BeTTer Outcomes Workgroup Health Quality Initiative to optimize bone health for prostate cancer patients in the British Columbia Cancer System.

INTRODUCTION: Bone-targeted therapies (BTTs) are integral to the management of bone metastases in metastatic castration-resistant prostate cancer (mCRPC). BTTs vary considerably in referral and drug access pathways and optimal BTT use requires multi-specialty consultation and supervision. Health quality improvement (HQI) has become the predominant framework to improve patient care in multidisciplinary settings. METHODS: HQI initiatives on use of BTT in mCRPC were developed and evaluated in five centers of a provincial cancer center network using Plan-Do-Study-Act (PDSA) methodology. Multidisciplinary teams (MDTs) completed a common quality assessment form and an HQI template and then implemented an HQI initiative. Feedback and findings were shared and discussed at regional events. It was subsequently determined whether to adopt, adapt, or abandon initiatives. RESULTS: Patterns of unmet needs varied across type of BTT. Gaps in use of radium-223 were mostly referral and education issues that could be directly addressed at the local level by participating clinician teams. Conversely, most supportive BTT gaps were related to coverage and resourcing support. HQI initiatives selected by each site consisted of implementation or expansion of local MDT meetings, referral documents, databases, and improvement charters. The main HQI initiative was completed in four sites and was adapted or adopted in three. Improvements in BTT use were observed in two of three centers with data on HQI process measures. CONCLUSIONS: Despite the overall heterogenous structure of the groups and metrics used, this study demonstrated that the PDSA framework provides the needed structure for improvements in BTT use in mCRPC across multiple sites.

Maximizing rectal dose sparing with hydrogel: A retrospective planning study.

External beam radiation therapy for prostate cancer can result in urinary, sexual, and rectal side effects, often impairing quality of life. A polyethylene glycol-based product, SpaceOAR© hydrogel (SOH), implanted into the connective tissue between the prostate gland and rectum can significantly reduce the dose received by the rectum and hence risk of rectal toxicity. The optimal way to manage the hydrogel and rectal structures for plan optimization is therefore of interest. In 13 patients, computerized tomography (CT) scans were taken pre- and post-SpaceOAR© implant. A prescription of 60 Gy in 20 fractions was planned on both scans. Six treatment plans were produced per anonymized dataset using either a structure of rectum plus the hydrogel, termed composite rectum wall (CRW), or rectal wall (RW) as an inverse optimization structure and intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) as a treatment technique. Dose-volume histogram metrics were compared between plans to determine which optimization structure and treatment technique offered the maximum rectal dose sparing. RW structures offered a statistically significant decrease in rectal dose over CRW structures, whereas the treatment technique (IMRT vs VMAT) did not significantly affect the rectal dose. There was improvement seen in bladder and penile bulb dose when VMAT was used as a treatment technique. Overall, treatment plans using the RW optimization structure offered the lowest rectal dose while VMAT treatment technique offered the lowest bladder and penile bulb dose.

Rectal Ulcers and Rectoprostatic Fistulas after (125)I Low Dose Rate Prostate Brachytherapy.

PURPOSE: Radiation induced rectal ulcers and fistulas are rare but significant complications of low dose rate prostate brachytherapy for localized prostate cancer. We describe the incidence of ulcers and fistulas, and associated risk factors. MATERIALS AND METHODS: We reviewed the records of 4,690 patients with localized prostate cancer who were treated with low dose rate (125)I prostate brachytherapy to a dose of 144 Gy with or without 6 months of androgen deprivation therapy. Patient, disease, comorbidity, treatment, dosimetric and posttreatment intervention factors were analyzed for an association with ulcer or fistula formation. RESULTS: At a median followup of 53 months 21 cases were identified, including 15 rectal ulcer cases, of which 6 progressed to fistulas, and an additional 6 cases of fistulas with no prior documented ulcers. Overall 9 rectal ulcer cases (0.19%) and 12 fistula cases (0.26%) were identified. In 8 of 15 patients ulcers healed with conservative management. No fistulas healed without surgical management. Two patients with fistulas died. Eight patients diagnosed with rectal ulcers subsequently underwent rectal biopsies, after which fistulas developed in 3. One patient with a de novo fistula underwent a preceding biopsy. Urinary interventions such as transurethral resection of the prostate were performed after brachytherapy in 5 of 12 patients with fistulas compared to 0 of 9 with ulcers alone. Argon plasma coagulation of the rectum for hematochezia was performed after brachytherapy in 3 of 12 patients with fistulas. CONCLUSIONS: Rates of post-brachytherapy rectal ulcers and fistulas are low as previously described. Post-brachytherapy interventions such as rectal biopsy, argon coagulation and urinary intervention may increase the risk of fistulas.

