Safer and More Convenient Modern Curative Radiotherapy for Patients With Early Prostate Cancer.

BACKGROUND/AIM: New fractionation schedules with modern tools are a very rapidly developing area in curative radiotherapy (RT) for early prostate cancer (PC). To apply these techniques in everyday clinical practice, we planned this phase II trial with different fractionation schedules and followed up patients using careful health-related quality of life (QoL) questionnaires for three years. PATIENTS AND METHODS: Seventy-three PC patients with one or two intermediate PC risk factors according to the National Comprehensive Cancer Network criteria were recruited. Forty-two patients were treated with 78/2 Gy (conventional fractionation, CF) or 60/3 Gy (moderately hypofractionation RT, MHF), and 31 patients were treated with 36.25/7.25 Gy (stereotactic body RT, SBRT). Their PSA levels were measured, and QoL data were assessed for genitourinary (GU), gastrointestinal (GI), and sexual well-being between the baseline and three years after treatment. A Rectafix™ (RF) fixation device was used in 30 patients in the CF/MHF group. RESULTS: Three years after radiotherapy (RT), there were no differences between the groups regarding GU, GI, sexual well-being, PSA response, or clinical outcomes. On QoL questionnaires, men in the SBRT group were more satisfied with their QoL at the end of RT. Urinary symptoms (p=0.004) and urinary incontinence were more common in the CF/MHF group (p=0.016) three months after RT. The use of RF reduced GI toxicity, especially urgency (p=0.002), at three years after RT. CONCLUSION: Modern, short, five-fraction stereotactic radiotherapy as a local curative treatment for PC is well tolerated and safe. Our novel results showing a decrease in GI toxicity using Rectafix™ fixation should be confirmed in future randomized trials.

Radium-223 dichloride treatment in metastatic castration-resistant prostate cancer in Finland: A real-world evidence multicenter study.

BACKGROUND: Radium-233 dichloride is an alpha emitter that specifically targets bone metastases in prostate cancer. Results of a previously reported phase III randomized trial showed survival benefit for radium-223 compared to best supportive care in castration-resistant prostate cancer (CRPC) with bone metastases. However, real-world data are also needed with wider inclusion criteria. METHODS: We report results of a retrospective multicenter study including all patients with metastatic CRPC treated with radium-223 in all five university hospitals in Finland since the introduction of the treatment. We identified 160 patients who had received radium-223 in Finland in 2014-2019. RESULTS: The median overall survival (OS) was 13.8 months (range 0.5-57 months), and the median real-world progression-free survival (rwPFS) was 4.9 months (range 0.5-29.8 months). Alkaline phosphatase (ALP) values within the normal range before and during the radium-223 treatment or the reduction of elevated ALP to normal range during treatment were associated with better OS when compared to elevated ALP values before and during treatment (p < 0.0001). High prostate-specific antigen (PSA) level (≥100 µg/L) before radium-223 treatment was associated with poor OS compared to low PSA level (<20 µg/L) (p = 0.0001). Most patients (57%) experienced pain relief. Pain relief indicated better OS (p = 0.002). Radium-223 treatment was well tolerated. Toxicity was mostly low grade. Only 12.5% of the patients had grade III-IV adverse events, most commonly anemia, neutropenia, leucopenia, and thrombocytopenia. CONCLUSION: Radium-223 was well tolerated in routine clinical practice, and most patients achieved pain relief. Pain relief, ALP normalization, lower baseline PSA, and PSA decrease during radium-223 treatment were prognostic for better survival. The efficacy of radium-223 in mCRPC as estimated using OS was comparable to earlier randomized trial in this retrospective real-world study. Our results support using radium-223 for mCRPC patients with symptomatic bone metastases even in the era of new-generation androgen receptor-targeted agents.

Health-related Quality of Life of Patients Treated With Different Fractionation Schedules for Early Prostate Cancer Compared to the Age-standardized General Male Population.

