bluuebunny/crossref_metadata_2025 huggingface dataset:
Cabazitaxel or mitoxantrone with prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel: Estimating mean overall survival (OS) for health economic analyses from a phase III trial (TROPIC).
Authors: Oudard S. , Joulain F. , De Geer A. , Sartor A. O.
Published: February 2017

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Background: TROPIC evaluated the efficacy and safety of the novel taxane cabazitaxel in men with mCRPC previously treated with docetaxel. Median OS was significantly improved, as previously reported (12.7 months in mitoxantrone arm vs 15.1 months in cabazitaxel arm, HR=0.72 [0.61 – 0.84], p<0.0001- updated OS results). Median OS is the most useful descriptive statistic for physicians and patients as it reflects a point estimate in time by which 50% patients may survive regardless of disease status or progression. It avoids assumptions on long-term survival beyond the follow-up period of the clinical trial. Payers however are interested in making a coverage and reimbursement decisions based on the overall therapeutic benefit relative to its risk, and the expected impact on healthcare expenditures. Analyses such as cost-effectiveness analysis therefore require the estimation of mean OS.

Methods: Mean OS is only observable when the last patient has died. Its estimation can be derived via an extrapolation of the trial Kaplan-Meier curve using a survival function. Several parametric distributions (exponential, weibull, lognormal, loglogistic and Gompertz) were tested. The parametric distribution that best fitted the trial Kaplan-Meier curves was selected using the Akaike's Information criteria (AIC), the Bayesian Information Criteria (BIC) and graphical method to evaluate the goodness of fit of the distributions. Mean OS from the best fitted model was generated to support payer decision making.

Results: Using AIC/BIC and graphical method, the Weibull survival function, S(t)=exp(-l ts) where l is a scale parameter and s a shape parameter, was selected as the distribution that best fitted the TROPIC data. Results of the estimated mean survival assuming a Weibull function are described in the table.

Conclusions: Assuming a Weibull distribution, mean OS is estimated at 14.5 months in mitoxantrone arm vs 18.5 months in cabazitaxel arm, leading to 4 months OS difference in favour of cabazitaxel.

[Table: see text] [Table: see text]
Phase III, randomized, open-label study of triweekly docetaxel versus biweekly docetaxel as treatments for advanced hormone-refractory prostate cancer: Findings from an interim safety analysis of the Finnish Uro-oncological Group Study 1-2003.
Authors: Hervonen P. , Joensuu H. , Joensuu T. K. , Nyandoto P. , Luukkaa M. , Nilsson S. , Hemminki A. E. , Asola R. , Luukkaala T. , Kellokumpu-Lehtinen P.
Published: February 2017

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Background: Docetaxel (T) administered at every three weeks is standard treatment for advanced HRPC. We compared 2-weekly to 3-weekly T as first- or second-line chemotherapy of advanced HRPC in this prospective randomized multicenter trial.

Methods: 360 pts were randomly allocated to receive T 75 mg/m2 i.v. d1 q3 wks (tT) or 50 mg/m2 i.v. d1 and d 14, q4 wks (bT) from March 2004 to May 2009. Prednisolon 10 mg/day was administered in both groups. The groups were well balanced according to the WHO performance status, mean age (70 vs. 68, range 45–87), and the median serum PSA level at study entry (109 vs. 98 μ g/L, range 11–1,490). The primary endpoint was TTF. Study identifier: NCT00255606 .

Results: 158 pts (tT, 79; bT, 79) were included in this preplanned interim safety analysis. 567 and 487 cycles were administered in the tT and bT groups, respectively. The most common grade 3–4 adverse events (expressed as %/cycles) in tT /bT were neutropenia 20%/14%, infection with/without neutropenia 8%/3%, fatigue 3%/ 3%, febrile neutropenia 2%/1%, and bone pain 2%/1%. Serious adverse events occurred more frequently in tT (n=60, 10.6% of cycles) than in bT (n=29, 6.0%, p=0.012). One pt. died from coronary infarction and one was diagnosed with ALL (both in bT group). 30 pts (38%) in bT group and 22 pts (28%) in tT group were receiving treatment at 6 months. (p=0.176).

Conclusions: Biweekly T has been better tolerated than the conventional triweekly T with fewer serious adverse events and may be associated with similar efficacy.

[Table: see text]
Intermittent chemotherapy (ICh) for metastatic castration-resistant prostate cancer (mCRPC): Results of a prospective randomized phase II trial of the DoD Prostate Cancer Clinical Trials Consortium.
Authors: Harzstark A. L. , Beer T. M. , Weinberg V. K. , Higano C. S. , Nordquist L. T. , Rosenberg J. E. , Alumkal J. J. , Yu E. Y. , Mi J. , Small E. J.
Published: February 2017

133

Background: Docetaxel remains the standard of care for patients (pts) with mCRPC. However, the optimal duration of chemotherapy (Ch) is not known. Providing Ch holidays is often undertaken, but is not well characterized. A randomized phase II trial was undertaken to test two ICh regimens.

Methods: Pts with Ch naive mCRPC and KPS > 60% were eligible. Pts were treated with “induction” docetaxel 75 mg/m2 q3 weeks, and prednisone 5 mg po bid. After 6 cycles, responding pts (PSAWG1 criteria) stopped Ch and were randomized to observation (Obs) or to GM-CSF, 250 mcg/m2 sq daily for 14 days out of every 28 day cycle. Pts were followed with monthly PSA and imaging every 2 cycles until progressive disease (PD) by PSAWG1 criteria, at which point they resumed treatment with Ch, again for 6 cycles, followed by the same “off Ch” regimen. The primary endpoint was the time to PD while on Ch (time to Ch resistance.)

