Radiation Oncologist Consultations Prior to Radical Prostatectomy: Disparities and Opportunities.

PURPOSE: In 2015, men undergoing radical prostatectomy in Ontario, Canada were recommended to undergo multidisciplinary care by seeing a radiation oncologist or discussion at multidisciplinary rounds before surgery. The a priori target rate was ≥76%. We used population-based data to explore factors associated with not receiving multidisciplinary care prior to radical prostatectomy. MATERIALS AND METHODS: Men who underwent radical prostatectomy for localized prostate cancer in Ontario between 2007 and 2017 were identified using administrative data. Physician billings identified patients who received multidisciplinary care. Multivariable logistic regression was used to predict receipt of multidisciplinary care. RESULTS: A total of 31,485 men underwent radical prostatectomy between 2007 and 2017. Of these patients 28.7% saw a radiation oncologist, 1.2% underwent multidisciplinary discussion and 1.9% had both before surgery. Multidisciplinary care receipt increased from 17.8% in 2007 to 47.8% in 2017 (p <0.001). The odds ratio between the highest and lowest geographic regions was 7.93 (95% CI 6.17-10.18, p <0.001). Lower odds of multidisciplinary care receipt were observed for men further from the nearest cancer center (OR 0.74 per 50 km, 95% CI 0.71-0.78, p <0.001) and higher odds for the highest versus lowest income quintile (OR 1.41, 95% CI 1.29-1.54, p <0.001). Of 128 urologists who performed ≥10 radical prostatectomies between 2016 and 2017, 29 (22.7%) met the target of having ≥76% of men seen for multidisciplinary care prior to surgery. CONCLUSIONS: Despite increasing utilization, many men do not receive multidisciplinary care prior to radical prostatectomy. While geography and the urologist appear to be the greatest factors predicting multidisciplinary care receipt, these factors are closely intertwined.

Hypofractionated Radiation Therapy for Localized Prostate Cancer: Executive Summary of an ASTRO, ASCO and AUA Evidence-Based Guideline.

PURPOSE: The aim of this guideline is to present recommendations regarding moderately hypofractionated (240-340 cGy per fraction) and ultrahypofractionated (500 cGy or more per fraction) radiation therapy for localized prostate cancer. METHODS AND MATERIALS: The American Society for Radiation Oncology convened a task force to address 8 key questions on appropriate indications and dose-fractionation for moderately and ultrahypofractionated radiation therapy, as well as technical issues, including normal tissue dose constraints, treatment volumes, and use of image guided and intensity modulated radiation therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and Society-approved tools for grading evidence quality and recommendation strength. RESULTS: Based on high-quality evidence, strong consensus was reached for offering moderate hypofractionation across risk groups to patients choosing external beam radiation therapy. The task force conditionally recommends ultrahypofractionated radiation may be offered for low- and intermediate-risk prostate cancer but strongly encourages treatment of intermediate-risk patients on a clinical trial or multi-institutional registry. For high-risk patients, the task force conditionally recommends against routine use of ultrahypofractionated external beam radiation therapy. With any hypofractionated approach, the task force strongly recommends image guided radiation therapy and avoidance of nonmodulated 3-dimensional conformal techniques. CONCLUSIONS: Hypofractionated radiation therapy provides important potential advantages in cost and convenience for patients, and these recommendations are intended to provide guidance on moderate hypofractionation and ultrahypofractionation for localized prostate cancer. The limits in the current evidentiary base-especially for ultrahypofractionation-highlight the imperative to support large-scale randomized clinical trials and underscore the importance of shared decision making between clinicians and patients.

Increasing hospital admission rates for urological complications after transrectal ultrasound guided prostate biopsy.

