 6 PSA responses of 0.2 ng/mL or lower, although 5 responses were observed. The overall survival and progression-free survival rates observed in this trial are encouraging compared with historical controls. The therapy was generally well tolerated, without any clear signal of any unexpected adverse effects.

Cancer mortality in Iowa farmers, 1971-78.

Age-adjusted cancer mortality rates from 1971 to 1978 for male farmers and nonfarmers were computed from Iowa death certificate information. Only data for white males were included in the study because of the limited number of nonwhite farmers in Iowa and because of incomplete occupational information available on females. Mortalities from major types of cancer for farmers and nonfarmers were compared by means of proportionate mortality ratios (PMR). The combined mortality rate for all types of cancer was significantly lower for farmers (PMR = 0.97), due primarily to the significantly lower rates for smoking-related cancers: lung, PMR = 0.78; esophagus, PMR = 0.74; mouth other than lip, PMR = 0.82; and other respiratory cancers, PMR = 0.65. However, the mortality rates for the following cancers were significantly higher for farmers: lip, PMR = 1.62; stomach, PMR = 1.14; leukemia, PMR = 1.10; lymphatic, PMR = 1.14; multiple myeloma, PMR = 1.27; and prostate, PMR = 1.10. Each of the six types of cancer with a significantly elevated mortality in Iowa farmers has also been reported as having an elevated mortality in farmers in other states.

An updated study of mortality among North American synthetic rubber industry workers.

AIM: This study evaluated the mortality experience of workers from the styrene-butadiene industry. METHODS: The authors added seven years of follow up to a previous investigation of mortality among 17 924 men employed in the North American synthetic rubber industry. Analyses used the standardised mortality ratios (SMRs) to compare styrene-butadiene rubber workers' cause specific mortality (1943-98) with those of the United States and the Ontario general populations. RESULTS: Overall, the observed/expected numbers of deaths were 6237/7242 for all causes (SMR = 86, 95% CI 84 to 88) and 1608/1741 for all cancers combined (SMR = 92, 95% CI 88 to 97), 71/61 for leukaemia, 53/53 for non-Hodgkin's lymphoma, and 26/27 for multiple myeloma. The 16% leukaemia increase was concentrated in hourly paid subjects with 20-29 years since hire and 10 or more years of employment in the industry (19/7.4, SMR = 258, 95% CI 156 to 403) and in subjects employed in polymerisation (18/8.8, SMR = 204, 95% CI 121 to 322), maintenance labour (15/7.4, SMR = 326, 95% CI 178 to 456), and laboratory operations (14/4.3, SMR = 326, 95% CI 178-546). CONCLUSION: The study found that some subgroups of synthetic rubber workers had an excess of mortality from leukaemia that was not limited to a particular form of leukaemia. Uncertainty remains about the specific agent(s) that might be responsible for the observed excesses and about the role of unidentified confounding factors. The study did not find any clear relation between employment in the industry and other forms of lymphohaematopoietic cancer. Some subgroups of subjects had more than expected deaths from colorectal and prostate cancers. These increases did not appear to be related to occupational exposure in the industry.

Trends in prostate cancer mortality in the state of São Paulo, 2000 to 2015 / Tendências na mortalidade por câncer de próstata no estado de São Paulo, 2000 a 2015

ABSTRACT OBJECTIVE To estimate the magnitude and identify patterns of change in prostate cancer mortality in the state of São Paulo and in the 17 regional health care networks, according to age groups from 50 years onwards, in the period between 2000 to 2015. METHODS Age-adjusted mortality rates (per 100,000 men) were calculated by the direct method using the Segi world population as standard. Joinpoint regression was used to calculate the average annual percent change (AAPC), with a confidence interval of 95% (95%CI), by regional network and age group (50-59, 60-69, 70-79 and 80 years or more). RESULTS For the state of São Paulo, age-adjusted mortality rates were 15.2, 13.3 and 11.9 per 100,000 men, respectively, in the periods between 2000 to 2005, 2006 to 2010 and 2011 to 2015, with a significant decrease trend (AAPC = -2.10%; 95%CI -2.42 - -1.79) each year. Among the 17 networks, 11 presented significant mean annual reductions, ranging from -1.72% to -3.05%. From the age of 50 onwards, there was a sharper reduction in the groups from 50 to 59 (AAPC = -2.33%; 95%CI -3.04 - -1.62) and 60 to 69 years (AAPC = -2.84%; 95%CI - 3.25 - -2.43). CONCLUSION Although reductions in mortality are still slight, they indicate progress in prostate cancer control actions. Screening actions and changes in therapeutic behaviors in recent decades may be modifying incidence and survival, resulting in changes in the mortality profile. More detailed studies will be useful in understanding the factors that lead to the interregional variations found.