Results: Of 97enrolled pts to date, 94 are evaluable (3 are still undergoing induction). 69 pts completed induction (25 did not due to PD, adverse events (AE), or MD choice), of which 27 had PD after 6 cycles. Thus, 42/94 evaluable pts (45%) were eligible for randomization. Of these, 21 pts underwent Obs and 21 received GM-CSF. To date, 23/42 (55%) pts who underwent a Ch holiday restarted Ch, all for PSA PD. 8/23 (35%) had a response to Ch re-initiation. (15 pts did not re-start Ch because of AE, other therapy being started, or patient choice, and 4 pts are still undergoing either Obs or GM-CSF.) Obs pts were “off Ch” for a median of 2 months (range 2-4), compared with 3 months (range 2-8) for GM-CSF pts.

Conclusions: While feasible, only 45% of pts met criteria for ICh. 35% of pts responded to Ch re-initiation. Insufficient data exist to assess the impact of GM-CSF on time off Ch or time to Ch resistance.

No significant financial relationships to disclose.
Antiprostate-specific membrane antigen (PSMA)-based radioimmunotherapy: A combined analysis of radiolabeled-J591 studies.
Authors: Akhtar N. H. , Nanus D. M. , Osborne J. , Vallabhajosula S. , Beltran H. , Tyrell L. , Nadeau K. , Goldsmith S. J. , Bander N. H. , Tagawa S. T.
Published: February 2017

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Background: J591 is a monoclonal antibody which selectively binds the external domain of PSMA with high affinity. Two phase I trials of radiolabeled-J591 have been published; two additional studies have been completed. 90Y is a beta-emitting particle optimal for tumor lesions 28-42 mm in size; 177Lu is best suited for lesions 1-3 mm in diameter [O'Donoghue J Nuc Med 1995].

Methods: With WCMC IRB approval, long-term follow-up of 4 clinical trials and the ongoing studies was analyzed. Prospectively collected data were supplemented with retrospective additions when necessary. Median survival (OS) was calculated by Kaplan- Meier methodology.

Results: Between 10/00 and 7/10, 132 pts with metastatic CRPC received radiolabeled J591 (103 received 177Lu-J591, 29 90Y-J591) with a median follow-up of 68.5 months (mo). Median age 70.3 yrs; all progressed after multiple lines of hormonal therapy, 41.7% received prior chemo, 48.5% received post-J591 chemo. Median Halabi nomogram score for the group was 146 (range 97- 196). OS for the entire group was 16.7 mo [95% CI 13.8, 19.7]. 26 (19.7%) experienced > 30% PSA decline, with OS of 22.4 mo (vs 13.6 mo for those with any PSA increase, p=0.08; p=0.006 at phase II doses). Pts receiving 177Lu-J591 had more 30% PSA declines than 90Y-J591 (21.3% vs 6.9%, p=0.06). 37.9% had measurable disease; those who received 90Y-J591 were more likely to have measurable response than 177Lu-J591 [p=0.04]. All objective tumor responses also had significant PSA declines. Of 15 pts with baseline and follow-up CTC counts (CellSearch methodology), 12 (80%) became or remained favorable at follow-up; 3 became or remained unfavorable.

Conclusions: Radiolabled J591 is tolerable and efficacious. As predicted based upon their physical properties, 177Lu-J591 appears more effective for lower volume disease, with objective responses in larger volume disease only with 90Y-J591. Current trials utilizing 177Lu-J591 focus on predictive biomarkers, dose fractionation to improve tolerance and efficacy, combination with chemotherapy, and “salvage radioimmunotherapy” to delay the onset of metastases in men with progressive biochemical (micrometastatic) disease best suitable for 177Lu-J591.

[Table: see text]
A phase I/II study of adenovirus-mediated interleukin-12 gene therapy for hormone refractory prostate cancer: An interim report.
Authors: Sasaki K. , Nasu Y. , Kaku H. , Watanabe M. , Nose H. , Kanbara D. , Saika T. , Kumon H. ,   Okayama Urological Research Group (OURG)
Published: February 2017

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Background: A phase I/II study of adenovirus-mediated interleukin-12 (IL–12) gene therapy for castration resistant prostate cancer has been initiated from May 2008 in Okayama University Hospital. Interim results of 10 cases including a positive clinical response are reported.

Methods: Major inclusion criteria was a recurrence of prostate cancer following hormonal therapy with/without metastasis. Replication–defective adenovirus vector expressing IL–12 (Adv.IL–12) was injected directly into the prostate (or metastatic lesion in patients who received prostatectomy) in escalating doses from 1.0×1010 to 5.0×1012 viral particle (vp). GMP grade vector was produced at Center for Cell and Gene Therapy, Baylor College of Medicine (Director: Malcolm K. Brenner). Each patient received total of 3 times viral injections every 4 weeks. In addition to the safety profile, cancer control efficacy and immunological changes after viral injections were evaluated.