PURPOSE: Transrectal ultrasound guided prostate biopsy is widely used to confirm the diagnosis of prostate cancer. The technique has been associated with significant morbidity in a small proportion of patients. MATERIALS AND METHODS: We conducted a population based study of 75,190 men who underwent a transrectal ultrasound guided biopsy in Ontario, Canada, between 1996 and 2005. We used hospital and cancer registry administrative databases to estimate the rates of hospital admission and mortality due to urological complications associated with the procedure. RESULTS: Of the 75,190 men who underwent transrectal ultrasound biopsy 33,508 (44.6%) were diagnosed with prostate cancer and 41,682 (55.4%) did not have prostate cancer. The hospital admission rate for urological complications within 30 days of the procedure for men without cancer was 1.9% (781/41,482). The 30-day hospital admission rate increased from 1.0% in 1996 to 4.1% in 2005 (p for trend <0.0001). The majority of hospital admissions (72%) were for infection related reasons. The probability of being admitted to hospital within 30 days of having the procedure increased 4-fold between 1996 and 2005 (OR 3.7, 95% CI 2.0-7.0, p <0.0001). The overall 30-day mortality rate was 0.09% but did not change during the study period. CONCLUSIONS: The hospital admission rates for complications following transrectal ultrasound guided prostate biopsy have increased dramatically during the last 10 years primarily due to an increasing rate of infection related complications.

Population based study of long-term rates of surgery for urinary incontinence after radical prostatectomy for prostate cancer.

PURPOSE: Urinary incontinence can be a significant complication of radical prostatectomy. It can be treated with post-prostatectomy surgical procedures. The long-term rate of patients who undergo these surgeries, including artificial urinary sphincter or urethral sling insertion, is not well described. We examined the long-term rate of post-prostatectomy incontinence surgery and factors influencing it. MATERIALS AND METHODS: We performed a population based study of 25,346 men who underwent radical prostatectomy for prostate cancer in Ontario, Canada between 1993 and 2006. We used hospital and cancer registry administrative data to identify patients from this cohort who were later treated with surgery for urinary incontinence. RESULTS: Of the 25,346 patients 703 (2.8%) underwent artificial urinary sphincter insertion and 282 (1.1%) underwent urethral sling placement a median of 2.9 years after prostatectomy. The probability of an artificial urinary sphincter/sling procedure increased with time from prostatectomy. Cumulative 5, 10 and 15-year Kaplan-Meier rates of an artificial urinary sphincter/sling procedure were 2.6% (95% CI 2.4-2.8), 3.8% (95% CI 3.6-4.1) and 4.8% (95% CI 4.4-5.3), respectively. Factors predicting surgery for incontinence were patient age at radical prostatectomy (HR 1.24 per decade, 95% CI 1.11-1.38, p = 0.0002), radiotherapy after surgery (HR 1.61, 95% CI 1.36-1.90, p <0.0001) and surgeon volume (49 or greater prostatectomies per year) (HR 0.59, 95% CI 0.46-0.77, p <0.0001). CONCLUSIONS: Of patients who undergo radical prostatectomy 5% are expected to be treated with surgery for urinary incontinence during a 15-year period. Increasing patient age, radiation treatment and low surgeon volume are associated with significantly higher risk.

Prostate cancer pathology audits: is central pathology review still warranted?

INTRODUCTION: Estimating the risk of extraprostatic extension and the probability of recurrence with different treatment modalities is common practice in cancer management. A strong predictor of recurrence and organ-confined disease is tumor grade. However, differences exist between genitourinary and non-specialist pathologists in grading prostate cancer. As such, the primary objective of this study was to assess the accuracy of non-specialist prostate cancer biopsies at our institution by analyzing the proportion of cases changing pathologic risk category upon expert review. MATERIALS AND METHODS: Log books from 2003 where our genitourinary pathologists reviewed prostate needle-core biopsies were used to identify cases. A retrospective chart review was completed and descriptive statistics were used to summarize the results for the following synoptic variables: 10 and 20 Gleason Score, number of biopsy sites, overall % involvement, perineural invasion--PNI (present/absent), extracapsular extension--ECE (present/absent). RESULTS: A total of 151 patients were reviewed. Twenty eight percent of cases (42/151) had a change in risk category after expert review. Of the 98 low risk cases, 33% were upgraded in risk category. Of the 24 intermediate risk cases, 12% were upgraded to high risk and none were downgraded. Of the 29 high risk cases, 24% were downgraded in risk category. CONCLUSION: All referred patients should continue to have their pathology centrally reviewed. This practice will help facilitate optimal prostate cancer management and improve quality of care. While these findings are dated given pathologic practice change, such changes do not necessarily equate with disparity elimination or reduction; conclusions can only be drawn with a more recent audit to see if such disparities still exist.

A Prospective Study of Magnetic Resonance Imaging-guided Focal Salvage High-dose-Rate Brachytherapy for Radiorecurrent Prostate Cancer: Updated Results of 30 Patients.

