SpaceOAR hydrogel spacer injection prior to stereotactic body radiation therapy for men with localized prostate cancer: A systematic review.

BACKGROUND: Conventionally fractionated radiotherapy is a common treatment for men with localized prostate cancer. A growing consensus suggests that stereotactic body radiation therapy (SBRT) is similarly effective but less costly and more convenient for patients. The SpaceOAR hydrogel rectal spacer placed between the prostate and rectum reduces radiation-induced rectal injury in patients receiving conventionally fractionated radiotherapy, but spacer efficacy with SBRT is unclear. The purpose of this research was to assess the clinical utility of the hydrogel rectal spacer in men receiving SBRT for prostate cancer. METHODS: We performed systematic searches of Medline, Embase, and the Cochrane Central Register of Controlled Trials for studies in men who received the SpaceOAR hydrogel spacer prior to SBRT (≥5.0 Gy fractions) for treatment of localized prostate center. Rectal irradiation results were compared to controls without spacer implant; all other outcomes were reported descriptively owing to lack of comparative data incuding perirectal separation distance, rectal irradiation on a dosimetric curve, gastrointestinal (GI) toxicity, and freedom from biochemical failure. GI toxicity was reported as the risk of a grade 2 or 3+ bowel complication in early (≤3 months) and late (>3 months) follow-up. RESULTS: In 11 studies with 780 patients, SBRT protocols ranged from 7 to 10 Gy per fraction with total dose ranging from 19 to 45 Gy. Perirectal distance achieved with the rectal spacer ranged from 9.6 to 14.5 mm (median 10.8 mm). Compared to controls receiving no spacer, SpaceOAR placement reduced the radiation delivered to the rectum by 29% to 56% across a dosimetric profile curve. In early follow-up, grade 2 GI complications were reported in 7.0% of patients and no early grade 3+ GI complications were reported. In late follow-up, the corresponding rates were 2.3% for grade 2 and 0.3% for grade 3 GI toxicity. Over 16 months median follow-up, freedom from biochemical failure ranged from 96.4% to 100% (pooled mean 97.4%). CONCLUSIONS: SpaceOAR hydrogel spacer placed between the prostate and rectum prior to SBRT is a promising preventative strategy that increases the distance between the prostate and rectum, reduces rectal radiation exposure, and may lower the risk of clinically important GI complications.

Association of the Placement of a Perirectal Hydrogel Spacer With the Clinical Outcomes of Men Receiving Radiotherapy for Prostate Cancer: A Systematic Review and Meta-analysis.

Importance: Perirectal spacers are intended to lower the risk of rectal toxic effects associated with prostate radiotherapy. A quantitative synthesis of typical clinical results with specific perirectal spacers is limited. Objective: To evaluate the association between perirectal hydrogel spacer placement and clinical outcomes of men receiving radiotherapy for prostate cancer. Data Sources: A systematic search was performed of the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for articles published through September 2019. Study Selection: Studies comparing men who received a hydrogel spacer vs men who did not receive a spacer (controls) prior to prostate radiotherapy. Data Extraction and Synthesis: Via random-effects meta-analysis, group comparisons were reported using the weighted mean difference for continuous measures and the risk ratio for binary measures. Main Outcomes and Measures: Procedural results, the percentage volume of rectum receiving at least 70 Gy radiation (v70), early (≤3 months) and late (>3 months) rectal toxic effects, and early and late changes in bowel-related quality of life on the Expanded Prostate Cancer Index Composite (minimal clinically important difference, 4 points). Results: The review included 7 studies (1 randomized clinical trial and 6 cohort studies) involving 1011 men (486 who received a hydrogel spacer and 525 controls), with a median duration of patient follow-up of 26 months (range, 3-63 months). The success rate of hydrogel spacer placement was 97.0% (95% CI, 94.4%-98.8% [5 studies]), and the weighted mean perirectal separation distance was 11.2 mm (95% CI, 10.1-12.3 mm [5 studies]). Procedural complications were mild and transient, occurring in 0% to 10% of patients within the studies. The hydrogel spacer group received 66% less v70 rectal irradiation compared with controls (3.5% vs 10.4%; mean difference, -6.5%; 95% CI, -10.5% to -2.5%; P = .001 [6 studies]). The risk of grade 2 or higher rectal toxic effects was comparable between groups in early follow-up (4.5% in hydrogel spacer group vs 4.1% in control group; risk ratio, 0.82; 95% CI, 0.52-1.28; P = .38 [6 studies]) but was 77% lower in the hydrogel spacer group in late follow-up (1.5% vs 5.7%; risk ratio, 0.23; 95% CI, 0.06-0.99; P = .05 [4 studies]). Changes in bowel-related quality of life were comparable between groups in early follow-up (mean difference, 0.2; 95% CI, -3.1 to 3.4; P = .92 [2 studies]) but were greater in the hydrogel spacer group in late follow-up (mean difference, 5.4; 95% CI, 2.8-8.0; P < .001 [2 studies]). Conclusions and Relevance: For men receiving prostate radiotherapy, injection of a hydrogel spacer was safe, provided prostate-rectum separation sufficient to reduce v70 rectal irradiation, and was associated with fewer rectal toxic effects and higher bowel-related quality of life in late follow-up.

