R. Bryan Rumble

Systemic Therapy in Men With Metastatic Castration-Resistant Prostate Cancer: American Society of Clinical Oncology and Cancer Care Ontario Clinical Practice Guideline

PURPOSE To provide treatment recommendations for men with metastatic castration-resistant prostate cancer (CRPC). METHODS The American Society of Clinical Oncology and Cancer Care Ontario convened an expert panel to develop evidence-based recommendations informed by a systematic review of the literature. RESULTS When added to androgen deprivation, therapies demonstrating improved survival, improved quality of life (QOL), and favorable benefit-harm balance include abiraterone acetate/prednisone, enzalutamide, and radium-223 ((223)Ra; for men with predominantly bone metastases). Improved survival and QOL with moderate toxicity risk are associated with docetaxel/prednisone. For asymptomatic/minimally symptomatic men, improved survival with unclear QOL impact and low toxicity are associated with sipuleucel-T. For men who previously received docetaxel, improved survival, unclear QOL impact, and moderate to high toxicity risk are associated with cabazitaxel/prednisone. Modest QOL benefit (without survival benefit) and high toxicity risk are associated with mitoxantrone/prednisone after docetaxel. No benefit and excess toxicity are observed with bevacizumab, estramustine, and sunitinib. RECOMMENDATIONS Continue androgen deprivation (pharmaceutical or surgical) indefinitely. Abiraterone acetate/prednisone, enzalutamide, or (223)Ra should be offered; docetaxel/prednisone should also be offered, accompanied by discussion of toxicity risk. Sipuleucel-T may be offered to asymptomatic/minimally symptomatic men. For men who have experienced progression with docetaxel, cabazitaxel may be offered, accompanied by discussion of toxicity risk. Mitoxantrone may be offered, accompanied by discussion of limited clinical benefit and toxicity risk. Ketoconazole or antiandrogens (eg, bicalutamide, flutamide, nilutamide) may be offered, accompanied by discussion of limited known clinical benefit. Bevacizumab, estramustine, and sunitinib should not be offered. There is insufficient evidence to evaluate optimal sequences or combinations of therapies. Palliative care should be offered to all patients.

Chemotherapy and Targeted Therapy for Women With Human Epidermal Growth Factor Receptor 2–Negative (or unknown) Advanced Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline

PURPOSE To identify optimal chemo- and targeted therapy for women with human epidermal growth factor 2 (HER2)- negative (or unknown) advanced breast cancer. METHODS A systematic review of randomized evidence (including systematic reviews and meta-analyses) from 1993 through to current was completed. Outcomes of interest included survival, progression-free survival, response, quality of life, and adverse effects. Guideline recommendations were evidence based and were agreed on by the Expert Panel via consensus. RESULTS Seventy-nine studies met the inclusion criteria, comprising 20 systematic reviews and/or meta-analyses, 30 trials on first-line treatment, and 29 trials on second-line and subsequent treatment. These trials form the evidence base for the guideline recommendations. RECOMMENDATIONS Endocrine therapy is preferable to chemotherapy as first-line treatment for patients with estrogen receptor-positive metastatic breast cancer unless improvement is medically necessary (eg, immediately life-threatening disease). Single agent is preferable to combination chemotherapy, and longer planned duration improves outcome but must be balanced against toxicity. There is no single optimal first-line or subsequent line chemotherapy, and choice of treatment will be determined by multiple factors including prior therapy, toxicity, performance status, comorbid conditions, and patient preference. The role of bevacizumab remains controversial. Other targeted therapies have not so far been shown to enhance chemotherapy outcome in HER2-negative breast cancer.

