Brachytherapy-Based Radiotherapy and Radical Prostatectomy Are Associated With Similar Survival in High-Risk Localized Prostate Cancer.

Purpose There are no randomized trials to guide treatment decisions between radiotherapeutic and surgical options for patients with high-risk localized prostate cancer. Comparative studies have been limited by their ability to match patients on the basis of pretreatment prognostic variables and to adjust for the cancer-related, medical, and socioeconomic differences between patients who choose radiotherapeutic or surgical approaches. Methods We analyzed the outcome of all patients in the National Cancer Database with high-risk, clinically localized prostate cancer with complete prognostic data who were treated with either radical prostatectomy (RP), external beam radiotherapy (EBRT) combined with androgen deprivation (AD), or EBRT plus brachytherapy with or without AD. Inverse probability of treatment weighting was used to adjust for covariable imbalance among treatment groups. The weighted time-dependent Cox proportional hazards model was then used to estimate the effects of treatment groups on survival, accounting for differential treatment initiation times. A predictive model of pathologic nodal (pLN) status was built using prostate-specific antigen level, Gleason score, and clinical T stage; predicted pLN status was used to repeat the inverse probability of treatment weighting and time-dependent Cox proportional hazards model. Results A total of 42,765 patients were analyzed. There was no statistically significant difference in survival between RP and EBRT plus brachytherapy with or without AD (hazard ratio [HR], 1.17; 95% CI, 0.88 to 1.55). However, EBRT plus AD was associated with higher mortality than RP (HR, 1.53; 95% CI, 1.22 to 1.92). Adjustment for predicted pLN status did not yield statistically different results. A sensitivity analysis showed that EBRT plus AD ≥ 7920 cGy narrowed the difference, but a significantly higher mortality remained (HR, 1.33; 95% CI, 1.05 to 1.68). Conclusion After comprehensively adjusting for imbalances in prostate cancer prognostic factors, other medical conditions, and socioeconomic factors, this analysis showed no statistical difference in survival between patients treated with RP versus EBRT plus brachytherapy with or without AD. EBRT plus AD was associated with lower survival.

Late small bowel toxicity after aggressive abdominopelvic intensity modulated radiation therapy.

PURPOSE: We retrospectively analyzed late small bowel toxicity in patients who received abdominal or pelvic intensity modulated radiation therapy (IMRT) to the small bowel with a maximum dose greater than the generally accepted maximal tolerable dose of 45 Gy. METHODS AND MATERIALS: All patients (N = 94) who received IMRT with a point dose of at least 45 Gy to tightly contoured small bowel between 2005 and 2014 at our institution were included. The median prescribed treatment dose was 70.2 Gy. The median follow-up was 20.1 months. Late small bowel toxicity was assessed using the Common Terminology Criteria for Adverse Events Version 3.0. Dosimetric variables and clinical factors were assessed for their relationship to small bowel toxicity. RESULTS: The median maximal small bowel point dose (Dmax) was 6546.5 cGy. The estimated 5-year rates of freedom from at least grade 1, at least grade 2, and at least grade 3 late small bowel toxicity were 72.4% (95% confidence interval [CI], 60.7%-86.5%), 91.9% (95% CI, 84.1%-100%), and 93.6% (95% CI, 86.2%-100%), respectively. One patient (1.1%) developed grade 3 late toxicity, and 2 patients (2.1%) developed grade 4 late toxicity. Use of capecitabine/5-fluorouracil treatment was a significant predictor (P < 0.001) of at least grade 1 and at least grade 2 small bowel toxicity. No other clinical factors were associated with toxicity. None of the dose-volume parameters were significant predictors of small bowel toxicity. CONCLUSION: It may be possible with IMRT to deliver high doses to small volumes of small bowel with low rates of significant long-term complications. Further studies should explore tolerable dose-volume relationships in cases in which aggressive abdominal or pelvic treatment may be warranted to treat the underlying malignancy.

Phase I/II prospective trial of cancer-specific imaging using ultrasound spectrum analysis tissue-type imaging to guide dose-painting prostate brachytherapy.