Results: Ten patients received the gene therapy in doses of 1.0×1010 to 5.0×1011 vp from May 2008 to October 2010. 9 cases completed, and 1 patient dropped out the study because of rapid cancer progression. Major adverse effects are following: urinary retention (G1), trasaminase elevation (G3), fever up (G3). These adverse effects were rapidly disappeared after proper treatments. One patient with highest dose (5.0×1011 vp) showed some clinical positive responses (PSA decrease, shrinkage of lymphnode metastasis), therefore received an additional viral injection. Temporal decreases just after each vector injections and gradual increases at the peak of 7-14 days after each vector injections in some immunocompetent cells (CD3+CD19–, CD3–CD19– CD16+CD56+, CD3+CD4–CD8–) were seen in relatively high dose group. Elevations of serum cytokines were observed in parallel with vector dose escalation.

Conclusions: This interim report suggests the favorable safety profile and positive clinical responses in a clinical trial of Adv.IL–12 gene therapy for hormone refractory prostate cancer in higher doses of viral vectors. Further evaluations in the next higher vector doses are needed and in progress.

No significant financial relationships to disclose.
Efficacy of triptorelin in lowering serum testosterone (sT) in patients with advanced prostate cancer.
Authors: Mounedji N. , Lundstroem E. A. , Purcea D. , Grosgurin P. , Porchet H. C.
Published: February 2017

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Background: Medical castration using gonadotropin-releasing hormone (GnRH) agonists is the mainstay of treatment for advanced prostate cancer. Achievement and maintenance of castrate serum testosterone (sT) levels <50 ng/dL (1.735 nmol/mL) has been the goal of therapy. However, patients are able to achieve and maintain sT levels <15 ng/dL after surgical castration (Oefelein M et al. J Urology 2000; 56: 1021-4). Some authors have suggested that 20 ng/dL should be the target threshold for medical castration(Perachino M et al. BJU Int 2010; 105: 648-51) but the clinical relevance of achieving such low sT levels (<20 ng/dL) remains unknown.

Methods: The efficacy and safety of sustained-release triptorelin pamoate 22.5 mg 6-month formulation was recently evaluated in a 12-month (48-week), multicentre, open-label, phase III study in 120 patients with locally advanced or metastatic prostate cancer and/or increased prostate specific antigen (PSA) after failed local therapy. Initial results based on the standard castration level of 50 ng/dL were previously presented in comparison to triptorelin 1- and 3-month formulations (Lundström E et al. Clin Drug Investig 2009; 29: 757-65). We report the proportions of patients achieving sT levels of <20 ng/dL with the triptorelin pamoate 1-, 3- and 6-month formulations.

Results: With the 6-month formulation, sT levels of <20 ng/dL were achieved in >90% of patients on Day 169 (6 months after first triptorelin injection) and on Day 337 (6 months after second injection; Table). Similar sT levels were achieved with triptorelin 1- and 3-month formulations in a phase III study over 9 months (Table).

Conclusions: A high proportion of patients receiving the 6-month triptorelin formulation achieve sT levels <20 ng/dL. This compares favorably to the triptorelin 1- and 3-month formulations.

[Table: see text]

[Table: see text]
Effect of the simultaneous blockade of androgen and estrogen receptors on prostate cancer: Preliminary results.
Authors: Nunez-Nateras R. , Castle E. P.
Published: February 2017

168

Background: Androgens and estrogens have been shown to play an important role in normal prostate development and function as well as carcinogenesis and development of the castration resistant phenotype of disease. The aim of this study was to evaluate the effect of a simultaneous administration of an androgen receptor antagonist (bicalutamide) and a selective estrogen receptor modulator (raloxifene) on both androgen sensitive and androgen insensitive prostate cancer cell lines.

Methods: Experiments were performed on LNCaP, PC3 and DU145 cell lines. Western blot was utilized for the identification of androgen and estrogen receptors (a andb) in the cell lines. Drug concentrations required to achieve IC 50 were obtained using the MTT assay; such concentrations were identified for the drugs individually and when used in combination. The effect of the drugs on apoptosis was assessed using flow cytometry.

Results: Results of the IC 50 for the drugs alone and in combination by each cell line are shown in the table. An enhanced effect was observed when the drugs were used in combination in all the cell lines. It was evident that the combination of the drugs decreased the total drug required to achieve the IC50 decreases considerably. Apoptosis rates were also affected by the simultaneous administration of bicalutamide and raloxifene. The synergistic effect of the combination was reflected in the increase of the apoptosis rate in all cell lines.

Conclusions: The simultaneous administration of bicalutamide and raloxifene has a synergistic effect on cell death and apoptosis of DU145, PC3 and LNCaP cell lines. The pathway(s) responsible for this observation may be independent of the androgen receptor as both AR negative cell lines were still affected by the combination over the SERM alone.

[Table: see text]

No significant financial relationships to disclose.
Use of epirubicin, carboplatin, and 5-fluorouracil (ECarboF) as a second-line treatment in metastatic castration-resistant prostate cancer.
Authors: McGovern U. B. , Harland S. J.
Published: February 2017

173

Background: ECarboF chemotherapy is an active first line chemotherapy treatment for metastatic prostate cancer. We have now investigated its efficacy and toxicity in patients who have progressed during or after docetaxel chemotherapy.

Methods: 37 patients with metastatic prostate cancer who had received ECarboF chemotherapy were retrospectively reviewed from a five year period (2005-2010). All patients had previously received first-line docetaxel chemotherapy and had either progressed following treatment (n=17) or were docetaxel refractory (n=20). Patients received epirubicin 50mg/m2 iv d1, carboplatin (AUC 5) d1, fluorouracil 440mg/m2 d1, d15 and folinic acid 20mg/m2 d1, d15 on a q4w cycle. 20% dose reductions were made for the first cycle in patients with poorer performance status. PSA was measured before each cycle of treatment and all patients were assessed for toxicity.

