Ahmed E. Abugharib

Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival

Purpose: Early salvage radiotherapy following radical prostatectomy for prostate cancer is commonly advocated in place of adjuvant radiotherapy. We aimed to determine the optimal definition of early salvage radiotherapy. Materials and Methods: We performed a multi‐institutional retrospective study of 657 men who underwent salvage radiotherapy between 1986 and 2013. Two comparisons were made to determine the optimal definition of early salvage radiotherapy, including 1) the time from radical prostatectomy to salvage radiotherapy (less than 9, 9 to 21, 22 to 47 or greater than 48 months) and 2) the level of detectable pre‐salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 or greater than 0.5 ng/ml). Outcomes included freedom from salvage androgen deprivation therapy, and biochemical relapse‐free, distant metastases‐free and prostate cancer specific survival. Results: Median followup was 9.8 years. Time from radical prostatectomy to salvage radiotherapy did not correlate with 10‐year biochemical relapse‐free survival rates (R2 = 0.18). Increasing pre‐salvage radiotherapy prostate specific antigen strongly correlated with biochemical relapse‐free survival (R2 = 0.91). Increasing detectable pre‐salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 and greater than 0.5 ng/ml) predicted worse 10‐year biochemical relapse‐free survival (62%, 44% and 27%), freedom from salvage androgen deprivation therapy (77%, 66% and 49%), distant metastases‐free survival (86%, 79% and 66%, each p <0.001) and prostate cancer specific survival (93%, 89% and 80%, respectively, p = 0.001). On multivariable analysis early salvage radiotherapy (prostate specific antigen greater than 0.2 to 0.5 ng/ml) was associated with a twofold increase in biochemical failure, use of salvage androgen deprivation therapy and distant metastases compared to very early salvage radiotherapy (prostate specific antigen 0.01 to 0.2 ng/ml). Conclusions: The duration from radical prostatectomy to salvage radiotherapy is not independently prognostic for outcomes after salvage radiotherapy and it should not be used to define early salvage radiotherapy. Grouping all patients with pre‐salvage radiotherapy prostate specific antigen 0.5 ng/ml or less may be inadequate to define early salvage radiotherapy and it has a relevant impact on ongoing and future clinical trials.

Independent validation of the prognostic capacity of the ISUP prostate cancer grade grouping system for radiation treated patients with long-term follow-up

Background:There has been a recent proposal to change the grading system of prostate cancer into a five-tier grade grouping system. The prognostic impact of this has been demonstrated in regards only to biochemical recurrence-free survival (bRFS) with short follow-up (3 years).Methods:Between 1990 and 2013, 847 consecutive men were treated with definitive external beam radiation therapy at a single academic center. To validate the new grade grouping system, bRFS, distant metastases-free survival (DMFS) and prostate cancer-specific survival (PCSS) were calculated. Adjusted Kaplan–Meier and multivariable Cox regression analyses were performed to assess the independent impact of the new grade grouping system. Discriminatory analyses were performed to compare the commonly used three-tier Gleason score system (6, 7 and 8–10) to the new system.Results:The median follow-up of our cohort was 88 months. The 5-grade groups independently validated differing risks of bRFS (group 1 as reference; adjusted hazard ratio (aHR) 1.35, 2.16, 1.79 and 3.84 for groups 2–5, respectively). Furthermore, a clear stratification was demonstrated for DMFS (aHR 2.03, 3.18, 3.62 and 13.77 for groups 2–5, respectively) and PCSS (aHR 3.00, 5.32, 6.02 and 39.02 for groups 2–5, respectively). The 5-grade group system had improved prognostic discrimination for all end points compared with the commonly used three-tiered system (that is, Gleason score 6, 7 and 8–10).Conclusions:In a large independent radiotherapy cohort with long-term follow-up, we have validated the bRFS benefit of the proposed five-tier grade grouping system. Furthermore, we have demonstrated that the system is highly prognostic for DMFS and PCSS. Grade group 5 had markedly worse outcomes for all end points, and future work is necessary to improve outcomes in these patients.

Predictors of multidomain decline in health‐related quality of life after stereotactic body radiation therapy (SBRT) for prostate cancer

Stereotactic body radiation therapy (SBRT) for localized prostate cancer involves high‐dose‐per‐fraction radiation treatments. Its use is increasing, but concerns remain about treatment‐related toxicity. The authors assessed the incidence and predictors of a global decline in health‐related quality of life (HRQOL) after prostate SBRT.

