Faculty Bibliography

Selecting the "optimal therapy" for the patient with localized prostate cancer may be one of the most challenging medical decisions facing the oncologist. Most patients will have a number of appropriate therapeutic options available to them. Before determining which therapy is most appropriate for a patient, a critical question which needs to be asked is whether any therapy is necessary, especially for those who present with early-stage, low-grade, low-volume disease. Furthermore, given the lack of randomized trials available to guide physicians regarding the superiority of one therapy over another, it is important to consider the different side-effect profiles relevant for each treatment modality. The potential toxicities of therapy impact quality-of-life outcomes and play an important role for most patients in their individual selection of a particular therapy. In addition, there are other important issues that need to be considered, which include the medical condition of the patient and emotional and psychological considerations, as well as family/peer viewpoints or perceived notions of a particular therapy. This review will discuss the relevant issues in the decision making and treatment selection for the patient.

UNLABELLED:Study Type--Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Radiation Therapy for prostate cancer can increase the risk for the development of second cancers after treatment. This study highlights the fact that such second cancers within the pelvis do occur but are not as common as previously reported. In this report we also note that even among patients who develop second cancers, if detected earlier, the majority are alive 5 years after the diagnosis. OBJECTIVE:• To report on the incidence of secondary malignancy (SM) development after external beam radiotherapy (EBRT) and brachytherapy (BT) for prostate cancer and to compare this with a cohort contemporaneously treated with radical prostatectomy (RP). MATERIALS AND METHODS/METHODS:• Between 1998 and 2001, 2658 patients with localized prostate cancer were treated with RP (n = 1348), EBRT (n = 897) or BT (n = 413). • Using the RP cohort as a control we compared the incidence of SMs, such as rectal or bladder cancers noted within the pelvis, and the incidence of extrapelvic SMs. RESULTS:• The 10-year SM-free survival for the RP, BT and EBRT cohorts were 89%, 87%, and 83%, respectively (RP vs EBRT, P = 0.002; RP vs BT, P = 0.37). • The 10-year likelihoods for bladder or colorectal cancer SM development in the RP, BT and EBRT groups were 3%, 2% and 4%, respectively (P = 0.29). • Multivariate analysis of predictors for development of all SMs showed that older age (P = 0.01) and history of smoking (P < 0.001) were significant predictors for the development of a SM, while treatment intervention was not found to be a significant variable. • Among 243 patients who developed a SM, the 5-year likelihood of SM-related mortality among patients with SMs in the EBRT and BT groups was 43.7% and 15.6%, respectively, compared with 26.3% in the RP cohort; P = 0.052). CONCLUSIONS:• The incidence of SM after radiotherapy was not significantly different from that after RP when adjusted for patient age and smoking history. • The incidence of bladder and rectal cancers was low for both EBRT- and BT-treated patients. • Among patients who developed a SM, the likelihood of mortality related to the SM was not significantly different among the treatment cohorts.

PURPOSE/OBJECTIVE:To investigate the utility of endorectal coil magenetic resonance imaging (eMRI) in predicting biochemical relapse in prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. METHODS AND MATERIALS/METHODS:Between 2000 and 2008, 279 men with intermediate- or high-risk prostate cancer underwent eMRI of their prostate before receiving brachytherapy and supplemental intensity-modulated radiotherapy. Endorectal coil MRI was performed before treatment and retrospectively reviewed by two radiologists experienced in genitourinary MRI. Image-based variables, including tumor diameter, location, number of sextants involved, and the presence of extracapsular extension (ECE), were incorporated with other established clinical variables to predict biochemical control outcomes. The median follow-up was 49 months (range, 1-13 years). RESULTS:The 5-year biochemical relapse-free survival for the cohort was 92%. Clinical findings predicting recurrence on univariate analysis included Gleason score (hazard ratio [HR] 3.6, p = 0.001), PSA (HR 1.04, p = 0.005), and National Comprehensive Cancer Network risk group (HR 4.1, p = 0.002). Clinical T stage and the use of androgen deprivation therapy were not correlated with biochemical failure. Imaging findings on univariate analysis associated with relapse included ECE on MRI (HR 3.79, p = 0.003), tumor size (HR 2.58, p = 0.04), and T stage (HR 1.71, p = 0.004). On multivariate analysis incorporating both clinical and imaging findings, only ECE on MRI and Gleason score were independent predictors of recurrence. CONCLUSIONS:Pretreatment eMRI findings predict for biochemical recurrence in intermediate- and high-risk prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Gleason score and the presence of ECE on MRI were the only significant predictors of biochemical relapse in this group of patients.