BACKGROUND: The effects of radiotherapy (RT) patients' health-related quality of life (HRQoL) are usually compared to those of other treatment modalities instead of HRQoL of the general population in oncological studies. We examined HRQoL of patients with an early prostate cancer (PC) not receiving hormonal treatment up to 3 years after RT using the 15D instrument and the FACT-P questionnaire. METHODS: The 15D results were compared to those in the age-standardized general male population (N = 952) using an independent-sample t test. The study population (N = 73) received RT either with 78/2 Gy, 60/3 Gy or 36.25/7.25 Gy fractionation. RESULTS: No significant differences in the mean total HRQoL scores were found between the RT groups and the general male population at any time point. Patients with PC had more depression (P = .015) and distress (P = .029) than the general male population before the treatment and depression up to 3 months after treatment (P = .019), which did not persist at 3 years. The sexual activity dimension had declined by the end of treatment, and this decline persisted 3 years later (P = .033). Excretion functions were worse compared to those in peers at the end of treatment (P < .001) but no longer at 3 months and later after RT. Regarding the FACT-P, HRQoL remained good at 3 years after RT in all the treatment groups and there were no significant differences between the different RT groups at this time point. CONCLUSION: This study demonstrated that patients treated with RT for early PC had similar HRQoL compared to the age-standardized general male population at 3 years after treatment.

Acute Side-effects of Different Radiotherapy Treatment Schedules in Early Prostate Cancer.

BACKGROUND: Optimal radiation therapy (RT) fractionation in early prostate cancer in elderly patients is controversial. We compared acute toxicities of fractionation schedules: 78/2 Gy, 60/3 Gy and 36.25/7.25 Gy, in this single-centre study. We also evaluated the effect of the rectal immobilization system Rectafix on quality of life (QoL). PATIENTS AND METHODS: Seventy-three patients with one or two intermediate prostate cancer risk factors according to National Comprehensive Cancer Network criteria were recruited. Twenty-one patients were treated with 78/2 Gy and 60/3 Gy, and 31 patients with 36.25/7.25 Gy. Their QoL data were assessed with regard to genitourinary, gastrointestinal and sexual wellbeing at the beginning and end of RT and at 3 months after treatment. Rectafix was used in the 78/2 Gy and 60/3 Gy groups. RESULTS: There were no statistically significant QoL differences in between the treatment groups 3 months after RT. The 78/2 Gy group had significantly increased bowel movements between baseline and 3 months after RT (p=0.036). At 3 months after RT, this group also had significantly more erectile dysfunction than the 60/3 Gy group (p=0.025). At the end of RT, the 78/2 Gy group had more symptoms than the 36.25/7.25 Gy group. Rectafix did not reduce acute toxicities in the 78/2 Gy or 60/3 Gy groups. CONCLUSION: Treatment with the 78/2 Gy schedule is no longer to be recommended due to its increased acute toxicity compared to treatments of 60/3 Gy and 36.25/7.25 Gy. The shortest schedule of 36.25 Gy in five fractions seems to be a convenient treatment option with tolerable acute toxicity.

Radiation-induced prostate swelling during SBRT of the prostate.

BACKGROUND: Reduced planning target volume (PTV) margins are commonly used in stereotactic body radiotherapy (SBRT) of the prostate. In addition, MR-only treatment planning is becoming more common in prostate radiotherapy and compared to CT-MRI-based contouring results in notable smaller clinical target volume (CTV). Tight PTV margins coupled with MR-only planning raise a concern whether the margins are adequate enough to cover possible volumetric changes of the prostate. The aim of this study was to evaluate the volumetric change of the prostate and its effect on PTV margin during 5x7.25 Gy SBRT of the prostate. MATERIAL AND METHODS: Twenty patients were included in the study. Three MRI scans, first prior to treatment (baseline), second after third fraction (mid-treatment) and third after fifth fraction (end-treatment) were acquired for each patient. Prostate contours were delineated on each MRI scan and used to assess the prostate volume and maximum prostate diameter on left-right (LR), anterior-posterior (AP) and superior-inferior (SI) directions at baseline, mid- and end-treatment. RESULTS: Median (IQR) change in the prostate volume relative to the baseline was 12.0% (3.1, 17.7) and 9.2% (2.0, 18.9) at the mid- and end-treatment, respectively, and the change was statistically significant (p = 0.004 and p = 0.020, respectively). Compared to the baseline, median increase in the maximum LR, SI and AP prostate diameters were 0.8, 2.3 and 1.5 mm at mid-treatment, and 0.5, 2.5 and 2.3 mm at end-treatment, respectively. CONCLUSION: If prostate contouring is based solely on MRI (e.g., in MR-only protocol), additional margin of 1-2 mm should be considered to account for prostate swelling. The study is part of clinical trial NCT02319239.

Both comorbidity and worse performance status are associated with poorer overall survival after external beam radiotherapy for prostate cancer.