Exercise for Men with Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Exercise could be beneficial for prostate cancer survivors. However, no systematic review across cancer stages and treatment types addressing potential benefits and harms exists to date. OBJECTIVE: To assess the effects of exercise on cancer-specific quality of life and adverse events in prostate cancer trials. EVIDENCE ACQUISITION: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED, CINAHL, PsycINFO, SPORTDiscus, and PEDro. We also searched grey literature databases, including trial registers. Searches were from database inception to March 2015. Standardised mean differences (SMDs) were calculated for meta-analysis. EVIDENCE SYNTHESIS: We included 16 randomised controlled trials (RCTs) involving 1574 men with prostate cancer. Follow-up varied from 8 wk to 12 mo. RCTs involved men with stage I-IV cancers. A high risk of bias was frequently due to problematic intervention adherence. Seven trials involving 912 men measured cancer-specific quality of life. Pooling of the data from these seven trials revealed no significant effect on this outcome (SMD 0.13, 95% confidence interval [CI] -0.08 to 0.34, median follow-up 12 wk). Sensitivity analysis of studies that were judged to be of high quality indicated a moderate positive effect estimate (SMD 0.33, 95% CI 0.08-0.58; median follow-up 12 wk). Similar beneficial effects were seen for cancer-specific fatigue, submaximal fitness, and lower body strength. We found no evidence of benefit for disease progression, cardiovascular health, or sexual function. There were no deaths attributable to exercise interventions. Other serious adverse events (eg, myocardial infarction) were equivalent to those seen in controls. CONCLUSIONS: These results support the hypothesis that exercise interventions improve cancer-specific quality of life, cancer-specific fatigue, submaximal fitness, and lower body strength. PATIENT SUMMARY: This review shows that exercise/physical activity interventions can improve quality of life, fatigue, fitness, and function for men with prostate cancer.

Radical radiotherapy for high-risk prostate cancer in older men.

Historical data for older men with high-risk nonmetastatic prostate cancer treated with radiotherapy alone have demonstrated a 10-year prostate-cancer-specific mortality of around 30%. The development of dose escalation, using techniques such as intensity-modulated radiotherapy, has enabled more targeted delivery of treatment with improved efficacy and a reduction in the risk of toxicity compared with conventional radiotherapy. The combination of radiotherapy and androgen-deprivation therapy (ADT) has been shown to improve overall survival compared with radiotherapy or ADT alone without a significant increase in toxicity in patients with minimal comorbidities. There is evidence that patient age has only a marginal effect on genitourinary and gastrointestinal toxicities following radiotherapy. Further research has shown that although age does have an effect on the likelihood of sexual dysfunction after radiation therapy, there is no significant difference in the proportion of men aged ≥ 75 years who feel that sexual dysfunction is a moderate or serious problem before or 24 months after diagnosis. Radical radiotherapy is effective and well tolerated in senior men with high-risk prostate cancer and should be offered in combination with long-term ADT to patients with minimal comorbidities. In case of significant comorbid conditions, shorter durations of ADT may be considered.

A comment on the International Society of Geriatric Oncology guidelines: evidence-based advice for the clinical setting.

Largely a disease of older men, prostate cancer is likely to become a growing burden in the developed world as the population ages and overall life expectancy increases. Furthermore, prostate cancer management in older men is not optimal, reflecting the lack of training dedicated to senior adults in fellowship programs and the lack of specific guidelines to manage senior adults. The International Society of Geriatric Oncology (SIOG) convened a multidisciplinary Prostate Cancer Working Group to review the evidence base and provide advice on the management of the disease in senior age groups. The Working Group reported that advancing age, by itself, is not a reliable guide to treatment decision making for men with either localized or advanced prostate cancer. Instead, the SIOG guidelines advise health care teams to assess the patient's underlying health status, which is largely dictated by associated comorbid conditions, but also by dependency in activities of daily living and nutritional status, and to use the findings to categorize the individual into one of four groups: healthy, vulnerable, frail, or terminally ill. The guidelines recommend that a patient categorized as healthy or vulnerable (i.e., with reversible problems following geriatric intervention) should receive the same approach to treatment as a younger patient. Frail patients should be managed using adapted treatment strategies, and the terminally ill should receive symptomatic/palliative care only. The guidelines may have ongoing relevance as the treatment options for prostate cancer expand.