Results: Patients had a median age of 70 years (range 48-77), median baseline PSA of 226.5 ng/mL (range 9.6-1,580) and the median number of ECarboF chemotherapy cycles received was 6 (range 1-10). 65% (n=24) of patients were ECOG 0-1, the remaining 35% (n=13) were ECOG 2-3. 16% (n=6) patients had a ≥ 30% decline in PSA and 16% (n=6) patients had a ≥ 50% decline in PSA. 35% (n=13) of patients experienced grade 3/4 toxicity, most commonly anaemia (13.5%), neutropenia (13.5%) and thrombocytopenia (8.1%) with one treatment related death (neutropenic sepsis) during the five year period analysed. Median time to PSA progression was 5.1 months.

Conclusions: ECarboF has activity with acceptable toxicity post docetaxel in the treatment of metastatic castration resistant prostate cancer. Although PSA response rates are modest, the time to progression is comparable to that of more toxic regimens. ECarboF should be considered as an active second-line chemotherapy regimen.

No significant financial relationships to disclose.
Disease-specific survival outcomes in lymph node–positive patients with prostate cancer treated with radiotherapy.
Authors: Crehange G. , Weinberg V. K. , Izaguirre A. , Hsu C. C. , Hsu I. J. , Gottschalk A. R. , Shinohara K. , Carroll P. , Roach M.
Published: February 2017

182

Background: Involvement of regional lymph nodes (LN+) at the time of prostate cancer (PCa) diagnosis is widely regarded as an adverse prognostic factor associated with poor outcome. No commonly utilized treatment, composed of any combination of androgen ablation, surgery and radiation, has proven to be superior for survival. This study will evaluate the clinical survival outcomes of patients (pts) with newly diagnosed LN+ PCa at the University of California San Francisco (UCSF).

Methods: All newly diagnosed LN+ PCa pts treated with External Beam Radiation Therapy (EBRT) as primary therapy or after surgery, each with and without androgen ablation between 1987 and 2009 were included. All pts had confirmed pathologic or radiologic LN+ whereas none had evidence of metastases on the work up. Cause Specific Survival (CSS), Disease Free survival (DFS) and biochemical control were measured from the start of treatment. PSA failure was determined by the Phoenix definition after EBRT and by a confirmed PSA >1 ng/mL following RP+EBRT.

Results: A retrospective analysis identified 91 pts with LN+ at the time of diagnosis (75.8% high risk pts) with disease follow-up. Thirty-four (37%) were managed with exclusive EBRT alone (eRT), 18 pts (20%) with a combination of radical prostatectomy (RP) and adjuvant EBRT (RP+aRT) and 39 pts (43%) were treated with a combination of RP + salvage RT (RP+sRT). Overall 78% of patients also received hormone therapy (HT): 74.0% with eRT, 89% with RP+aRT and 79% with RP+sRT. The 10 years CSS estimates was 89% for eRT, 0% after RP+aRT and 88% after RP+sRT. The 10 years DFS estimates was 33% for eRT, 0% after RP+aRT and 75% after RP+sRT. Among pts remaining disease free the median follow-up is 38 mos for eRT, 26 mos for RP+aRT and 64 mos for RP+sRT. The last PSA for these patients was <0.1 for 85% of all patients which included 47% following eRT, 100% after RP+aRT and 97% after RP+sRT. There were 7 deaths due to PCa occurring between 5 and 73 mos from the start of EBRT.

Conclusions: The results of the current analysis indicate that some pts with LN+ from PCa have prolonged disease free outcomes; and for these men, aggressive treatment may be appropriate.

No significant financial relationships to disclose.
Association of baseline risk factors with cardiovascular (CV) events during long-term degarelix therapy in men with prostate cancer.
Authors: Smith M. R. , Klotz L. , van der Meulen E. , Colli E. , Tanko L. B.
Published: February 2017

190

Background: GnRH agonists have been associated with a greater incidence of CV events in men with prostate cancer. Less is known about GnRH antagonists and CVD. We used prospective data to evaluate the relationships of baseline CV risk, dosing regimen and duration of degarelix therapy, and CV events.

Methods: Data from 16 phase II/III and one extended phase III trial was pooled (n=1,704). Maintenance doses and exposure time varied between 20-480 mg and 1-66 months, respectively. Baseline CV risk was assessed based on established CVD, BMI (>30 kg/m2), smoking, hypertension, type 2 diabetes, and hyperlipidemia. Patients were stratified into 3 groups: 1) no CV risk factors (n=337), 2) ≥1 CV risk factors without CVD (n=803), 3) established CVD (n=564). Acute CV events were collected prospectively.

Results: The incidence of CV events in patients with established CVD, ≥1 CV risk factors, and no CV risk factors was 20% (n=112), 8% (n=57) and 7% (n=28), respectively. Established CVD was associated with a 3.1-fold increased risk for CV events (p<0.0001), whereas presence of ≥1 CV risk factors with 1.3-fold (p=0.28). The cumulative hazard curve indicated no increases in hazards with increasing duration of treatment. Hazards of primary CV events during degarelix treatment (0.049) were not statistically different from that during the 2 years prior treatment (0.48, p=0.85). In multivariate models, age, established CV disease, high BMI and no alcohol consumption were independently associated with greater risk for CV events (Table); type 2 diabetes (p=0.13) and smoking (p=0.08) were of borderline significance. Degarelix dose and schedule were not associated with CV risk (p=0.78) in the model.

