Radiotherapy For Localized Prostate Cancer Research Articles

Monitoring radiotherapy induced tissue changes in localized prostate cancer by multi-parametric magnetic resonance imaging (MP-MRI)

PurposeTo evaluate the utility of multi-parametric magnetic resonance imaging (MP-MRI), including dynamic contrast-enhanced MRI and diffusion-weighted MRI, for monitoring tumor tissue changes after volumetric-modulated arc radiotherapy in localized prostate cancer (PCa), and to compare the radiotherapy induced tumor tissue changes between conventional, moderate and extreme hypofractionated groups. Furthermore, we aimed to evaluate if follow-up by MRI has an incremental value compared to the standard care by prostate-specific antigen (PSA) serum level measurement. Materials and methodsFifty-five men (mean age: 70±5 [SD] years; range: 60–79 years) with biopsy-proven PCa underwent MRI examination before radiotherapy, and at 3 and 12 months after radiotherapy. Pharmacokinetic analysis post-processing platform with dedicated software (Tissue 4D) was used to generate colorized parametric maps of enhancing tumors. The volume transfer constant (Ktrans), reflux constant (Kep), and initial area under curve (iAUC) were calculated from the tumors. Tumor apparent diffusion coefficient (ADC) value was measured on the ADC map. The patients were allocated into three radiotherapy groups: 17 conventional (39×2Gy), 16 moderate (20×3Gy) and 22 extreme hypofractionated (5×7.25Gy) regimen. ResultsSixty lesions were detected in the prostates of the 55 patients. Follow-up MRI showed decreases in tumor size and degree of enhancement. Ktrans, Kep, and iAUC all decreased at 3 months (P<0.001, respectively) and decreased further at 12 months (P<0.001, respectively). ADC increased at 3 months (P<0.001) and increased further at 12 months (P<0.001). There were no significant differences in the percentage changes of the measured MP-MRI parameters of the tumors from baseline to 12 months between the conventional, moderate and extreme hypofractionated regimen groups. ConclusionMP-MRI is a reliable tool for lesion detection and follow-up, providing both qualitative and quantitative data.

Dose escalation (81 Gy) with image-guided radiation therapy and volumetric-modulated arc therapy for localized prostate cancer: A retrospective preliminary result.

Objectives:The objective of the study is to report the acute and late toxicity and preliminary results of localized prostate cancer treated with high-dose radiation therapy (RT).Materials and Methods:Between March 2010 and October 2018, a total of 53 patients with clinically localized prostate cancer were treated with definitive RT at our institution. All patients were planned to receive a total dose of 81 Gy with the volumetric-modulated arc therapy technique. Patients were stratified by prognostic risk groups based on the National Comprehensive Cancer Network risk classification criteria. Acute and late toxicities were scored by the Radiation Therapy Oncology Group morbidity grading scales. The definition of biochemical failure was using the 2005 ASTRO Phoenix consensus definition. Median follow-up time was 46.5 months (range: 4.7–81.0 months).Results:The 3-year biochemical failure-free survival rates for low-, intermediate-, and high-risk group patients were 100%, 87.5%, and 84%, respectively. The 3- and 5-year overall survival rates were 83% and 62%, respectively. Three (5.6%) patients developed Grade II acute gastrointestinal (GI) toxicity. Four (7.5%) patients developed Grade II acute genitourinary (GU) toxicity, and none experienced Grade III or higher acute GI or GU symptoms. One (1.8%) patient developed Grade II or higher late GI toxicity. Six (11.3%) patients experienced Grade II late GU toxicity. No Grade III or higher late GI and GU complications have been observed.Conclusions:Data from the current study demonstrated the feasibility of dose escalation with image-guided and volumetric-modulated arc therapy techniques for the treatment of localized prostate cancer. Minimal acute and late toxicities were observed from patients in this study. Long-term prostate-specific antigen controls are comparable to previously published results of high-dose intensity-modulated RT for localized prostate cancer. Based on this favorable outcome, dose escalation (81 Gy) has become the standard treatment for localized prostate cancer at our institution.