PURPOSE: Limited prospective data on focal salvage high-dose-rate (HDR) prostate brachytherapy is available. We sought to explore the toxicities, health-related quality of life (HRQoL), and efficacy of focal salvage HDR brachytherapy in a prospective clinical trial. This report presents the updated results of previously published data. METHODS AND MATERIALS: Patients with locally recurrent prostate cancer after previous external beam radiation therapy and/or brachytherapy were enrolled. Patients received magnetic resonance imaging (MRI)-guided, ultrasound-based focal HDR brachytherapy delivered over 2 fractions of 13.5 Gy delivered 1 to 2 weeks apart. Androgen deprivation therapy (ADT) was not used. RESULTS: Thirty patients were treated between 2012 and 2019. At a median follow-up time of 39 months, the 3-year biochemical failure-free rate was 61.8% (95% confidence interval, 44.0%-86.6%), and the 3-year ADT/salvage therapy-free rate was 86.0% (95% confidence interval, 74.1%-99.8%). Seventeen patients experienced subsequent biochemical failure, 9 received ADT and/or further local salvage, and no patients died of prostate cancer. Of the 28 patients who had posttreatment MRI, 26 had a local treatment response. No acute grade ≥3 genitourinary/gastrointestinal toxicity was observed. One temporary late grade 3 genitourinary toxicity event occurred, but no late grade ≥3 gastrointestinal toxicity was seen. No significant decline in urinary or bowel HRQoL was observed. CONCLUSIONS: Focal salvage HDR brachytherapy has a favorable side effect profile, no significant decline in HRQoL, and the 3-year biochemical control rates are in line with those of other salvage options. Early MRI response at the treated site is common, but does not preclude subsequent biochemical failure.

Refining the definition of biochemical failure in the era of stereotactic body radiation therapy for prostate cancer: The Phoenix definition and beyond.

BACKGROUND AND PURPOSE: The Phoenix definition for biochemical failure (BCF) after radiotherapy uses nadir PSA (nPSA) + 2 ng/mL to classify a BCF and was derived from conventionally fractionated radiotherapy, which produces significantly higher nPSAs than stereotactic body radiotherapy (SBRT). We investigated whether an alternative nPSA-based threshold could be used to define post-SBRT BCFs. MATERIALS AND METHODS: PSA kinetics data on 2038 patients from 9 institutions were retrospectively analyzed for low- and intermediate-risk PCa patients treated with SBRT without ADT. We evaluated the performance of various nPSA-based definitions. We also investigated the relationship of relative PSA decline (rPSA, PSA18month/PSA6month) and timing of reaching nPSA + 2 with BCF. RESULTS: Median follow-up was 71.9 months. BCF occurred in 6.9% of patients. Median nPSA was 0.16 ng/mL. False positivity of nPSA + 2 was 30.2%, compared to 40.9%, 57.8%, and 71.0% for nPSA + 1.5, nPSA + 1.0, and nPSA + 0.5, respectively. Among patients with BCF, the median lead time gained from an earlier nPSA + threshold definition over the Phoenix definition was minimal. Patients with BCF had significantly lower rates of early PSA decline (mean rPSA 1.19 vs. 0.39, p < 0.0001) and were significantly more likely to reach nPSA + 2 ≥ 18 months (83.3% vs. 21.1%, p < 0.0001). The proposed criterion (rPSA ≥ 2.6 or nPSA + 2 ≥ 18 months) had a sensitivity and specificity of 92.4% and 81.5%, respectively, for predicting BCF in patients meeting the Phoenix definition and decreased its false positivity to 6.4%. CONCLUSION: The Phoenix definition remains an excellent definition for BCF post-SBRT. Its high false positivity can be mitigated by applying additional criteria (rPSA ≥ 2.6 or time to nPSA + 2 ≥ 18 months).

The optimal dose fractionation schema for malignant extradural spinal cord compression.

Malignant epidural spinal cord compression is a dreaded complication of malignancy. Fortunately, it does not happen very often. Estimating the prognosis is critical to achieving a balance between effective therapy and the burden of treatment. Treatment can be individualized by reviewing simple prognosis scales. For patients with a poor prognosis, a single fraction of 8 Gy is just as effective as multiple fractions and much more convenient. Surgery and radiation should be considered for patients with a more positive prognosis. For patients not getting surgery, enrollment in clinical trials of single vs. multiple fractions of radiation should be a priority.