PURPOSE/OBJECTIVE:To compare toxicity profiles and biochemical tumor control outcomes between patients treated with high-dose image-guided radiotherapy (IGRT) and high-dose intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer. MATERIALS AND METHODS/METHODS:Between 2008 and 2009, 186 patients with prostate cancer were treated with IGRT to a dose of 86.4 Gy with daily correction of the target position based on kilovoltage imaging of implanted prostatic fiducial markers. This group of patients was retrospectively compared with a similar cohort of 190 patients who were treated between 2006 and 2007 with IMRT to the same prescription dose without, however, implanted fiducial markers in place (non-IGRT). The median follow-up time was 2.8 years (range, 2-6 years). RESULTS:A significant reduction in late urinary toxicity was observed for IGRT patients compared with the non-IGRT patients. The 3-year likelihood of grade 2 and higher urinary toxicity for the IGRT and non-IGRT cohorts were 10.4% and 20.0%, respectively (p = 0.02). Multivariate analysis identifying predictors for grade 2 or higher late urinary toxicity demonstrated that, in addition to the baseline Internatinoal Prostate Symptom Score, IGRT was associated with significantly less late urinary toxicity compared with non-IGRT. The incidence of grade 2 and higher rectal toxicity was low for both treatment groups (1.0% and 1.6%, respectively; p = 0.81). No differences in prostate-specific antigen relapse-free survival outcomes were observed for low- and intermediate-risk patients when treated with IGRT and non-IGRT. For high-risk patients, a significant improvement was observed at 3 years for patients treated with IGRT compared with non-IGRT. CONCLUSIONS:IGRT is associated with an improvement in biochemical tumor control among high-risk patients and a lower rate of late urinary toxicity compared with high-dose IMRT. These data suggest that, for definitive radiotherapy, the placement of fiducial markers and daily tracking of target positioning may represent the preferred mode of external-beam radiotherapy delivery for the treatment of prostate cancer.

PURPOSE/OBJECTIVE:To review the impact of high-dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases-free survival, and to identify clinical and pathologic predictors of outcomes. METHODS AND MATERIALS/METHODS:During 1988-2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose ≥66 Gy, of whom 205 (72%) received doses ≥70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. RESULTS:The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p < 0.01), negative surgical margins (p < 0.01), presalvage PSA level >0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score ≥7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose ≥70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose ≥70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07). CONCLUSION/CONCLUSIONS:Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in patients with greater burden of disease at time of SRT as reflected by either radiographic imaging or a greater PSA level. Salvage radiation doses ≥70 Gy may ultimately be most beneficial in these patients, but this needs to be further studied.

Selecting the "optimal therapy" for the patient with localized prostate cancer may be one of the most challenging medical decisions facing the oncologist. Most patients will have a number of appropriate therapeutic options available to them. Before determining which therapy is most appropriate for a patient, a critical question which needs to be asked is whether any therapy is necessary, especially for those who present with early-stage, low-grade, low-volume disease. Furthermore, given the lack of randomized trials available to guide physicians regarding the superiority of one therapy over another, it is important to consider the different side-effect profiles relevant for each treatment modality. The potential toxicities of therapy impact quality-of-life outcomes and play an important role for most patients in their individual selection of a particular therapy. In addition, there are other important issues that need to be considered, which include the medical condition of the patient and emotional and psychological considerations, as well as family/peer viewpoints or perceived notions of a particular therapy. This review will discuss the relevant issues in the decision making and treatment selection for the patient.

PURPOSE/OBJECTIVE:To report the incidence and excess risk of second malignancy (SM) development compared with the general population after external beam radiotherapy (EBRT) and brachytherapy to treat prostate cancer. METHODS AND MATERIALS/METHODS:Between 1998 and 2001, 1,310 patients with localized prostate cancer were treated with EBRT (n = 897) or brachytherapy (n = 413). We compared the incidence of SMs in our patients with that of the general population extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results data set combined with the 2000 census data. RESULTS:The 10-year likelihood of SM development was 25% after EBRT and 15% after brachytherapy (p = .02). The corresponding 10-year likelihood for in-field SM development in these groups was 4.9% and 1.6% (p = .24). Multivariate analysis showed that EBRT vs. brachytherapy and older age were the only significant predictors for the development of all SMs (p = .037 and p = .030), with a trend for older patients to develop a SM. The increased incidence of SM for EBRT patients was explained by the greater incidence of skin cancer outside the radiation field compared with that after brachytherapy (10.6% and 3.3%, respectively, p = .004). For the EBRT group, the 5- and 10-year mortality rate was 1.96% and 5.1% from out-of field cancer, respectively; for in-field SM, the corresponding mortality rates were 0.1% and 0.7%. Among the brachytherapy group, the 5- and 10-year mortality rate related to out-of field SM was 0.8% and 2.7%, respectively. Our observed SM rates after prostate RT were not significantly different from the cancer incidence rates in the general population. CONCLUSIONS:Using modern sophisticated treatment techniques, we report low rates of in-field bladder and rectal SM risks after prostate cancer RT. Furthermore, the likelihood of mortality secondary to a SM was unusual. The greater rate of SM observed with EBRT vs. brachytherapy was related to a small, but significantly increased, number of skin cancers in the EBRT patients compared with that of the general population.