Programmed Death-ligand 1 Expression in Upper Tract Urothelial Carcinoma

BACKGROUND Urothelial carcinoma (UC) is the most common malignancy of the urinary tract. Upper tract (renal pelvis and ureter) urothelial carcinomas (UTUC) account for approximately 5% of UCs but a significant subset are invasive and associated with poor clinical outcomes. OBJECTIVE To evaluate programmed death-ligand 1 (PD-L1) expression in UTUC. DESIGN, SETTING, AND PARTICIPANTS UTUC cases from 1997-2016 were retrospectively identified from the surgical pathology database at a single large academic institution. The cohort included 149 cases: 27 low-grade and 24 high-grade pathologic T (pT)a, 29 pT1, 23 pT2, 38 pT3, and eight pT4. PD-L1 immunohistochemistry (IHC) was performed on representative whole tumor sections using anti-PD-L1 primary antibody clone 5H1. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS PD-L1 expression was evaluated using a previously established cut-off for positivity (≥ 5% membranous staining). Association between PD-L1 IHC expression and clinicopathologic parameters was examined with Fishers exact test; the effect of PD-L1 expression on cancer-specific mortality was assessed using the Cox proportional hazard model. RESULTS AND LIMITATIONS Approximately one-third (32.7%) of invasive primary UTUC and 23.5% of all primary UTUC (invasive and noninvasive tumors) demonstrated positive PD-L1 expression. Positive PD-L1 expression was associated with high histologic grade, high pathologic stage, and angiolymphatic invasion. Cancer-specific survival was not significantly associated with positive PD-L1 expression using a 5% cut-off. Study limitations include the retrospective nature and the fact that PD-L1 expression by IHC is an imperfect surrogate for response to therapy. CONCLUSIONS Positive PD-L1 expression in approximately one-third of primary invasive UTUC and association with high-risk clinicopathologic features provide a rational basis for further investigation of PD-L1-based immunotherapeutics in these patients. PATIENT SUMMARY Upper tract urothelial carcinoma is often associated with poor clinical outcome. While current treatment options for advanced upper tract urothelial carcinoma are limited, programmed death-ligand 1 positivity in approximately one-third of invasive tumors provides a rational basis for further investigation of programmed death-ligand 1-based immunotherapeutics in these patients.

Erectile function after stereotactic body radiotherapy for localized prostate cancer

To elucidate the functional erection rate after prostate stereotactic body radiotherapy (SBRT) and to develop a comprehensive prognostic model of outcomes after treatment.

Natural history of 'second' biochemical failure after salvage radiation therapy for prostate cancer: A multi-institution study

To describe the natural history of prostate cancer in men who experience a second biochemical recurrence (BCR) after salvage radiotherapy (SRT) after prostatectomy.

Impact of xerostomia and dysphagia on health-related quality of life for head and neck cancer patients

ABSTRACT Introduction: Over the last two decades there have been dramatic intensifications in the treatment of head and neck cancer with altered fractionation or concurrent chemotherapy, both of which have been shown to improve survival at the cost of increased toxicity. Specifically, xerostomia and dysphagia negatively impact health-related quality of life (HR-QOL), and incorporation of modern radiotherapy techniques including intensity-modulated radiotherapy and volumetric arc radiotherapy have been designed to mitigate toxicity and impaired HR-QOL. Areas covered: We review the measurement of toxicity and HR-QOL, the impact of xerostomia and dysphagia on HR-QOL, and methods of preserving HR-QOL after head and neck radiotherapy. We also discuss the implications on HR-QOL of de-intensification trials for favorable-risk human papilloma virus related oropharyngeal cancer as well as a randomized trial comparing photon and proton therapy for oropharygeal cancer patients. The role of salivary stem cells and their potential impact on HR-QOL is explored. Expert commentary: With the rise of favorable-risk oropharyngeal cancer, the importance of HR-QOL in these patients has become paramount. Approaches to improve radiation-related xerostomia and dysphagia are emerging from both the physics and biological realms, but these approaches must demonstrate HR-QOL gains with sufficient rigor to justify their use in clinical practice.

Anatomical patterns of recurrence following biochemical relapse after post‐prostatectomy salvage radiation therapy: a multi‐institutional study

To characterise the frequency and detailed anatomical sites of failure for patients receiving post‐radical prostatectomy (RP) salvage radiation therapy (SRT).