BACKGROUND: In this retrospective study, we evaluated the biochemical recurrence rate, metastatic disease progression, and prostate cancer-specific and overall survival in patients curatively treated with external beam radiotherapy (EBRT) for early prostate cancer (PC). We also examined the prognostic effect of comorbidity by Charlson Comorbidity Index (CCI) and overall performance status by Eastern Clinical Oncology Group (ECOG) score. METHODS: A total of 665 men treated between 2008 and 2013 were enrolled from Tampere University Hospital, Finland. Prostate-specific antigen (PSA) tests and hospital records were used to determine the 5-year survival for each aforementioned endpoint using a Kaplan-Meyer estimate. To analyze the impact of the selected prognostic factor, we used a Cox regression model to calculate the corresponding hazard ratio (HR) and 95% confidence interval (CI). RESULTS: With a median follow-up-time of 7.12 years, the 5-year overall survival (OS) after EBRT was 88.9% [86.5 -91.3%], prostate cancer-specific survival (PCSS) was 97.9% [96.7 -99.1%], metastasis-free survival (MFS) 94.8% [93.0 -96.6%] and biochemical recurrence-free survival (BRFS) 88.7% [86.2 -91.2%]. Both CCI (HR = 1.38, [1.25-1.51]) and ECOG score (HR = 1.63, [1.29-2.05]) declined OS, as well as Gleason score and T score (P <  0.05). Gleason score and T grade also associated to worse PCSS, MFS and BRFS. CONCLUSIONS: CCI and ECOG score are useful tools in evaluating the overall life expectancy of the patient after EBRT for PC. T-stage and Gleason score remain still the major prognostic factors.

Dynamic Contrast-Enhanced Imaging as a Prognostic Tool in Early Diagnosis of Prostate Cancer: Correlation with PSA and Clinical Stage.

Background and Purpose: Although several methods have been developed to predict the outcome of patients with prostate cancer, early diagnosis of individual patient remains challenging. The aim of the present study was to correlate tumor perfusion parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and clinical prognostic factors and further to explore the diagnostic value of DCE-MRI parameters in early stage prostate cancer. Patients and Methods: Sixty-two newly diagnosed patients with histologically proven prostate adenocarcinoma were enrolled in our prospective study. Transrectal ultrasound-guided biopsy (12 cores, 6 on each lobe) was performed in each patient. Pathology was reviewed and graded according to the Gleason system. DCE-MRI was performed and analyzed using a two-compartmental model; quantitative parameters including volume transfer constant (K trans), reflux constant (K ep), and initial area under curve (iAUC) were calculated from the tumors and correlated with prostate-specific antigen (PSA), Gleason score, and clinical stage. Results: K trans (0.11 ± 0.02 min-1 versus 0.16 ± 0.06 min-1; p < 0.05), K ep (0.38 ± 0.08 min-1 versus 0.60 ± 0.23 min-1; p < 0.01), and iAUC (14.33 ± 2.66 mmoL/L/min versus 17.40 ± 5.97 mmoL/L/min; p < 0.05) were all lower in the clinical stage T1c tumors (tumor number, n=11) than that of tumors in clinical stage T2 (n=58). Serum PSA correlated with both tumor K trans (r=0.304, p < 0.05) and iAUC (r=0.258, p < 0.05). Conclusions: Our study has confirmed that DCE-MRI is a promising biomarker that reflects the microcirculation of prostate cancer. DCE-MRI in combination with clinical prognostic factors may provide an effective new tool for the basis of early diagnosis and treatment decisions.

Diffusion-weighted MRI Provides a Useful Biomarker for Evaluation of Radiotherapy Efficacy in Patients with Prostate Cancer.

BACKGROUND: Diffusion-weighted imaging (DWI) with measurement of apparent diffusion coefficient (ADC) allows for assessment of tumor aggressiveness. The objective of this study was to evaluate the changes of ADC value in prostate cancer after volumetric-modulated arc radiotherapy (VMAT) and to identify magnetic resonance imaging (MRI) biomarkers for monitoring tissue changes after radiotherapy. PATIENTS AND METHODS: Thirty-seven patients with biopsy-proven prostate cancer treated with VMAT underwent serial MRI examinations including DWI before radiotherapy, and at 3 and 12 months after radiotherapy. ADC values of the tumor and healthy prostate tissue were measured and compared at these three time points. RESULTS: The tumor ADC value increased significantly 3 months after radiotherapy (p<0.0001). There was a further increase of tumor ADC from 3 to 12 months after radiotherapy (p<0.01). The ADC of healthy prostate tissue did not show any significant changes. CONCLUSION: The ADC value is a useful biomarker for evaluating the efficacy of radiotherapy in prostate cancer.