RESUMO OBJETIVO Estimar a magnitude e identificar padrões de mudança na mortalidade por câncer de próstata no estado de São Paulo e nas 17 redes regionais de atenção à saúde, segundo grupos etários a partir dos 50 anos, no período de 2000 a 2015. MÉTODOS As taxas de mortalidade ajustadas por idade (por 100 mil homens) foram calculadas pelo método direto usando a população mundial de Segi como padrão. A análise de regressão Joinpoint foi utilizada para calcular as variações percentuais anuais médias (AAPC), com intervalo de confiança de 95% (IC95%), por rede regional e grupo etário (50-59, 60-69, 70-79 e 80 anos ou mais). RESULTADOS Para o estado de São Paulo, as taxas ajustadas de mortalidade foram de 15,2, 13,3 e 11,9/100 mil homens, respectivamente, nos períodos de 2000 a 2005, 2006 a 2010 e 2011 a 2015, com tendência de decréscimo significativo (AAPC = -2,10%; IC95% -2,42 - -1,79) a cada ano. Das 17 redes, 11 apresentaram reduções médias anuais significativas, que variaram entre -1,72% e -3,05%. A partir dos 50 anos, verificou-se redução mais acentuada nos grupos de 50 a 59 (AAPC = -2,33%; IC95% -3,04 - -1,62) e 60 a 69 anos (AAPC = -2,84%; IC95% -3,25 - -2,43). CONCLUSÕES Embora as reduções na mortalidade ainda sejam discretas, indicam progresso nas ações de controle do câncer de próstata. Ações de rastreamento e mudanças nas condutas terapêuticas nas últimas décadas podem estar modificando a incidência e a sobrevida, resultando em mudanças no perfil de mortalidade. Estudos mais detalhados serão úteis na compreensão dos fatores que levam às variações inter-regionais encontradas.

Phase II trial of hormonal cytoreduction with megestrol and diethylstilbestrol in conjunction with radiotherapy for carcinoma of the prostate: outcome results of RTOG 83-07.

PURPOSE: RTOG 83-07 is a Phase II randomized protocol designed to compare the efficacy and toxicity of Megestrol vs. Diethylstilbestrol (DES) used as cytoreductive agents prior to and during radiotherapy. The end points of this study include tumor clearance rate, effect on serum testosterone, loco-regional control, disease-free interval, and survival. METHODS AND MATERIALS: Eligible patients were those with histologically confirmed locally advanced adenocarcinoma, clinical Stage B2 (T2B) and C (T3) without regional lymph node involvement, or with lymph node involvement limited to the pelvis. Patients were stratified by clinical stage, histological grade, and nodal status, and were randomized to receive either Megestrol 40 mg three times per day by mouth, or Diethylstilbestrol 1 mg three times per day by mouth. The drugs were started 2 months prior to initiation of radiotherapy and were continued throughout the radiotherapy course. Radiotherapy consisted of 44-46 Gy, 1.8-2 Gy per day to the regional lymphatics, followed by a boost to the prostate consisting of 20-25 Gy, 1.8-2 Gy per day, to a total of 65-70 Gy. Serum testosterone levels were recorded throughout the treatment course. Tumor response was assessed clinically and radiographically (CT scan). From March 1983 through June 1986 a total of 203 patients were accessioned to the study; 198 were analyzable. RESULTS: Correlation of the incidence of drug-related toxicity and treatment arm assignment revealed a significantly higher incidence of complications in the Diethylstilbestrol (DES) arm. The most prominent were the differences in the incidence of gynecomastia (55% vs. 7%) and fluid retention (21% vs. 6%). The incidence of thromboembolic phenomena was comparable (8% vs. 5% in the Megestrol arm). Patients on the DES arm demonstrated a significantly greater median decrease in testosterone level. Correlation of the treatment arm assignment and the rate of tumor regression and the incidence of complete response revealed no significant difference between the arms. At 7 years, 16% of patients on the Megace arm and 21% of patients on the DES arm manifested evidence of local failure. CONCLUSIONS: The results of the study indicate comparable efficacy (using tumor clearance as an end point) of DES and Megestrol. Although DES appears more effective in suppressing testosterone, it is also associated with a higher incidence of drug-related toxicity.

Cancer mortality among rubber workers: an epidemiologic study.

