Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part III: Salvage Therapy After Radiotherapy or Focal Therapy, Pelvic Nodal Recurrence and Oligometastasis, and Future Directions.

PURPOSE: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part III of a three-part series focusing on evaluation and management of suspected non-metastatic recurrence after radiotherapy (RT) and focal therapy, evaluation and management of regional recurrence, management for molecular imaging metastatic recurrence, and future directions. Please refer to Part I for discussion of treatment decision-making and Part II for discussion of treatment delivery for non-metastatic biochemical recurrence (BCR) after radical prostatectomy (RP). MATERIALS AND METHODS: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. RESULTS: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Guideline Panel developed evidence- and consensus-based guideline statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. CONCLUSIONS: Continuous and deliberate efforts for multidisciplinary care in prostate cancer will be required to optimize and improve the oncologic and functional outcomes of patients treated with salvage therapies in the future.

Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part I: Introduction and Treatment Decision-Making at the Time of Suspected Biochemical Recurrence after Radical Prostatectomy.

PURPOSE: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part I of a three-part series focusing on treatment decision-making at the time of suspected biochemical recurrence (BCR) after radical prostatectomy (RP). Please refer to Part II for discussion of treatment delivery for non-metastatic BCR after RP and Part III for discussion of evaluation and management of recurrence after radiotherapy (RT) and focal therapy, regional recurrence, and oligometastasis. MATERIALS AND METHODS: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. RESULTS: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Panel developed evidence- and consensus-based statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. CONCLUSIONS: Advancing work in the area of diagnostic tools (particularly imaging), biomarkers, radiation delivery, and biological manipulation with the evolving armamentarium of therapeutic agents will undoubtedly present new opportunities for patients to experience long-term control of their cancer while minimizing toxicity.

Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part II: Treatment Delivery for Non-metastatic Biochemical Recurrence After Primary Radical Prostatectomy.

PURPOSE: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part II of a three-part series focusing on treatment delivery for non-metastatic biochemical recurrence (BCR) after primary radical prostatectomy (RP). Please refer to Part I for discussion of treatment decision-making and Part III for discussion of evaluation and management of recurrence after radiotherapy (RT) and focal therapy, regional recurrence, and oligometastasis. MATERIALS AND METHODS: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. RESULTS: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. CONCLUSIONS: Optimizing and personalizing the approach to salvage therapy remains an ongoing area of work in the field of genitourinary oncology and represents an area of research and clinical care that requires well-coordinated, multi-disciplinary efforts.

NCCN Guidelines® Insights: Bladder Cancer, Version 3.2024.

Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non-muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)-unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.

Prostate cancer - major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

Answer questions and earn CME/CNE The eighth edition of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) Staging Manual has been updated and improved to ensure the highest degree of clinical relevance and to improve its utility for patient evaluation and clinical research. Major changes include: 1) pathologically organ-confined disease is now considered pT2 and is no longer subclassified by extent of involvement or laterality, 2) tumor grading now includes both the Gleason score (as in the seventh edition criteria) and the grade group (introduced in the eighth edition criteria), 3) prognostic stage group III includes select, organ-confined disease based on prostate-specific antigen and Gleason/grade group status, and 4) 2 statistical prediction models are included in the staging manual. The AJCC will continue to critically analyze emerging prostate cancer biomarkers and tools for their ability to prognosticate and guide treatment decision making with the highest level of accuracy and confidence for patients and physicians. CA Cancer J Clin 2017;67:245-253. © 2017 American Cancer Society.

NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022.

The NCCN Guidelines for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer and other urinary tract cancers (upper tract tumors, urothelial carcinoma of the prostate, primary carcinoma of the urethra). These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines regarding the treatment of non-muscle-invasive bladder cancer, including how to treat in the event of a bacillus Calmette-Guérin (BCG) shortage; new roles for immune checkpoint inhibitors in non-muscle invasive, muscle-invasive, and metastatic bladder cancer; and the addition of antibody-drug conjugates for metastatic bladder cancer.