Increasing hospital admission rates for urological complications after transrectal ultrasound guided prostate biopsy.

PURPOSE: Transrectal ultrasound guided prostate biopsy is widely used to confirm the diagnosis of prostate cancer. The technique has been associated with significant morbidity in a small proportion of patients. MATERIALS AND METHODS: We conducted a population based study of 75,190 men who underwent a transrectal ultrasound guided biopsy in Ontario, Canada, between 1996 and 2005. We used hospital and cancer registry administrative databases to estimate the rates of hospital admission and mortality due to urological complications associated with the procedure. RESULTS: Of the 75,190 men who underwent transrectal ultrasound biopsy 33,508 (44.6%) were diagnosed with prostate cancer and 41,682 (55.4%) did not have prostate cancer. The hospital admission rate for urological complications within 30 days of the procedure for men without cancer was 1.9% (781/41,482). The 30-day hospital admission rate increased from 1.0% in 1996 to 4.1% in 2005 (p for trend <0.0001). The majority of hospital admissions (72%) were for infection related reasons. The probability of being admitted to hospital within 30 days of having the procedure increased 4-fold between 1996 and 2005 (OR 3.7, 95% CI 2.0-7.0, p <0.0001). The overall 30-day mortality rate was 0.09% but did not change during the study period. CONCLUSIONS: The hospital admission rates for complications following transrectal ultrasound guided prostate biopsy have increased dramatically during the last 10 years primarily due to an increasing rate of infection related complications.

Utility of incorporating genetic variants for the early detection of prostate cancer.

PURPOSE: Several single nucleotide polymorphisms (SNP) have been associated with the risk of prostate cancer. The clinical utility of using SNPs in the early detection of prostate cancer has not been evaluated. EXPERIMENTAL DESIGN: We examined a panel of 25 SNPs from candidate genes and chromosomal regions in 3,004 unselected men who were screened for prostate cancer using serum prostate-specific antigen (PSA) and digital rectal examination. All underwent a prostate biopsy. We evaluated the ability of these SNPs to help predict the presence of prostate cancer at biopsy. RESULTS: Of the 3,004 patients, 1,389 (46.2%) were found to have prostate cancer. Fifteen of the 25 SNPs studied were significantly associated with prostate cancer (P=0.02-7x10(-8)). We selected a combination of 4 SNPs with the best predictive value for further study. After adjusting for other predictive factors, the odds ratio for patients with all four of the variant genotypes compared with men with no variant genotype was 5.1 (95% confidence interval, 1.6-16.5; P=0.006). When incorporated into a nomogram, genotype status contributed more significantly than PSA, family history, ethnicity, urinary symptoms, and digital rectal examination (area under the curve=0.74). The positive predictive value of the PSA test ranged from 42% to 94% depending on the number of variant genotypes carried (P=1x10(-15)). CONCLUSIONS: SNP genotyping can be used in a clinical setting for the early detection of prostate cancer in a nomogram approach and by improving the positive predictive value of the PSA test.

Urolith masquerading as severe acute radiation toxicity: case report.

INTRODUCTION: Postoperative radiotherapy after radical prostatectomy has been shown to improve numerous outcomes for selected patients in mature randomized controlled trials. During treatment patients usually experience mild to moderate urinary symptoms, lower gastrointestinal symptoms and tiredness. We describe an unusual case of a patient experiencing severe, culture negative urinary symptoms early in a course of salvage radiotherapy. MATERIALS AND METHODS: A patient's history was retrospectively derived from a single institution. RESULTS: A total radiation dosage of 66 Gy in 33 fractions was to be delivered to the prostate bed by intensity modulated radiation therapy. Urinary symptoms consisting of hematuria, dysuria and urination of cellular debris developed very early during the treatment, were not related to infection and were refractory to breaks from radiation therapy. Computed tomography imaging revealed a 3.5 cm diameter urolith in the posterior bladder. Urinary symptoms resolved after surgical management consisting of, cystolitholapaxy with laser cystoscopy. CONCLUSIONS: While rare, urolithiasis should be considered when severe, early, culture negative dysuria develops on radiotherapy for prostate cancer.

Gantry-Mounted Linear Accelerator-Based Stereotactic Body Radiation Therapy for Low- and Intermediate-Risk Prostate Cancer.