Conclusions: CV events during degarelix treatment were largely confined to those with established CVD and further modulated by aging and modifiable risk factors. Rates of CV events were similar before and after degarelix treatment.

[Table: see text]

[Table: see text]
Analysis of the risk of fracture in an unselected cohort of patients undergoing androgen deprivation.
Authors: Ennis R. D. , Clerkin K. J. , Cohen S. M.
Published: February 2017

193

Background: Androgen deprivation therapy (ADT) is a therapeutic approach for men with various prostate cancer disease states. Treatment related side effects of ADT include rapid bone loss. A large 2005 NEJM study found that the bone loss related to ADT leads to the development of fractures.

Methods: This is a retrospective cohort study of patients treated with ADT in a radiation oncology (RDE) and medical oncology (SC) practice at an urban academic medical center from 1998-2010. Patients with evidence of bone metastases responsive to ADT were included. Those with androgen independent prostate cancer were excluded.

Results: 130 patients met the criteria for inclusion and had the characteristics listed in the table. Among the 130 only 3 fractures occurred during 373 patient years of follow up, all within 5 months of ADT initiation. The fracture free survival (FFS) rate at 3 years for all was 97.7%. Excluding fractures occurring within 6 months of ADT initiation the FFS rate was 100% at 3 years. No significant difference was demonstrated in those screened with a pretreatment DEXA scan; there was no relationship between the number of AD cycles, recovery of testosterone to normal or total time on AD. Those with any baseline risk factor of osteoporosis had a trend to an increased risk of fractures (p=0.065); older patients, surprisingly, had a lower risk (p=0.054). Patients with normal BMD had a FFS of 93.8% at 3 yrs, osteopenic patients had 94.7%, and patients with osteoporosis and hormone responsive metastases had 100%.

Conclusions: The prevalence of fracture among this group is significantly less than what has previously been reported for men receiving ADT, potentially suggesting an overstatement of risk. Further prospective study with a larger sample size is needed.

[Table: see text]

No significant financial relationships to disclose.
The relationship between prostate volume and histopathologic criteria of known prognostic importance in 2,207 men with prostate cancer.
Authors: Sooriakumaran P. , Srivastava A. , John M. , Bhagat D. , Grover S. , Rajan S. , El-Douaihy Y. , Leung R. , Tewari A.
Published: February 2017

197

Background: There is a paucity of data investigating the relationship between histopathologic variables of oncologic importance and prostate volume, and we aimed to investigate this.

Methods: 2,207 consecutive patients who underwent robotic-assisted radical prostatectomy (RARP) were studied. Preoperative demographic and both pre- and post-operative histopathologic parameters were compared among the small prostate (< 40cc), intermediate size (40-70cc), and large prostate (> 70cc) groups.

Results: Patients with smaller prostates were younger, had slightly lower BMIs, and lower PSAs than those with smaller prostates (p < 0.001). They also had worse histopathologic criteria (Gleason, core positivity, and maximum percent cancer) on preoperative biopsy and had worse radical specimen Gleason sums (p < 0.001), percent cancer (p < 0.001), and pathologic stage (p = 0.016). 11.5% of men in the small prostate group suffered a positive surgical margin (PSM) compared to 8.3% and 5.6% in the intermediate and large prostate groups, respectively (p = 0.008; Table). Basilar, posterolateral, and multifocal PSMs were commoner in the small prostate group.

Conclusions: Younger men have smaller prostates and worse preoperative histopathologic parameters despite lower PSAs. Men with small prostates undergoing RARP have worse final Gleason sums, tumor volume, extraprostatic extension (EPE), and PSM rates than those with larger prostates. We would thus caution against conservative management of men with clinically localized prostate cancer who have small prostates.

[Table: see text]

No significant financial relationships to disclose.
Cardiovascular events and clinical responses in prostate cancer patients treated with transcutaneous estrogen patches compared with LHRH analogues: Results from a randomized phase II trial (MRC PR09 PATCH).
Authors: Abel P. D. , Sundaram S. K. , Kynaston H. G. , Clarke N. , Alhasso A. A. , Rosen S. D. , Jinks R. C. , Pollock P. , Cafferty F. , Langley R. E. ,   PATCH Trial Management Group
Published: February 2017

201

Background: Androgen-deprivation therapy (ADT) with a luteinising hormone-releasing hormone analogue (LHRHa) is widely used in the management of prostate cancer. LHRHa suppresses testosterone to castrate levels but can lead to long term toxicities including osteoporosis, adverse metabolic effects and cardiovascular (CV) complications. Transcutaneous oestrogen is an attractive potential alternative to ADT. This approach circumvents first-pass hepatic metabolism and so should avoid the CV effects previously reported with oral oestrogen in men with prostate cancer. Castrate levels of testosterone, and hence prostate cancer outcomes, are expected to be equivalent but the side-effects associated with ADT will potentially be avoided.

Methods: PATCH is a multi-centre phase II randomized study of 254 men with locally advanced or metastatic prostate cancer assigned (2:1) to either oestrogen patches (Merck FemSeven 100mcg/24hr; 4 patches changed twice-weekly, reducing to 3 after 4 weeks) or LHRHa. The primary outcome is CV morbidity and mortality, including arterial and venous thromboembolic events, acute coronary syndrome and heart failure. These have been assessed by an independent committee, blind to the treatment arm. Secondary outcome measures include PSA response, serum testosterone and also toxicities.