Syndrome of inappropriate secretion of antidiuretic hormone following high dose rate brachytherapy for prostate cancer: a case report.

BACKGROUND: The syndrome of inappropriate secretion of antidiuretic hormone is a disorder characterized by the excess release of antidiuretic hormone and can result in hyponatremia. If managed inappropriately, severe hyponatremia can cause seizures, cerebral edema, and even death. There are various known causes of this inappropriate release of antidiuretic hormone, including malignancy, CNS disorders, and disturbances in the hypothalamic-pituitary-renal axis. However, reports of syndrome of inappropriate secretion of antidiuretic hormone after brachytherapy for prostate cancer are exceedingly rare. CASE PRESENTATION: We report a case of symptomatic hyponatremia secondary to the inappropriate secretion of antidiuretic hormone after prostate high-dose rate brachytherapy under general anesthesia in a patient with adenocarcinoma of the prostate. CONCLUSIONS: In rare instances, inappropriate secretion of antidiuretic hormone can occur after high-dose rate brachytherapy for prostate cancer. The cause is likely multifactorial, involving pain or discomfort ensuing from the surgical procedure, the general anesthesia or intraoperative drugs administered. However, due to the potential severity of the side effects, timely diagnosis is crucial to ensure prompt, and effective management.

A personalized decision aid for prostate cancer shared decision making.

BACKGROUND: A shared decision-making model is preferred for engaging prostate cancer patients in treatment decisions. However, the process of assessing an individual's preferences and values is challenging and not formalized. The purpose of this study is to develop an automated decision aid for patient-centric treatment decision-making using decision analysis, preference thresholds and value elicitations to maximize the compatibility between a patient's treatment expectations and outcome. METHODS: A template for patient-centric medical decision-making was constructed. The inputs included prostate cancer risk group, pre-treatment health state, treatment alternatives (primarily focused on radiation in this model), side effects (erectile dysfunction, urinary incontinence, nocturia and bowel incontinence), and treatment success (5-year freedom from biochemical failure). A linear additive value function was used to combine the values for each attribute (side effects, success and the alternatives) into a value for all prospects. The patient-reported toxicity probabilities were derived from phase II and III trials. The probabilities are conditioned on the starting state for each of the side effects. Toxicity matrices for erectile dysfunction, urinary incontinence, nocturia and bowel incontinence were created for the treatment alternatives. Toxicity probability thresholds were obtained by identifying the patient's maximum acceptable threshold for each of the side effects. Results are represented as a visual. R and Rstudio were used to perform analyses, and R Shiny for application creation. RESULTS: We developed a web-based decision aid. Based on preliminary use of the application, every treatment alternative could be the best choice for a decision maker with a particular set of preferences. This result implies that no treatment has determinist dominance over the remaining treatments and that a preference-based approach can help patients through their decision-making process, potentially affecting compliance with treatment, tolerance of side effects and satisfaction with the decision. CONCLUSIONS: We present a unique patient-centric prostate cancer treatment decision aid that systematically assesses and incorporates a patient's preferences and values to rank treatment options by likelihood of achieving the preferred outcome. This application enables the practice and study of personalized medicine. This model can be expanded to include additional inputs, such as genomics, as well as competing, concurrent or sequential therapies.

Bladder Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non-muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non-muscle-invasive bladder cancer in the event of a bacillus Calmette-Guérin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.

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.

NCCN Guidelines Insights: Bladder Cancer, Version 5.2018.

The NCCN Clinical Practice Guidelines in Oncology for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer. These NCCN Guidelines Insights discuss important updates to the 2018 version of the guidelines, including implications of the 8th edition of the AJCC Cancer Staging Manual on treatment of muscle-invasive bladder cancer and incorporating newly approved immune checkpoint inhibitor therapies into treatment options for patients with locally advanced or metastatic disease.

Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The complete version of the NCCN Guidelines for Bladder Cancer addresses additional aspects of the management of bladder cancer, including non-muscle-invasive urothelial bladder cancer and nonurothelial histologies, as well as staging, evaluation, and follow-up.

NCCN Guidelines Insights: Bladder Cancer, Version 2.2016.

These NCCN Guidelines Insights discuss the major recent updates to the NCCN Guidelines for Bladder Cancer based on the review of the evidence in conjunction with the expert opinion of the panel. Recent updates include (1) refining the recommendation of intravesical bacillus Calmette-Guérin, (2) strengthening the recommendations for perioperative systemic chemotherapy, and (3) incorporating immunotherapy into second-line therapy for locally advanced or metastatic disease. These NCCN Guidelines Insights further discuss factors that affect integration of these recommendations into clinical practice.

Tadalafil for prevention of erectile dysfunction after radiotherapy for prostate cancer: the Radiation Therapy Oncology Group [0831] randomized clinical trial.

IMPORTANCE: Tadalafil is used to treat erectile dysfunction after prostate cancer treatment, but its role as a preventive agent is undefined. OBJECTIVES: To determine primarily whether tadalafil preserved erectile function in men treated with radiotherapy for prostate cancer, and secondarily to determine whether participant- or partner-reported overall sexual function and sexual and marital satisfaction were affected. DESIGN, SETTING, AND PARTICIPANTS: Stratified, placebo-controlled, double-blind, parallel-group study with 1:1 randomization at 76 community-based and tertiary medical sites in the United States and Canada. Two hundred forty-two participants with intact erectile function scheduled to receive radiotherapy for prostate cancer were recruited between November 2009 and February 2012 with follow-up through March 2013. INTERVENTIONS: One hundred twenty-one participants were assigned 5 mg of tadalafil daily and 121 were assigned placebo for 24 weeks starting with external radiotherapy (63%) or brachytherapy (37%). Participant-reported International Index of Erectile Function response before radiotherapy and at weeks 2 and 4, between weeks 20 and 24, between weeks 28 and 30, and 1 year thereafter. Participants and partners could respond also to the Sexual Adjustment Questionnaire and to the Locke Marital Adjustment Test before radiotherapy, between weeks 20 and 24 and weeks 28 and 30, and at 1 year. MAIN OUTCOMES AND MEASURES: Primary outcome was off-drug spontaneous erectile function 28 to 30 weeks after radiotherapy started. Secondary end points were spontaneous erection at 1 year; overall sexual function and satisfaction; marital adjustment; and partner-reported satisfaction and marital adjustment at 28 to 30 weeks and 1 year, predictors of tadalafil response; and adverse events. RESULTS: Among 221 evaluable participants, 80 (79%; 95% CI, 70%-88%) assigned to receive tadalafil retained erectile function between weeks 28 and 30 compared with 61 (74%; 95% CI, 63%-85%) assigned to receive placebo (P = .49); an absolute difference of 5% (95% CI, -9% to 19%). A significant difference was also not observed at 1 year (72%; 95% CI, 60%-84% vs 71%; 95% CI, 59%-84%; P = .93). Tadalafil was not associated with significantly improved overall sexual function or satisfaction; a significant difference was not observed in any domain subscale. Partners of men assigned tadalafil noted no significant effect on sexual satisfaction, and marital adjustment was not significantly improved in participants or partners. CONCLUSIONS AND RELEVANCE: Among men undergoing radiotherapy for prostate cancer, daily use of tadalafil compared with placebo did not result in improved erectile function. These findings do not support daily use of tadalafil to prevent erectile dysfunction in these patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00931528.

Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial.