PURPOSE: To establish the safety and efficacy of gantry-mounted linear accelerator-based stereotactic body radiation therapy (SBRT) for low- and intermediate-risk prostate cancer. METHODS: We pooled 921 patients enrolled on 7 single-institution prospective phase II trials of gantry-based SBRT from 2006 to 2017. The cumulative incidences of biochemical recurrence (defined by the Phoenix definition) and physician-scored genitourinary (GU) and gastrointestinal (GI) toxicities (defined per the original trials using Common Terminology Criteria for Adverse Events) were estimated using a competing risk framework. Multivariable logistic regression was used to evaluate the relationship between late toxicity and prespecified covariates: biologically effective dose, every other day versus weekly fractionation, intrafractional motion monitoring, and acute toxicity. RESULTS: Median follow-up was 3.1 years (range, 0.5-10.8 years). In addition, 505 (54.8%) patients had low-risk disease, 236 (25.6%) had favorable intermediate-risk disease, and 180 (19.5%) had unfavorable intermediate-risk disease. Intrafractional motion monitoring was performed in 78.0% of patients. The 3-year cumulative incidence of biochemical recurrence was 0.8% (95% confidence interval [CI], 0-1.7%), 2.2% (95% CI, 0-4.3%), and 5.1% (95% CI, 1.0-9.2%) for low-, favorable intermediate-, and unfavorable intermediate-risk disease. Acute grade ≥2 GU and GI toxicity occurred in 14.5% and 4.6% of patients, respectively. Three-year cumulative incidence estimates of late grade 2 GU and GI toxicity were 4.1% (95% CI, 2.6-5.5%) and 1.3% (95% CI, 0.5-2.1%), respectively, with late grade ≥3 GU and GI toxicity estimates of 0.7% (95% CI, 0.1-1.3%) and 0.4% (95% CI, 0-0.8%), respectively. The only identified significant predictors of late grade ≥2 toxicity were acute grade ≥2 toxicity (P < .001) and weekly fractionation (P < .01), although only 12.4% of patients were treated weekly. CONCLUSIONS: Gantry-based SBRT for prostate cancer is associated with a favorable safety and efficacy profile, despite variable intrafractional motion management techniques. These findings suggest that multiple treatment platforms can be used to safely deliver prostate SBRT.

Long-term Outcomes of Stereotactic Body Radiotherapy for Low-Risk and Intermediate-Risk Prostate Cancer.

Importance: Stereotactic body radiotherapy harnesses improvements in technology to allow the completion of a course of external beam radiotherapy treatment for prostate cancer in the span of 4 to 5 treatment sessions. Although mounting short-term data support this approach, long-term outcomes have been sparsely reported. Objective: To assess long-term outcomes after stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer. Design, Setting, and Participants: This cohort study analyzed individual patient data from 2142 men enrolled in 10 single-institution phase 2 trials and 2 multi-institutional phase 2 trials of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer between January 1, 2000, and December 31, 2012. Statistical analysis was performed based on follow-up from January 1, 2013, to May 1, 2018. Main Outcomes and Measures: The cumulative incidence of biochemical recurrence was estimated using a competing risk framework. Physician-scored genitourinary and gastrointestinal toxic event outcomes were defined per each individual study, generally by Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events scoring systems. After central review, cumulative incidences of late grade 3 or higher toxic events were estimated using a Kaplan-Meier method. Results: A total of 2142 men (mean [SD] age, 67.9 [9.5] years) were eligible for analysis, of whom 1185 (55.3%) had low-risk disease, 692 (32.3%) had favorable intermediate-risk disease, and 265 (12.4%) had unfavorable intermediate-risk disease. The median follow-up period was 6.9 years (interquartile range, 4.9-8.1 years). Seven-year cumulative rates of biochemical recurrence were 4.5% (95% CI, 3.2%-5.8%) for low-risk disease, 8.6% (95% CI, 6.2%-11.0%) for favorable intermediate-risk disease, 14.9% (95% CI, 9.5%-20.2%) for unfavorable intermediate-risk disease, and 10.2% (95% CI, 8.0%-12.5%) for all intermediate-risk disease. The crude incidence of acute grade 3 or higher genitourinary toxic events was 0.60% (n = 13) and of gastrointestinal toxic events was 0.09% (n = 2), and the 7-year cumulative incidence of late grade 3 or higher genitourinary toxic events was 2.4% (95% CI, 1.8%-3.2%) and of late grade 3 or higher gastrointestinal toxic events was 0.4% (95% CI, 0.2%-0.8%). Conclusions and Relevance: In this study, stereotactic body radiotherapy for low-risk and intermediate-risk disease was associated with low rates of severe toxic events and high rates of biochemical control. These data suggest that stereotactic body radiotherapy is an appropriate definitive treatment modality for low-risk and intermediate-risk prostate cancer.