Several previous epidemiologic studies of the rubber industry--an industry that uses many chemicals--have identified excess mortality from certain specific cancers. In this study, four cohorts of active and retired workers, at four major rubber-tire plants, were identified historically and followed for the ten-year period from 1964 to 1973. The cancer mortality of these four population was compared, separately and combined, with that of the general community. For all cancers combined, there was a slight excess above the expected number of deaths, whereas for some specific cancers (stomach, colon, prostate, and neoplasms of the lymphatic and hematopoietic system) there was a marked excess of deaths. Proportional mortality analysis at other small plants revealed similar excesses for these cancers, and some excess for lung, bladder, and CNS cancers. Analysis of detailed individual work histories reveals an association of certain cancers with specific job exposures; in particular, lymphatic leukemia and solvent exposure, and lung cancer and curing-room exposure. For both bladder cancer and stomach cancer, preliminary analyses indicate an association with groups of jobs in adjacent production stages (handling and mixing raw ingredients, and processing the "green" precured rubber, respectively). Further analytic studies are currently under way to identify groups of rubber workers at increased risk of other specific cancers.

A cohort mortality study of cellulose triacetate-fiber workers exposed to methylene chloride.

The purpose of this study of 3211 cellulose-fiber production workers was to evaluate earlier findings of excess biliary tract and liver cancer in a similarly exposed cohort reported in 1990. Mortality from biliary tract and liver cancer was not increased in this study population, and there was no excess mortality from pancreatic cancer. Mortality was not elevated for cancers of the lung or liver, sites at which tumors were induced in experimental animals exposed to methylene chloride. Men with 20 or more years of employment exhibited increased mortality from prostate cancer, whereas women who also had 20 or more years of employment experienced higher-than-expected mortality from cervical cancer. Although these apparent increases in mortality are difficult to interpret biologically and are not consistent with previous studies, they require further investigation.

Effect of oral clodronate on bone pain. A controlled study in patients with metastic prostatic cancer.

Although osteosclerotic metastases are characteristic of prostatic carcinoma, bone resorption is also accelerated. Since clodronate inhibits bone resorption and relieves bone pain, we have given it to patients with painful bone disease from prostatic cancer after failure of hormonal therapy. All patients received estramustine phosphate orally. Simultaneously they were randomly allocated to clodronate (36) and placebo (39) groups. Clodronate was given by mouth. The dose was 3.2 g for the first month, thereafter 1.6 g. Pain relief was more distinct in the clodronate group where one third of patients were totally free of bone pain. The use of analgesics stopped in 38% of patients on clodronate and in 18% on placebo which effect probably belongs to estramustine phosphate. Serum calcium concentration decreased more markedly in the clodronate group. Clodronate dose of 3.2 g seemed to be more potent than that of 1.6 g. Side effects were uncommon and occurred equally in both groups. No significant differences were seen in median survival or survival rates between the groups.

Use of a rectal spacer with low-dose-rate brachytherapy for treatment of prostate cancer in previously irradiated patients: Initial experience and short-term results.

BACKGROUND: Salvage brachytherapy in patients with prior pelvic radiation carries a risk of rectal injury. Herein, we report our initial experience using a hydrogel spacer between the prostate and the rectum during salvage brachytherapy. METHODS AND MATERIALS: A total of 11 patients with prostate cancer and prior radiotherapy (5 prostate brachytherapy, 2 prostate external beam radiation therapy [EBRT], and 4 rectal cancer EBRT) received (125)I brachytherapy after attempted placement of 10cc of a diluted hydrogel spacer between the prostate and rectum. RESULTS: Spacing was achieved in 8 of the 11 (73%) patients but was not possible in 3 (1 prior brachytherapy and 2 prior EBRT) owing to fibrosis and adhesions. For the 8 patients in whom spacing was accomplished, the median space between the prostate and rectum was 10.9mm (prior EBRT) vs. 7.7mm (prior brachytherapy), p=0.048. Median followup was 15.7 months. One patient developed a prostato-rectal fistula requiring a diverting colostomy. The 16-month estimate of late Grade 3 or 4 gastrointestinal or genitourinary toxicity was 26%. One patient developed lymph node-positive recurrence. The 16-month prostate-specific antigen failure-free survival rate was 89%. Compared with baseline, Expanded Prostate Cancer Index Composite for Clinical Practice urinary quality of life (QoL) was significantly worse at 3 and 6 months but not significantly worse by 1 year. There were no significant changes throughout the study period in bowel or sexual QoL. CONCLUSION: Hydrogel spacer placements may be feasible in most patients with prior pelvic radiation. Further followup is needed to determine whether spacer placement will produce long-term improvements in toxicity or QoL.