Tumor-associated autoantibodies correlate with poor outcome in prostate cancer patients treated with androgen deprivation and external beam radiation therapy.

Standard cancer treatments trigger immune responses that may influence tumor control. The nature of these responses varies depending on the tumor and the treatment modality. We previously reported that radiation and androgen-deprivation therapy (ADT) induce tumor-associated autoantibody responses in prostate cancer patients. This follow-up analysis was conducted to assess the relationship between autoantibody responses and clinical outcome. Patients with non-metastatic prostate cancer received external beam radiation therapy (EBRT) plus neoadjuvant and concurrent androgen deprivation. Treatment-induced autoantibodies were detected in almost a third of patients receiving combinatorial ADT and EBRT. Unexpectedly, patients that developed autoantibody responses to tumor antigens had a significantly lower 5-year biochemical failure-free survival (BFFS) than patients that did not develop an autoantibody response. Thus, tumor-reactive autoantibodies may be associated with increased risk of biochemical failure and immunomodulation to prevent autoantibody development may improve BFFS for select, high-risk prostate cancer patients receiving both ADT and EBRT.

Toxicity after (125)I prostate brachytherapy in patients with inflammatory bowel disease.

PURPOSE: To determine gastrointestinal (GI) toxicity after (125)I prostate brachytherapy in patients with inflammatory bowel disease (IBD). METHODS AND MATERIALS: We retrospectively reviewed 13 patients diagnosed with IBD from a cohort of over 3200 patients with low- to intermediate-risk prostate cancer treated with (125)I brachytherapy (144Gy). Acute (i.e. <12 months) and late lower GI toxicity after brachytherapy using the Radiation Therapy Oncology Group (RTOG) grading system was assessed. Possible factors (e.g. patient, treatment, dosimetry, and characteristics of IBD) influencing GI toxicity were assessed. RESULTS: Median followup was 4.2 years. Ten patients had ulcerative colitis (UC) and 3 had Crohn's disease. Seven patients with UC had known involvement of the rectum. Acute RTOG GI Grade 0, 1, 2, 3, 4 toxicity was seen in 7, 1, 2, 2, 1 patients, respectively. The corresponding late RTOG GI toxicity was seen in 7, 1, 3, 1, 1 patients, respectively. Two patients required major surgery. All patients with severe GI toxicity (i.e., Grade ≥3) had UC with disease involving the rectum and underwent endoscopic biopsies of the rectum within 3 months after the implant. There was no clear association with other factors with toxicity. CONCLUSIONS: Twenty-three percent and 15% patients with IBD experienced Grade 3 or higher acute and late GI toxicity, respectively, after brachytherapy. Prostate brachytherapy should be used with great caution or avoided, particularly for men with active IBD involving the rectum. Biopsies of the rectum after brachytherapy should be avoided as it may lead to ulceration.

Castration induces autoantibody and T cell responses that correlate with inferior outcomes in an androgen-dependent murine tumor model.