Hypofractionated accelerated radiotherapy using concomitant intensity-modulated radiotherapy boost technique for localized high-risk prostate cancer: acute toxicity results.

PURPOSE: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. METHODS AND MATERIALS: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score >or=8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. RESULTS: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. CONCLUSION: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity.

Dose escalation for prostate stereotactic ablative radiotherapy (SABR): Late outcomes from two prospective clinical trials.

PURPOSE: Optimal prostate SABR dose-fractionation is unknown. This study compares long-term outcomes from two prospective trials. METHODS: Study1 patients had low-risk PCa and received 35 Gy/5. Study2 patients had low/intermediate-risk PCa and received 40 Gy/5. Biochemical failure (BF) was defined as nadir + 2. RESULTS: 114 patients were included (study1, n = 84; study2, n = 30). Median follow-up was 9.6 years and 6.9 years. Median nPSA was 0.4 and 0.1 ng/ml. Nine patients had BF (8 in study1, 1 in study2); two were managed with ADT and four had local salvage. The BF rate was 2.5% and 12.8% at 5 and 10 years for study1 and 3.3% at 5 years for study 2. BF probability was 0% if PSA <0.4 at 4 years, and 20.5% at 10 years if PSA ≥0.4 (p = 0.02). Nine patients died, none of PCa. No patient has metastases or castrate-resistance. At 10 years, OS and CSS were 90.4% (p = 0.25) and 100%. CONCLUSIONS: Dose-escalated prostate SABR was associated with lower nPSAs but no difference in BF, OS, CSS or MFS. PSA <0.4 at 4 years was a predictor of biochemical control. Half of patients with BF were successfully salvaged. Given that this is a favorable-risk cohort, longer follow-up will be needed to see if the lower nPSA translates into lower BF rates.

Hypofractionated Radiation Therapy for Localized Prostate Cancer: Executive Summary of an ASTRO, ASCO, and AUA Evidence-Based Guideline.

PURPOSE: The aim of this guideline is to present recommendations regarding moderately hypofractionated (240-340 cGy per fraction) and ultrahypofractionated (500 cGy or more per fraction) radiation therapy for localized prostate cancer. METHODS AND MATERIALS: The American Society for Radiation Oncology convened a task force to address 8 key questions on appropriate indications and dose-fractionation for moderately and ultrahypofractionated radiation therapy, as well as technical issues, including normal tissue dose constraints, treatment volumes, and use of image guided and intensity modulated radiation therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and Society-approved tools for grading evidence quality and recommendation strength. RESULTS: Based on high-quality evidence, strong consensus was reached for offering moderate hypofractionation across risk groups to patients choosing external beam radiation therapy. The task force conditionally recommends ultrahypofractionated radiation may be offered for low- and intermediate-risk prostate cancer but strongly encourages treatment of intermediate-risk patients on a clinical trial or multi-institutional registry. For high-risk patients, the task force conditionally recommends against routine use of ultrahypofractionated external beam radiation therapy. With any hypofractionated approach, the task force strongly recommends image guided radiation therapy and avoidance of nonmodulated 3-dimensional conformal techniques. CONCLUSIONS: Hypofractionated radiation therapy provides important potential advantages in cost and convenience for patients, and these recommendations are intended to provide guidance on moderate hypofractionation and ultrahypofractionation for localized prostate cancer. The limits in the current evidentiary base-especially for ultrahypofractionation-highlight the imperative to support large-scale randomized clinical trials and underscore the importance of shared decision making between clinicians and patients.

Clinically Localized Prostate Cancer: ASCO Clinical Practice Guideline Endorsement of an American Urological Association/American Society for Radiation Oncology/Society of Urologic Oncology Guideline.