A model approach to calculate cancer prevalence from 5 years survival data for selected cancer sites in India--part II.

OBJECTIVE: Prevalence is a statistic of primary interest in public health. In the absence of good follow-up facilities, it is often difficult to assess the complete prevalence of cancer for a given registry area. An attempt is made to arrive at the complete prevalence including limited duration prevalence with respect of selected sites of cancer for India by fitting appropriate models to 1, 3 and 5 year cancer survival data available for selected registries of India. METHODOLOGY: Cancer survival data, available for the registries of Bhopal, Chennai, Karunagappally, and Mumbai was pooled to generate survival for the selected cancer sites. With the available data on survival for 1, 3 and 5 years, a model was fitted and the survival curve was extended beyond 5 years (up to 30 years) for each of the selected sites. This helped in generation of survival proportions by single year and thereby survival of cancer cases. With the help of estimated survived cases available year wise and the incidence, the prevalence figures were arrived for selected cancer sites and for selected periods. In our previous paper, we have dealt with the cancer sites of breast, cervix, ovary, lung, stomach and mouth (Takiar and Jayant, 2013). RESULTS: The prevalence to incidence ratio (PI ratio) was calculated for 30 years duration for all the selected cancer sites using the model approach showing that from the knowledge of incidence and P/I ratio, the prevalence can be calculated. The validity of the approach was shown in our previous paper (Takiar and Jayant, 2013). The P/I ratios for the cancer sites of lip, tongue, oral cavity, hypopharynx, oesophagus, larynx, nhl, colon, prostate, lymphoid leukemia, myeloid leukemia were observed to be 10.26, 4.15, 5.89, 2.81, 1.87, 5.43, 5.48, 5.24, 4.61, 3.42 and 2.65, respectively. CONCLUSION: Cancer prevalence can be readily estimated with use of survival and incidence data.

Serum androgens as prognostic biomarkers in castration-resistant prostate cancer: results from an analysis of a randomized phase III trial.

PURPOSE: In the phase III study COU-AA-301, abiraterone acetate (AA) plus prednisone (P) prolonged overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel administration. In this article, we investigate the relationship between baseline serum androgen (SA) levels and OS. PATIENTS AND METHODS: COU-AA-301 is a randomized, double-blind study of AA (1,000 mg every day) plus P (5 mg by mouth twice daily; n = 797) versus P alone (n = 398). Randomization was stratified by Eastern Cooperative Oncology Group performance status (0 to 1 v 2), pain (Brief Pain Inventory-Short Form over past 24 hours: 4 to 10, present; v 0 to 3, absent), prior chemotherapy (1 v 2), and progression (prostate-specific antigen v radiographic). Association of baseline SA (testosterone, androstenedione, dehydroepiandrosterone sulfate), was measured by ultrasensitive liquid-liquid extraction or protein precipitation and two-dimensional liquid chromatography coupled to mass spectrometry, with OS determined by bivariate and multivariable Cox models. OS was examined with SA as greater than median and less than or equal to the median. RESULTS: Median survival increased with each quartile increase in testosterone level regardless of treatment arm. SA levels at baseline strongly associated with survival (P < .0001) in bivariate and multivariable analyses. Longer survival was observed for patients with SA above median compared with below median in both the AA and P arms (eg, testosterone, AA; hazard ratio, 0.64; 95% CI, 0.53 to 0.77; P < .0001). Treatment with AA led to longer survival versus P alone in the above- or below-median group for all androgens. CONCLUSION: SA, measured with a novel ultrasensitive assay in COU-AA-301, is prognostic for OS and may be useful for risk stratification in mCRPC clinical trials.

Multiple sclerosis and prostate cancer: what do their similar geographies suggest?

Mortality rates from multiple sclerosis show a well-known north-south gradient, both within the United States and internationally. Mortality rates from prostate cancer show a similar gradient and are significantly correlated with multiple sclerosis (MS) mortality and MS prevalence. This finding adds prostate cancer to the set of diseases whose geographic distributions are significantly correlated with MS and whose members include colon cancer, dental caries, and Parkinson's disease. Review of the literature indicates that these clinically dissimilar diseases may share an aberration in vitamin (hormone) D. Recent evidence demonstrating a multi-faceted role for vitamin D in immunoregulation suggests that a vitamin D aberration may also contribute to the etiology of MS. A vitamin D hypothesis can illuminate several unexplained features of the epidemiology of MS and suggests opportunities for epidemiologic, laboratory, and clinical investigation.