We recently reported that hormone therapy induces antigen-specific autoantibody responses in prostate cancer patients. However, the contribution of autoantibody responses to clinical outcomes is unknown. We used an animal model to test the hypothesis that hormone therapy-induced immune responses may be associated with delayed tumor recurrence. Male DD/S mice bearing established tumors from the androgen-dependent Shionogi carcinoma line were castrated to induce tumor regression. Tumor-specific autoantibody responses were measured by immunoblot, and the underlying antigen was identified by serological screening of a cDNA expression library. T cell responses were assessed by immunohistochemistry and IFN-gamma ELISPOT. Following castration, 97% of mice underwent complete tumor regression. Of these, 72% experienced tumor recurrence 18-79 days postcastration, whereas the remaining 28% remained tumor-free for the duration of the experiment. In 55% of mice, castration induced autoantibody responses to an antigen identified as poly(A) binding protein nuclear 1 (PABPN1). Castration also induced PABPN1-specific T cell responses, which were highly correlated to autoantibody responses, and this was accompanied by dense infiltration of tumors by CD3+ T cells 1-2 weeks after castration. Unexpectedly, mice that developed autoantibody and T cell responses to PABPN1 showed a higher rate and shorter latency of tumor recurrence. In mice with recurrent tumors, T cell responses to PABPN1 were still detectable; however, T cell infiltrates were restricted to the peripheral stroma of tumors. In conclusion, castration-induced immune responses are associated with inferior outcomes in the Shionogi carcinoma model, raising concerns about the influence of treatment-induced immune responses on clinical outcomes in humans.

What is the optimal duration of androgen deprivation therapy in prostate cancer patients presenting with prostate-specific antigen levels > 20 ng/ml?

PURPOSE: To evaluate the optimal duration of androgen deprivation therapy (ADT) in patients with prostate cancer treated with external beam radiotherapy (EBRT), who present with PSA levels > 20 ng/mL. METHODS AND MATERIALS: A total of 307 patients presenting with a PSA > 20 ng/ml were treated with EBRT and ADT. The cohort was divided into four groups according to the duration of ADT: Group 1 received < 6 months (n = 71), group 2 received 6-12 months (n = 80), group 3 received 12-24 months (n = 72), and group 4 received > 24 months (n = 84) of ADT. The endpoints analyzed were biochemical control (bNED), overall survival (OS) and cause-specific survival (CSS). Statistical analysis was conducted using Kaplan-Meier estimates and Cox regression models. RESULTS: Compared to patients who received < 6 months of ADT, patients treated with 12-24 months or > 24 months of ADT experienced significantly improved bNED (p = 0.01 and p < 0.0001, respectively). Cause-specific survival with ADT durations 12-24 and > 24 months were significantly higher compared to < 6 months (p < 0.007 and 0.024, respectively). Overall survival with ADT durations > 24 months was also significantly higher compared to < 6 months (p = 0.0025). CONCLUSIONS: The present analysis supports the hypothesis that longer durations of ADT improves bNED, CSS and OS in patients presenting with a PSA > 20 ng/ml.

Web-based electronic health information systems for prostate cancer patients.

INTRODUCTION: Providing men with prostate cancer (MPC) timely access to their health records and information (HRI) can enhance their ability to understand their condition and engage in shared medical decision making with their health care provider (HCP). The Internet is a potential means of enhancing such interactions. MATERIALS AND METHODS: Two surveys were conducted at a PC support group in Victoria, BC to identify the health information needs of MPC and the ability to access their HRI. Another objective was to identify the potential role of web-enabled HRI systems at meeting these needs. Sixty-one participants (41 men and 18 spouses/significant others (SS)) completed the first convenience survey and 16 participants then took part in a focus group meeting using a second questionnaire. RESULTS: The majority of men (median age 70 years) were knowledgeable with the computer and Internet. The majority of men (75%) desired the ability to access their HRI through means other than by meeting with their HCP, with the Internet ranking as one of the most desired methods. There was broad interest in accessing various parts of their health record and during different phases of their care. Most men were willing to try a personalized patient web-enabled HRI system. Over 70% of SS desired the ability to access their men's HRI. CONCLUSIONS: The surveys indicate that the Internet is a desirable means of accessing electronic HRI and support the potential role of web-enabled HRI systems for PC patients.