Active Surveillance for the Management of Localized Prostate Cancer (Cancer Care Ontario Guideline): American Society of Clinical Oncology Clinical Practice Guideline Endorsement

PURPOSE To endorse Cancer Care Ontarios guideline on Active Surveillance for the Management of Localized Prostate Cancer. The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing clinical practice guidelines developed by other professional organizations. METHODS The Active Surveillance for the Management of Localized Prostate Cancer guideline was reviewed for developmental rigor by methodologists. The ASCO Endorsement Panel then reviewed the content and the recommendations. RESULTS The ASCO Endorsement Panel determined that the recommendations from the Active Surveillance for the Management of Localized Prostate Cancer guideline, published in May 2015, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed the Active Surveillance for the Management of Localized Prostate Cancer guideline with added qualifying statements. The Cancer Care Ontario recommendation regarding 5-alpha reductase inhibitors was not endorsed by the ASCO panel. RECOMMENDATIONS For most patients with low-risk (Gleason score ≤ 6) localized prostate cancer, active surveillance is the recommended disease management strategy. Factors including younger age, prostate cancer volume, patient preference, and ethnicity should be taken into account when making management decisions. Select patients with low-volume, intermediate-risk (Gleason 3 + 4 = 7) prostate cancer may be offered active surveillance. Active surveillance protocols should include prostate-specific antigen testing, digital rectal examinations, and serial prostate biopsies. Ancillary radiologic and genomic tests are investigational but may have a role in patients with discordant clinical and/or pathologic findings. Patients who are reclassified to a higher-risk category (Gleason score ≥ 7) or who have significant increases in tumor volume on subsequent biopsies should be offered active therapy.

Endocrine Therapy for Hormone Receptor–Positive Metastatic Breast Cancer: American Society of Clinical Oncology Guideline

PURPOSE To develop recommendations about endocrine therapy for women with hormone receptor (HR) -positive metastatic breast cancer (MBC). METHODS The American Society of Clinical Oncology convened an Expert Panel to conduct a systematic review of evidence from 2008 through 2015 to create recommendations informed by that evidence. Outcomes of interest included sequencing of hormonal agents, hormonal agents compared with chemotherapy, targeted biologic therapy, and treatment of premenopausal women. This guideline puts forth recommendations for endocrine therapy as treatment for women with HR-positive MBC. RECOMMENDATIONS Sequential hormone therapy is the preferential treatment for most women with HR-positive MBC. Except in cases of immediately life-threatening disease, hormone therapy, alone or in combination, should be used as initial treatment. Patients whose tumors express any level of hormone receptors should be offered hormone therapy. Treatment recommendations should be based on type of adjuvant treatment, disease-free interval, and organ function. Tumor markers should not be the sole criteria for determining tumor progression; use of additional biomarkers remains experimental. Assessment of menopausal status is critical; ovarian suppression or ablation should be included in premenopausal women. For postmenopausal women, aromatase inhibitors (AIs) are the preferred first-line endocrine therapy, with or without the cyclin-dependent kinase inhibitor palbociclib. As second-line therapy, fulvestrant should be administered at 500 mg with a loading schedule and may be administered with palbociclib. The mammalian target of rapamycin inhibitor everolimus may be administered with exemestane to postmenopausal women with MBC whose disease progresses while receiving nonsteroidal AIs. Among patients with HR-positive, human epidermal growth factor receptor 2-positive MBC, human epidermal growth factor receptor 2-targeted therapy plus an AI can be effective for those who are not chemotherapy candidates.

Extended RAS Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict Response to Anti–Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015

PURPOSE An American Society of Clinical Oncology Provisional Clinical Opinion (PCO) offers timely clinical direction after publication or presentation of potentially practice-changing data from major studies. This PCO update addresses the utility of extended RAS gene mutation testing in patients with metastatic colorectal cancer (mCRC) to detect resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) therapy. CLINICAL CONTEXT Recent results from phase II and III clinical trials in mCRC demonstrate that patients whose tumors harbor RAS mutations in exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146) are unlikely to benefit from therapy with MoAbs directed against EGFR, when used as monotherapy or combined with chemotherapy. RECENT DATA In addition to the evidence reviewed in the original PCO, 11 systematic reviews with meta-analyses, two retrospective analyses, and two health technology assessments based on a systematic review were obtained. These evaluated the outcomes for patients with mCRC with no mutation detected or presence of mutation in additional exons in KRAS and NRAS. PCO: All patients with mCRC who are candidates for anti-EGFR antibody therapy should have their tumor tested in a Clinical Laboratory Improvement Amendments-certified laboratory for mutations in both KRAS and NRAS exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146). The weight of current evidence indicates that anti-EGFR MoAb therapy should only be considered for treatment of patients whose tumor is determined to not have mutations detected after such extended RAS testing.