Results: Baseline data on the 254 men will be presented including age, cardiovascular risk factors (smoking history, lipid levels and family history), and stage/grade of tumour at presentation and randomisation. CV events will be presented by randomisation arm and by treatment at the time of the event. Data relating to rates of castrate levels of hormones, PSA responses, sexual dysfunction, other toxicities (including gynaecomastia, hot flushes, anaemia and bone fractures) and compliance will also be available.

Conclusions: Providing the data demonstrate that the patches are a safe and potentially efficacious therapy we propose to recruit a further 410 patients with progression-free survival as the primary outcome. CV events will continue to be closely monitored, alongside other outcomes.

[Table: see text]
Factors associated with a delay in diagnosis of recurrent prostate cancer after radical prostatectomy.
Authors: Hoffman K. E. , Chen M. , Nguyen P. L. , Bennett C. L. , Sartor A. O. , Stein K. , Kuban D. A. , D'Amico A. V.
Published: February 2017

208

Background: Salvage radiation therapy has an improved chance of increasing prostate cancer survival if it is administered at the earliest sign of recurrence, when prostate-specific antigen (PSA) is low. We identified factors associated with delay in diagnosis of recurrent prostate cancer after prostatectomy.

Methods: We analyzed 375 men with PSA recurrence after prostatectomy enrolled in the Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma Registry. Delay in diagnosis was defined as the time, in months, between recorded PSA greater than or equal to 0.2 ng/ml and enrollment in the registry. Multivariable regression analysis was used to identify sociodemographic and clinical factors associated with diagnosis delay. Diagnosis delay was dichotomized at the median (10 months) for the analysis.

Results: At enrollment the median age was 70 years, median time since prostatectomy was 71 months, and median PSA was 0.7 ng/ml. On multivariable analysis, older men (p=0.043), men with greater length of time since surgery (p<0.001), and men who contemplated delaying their PSA test (p=0.004) were more likely to have a delay in diagnosis of PSA recurrence. Men with Gleason 8 or higher disease at initial cancer diagnosis were less likely to have a delay (p=0.028).

Conclusions: Older men, men with greater time interval since prostatectomy, and men who contemplate delaying their PSA test are more likely to have a delay in diagnosis of recurrent prostate cancer. Since early salvage radiation therapy may be curative, physicians should encourage PSA vigilance and early referral if a rising PSA is noted among men with these characteristics.

[Table: see text]
Educating African American men on prostate health and informed decision making: Initial report from a peer-education program in Louisiana.
Authors: Robinson M. M. , Sartor A. O. , Jack L.
Published: February 2017

211

Background: Informed decision making for prostate cancer health is widely endorsed but systematic programs to address this need are sparse. Herein we report initial progress in a statewide effort targeting African American men.

Methods: The Louisiana Cancer and Lung Trust Fund Board (LCLTFB) Prostate Cancer Program is funded via a “check box” on the state income tax form, in which a portion of refunds could be allocated for prostate cancer efforts. The LCLTFB partnered with the statewide comprehensive cancer control program to develop a pilot lay program to educate men on prostate informed decision. The program was developed and modeled after “My Brother's Keeper,” a CDC funded program and implemented in five regions of the state. African American men active in the cancer community and regional cancer coalitions were identified as possible trainers for the program. Staff members from “My Brother's Keeper” trained the Cancer Control regional staff, as well as the community trainers in a two day session. Upon completion, the community trainers were charged to go into their community and convene three education sessions. Educational sessions were conducted in local churches, head start centers, men social club meeting, Greek organizational meetings, and labor union meetings. Men attending the session received a short pre- and post-test assessing whether or not they had discussed prostate informed decision making with a health care provider, if they had made an appointment with a health care provider, or was any follow up from the educational session initiated.

Results: A total of 250 African American men in Louisiana were educated by the program. Upon followup phone calls, 172 men self-reported that they had initiated some form of follow up as a consequence of the participation. 35 men were unable to be contacted for follow up (number no longer in service or no phone number listed) 43 men (messages left but no returned call).

Conclusions: Peer education can engage African American men regarding informed decision making on prostate cancer health issues. More data are needed to verify and determine the type of followup that was initiated after the educational sessions.

[Table: see text]
The impact of pathologic review by central pathologist on selection for treatment modality of localized prostate cancer in candidate for brachytherapy.
Authors: Kishimoto R. , Saika T. , Bekku K. , Nose H. , Abarzua F. , Kobayashi Y. , Yanai H. , Nasu Y. , Kumon H.
Published: February 2017

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Background: To evaluate the impact of pathological review by pathologist with genitourinary expertise (PGU) on treatment modality of localized prostate cancer, we analyzed migration of Gleason grade (GG), and final treatment decision in a cohort of patients who were candidate of permanent prostate brachytherapy (PPB).

Methods: From February 2005 to July 2010, a total of 247 patients with localized prostate cancer diagnosed by local community hospital were referred to our hospital for PPB, and all pathological slides of the prostate biopsy were reviewed by single PGU. The patient finally selected their treatment modality based on our recommendation made by reference to the pathological review. Our indication of PPB, basically, is a patient classified good or intermediate risk by NCCN classification. In addition, a patient with primary GS 4 was regarded as unadapted case.