Calculating cancer latency using data from a nested case-control study of prostatic cancer.

Assessing latency for neoplastic diseases is crucial for determining the causal effects of a complex mix of carcinogenic exposures. An initial assessment of cancer risks in a U.S. tire and rubber plant revealed a significant SMR of 140 for prostatic cancer. Using an industry-based, case-control death certificate study of prostatic malignancies, we found matched odds ratios of about 3 (p less than 0.025) for Batch Preparation, the work area with the greatest exposure to carbon black, solvents, and heavy metal oxides. To assess latency, we used the matched case-control series to calculate annual estimates of the odds ratio by determining the proportion of cases and controls employed for greater than 1 month in Batch Preparation during each year under study. This approach produced a plot with great fluctuations. To reduce variability in the resulting curve, a method was developed that measured the "etiologic fraction", which is its highest point represents an estimate of the peak of the latency distribution. For Batch Preparation the modal point was 29 years before death with the greatest risk occurring from employment in the mid-1940's. The latency method allows risk assessment for time and year of greatest exposure difference, thus suggesting appropriate prevention strategies. Applications of this method for other types of studies and exposures are discussed.

Vinorelbine and estramustine in androgen-independent metastatic prostate cancer: a phase II study.

BACKGROUND: The aim of this study was to determine the safety and activity of vinorelbine in combination with estramustine in men with androgen-independent metastatic prostate cancer. METHODS: Twenty-five men with androgen-independent metastatic prostate cancer were treated with the combination of vinorelbine and estramustine. Vinorelbine 25 mg/m(2) was administered by intravenous bolus on Days 1 and 8. Estramustine 140 mg was administered three times a day by mouth on Days 1 through 14. Treatment was repeated every 21 days. RESULTS: A total of 132 cycles of treatment were administered. The median number of cycles per patient was 5 (range: 1-16). Mild Grade 1 or 2 gastrointestinal toxicity and fatigue were the most common adverse effects. Hematologic toxicity was minimal. Treatment resulted in a sustained > 50% decrease in serum prostate-specific antigen (PSA) in 6 of 25 patients (24% of patients; 95% confidence interval (CI) 9-45%). The median duration of PSA response was 10 weeks (range: 3-39 weeks). Of the five men with bidimensionally measurable disease, none achieved a complete or partial response. There were no documented improvements in post-treatment bone scans. Median overall survival time was 14.1 months. CONCLUSIONS: The combination of vinorelbine and estramustine is a well-tolerated and modestly active regimen in men with androgen-independent metastatic prostate cancer.

Primary orchiectomy versus estrogen therapy in advanced prostatic cancer--a randomized study: results after 7 to 10 years of followup.

Of 163 new consecutively diagnosed cases of advanced (T3-4 M0 or T04M1) prostatic cancer 13 had contraindications for estrogen treatment, and the remainder were randomized to orchiectomy (76) or to estrogen treatment (74), consisting of 150 micrograms ethinyl estradiol daily and 80 mg. polyestradiol monthly. During the followup period of 7 to 10 years disease progression was noted in 27 patients (36%) treated with estrogen and 39 (51%) orchiectomized patients. The free of progression survival rate was significantly better (less than 0.05) among the estrogen treated patients but the over-all survival rates after orchiectomy and estrogen treatment were almost identical. A significantly higher frequency of cardiovascular side effects was noted in the estrogen group (23 cases) compared to the orchiectomy group (4 cases). Therefore, estrogen treatment in this form cannot be recommended for the palliative treatment of prostate cancer.

Cancer mortality in an Italian rubber factory.

The purpose of the study was to describe the mortality experience of an Italian cohort of rubber workers and an attempt was made to identify any occupational cancer hazards that might currently be affecting men employed in this type of work. A total of 4917 male workers who first started working in a large rubber factory between 1962 and 1972 have been followed up until 31 January 1983. The number of deaths from all causes and from malignant neoplasms was determined and compared with the expected number of deaths calculated from mortality rates for the province in which the population of the plant lived. Mortality from all causes was 85% of that expected. A slight overall excess of deaths from cancer (SMR = 119) was found; this was entirely due to the excess mortality in the 35-44 age group. In order further to evaluate the possible existence of a cancer risk SMRs were analysed by duration of exposure, time since first exposure, and for specific sites of cancer. A trend in SMR with duration of exposure was found for employees with 10 years of follow up or more. A high risk for some tumour sites emerged.