Faculty Bibliography

Prostate cancer survivors approach 2.8 million in number and represent 1 in 5 of all cancer survivors in the United States. While guidelines exist for timely treatment and surveillance for recurrent disease, there is limited availability of guidelines that facilitate the provision of posttreatment clinical follow-up care to address the myriad of long-term and late effects that survivors may face. Based on recommendations set forth by a National Cancer Survivorship Resource Center expert panel, the American Cancer Society developed clinical follow-up care guidelines to facilitate the provision of posttreatment care by primary care clinicians. These guidelines were developed using a combined approach of evidence synthesis and expert consensus. Existing guidelines for health promotion, surveillance, and screening for second primary cancers were referenced when available. To promote comprehensive follow-up care and optimal health and quality of life for the posttreatment survivor, the guidelines address health promotion, surveillance for prostate cancer recurrence, screening for second primary cancers, long-term and late effects assessment and management, psychosocial issues, and care coordination among the oncology team, primary care clinicians, and nononcology specialists. A key challenge to the development of these guidelines was the limited availability of published evidence for management of prostate cancer survivors after treatment. Much of the evidence relies on studies with small sample sizes and retrospective analyses of facility-specific and population databases.

BACKGROUND:Treatment-related toxicity and quality of life (QoL) considerations are important when counseling patients with localized prostate cancer (PCa). OBJECTIVE:To determine the incidence and longitudinal pattern of late genitourinary (GU) toxicity and QoL after high-dose, intensity-modulated radiotherapy (IMRT). DESIGN, SETTING, AND PARTICIPANTS/METHODS:A total of 268 patients with localized PCa were treated between June 2004 and December 2008 at a tertiary referral center. Median follow-up was 5 yr (range: 3-7.7 yr). INTERVENTION/METHODS:Patients underwent IMRT to a total dose of 86.4Gy; 50% of patients underwent neoadjuvant and concurrent androgen-deprivation therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/METHODS:Patients were evaluated with the prospectively obtained International Prostate Symptom Score (IPSS) questionnaire. GU toxicity was also scored using the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0; toxicity events were defined as increase over baseline. Differences in increases in IPSS sums and QoL index between baseline IPSS sum and QoL index groups were analyzed using the Kruskal-Wallis and Mann-Whitney tests. Univariate and multivariate Cox regression models were applied. RESULTS AND LIMITATIONS/CONCLUSIONS:The overall median IPSS sum increase during follow-up was 3 and was less pronounced among patients with severe baseline symptoms compared with those with mild baseline symptoms (median increase: 0 vs 4; p<0.0001). Overall QoL index was unchanged after IMRT but appeared to improve in patients with dissatisfied baseline QoL compared with satisfied baseline QoL (p<0.0001). Fifty-five (20%) and 2 (1%) patients developed grade 2 and 3 late GU toxicities, respectively; however, in 28 of 57 patients (49%), toxicity resolved during follow-up. Even though the IPSS data were prospectively obtained, most patients were not treated within a prospective protocol. CONCLUSIONS:Late GU toxicity after high-dose IMRT was mild; severe, late GU toxicity was rare. Changes in IPSS sum and QoL index were dependent on the baseline GU function, which might be useful for future patient counseling.

BACKGROUND:The management of intermediate-risk prostate cancer (PCa) is controversial, in part due to the heterogeneous nature of patients falling within this classification. OBJECTIVE:We propose a new risk stratification system for intermediate-risk PCa to aid in prognosis and therapeutic decision making. DESIGN, SETTING, AND PARTICIPANTS/METHODS:Between 1992 and 2007, 1024 patients with National Comprehensive Cancer Network intermediate-risk PCa and complete biopsy information were treated with definitive external-beam radiation therapy (EBRT) utilizing doses ≥ 81 Gy. Unfavorable intermediate-risk (UIR) PCa was defined as any intermediate-risk patient with a primary Gleason pattern of 4, percentage of positive biopsy cores (PPBC) ≥ 50%, or multiple intermediate-risk factors (IRFs; cT2b-c, prostate-specific antigen [PSA] 10-20, or Gleason score 7). INTERVENTION/METHODS:All patients received EBRT with ≥ 81 Gy with or without neoadjuvant and concurrent androgen-deprivation therapy (ADT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/METHODS:Univariate and multivariate analyses were performed using a Cox proportional hazards model for PSA recurrence-free survival (PSA-RFS) and distant metastasis (DM). PCa-specific mortality (PCSM) was analyzed using a competing-risk method. RESULTS AND LIMITATIONS/CONCLUSIONS:Median follow-up was 71 mo. Primary Gleason pattern 4 (hazard ratio [HR]: 3.26; p<0.0001), PPBC ≥ 50% (HR: 2.72; p=0.0007), and multiple IRFs (HR: 2.20; p=0.008) all were significant predictors of increased DM in multivariate analyses. Primary Gleason pattern 4 (HR: 5.23; p<0.0001) and PPBC ≥ 50% (HR: 4.08; p=0.002) but not multiple IRFs (HR: 1.74; p=0.21) independently predicted for increased PCSM. Patients with UIR disease had inferior PSA-RFS (HR: 2.37; p<0.0001), DM (HR: 4.34; p=0.0003), and PCSM (HR: 7.39; p=0.007) compared with those with favorable intermediate-risk disease, despite being more likely to receive neoadjuvant ADT. Short follow-up and retrospective study design are the primary limitations. CONCLUSIONS:Intermediate-risk PCa is a heterogeneous collection of diseases that can be separated into favorable and unfavorable subsets. These groups likely will benefit from divergent therapeutic paradigms.

PURPOSE/OBJECTIVE:To assess radiotherapy (RT)-induced changes in the urethra and periurethral tissues after treatment for prostate cancer (PCa). METHODS AND MATERIALS/METHODS:This retrospective study included 108 men (median age, 64 years; range, 43-87 years) who received external-beam radiotherapy (EBRT) and/or brachytherapy for PCa and underwent endorectal-coil MRI of the prostate within 180 days before RT and a median of 20 months (range, 2-62 months) after RT. On all MRIs, two readers independently measured the urethral length (UL) and graded the margin definition (MD) of the urethral wall and the signal intensities (SIs) of the urethral wall and pelvic muscles on 4-point scales. RESULTS:The mean urethral length decreased significantly from pre- to post-RT MRI (from 15.2 to 12.6mm and from 14.4 to 12.9 mm for readers 1 and 2, respectively; both p-values <0.0001). Brachytherapy resulted in greater urethral shortening than EBRT. After RT, SI in the urethral wall increased in 57% (62/108) and 35% (38/108) of patients (readers 1 and 2, respectively). The frequency and magnitude of SI increase in pelvic muscles depended on muscle location. In the obturator internus muscle, SI increased more often after EBRT than after brachytherapy, while in the periurethral levator ani muscle SI increased more often after brachytherapy than after EBRT. CONCLUSION/CONCLUSIONS:After RT for PCa, MRI shows urethral shortening and increased SI of the urethral wall and pelvic muscles in substantial percentages of patients.