Results: Six cases were reinterpreted as no cancer (2.4%), and GG change occurred in 95 cases (38.4%). GG was upgraded in 77 cases (31.2%), and downgraded in 18 cases (7.3%). As a result, a total of 86 patients changed their therapies, and 25 of 86 patients (29%) were changed their therapy based on the pathological review.

Conclusions: Approximately 10% of patients were changed to proper therapies by PPB's pathological review. This study shows pathological review for biopsy specimen is mandatory for determination of treatment modality, especially in candidate for PPB.

No significant financial relationships to disclose.
Clinical management of small cell carcinoma of the urinary tract (SCCUT): A single-center experience.
Authors: Abella L. E. , Zudaire M. , Castillo A. , Del Barrio A. , Carranza O. E. , Arevalo E. , Perez-Gracia J. L. , Zudaire J. J. , Cambeiro M. , Gil- Bazo I.
Published: February 2017

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Background: SCCUT is a rare but aggressive condition. No standard treatment has been established. The management of small cell lung cancer has been adopted by analogy. We aim to review the clinical features, therapy and natural course of patients with SCCUT.

Methods: From 2002 to 2010 12 patients (pts) were diagnosed with SCCUT and treated at the Clínica Universidad de Navarra, Pamplona (Spain).

Results: The median age was 62 (50-78). Male to female ratio was 11:1. The primary disease was prostate in 6/12 (50%) of cases, urinary bladder in 5/12 (41.7%) and kidney in 1/12 (8.3%). Overall, 5 pts (41.7%) had limited disease (LD) and 7 (58.3%) had extensive disease (ED) at onset. Basal serum levels of Neuronal Specific Enolase (NSE) were determined in 6 pts. In all of them levels over the upper-limit were observed. Treatment information was available for 10 pts, 5 with LD and 5 with ED. LD pts received multimodal therapy. Surgery (S) was the initial treatment in 4 pts (80%), 3 of them additionally received adjuvant treatment either with platinum-based chemotherapy (C) (2 pts) or chemoradiation (1 pt). The remainder received neoadjuvant C followed by radical S. Prophylactic whole brain radiation (WBR) was administered in 1 pt. Median progression-free-survival (PFS) for pts with LD was 9.3 months (m) (2-22 months). Median overall survival (OS) was 26 m. Pts with ED mostly received palliative chemotherapy with platinum-etoposide (80%) while 1 pt underwent palliative radiotherapy as exclusive therapy. Response rate for C was 75%: 2/4 complete response, 1/4 partial response and 1/4 disease stabilization. Median PFS was 3.3 m. WBR was administered in 2 pts with ED, 1 of them with prophylactic intent. Median OS was 14 m for ED pts.

Conclusions: In our experience, SCCUT was more common among male pts and the prostate the most frequent primary site. Despite its chemosensitivity SCCUT showed an aggressive clinical course and poor prognosis in our series. SCCUT must be suspected in any genitourinary neoplasm of atypical or aggressive behavior. NSE serum levels may help to achieve an early diagnosis and to provide a proper systemic treatment up-front.

[Table: see text]

No significant financial relationships to disclose.
Brain and meningeal metastases (BMm) from castration-resistant prostate cancer (CRPC) in the era of docetaxel (DOC).
Authors: Caffo O. , Gernone A. , Ortega C. , Sava T. , Carteni G. , Facchini G. , Amadio P. , Veccia A. , Pagliarulo A. , Galligioni E.
Published: February 2017

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Background: The occurrence of BMm is usually viewed as an exceptional event in the history of prostate cancer (PC) patients (pts). In two large retrospective series the incidence of BMm in PC pts was about 0.5%. Since the introduction of DOC as first line treatment has improved survival of CRPC pts, we have retrospectively evaluated the occurrence of BMm in such setting of pts, to explore whether the incidence of BMm has changed.

Methods: The clinical records of a series of 801 pts with CRPC treated from 2002 to 2010 were reviewed. All pts met the definition of CRPC according to international guidelines: all pts received or were eligible for DOC-based treatment.

Results: We collected a series of 28 pts with BMm (incidence 2.9%). Sixteen pts had a median number of 1 brain metastases (range 1-8) and neurological symptoms were present in 11 cases. Teen cases presented meningeal metastases: in this case all but one pt were symptomatic. To date, no detailed information are available for the 2 remaining cases. After BMm diagnosis, local treatments were proposed in 16 pts: 5 pts underwent metastasectomy (M) + external brain irradiation (BI), 1 M alone, 9 BI alone, 1 gamma-knife. Eleven pts received chemotherapy after BMm, while the remaining received only best supportive care. The median interval from the PC diagnosis and the achievement of CRPC was 23 mos (range 7-141) while the appearance of BMm was documented after 6-173 mos (median 42) The median survival after BMm was 3 mos (range 1-29) with 6 pts surviving more than 1 year. These long-term survivors had brain metastases in 5 cases and meningeal metastases in 1 case and were managed with surgery in 3 cases, radiotherapy in 2 cases and DOC in 1 case.

Conclusions: It appears from our data that in the DOC era 1) the incidence of BMm in CRPC pts is higher than in the historical reports; 2) the interval from PC diagnosis and the appearance of BMm is clearly longer (42 mos) compared to that reported in historical series (28 mos). These findings could be related to the changes in survival of CRPC, produced by DOC introduction in the clinical practice. A special attention should be reserved to the appearance of neurological symptoms in a long-term CRPC survivor due to a possible relation with BMm.