Differences and commonalities in the management of locally advanced prostate cancer: results from a survey of oncologists and urologists in the UK.

OBJECTIVE: To determine the management practices used by UK oncologists and urologists for patients with locally advanced (non-metastatic) prostate cancer. METHODS: Using a postal questionnaire, 155 practising specialist oncologists and urologists were surveyed in the UK. Their views were sought on a multidisciplinary approach to the management of locally advanced prostate cancer and their current management practices. RESULTS: Over half of respondents recognized the need for both oncologists and urologists to take the lead in management decisions, but almost as many still expected the sole responsibility to lie within their own speciality. Radical radiotherapy (RT) was considered the current optimum treatment by most respondents, but 22% of urologists thought that radical prostatectomy is optimal. Most responders would use luteinizing hormone-releasing hormone agonists as neoadjuvant and adjuvant to RT but there was significant variation in the favoured duration of treatment of these drugs, and in the dose of RT. CONCLUSION: This survey suggests that there are still wide variations in the management practices for locally advanced prostate cancer in the UK, and between urologists and oncologists. Improved consensus guidelines are required.

Tumour markers for managing men who present with metastatic prostate cancer and serum prostate-specific antigen levels of <10 ng/mL.

OBJECTIVE: To define immunohistochemical features of the primary cancers that might help in the differential diagnosis and monitoring of treatment in men presenting with metastatic prostate cancer and low serum levels of prostate-specific antigen (PSA), who can be difficult to diagnose and manage. PATIENTS AND METHODS: Paraffin blocks of prostate biopsies were obtained for 33 patients presenting with untreated metastatic prostate cancer and serum PSA levels of <10 ng/mL. Sections were immunostained for PSA, prostatic acid phosphatase (PAP), prostate-specific membrane antigen (PSMA), androgen receptor (AR), chromogranin A and CD 56. RESULTS: The combined Gleason scores were 8-10 in 25 men (76%) and 6 or 7 in the other eight (24%). Morphologically, there were no neuroendocrine features. PSA immunostaining was equivocal in 12 (36%) cases and in a further 19 (58%) was strong but focal and could be missed on biopsy sampling. PSMA was expressed in 90% of cases, and staining was widely distributed in nine of the 12 in which PSA staining was equivocal. There was strong AR expression in 30 (91%) cases and it was present in areas where PSA was absent. CONCLUSION: In this patient group, immunohistochemical assessments of PSMA and AR are potentially useful as diagnostic markers.

Clinical features of patients who present with metastatic prostate carcinoma and serum prostate-specific antigen (PSA) levels < 10 ng/mL: the "PSA negative" patients.

BACKGROUND: Although < 1% of men present with prostate-specific antigen (PSA)-negative prostate carcinoma, in that they have serum PSA levels much lower than the tumor burden would suggest, such patients represent a management dilemma. To the authors' knowledge, little information exists in the literature regarding patterns of disease and response to treatment. The authors wished to define the clinical features of this patient group. METHODS: The British Association of Urological Surgeons Cancer Registry 2000 and 2001 data bases were used to identify the clinical features and outcome of 33 men with metastatic prostate carcinoma who presented with serum PSA levels < 10 ng/mL. Clinical notes and histopathology were reviewed for each patient. RESULTS: Seventeen patients (51%) presented with urinary symptoms and/or pelvic pain, 6% with cachexia and 21% with bone pain. Characteristic bone metastases were present in 81% of patients, similar to the presentation of men with high serum PSA levels. Hypercalcemia was a feature in 9% of patients. Visceral metastases were present in two patients. The median response duration to first-line hormone manipulation was 7 months. No responses were seen in 11 of 13 patients who received second-line hormones or to any third-line treatment. Three of 5 patients who received chemotherapy responded but developed recurrent disease within 8 weeks of treatment cessation. The median overall survival was 12 months. CONCLUSIONS: The presentation of patients with treatment-naïve PSA-negative metastatic prostate carcinoma is similar to that of patients with high serum PSA levels, but their median survival and response duration to first-line hormone therapy are of much shorter duration. Second-line hormone therapy is ineffective, but early chemotherapy may be beneficial. Hypercalcemia is a particular feature in this group of patients.