PURPOSE: In April 2017, the American Urological Association, American Society for Radiation Oncology, and Society of Urologic Oncology released a joint evidence-based practice guideline on clinically localized prostate 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 Clinically Localized Prostate Cancer guideline was reviewed for developmental rigor by methodologists. An ASCO Expert Panel then reviewed the content and the recommendations. RESULTS: The ASCO Expert Panel determined that the recommendations from the Clinically Localized Prostate Cancer guideline were clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed the Clinically Localized Prostate Cancer guideline except for two recommendations on cryosurgery. The two recommendations covering cryosurgery were not endorsed because the panel found that there is insufficient evidence to support the use of cryotherapy in this setting. RECOMMENDATIONS: The ASCO Expert Panel endorsed all but two of the original guideline recommendations as written and offered a series of discussion points to guide practice.

Second-Line Hormonal Therapy for Men With Chemotherapy-Naïve, Castration-Resistant Prostate Cancer: American Society of Clinical Oncology Provisional Clinical Opinion.

Purpose ASCO provisional clinical opinions (PCOs) offer direction to the ASCO membership after publication or presentation of potential practice-changing data. This PCO addresses second-line hormonal therapy for chemotherapy-naïve men with castration-resistant prostate cancer (CRPC) who range from being asymptomatic with only biochemical evidence of CRPC to having documented metastases but minimal symptoms. Clinical Context The treatment goal for CRPC is palliation. Despite resistance to initial androgen deprivation therapy, most men respond to second-line hormonal therapies. However, guidelines have neither addressed second-line hormonal therapy for nonmetastatic CRPC nor provided specific guidance with regard to the chemotherapy-naïve population. Recent Data Six phase III randomized controlled trials and expert consensus opinion inform this PCO. Provisional Clinical Opinion For men with CRPC, a castrate state should be maintained indefinitely. Second-line hormonal therapy (eg, antiandrogens, CYP17 inhibitors) may be considered in patients with nonmetastatic CRPC at high risk for metastatic disease (rapid prostate-specific antigen doubling time or velocity) but otherwise is not suggested. In patients with radiographic evidence of metastases and minimal symptoms, enzalutamide or abiraterone plus prednisone should be offered after discussion with patients about potential harms, benefits, costs, and patient preferences. Radium-223 and sipuleucel-T also are options. No evidence provides guidance about the optimal order of hormonal therapies for CRPC beyond second-line treatment. Prostate-specific antigen testing every 4 to 6 months is reasonable for men without metastases. Routine radiographic restaging generally is not suggested but can be considered for patients at risk for metastases or who exhibit symptoms or other evidence of progression. Additional information is available at www.asco.org/genitourinary-cancer-guidelines 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 .

Systematic review of the diagnosis and management of malignant extradural spinal cord compression: the Cancer Care Ontario Practice Guidelines Initiative's Neuro-Oncology Disease Site Group.

PURPOSE: This systematic review describes the diagnosis and management of adult patients with a suspected or confirmed diagnosis of extradural malignant spinal cord compression (MSCC). METHODS: MEDLINE, CANCERLIT, and the Cochrane Library databases were searched to January 2004 using the following terms: spinal cord compression, nerve compression syndromes, spinal cord neoplasms, clinical trial, meta-analysis, and systematic review. RESULTS: Symptoms for MSCC include sensory changes, autonomic dysfunction, and back pain; however, back pain was not predictive of MSCC. The sensitivity and specificity for magnetic resonance imaging (MRI) range from 0.44 to 0.93 and 0.90 to 0.98, respectively, in the diagnosis of MSCC. The sensitivity and specificity for myelography range from 0.71 to 0.97 and 0.88 to 1.00, respectively. A randomized study detected higher ambulation rates in patients with MSCC who received high-dose dexamethasone before radiotherapy (RT) compared with patients who did not receive corticosteroids before RT (81% v 63% at 3 months, respectively; P = .046). There is no direct evidence that supports or refutes the type of surgery patients should have for the treatment of MSCC, whether surgical salvage should be attempted if patient is progressing on or shortly after RT, and whether patients with spinal instability should be treated with surgery. CONCLUSION: Patients with symptoms of MSCC should be managed to minimize treatment delay. MRI is the preferred imaging technique. Treatment for patients with MSCC should consider pretreatment ambulatory status, comorbidities, technical surgical factors, the presence of bony compression and spinal instability, potential surgical complications, potential RT reactions, and patient preferences.