BACKGROUND: We assessed effectiveness, safety, and tolerability of paclitaxel or fluorouracil when added to radiation plus cisplatin followed by adjuvant chemotherapy in a programme of selected bladder preservation for patients with muscle invasive bladder cancer. METHODS: In our randomised phase 2 trial, we enrolled patients with T2-4a transitional cell carcinoma of the bladder at 24 medical centres in the USA. We randomly allocated patients to receive paclitaxel plus cisplatin (paclitaxel group) or fluorouracil plus cisplatin (fluorouracil group) with twice-daily radiation in random block sizes per site on the basis of clinical T-stage (T2 vs T3-4). Patients and physicians were aware of treatment assignment. All patients had transurethral resection of bladder tumour and twice-daily radiotherapy to 40·3 Gy, along with allocated chemotherapy, followed by cystoscopic and biopsy assessment of response. Patients who had a tumour response with downstaging to T0, Tcis, or Ta received consolidation chemoradiotherapy to 64·3 Gy, with the same chemotherapy regimen as in the induction phase. Patients received adjuvant cisplatin-gemcitabine-paclitaxel after the end of chemoradiotherapy. If, after induction, persistent disease was graded as T1 or worse, we recommended patients undergo cystectomy and adjuvant chemotherapy. We assessed the primary endpoints of rates of treatment completion and toxic effects in all randomly allocated patients. This study is registered with ClinicalTrials.gov, number NCT00055601. FINDINGS: Between Dec 13, 2002, and Jan 11, 2008, we enrolled 97 patients, of whom 93 were eligible for analysis. Median follow-up was 5·0 years (IQR 5·0-6·2). Of 46 patients in the paclitaxel group, 45 (98%) completed induction (16 [35%] with grade 3-4 toxicity), 39 (85%) completed induction and consolidation (11 [24%] with grade 3-4 toxicity due to consolidation), and 31 (67%) completed the entire protocol with adjuvant chemotherapy. 34 (85%) of 40 assessable patients in the paclitaxel group had grade 3-4 toxicity during adjuvant chemotherapy. Of 47 patients in the fluorouracil group, 45 (96%) completed induction (nine [19%] with grade 3-4 toxicity), 39 (83%) completed induction and consolidation (12 [26%] had grade 3-4 toxicity due to consolidation), and 25 (53%) completed the entire protocol with adjuvant chemotherapy. 31 (76%) of 41 assessable patients in the fluorouracil group had grade 3-4 toxicity during adjuvant chemotherapy. Five (11%) patients treated with the paclitaxel regimen and three (6%) patients treated with the fluorouracil regimen developed late grade 3-4 radiotherapy toxicities. 11 (24%) patients treated with the paclitaxel regimen and 16 (34%) patients treated with the fluorouracil regimen developed late grade 3-4 toxicities unrelated to radiotherapy. One patient (in the fluorouracil group) died during follow-up. Six (13%) patients in the paclitaxel group and in three (6%) patients in the fluorouracil group discontinued due to treatment-related toxicity. INTERPRETATION: In the absence of phase 3 data, our findings could inform selection of a bladder-sparing trimodality chemotherapy regimen for patients with muscle invasive bladder cancer. FUNDING: US National Cancer Institute.

Noninferiority of Hypofractionated vs Conventional Postprostatectomy Radiotherapy for Genitourinary and Gastrointestinal Symptoms: The NRG-GU003 Phase 3 Randomized Clinical Trial.