Fecal immunochemical tests compared with guaiac fecal occult blood tests for population-based colorectal cancer screening

Colorectal cancer (CRC) is the second most common cause of cancer deaths in Canadian men and women - accounting for almost 12% of all cancer deaths. In Ontario, it is estimated that 8100 persons were diagnosed with CRC in 2011, and 3250 died from the disease. CRC incidence and mortality rates in Ontario are among the highest in the world. Screening offers the best opportunity to reduce this burden of disease. The present report describes the findings and recommendations of Cancer Care Ontarios Fecal Immunochemical Tests (FIT) Guidelines Expert Panel, which was convened in September 2010 by the Program in Evidence-Based Care. The purpose of the present guideline is to evaluate the existing evidence concerning FIT to inform the decision on how to replace the current guaiac fecal occult blood test with FIT in the Ontario ColonCancerCheck Program. Eleven articles were included in the present guideline, comprising two systematic reviews, five articles reporting on three randomized controlled trials, and reports of four other studies. Additionally, one laboratory study was obtained that reported on several parameters of FIT tests that helped to inform the present recommendation. The performance of FIT is superior to the standard guaiac fecal occult blood test in terms of screening participation rates and the detection of CRC and advanced adenoma. Given greater specimen instability with the use of FIT, a pilot study should be undertaken to determine how to implement the FIT in Ontario.

Guideline on Muscle-Invasive and Metastatic Bladder Cancer (European Association of Urology guideline): American Society of Clinical Oncology Clinical Practice Guideline Endorsement

PURPOSE To endorse the European Association of Urology guideline on muscle-invasive (MIBC) and metastatic bladder cancer. The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. METHODS The guideline on MIBC and metastatic bladder cancer was reviewed for developmental rigor by methodologists. The ASCO Endorsement Panel then reviewed the content and recommendations. RESULTS The ASCO Endorsement Panel determined that the recommendations from the European Association of Urology guideline on MIBC and metastatic bladder cancer, published online in March 2015, are clear, thorough, and based on the most relevant scientific evidence. ASCO endorses the guideline on MIBC and metastatic bladder cancer and has added qualifying statements, including highlighting the use of chemoradiotherapy for select patients with MIBC and recommending a preference for clinical trials in the treatment of metastatic disease in the second-line setting. RECOMMENDATIONS Multidisciplinary care for patients with MIBC and metastatic bladder cancer is critical. The standard treatment of MIBC (cT2-T4a N0M0) is neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy. In cisplatin-ineligible patients, radical cystectomy alone is recommended. Adjuvant cisplatin-based chemotherapy may be offered to high-risk patients who have not received neoadjuvant therapy. Chemoradiotherapy may be offered as an alternative to cystectomy in appropriately selected patients with MIBC and in some patients for whom cystectomy is not an option. Metastatic disease should be treated with cisplatin-containing combination chemotherapy or with carboplatin combination chemotherapy or single agents in patients ineligible for cisplatin.Additional information is available at http://www.asco.org/endorsements/MIBC and www.asco.org/guidelineswiki.

Adjuvant and Salvage Radiotherapy After Prostatectomy: American Society of Clinical Oncology Clinical Practice Guideline Endorsement