No significant financial relationships to disclose.
Extramammary Paget's disease of the penis and anogenital area: SEER analysis.
Authors: Master V. A. , Herrel L. , Johnson T. V. , Delman K. A.
Published: February 2017

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Background: Extramammary Paget's disease (EMPD) is a rare cancer with poorly described outcomes comprising primarily single-institution small case series. We used the Surveillance, Epidemiology, and End Results (SEER) registries to further define survival and predictors of survival in EMPD.

Methods: 17 SEER registries were queried for male patients diagnosed with EMPD from 1973 to 2007. Patients were categorized by: penis and anogenital structures (anorectum, scrotum, and skin). Descriptive analyses were conducted to characterize each group including age, year of diagnosis, race, tumor stage, and treatment. Kaplan-Meier and multivariate Cox regression analyses were performed.

Results: The cohort consisted of 328 patients. Overall survival based on primary sites of EMPD were: anorectum (24.3%), scrotum (62.4%), penis (62.5%), skin (50.8%). Controlling for patient and disease characteristics, significant factors negatively impacting survival were primary site in the anorectal region compared to scrotum, penis and skin (p<0.001, p=0.008, p=0.005 respectively), presence of distant disease versus localized disease (p=0.01) and radiation only (RT) treatment versus surgery alone (p=0.016). Survival benefit was not increased in patients who underwent combined RT and surgery treatment, as compared to those who were treated with surgery alone (p=0.61).

Conclusions: Predictors of lower survival in men with EMPD in this cohort include anorectal location, distant disease and RT-only treatment. RT in addition to surgery does not appear to confer increased survival.

[Table: see text]

No significant financial relationships to disclose.
Knowledge of testicular cancer and screening acceptance: Results from a prospective study.
Authors: Kedzeriewicz R. , Chargari C. , Le Moulec S. , Jacques Ferrandes N. , Houlgatte A. , Vedrine L.
Published: February 2017

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Background: A delayed diagnosis of testicular cancer is associated with both greater morbidity and poorer prognosis. We conducted a prospective study in the French Armed Forces to assess whether a short medical education could increase the degree of acceptance of the routine clinical screening for testicular cancer.

Methods: We enrolled 415 consecutive military patients aged 18-45 years and consulting their army general practitioner. The degree of knowledge on the testicular cancer was assessed using a self-questionnaire, which also served as short medical education. We compared the degree of acceptance for testicular palpation before and after the education delivery.

Results: Only 26.8% of patients (n = 107) assumed that they had previously received general information on testicular cancer and 31 patients (7.8%) reported that they were informed on the risk factors of testicular cancer (CI95: 5.5-10.8). In the population, 16.3% of patients (n = 65) had been informed on the usefulness of self-palpation of testes. Wilcoxon tests show significant differences between baseline acceptance level before any intervention and after information delivery (p<0.000001). In details, acceptance of testicular palpation after responding the questionnaire did not change in 82.25%, increased in 15%, and decreased in 2.75%.

Conclusions: Young males in military environment are poorly aware of testicular cancer, but there is a demand on medical education regarding this disease. The time of annual medical visit for aptitude is probably the optimal time for this education.

No significant financial relationships to disclose.
Accelerated MVAC as neoadjuvant chemotherapy for patients with muscle-invasive transitional cell carcinoma of the bladder.
Authors: Blick C. , Hall P. , Pwint T. , Munro N. , Crew J. , Powles T. , Macaulay V. M. , Al-Terkait F. , Protheroe A. , Chester J. D.
Published: February 2017

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Background: Meta-analysis data demonstrate a 5% absolute survival benefit for the use of neoadjuvant chemotherapy (NAC) using cisplatin-based combination regimens in the radical treatment of muscle-invasive bladder cancer (MIBC). However, there is currently no randomized controlled trial data on the optimum regimen for this setting. Accelerated MVAC (AMVAC) is effective in advanced disease, and has the potential advantage over other NAC regimens of minimising delays to definitive, potentially curative therapy. We present data regarding its use as NAC in MIBC patients.

Methods: Retrospective analysis was performed on all 80 consecutive patients with muscle-invasive transitional cell carcinoma of the bladder, treated during a 50-month period at 2 U.K. centers. Patients received either 3 or 4 cycles of methotrexate 30mg/m2, vinblastine 3mg/m2, doxorubicin 30mg/m2 and 4-hour infusion of cisplatin 70mg/m2 at 2-week intervals, with G-CSF support, prior to definitive therapy with either radical surgery (RS) or radical radiotherapy (RT).

Results: All planned cycles of chemotherapy were completed in 84% of patients. All 80 patients received their planned definitive therapy. Pathological complete response (pCR) was seen in 43% of 60 patients treated with surgery following chemotherapy. There were no chemotherapy-related deaths and grade 3 or 4 toxicities were seen in 11% of patients. Median duration of chemotherapy was 34 days. Dose reduction or delay was required in 7% and 9% of patients, respectively. Objective radiological local response was seen in 75% of patients. At a median follow-up of 27.5 months, 25 (32%) patients have relapsed and 11 (14%) died. Two-year disease-free survival was 65% overall, and was statistically significantly superior in patients who were radiologically node-negative prior to chemotherapy.

Conclusions: AMVAC is a safe, well-tolerated, and easily deliverable regimen with excellent treatment outcomes and minimizes delays to definitive treatment. It is an appropriate comparator for future randomized trials.

No significant financial relationships to disclose.