PURPOSE: To assess the technical feasibility, toxicity, dosimetry, and preliminary efficacy of dose-painting brachytherapy guided by ultrasound spectrum analysis tissue-type imaging (TTI) in low-risk, localized prostate cancer. METHODS AND MATERIALS: Fourteen men with prostate cancer who were candidates for brachytherapy as sole treatment were prospectively enrolled. Treatment planning goal was to escalate the tumor dose to 200% with a modest de-escalation of dose to remaining prostate compared with our standard. Primary end points included technical feasibility of TTI-guided brachytherapy and equivalent or better toxicity compared with standard brachytherapy. Secondary end points included dose escalation to tumor regions and de-escalated dose to nontumor regions on the preimplant plan, negative prostate biopsy at 2 years, and freedom from biochemical failure. RESULTS: Thirteen of fourteen men successfully completed the TTI-guided brachytherapy procedure for a feasibility rate of 93%. A software malfunction resulted in switching one patient from TTI-guided to standard brachytherapy. An average of 2.7 foci per patient was demonstrated and treated with an escalated dose. Dosimetric goals on preplan were achieved. One patient expired from unrelated causes 65 days after brachytherapy. Toxicity was at least as low as standard brachytherapy. Two-year prostate biopsies were obtained from six men; five (83%) were definitively negative, one showed evidence of disease with treatment effect, and none were positive. No patients experienced biochemical recurrence after a median followup of 31.5 (24-52) months. CONCLUSIONS: We have demonstrated that TTI-guided dose-painting prostate brachytherapy is technically feasible and results in clinical outcomes that are encouraging in terms of low toxicity and successful biochemical disease control.

The Impact of Economic Recession on the Incidence and Treatment of Cancer.

PURPOSE: The impact of economic recessions on the incidence and treatment of cancer is unknown. We test the hypothesis that cancer incidence and treatment rates decrease during a recession, and that this relationship is more pronounced in cancers that present with mild, more easily ignored symptoms. METHODS AND MATERIALS: Data on incidence and treatment for all cancers, and breast and pancreatic cancers specifically, from 1973-2008, were collected using Surveillance Epidemiology and End RESULTS (SEER). The data was adjusted for race, income, and education. Unemployment rate was used as the measure of economic recession. Data was log-transformed, and multivariate linear mixed regression was used. RESULTS: Adjusting for socioeconomic factors, the data revealed a significant inverse correlation between unemployment and rates of cancer incidence and treatment. Every 1% increase in unemployment was associated with a 2.2% (95% CI: 1.6-2.8%, p<0.001) reduction in cancer incidence, a 2.0% (1.2-2.8%, p=0.0157) decrease in surgery, and a 9.1% (8.2-10.0% p<0.001) decrease in radiation therapy (RT). Breast cancer incidence and treatment had a dramatic inverse relationship - 7.2% (6.3-8.1%), 6.7% (5.7-7.6%), and 19.0% (18.1-19.8%), respectively (p<0.001 for all). The decrease in incidence was only significant for in situ and localized tumors, but not in regional or distant breast cancer. Compared to breast cancer, pancreatic cancer had a weaker relationship between unemployment and incidence: 2.6% (1.8-3.3%, p=0.0005), surgery: 2.4% (2.0-2.7%, p<0.001), and RT: 1.9% (1.5-2.2% p<0.001). CONCLUSIONS: Increasing unemployment rates are associated with a decrease in the incidence and treatment of all cancers. This effect is exaggerated in breast cancer, where symptoms can more easily be ignored and where there are widely used screening tests relative to pancreatic cancer.

Cancer trends among the extreme elderly in the era of cancer screening.

BACKGROUND: The extreme elderly (EE; >84 years) are among the fastest growing segments of the population and bear a substantial cancer burden. We examined cancer incidence and cancer specific mortality changes among the EE during the implementation of cancer screening from the 1980s to 2000s. METHODS: We examined incidence and mortality rates for breast, colon, prostate, and lung cancer by age group between 1973 and 2009 in the SEER database. We compared incidence/mortality between EE and middle aged (MA; age 50-69) patients. RESULTS: Prostate cancer incidence and mortality rose and then, in the early 1990s, declined (-3.61%/year and -2.91%/year, respectively) among EE. Prostate cancer incidence rose steadily throughout the study period for MA. Breast cancer incidence rose and then declined for both MA and EE, with the decline starting in 1990 for EE (-1.34%/year), and 1998 for MA (-1.24%/year). Both age groups experienced an increase and then decrease in colon cancer incidence. The decrease in colon cancer mortality over the last decade was profound for all patients (-2.88%/year MA, and -3.29%/year EE). Lung cancer incidence (+2.35%/year to 2005) and mortality (+1.25%/year from 1995) increased for EE. Lung cancer incidence and mortality increased and then decreased (-2.54%/year for mortality from 1990) for MA. CONCLUSION: Recent trends in incidence and mortality for screened cancers (breast, colon, prostate) show substantial gains for the extreme elderly, likely due in part to the effect of screening. Incidence and mortality from lung cancer, with no recommended screening during the study period, have continued to worsen for the extreme elderly, despite improvements in younger patient populations.