Importance: No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy. Objective: To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years. Design, Setting, and Participants: In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (<0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed. Intervention: Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT). Main Outcomes and Measures: The coprimary end points were the 2-year change in score from baseline for the bowel and urinary domains of the Expanded Prostate Cancer Composite Index questionnaire. Secondary objectives were to compare between arms freedom from biochemical failure, time to progression, local failure, regional failure, salvage therapy, distant metastasis, prostate cancer-specific survival, overall survival, and adverse events. Results: Of the 296 patients randomized (median [range] age, 65 [44-81] years; 100% male), 144 received HYPORT and 152 received COPORT. At the end of RT, the mean GU change scores among those in the HYPORT and COPORT arms were neither clinically significant nor different in statistical significance and remained so at 6 and 12 months. The mean (SD) GI change scores for HYPORT and COPORT were both clinically significant and different in statistical significance at the end of RT (-15.52 [18.43] and -7.06 [12.78], respectively; P < .001). However, the clinically and statistically significant differences in HYPORT and COPORT mean GI change scores were resolved at 6 and 12 months. The 24-month differences in mean GU and GI change scores for HYPORT were noninferior to COPORT using noninferiority margins of -5 and -6, respectively, rejecting the null hypothesis of inferiority (mean [SD] GU score: HYPORT, -5.01 [15.10] and COPORT, -4.07 [14.67]; P = .005; mean [SD] GI score: HYPORT, -4.17 [10.97] and COPORT, -1.41 [8.32]; P = .02). With a median follow-up for censored patients of 2.1 years, there was no difference between HYPORT vs COPORT for biochemical failure, defined as a PSA of 0.4 ng/mL or higher and rising (2-year rate, 12% vs 8%; P = .28). Conclusions and Relevance: In this randomized clinical trial, HYPORT was associated with greater patient-reported GI toxic effects compared with COPORT at the completion of RT, but both groups recovered to baseline levels within 6 months. At 2 years, HYPORT was noninferior to COPORT in terms of patient-reported GU or GI toxic effects. HYPORT is a new acceptable practice standard for patients receiving postprostatectomy radiotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03274687.

The impact of dose-escalated radiotherapy plus androgen deprivation for prostate cancer using 2 linked nomograms.

BACKGROUND: Randomized trials have demonstrated that escalated-dose external-beam radiotherapy (EDRT) is better than standard-dose radiotherapy (SDRT) for patients with prostate cancer and that adding androgen-deprivation therapy (ADT) to SDRT is better than SDRT alone; however, no trials have compared EDRT versus SDRT plus ADT or EDRT versus EDRT plus ADT. The authors designed a model to estimate the results of various doses of radiotherapy (RT) combined with various durations of ADT. METHODS: From 1989 to 2007, 3215 men consecutively received definitive EDRT with or without ADT. In total, 2012 patients had complete records available for creating the nomogram. The duration of ADT varied for patients who received no RT (n = 1562), ≤6 months of RT (n = 145), from >6 months to <24 months of RT (n = 140), and ≥24 months of RT (n = 165) with a median follow-up of 65.7 months, 66.2 months, 60.1 months, and 63 months, respectively. The model included the following covariates: palpation T-category, biopsy Gleason score, the percentage of tumor cells with a Gleason pattern of 4 or 5, the percentage of tumor tissue, initial pretreatment prostate-specific antigen (PSA) level, ADT duration, and RT dose. Two nomograms, for outcomes with and without ADT, were created from a single competing-risks model. Biochemical failure was defined as a rise in serum PSA of 2 ng/mL over the post-treatment PSA nadir. RESULTS: According to the results from analyzing representative intermediate-risk to high-risk patient parameters, the gains from increasing the RT dose from 70 Gray (Gy) to 80 Gy were far less than the gains from adding ≥3 months of ADT. CONCLUSIONS: The nomograms provided unique patient-specific estimates of the effects of various doses and durations of RT and ADT. The results indicated that adding ADT to treatment for intermediate-risk and high-risk prostate cancer is far more beneficial than a modest RT dose escalation.

Gleason scoring at a comprehensive cancer center: what's the difference?