PURPOSE To endorse the American Urological Association (AUA)/American Society for Radiation Oncology (ASTRO) guideline on adjuvant and salvage radiotherapy after prostatectomy. The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing clinical practice guidelines developed by other professional organizations. METHODS The guideline on adjuvant and salvage radiotherapy after prostatectomy was reviewed for developmental rigor by methodologists. An ASCO endorsement panel then reviewed the content and recommendations. RESULTS The panel determined that the guideline recommendations on adjuvant and salvage radiotherapy after prostatectomy, published in August 2013, are clear, thorough, and based on the most relevant scientific evidence. ASCO endorsed the guideline on adjuvant and salvage radiotherapy after prostatectomy, adding one qualifying statement that not all candidates for adjuvant or salvage radiotherapy have the same risk of recurrence or disease progression, and thus, risk-benefit ratios are not the same for all men. Those at the highest risk for recurrence after radical prostatectomy include men with seminal vesicle invasion, Gleason score 8 to 10, extensive positive margins, and detectable postoperative prostate-specific antigen (PSA). RECOMMENDATIONS Physicians should discuss adjuvant radiotherapy with patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invasion, positive surgical margins, extraprostatic extension) and salvage radiotherapy with patients with PSA or local recurrence after prostatectomy. The discussion of radiotherapy should include possible short- and long-term adverse effects and potential benefits. The decision to administer radiotherapy should be made by the patient and multidisciplinary treatment team, keeping in mind that not all men are at equal risk of recurrence or clinically meaningful disease progression. Thus, the risk-benefit ratio will differ for each patient.

Molecular biomarkers for the evaluation of colorectal cancer: Guideline from The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology

Purpose Molecular testing of colorectal cancers (CRCs) to improve patient care and outcomes of targeted and conventional therapies has been the center of many recent studies, including clinical trials. Evidence-based recommendations for the molecular testing of CRC tissues to guide epidermal growth factor receptor (EGFR) -targeted therapies and conventional chemotherapy regimens are warranted in clinical practice. The purpose of this guideline is to develop evidence-based recommendations to help establish standard molecular biomarker testing for CRC through a systematic review of the literature. Methods The American Society for Clinical Pathology (ASCP), College of American Pathologists (CAP), Association for Molecular Pathology (AMP), and the American Society of Clinical Oncology (ASCO) convened an Expert Panel to develop an evidence-based guideline to help establish standard molecular biomarker testing, guide targeted therapies, and advance personalized care for patients with CRC. A comprehensive literature search that included over 4,000 articles was conducted to gather data to inform this guideline. Results Twenty-one guideline statements (eight recommendations, 10 expert consensus opinions and three no recommendations) were established. Recommendations Evidence supports mutational testing for genes in the EGFR signaling pathway, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize molecular testing for predictive and prognostic molecular biomarkers involve selection of assays, type of specimens to be tested, timing of ordering of tests and turnaround time for testing results. Additional information is available at: www.asco.org/CRC-markers-guideline and www.asco.org/guidelineswiki.

Brachytherapy for Patients With Prostate Cancer: American Society of Clinical Oncology/Cancer Care Ontario Joint Guideline Update

Purpose To jointly update the Cancer Care Ontario guideline on brachytherapy for patients with prostate cancer to account for new evidence. Methods An Update Panel conducted a targeted systematic literature review and identified more recent randomized controlled trials comparing dose-escalated external beam radiation therapy (EBRT) with brachytherapy in men with prostate cancer. Results Five randomized controlled trials provided the evidence for this update. Recommendations For patients with low-risk prostate cancer who require or choose active treatment, low-dose rate brachytherapy (LDR) alone, EBRT alone, and/or radical prostatectomy (RP) should be offered to eligible patients. For patients with intermediate-risk prostate cancer choosing EBRT with or without androgen-deprivation therapy, brachytherapy boost (LDR or high-dose rate [HDR]) should be offered to eligible patients. For low-intermediate risk prostate cancer (Gleason 7, prostate-specific antigen < 10 ng/mL or Gleason 6, prostate-specific antigen, 10 to 20 ng/mL), LDR brachytherapy alone may be offered as monotherapy. For patients with high-risk prostate cancer receiving EBRT and androgen-deprivation therapy, brachytherapy boost (LDR or HDR) should be offered to eligible patients. Iodine-125 and palladium-103 are each reasonable isotope options for patients receiving LDR brachytherapy; no recommendation can be made for or against using cesium-131 or HDR monotherapy. Patients should be encouraged to participate in clinical trials to test novel or targeted approaches to this disease. Additional information is available at www.asco.org/Brachytherapy-guideline and www.asco.org/guidelineswiki .