This study attempted to determine whether the Gleason score (GS) assigned at a comprehensive cancer center better predicts risk of biochemical failure (BF) after prostate radiotherapy compared with the GS of the referring institution (RI). Between 1994 and 2007, 1649 men received radiotherapy for prostate cancer at Fox Chase Cancer Center (FCCC). The Cox proportional hazard regression was used for inferences about the relationship of time to BF and GS. Harrell's C-index (HCI) was used to assess concordance in the Cox regression between predicted and observed events. The discordance rate was 26% for any change in either major or minor Gleason pattern. In the RI GS 2 through 6 group, 79 (8%) patients were upgraded to GS 7. Twenty percent of patients with RI GS 7 were downgraded and 2% were upgraded. In the RI GS 8 through 9 group, 58% were downgraded to GS 6 (12%) or GS 7 (88%). The FCCC GS altered the NCCN risk group assignment in 144 men (9%): 92 (64%) men to lower risk and 52 (36%) to higher risk. FCCC GS was a stronger predictor of BF; the hazard ratios for GS 2 through 6 (ref), 3+4, 4+3, and 8 through 9 were 1.00 (ref), 1.82, 4.14, and 2.92, respectively. In contrast, the hazard ratios for the RI GS were 1.00 (ref), 1.53, 2.44, and 1.76, respectively. FCCC GS (HCI=0.76) had improved performance compared with RI GS (HCI=0.74). Changes in GS were common and the GS assigned by a comprehensive cancer center provided better BF risk stratification and prognostication for patients. Changes in GS may impact treatment recommendations in 9% to 26% of patients.

Long-Term Results of a Phase 3 Randomized Prospective Trial of Erectile Tissue-Sparing Intensity-Modulated Radiation Therapy for Men With Clinically Localized Prostate Cancer.

PURPOSE: The objective of this study was to determine whether limiting the doses delivered to the penile bulb (PB) and corporal bodies with intensity modulated radiation therapy (IMRT) preserves erectile function compared with standard IMRT in men with prostate cancer. METHODS AND MATERIALS: A total of 117 patients with low- to intermediate-risk, clinical T1a-T2c prostate adenocarcinoma were enrolled in a single-institution, prospective, single-blind, phase 3 randomized trial. All received definitive IMRT to 74 to 80 Gy in 37 to 40 fractions and standard IMRT (s-IMRT) or erectile tissue-sparing IMRT (ETS-IMRT), which placed additional planning constraints that limited the D90 to the penile bulb and corporal bodies to ≤15 Gy and ≤7 Gy, respectively. Erectile potency was assessed with components of the International Index of Erectile Function and phosphodiesterase type 5 inhibitor (PDE5) medication records. RESULTS: Sixty-two patients received ETS-IMRT, and 54 received s-IMRT; 1 patient did not receive radiation therapy. Before treatment, all patients reported erectile potency. No patients received androgen deprivation therapy. In the intention-to-treat analysis, treatment arms did not differ in potency preservation at 24 months (37.1% ETS-IMRT vs 31.5% s-IMRT, P = .53). Of 85 evaluable patients with International Index of Erectile Function and PDE5 medication follow-up, erectile potency was seen in 47.9% of patients in the ETS-IMRT arm and 46.0% of patients in the s-IMRT arm (P = .86). PDE5 inhibitors were initiated in 41.7% of ETS-IMRT patients and 35.1% of s-IMRT patients (P = .54). Among all patients enrolled, there was no difference in freedom from biochemical failure between those treated with ETS-IMRT and s-IMRT (5-year 91.8% vs 90.7%, respectively, P = .77), with a median follow-up of 7.4 years. There were no differences in acute or late gastrointestinal or genitourinary toxicity. An unplanned per-protocol analysis demonstrated no differences in potency preservation or secondary endpoints between patients who exceeded erectile tissue-sparing constraints and those who met constraints, although power was limited by attrition and unplanned dosimetric crossover. CONCLUSIONS: ETS-IMRT that strictly limits dose to the penile bulb and corporal bodies is safe and feasible. Use of this planning technique did not show an effect on potency preservation outcomes at 2 years, though power to detect a difference was limited.

Salvage prostate brachytherapy in radiorecurrent prostate cancer: An international Delphi consensus study.

BACKGROUND AND PURPOSE: Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. MATERIALS AND METHODS: International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%. RESULTS: Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2-3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. CONCLUSION: Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study.