Forward- and Inverse-Planned Intensity-Modulated Radiotherapy in the CHHiP Trial: A Comparison of Dosimetry and Normal Tissue Toxicity

AimsThe CHHiP (Conventional or Hypofractionated High-dose Intensity Modulated Radiotherapy In Prostate Cancer; CRUK/06/016) trial investigated hypofractionated radiotherapy for localised prostate cancer. Forward- (FP) or inverse-planned (IP) intensity-modulated techniques were permitted. Dose–volume histogram and toxicity data were compared to explore the effects of planning method. Materials and methodsIn total, 337 participants with intermediate-risk disease and prospectively collected toxicity data were included. Patients were matched on prostate and rectum/bladder volumes and on radiotherapy dose for toxicity comparisons. The primary outcome was grade 2 or higher Radiation Therapy Oncology Group (RTOG) bowel or bladder toxicity at 2 years. ResultsIP patients had smaller volumes of rectum irradiated to 50–70 Gy (P < 0.001); FP patients had smaller volumes of bladder irradiated to 74 Gy (P = 0.001). Acute grade 2 + bowel toxicity was worse with FP (27/53 [52%]; 11/53 [21%] IP; P = 0.0002); with no significant differences in acute urinary toxicity. At 2 years, RTOG grade 2 + bowel toxicity rates were FP 0/53 and IP 2/53 and RTOG grade 2 + bladder rates were FP 0/54 and IP 1/57. ConclusionsSignificant differences were found between dose–volume histograms from FP and IP methods. IP may result in small reductions in acute bowel toxicity but both techniques were associated with low rates of late radiotherapy side-effects.

Quality of life after external beam radiotherapy for localized prostate cancer: Comparison with other modalities.

In external beam radiotherapy for localized prostate cancer, acute toxicities are typically transient and mild. These symptoms will disappear within 4-8weeks after external beam radiotherapy. Some patients might suffer from proctitis with bloody stools as late rectal toxicity. Therefore, it has been shown that external beam radiotherapy has a more pronounced negative impact on bowel function compared with other treatment modalities. However, the recent development of modern beam delivery techniques, including intensity-modulated radiotherapy, allows us not only to deliver higher doses to the prostate, but also to decrease the doses to the critical organs, resulting in the maintenance of patients' quality of life within satisfactory levels. Patients' quality of life after external beam radiotherapy is also strongly related to the total dose, fractionation regimens, dose parameters of the critical organs and treatment plan quality, with a trade-off between the radicality of external beam radiotherapy and potentially increased toxicity. Radiation oncologists should choose treatment parameters carefully to achieve a reasonable balance between a good oncological outcome and the patient's quality of life.

PO-1124 A pilot study: Utilization of PROMs in hypofractionated radiotherapy for localized prostate cancer

PO-1124 A pilot study: Utilization of PROMs in hypofractionated radiotherapy for localized prostate cancer

MP78-18 LONG TERM ONCOLOGICAL OUTCOMES OF CRYOABLATION AND HIFU IN WHOLE GLAND AND FIRST LINE TREATMENT FOR LOCALIZED PROSTATE CANCER

INTRODUCTION AND OBJECTIVES:Cryoablation (CA) and High-Intensity Focused Ultrasound (HIFU) are alternative treatments to surgery or radiotherapy in localized prostate cancer (PCa). Both techniques ...

EP-1517 The long-term result of stereotactic body radiotherapy for localized prostate cancer

EP-1517 The long-term result of stereotactic body radiotherapy for localized prostate cancer

EP-1523 Predictors of severe late urinary toxicity after curative radiotherapy for localised prostatecancer

EP-1523 Predictors of severe late urinary toxicity after curative radiotherapy for localised prostatecancer

CYBERKNIFE ROBOTIC RADIOSURGERY SYSTEM

The latest addition to the CyberKnife product family, which was released in September 2009. This review updates the previous technical reviews of the original system version published in the late 1990s. There is a clear dose response for localized prostate cancer radiotherapy and there probablyis a radiobiological rationale for hypo-fractionation. Combining the two should maximize tumor control and increase the therapeutic ratio. Technical developments over the last decade have impacted virtually every aspect of the CyberKnife System. These developments have increased the geometric accuracy of the system and have enhanced the dosimetric accuracy and quality of treatment, with advanced inverse treatment planning algorithms, rapid Monte Carlo dose calculation, and post-processing tools that allow trade-offs between treatment efficiency and dosimetric quality to be explored. The CyberKnife can produce superior DVHs for sparing of rectum and bladder and excellent DVHs for target coverage compared with IMRT, and possesses dose heterogeneities to the same degree as IMRT plans.&#x0D; Keywords: CyberKnife System; Radiosurgery; Stereotactic Body Radiation Therapy; Hypofractionation; IMRT Hetrogeneities

Rectal toxicity results for patients treated with HDR brachytherapy as monotherapy versus dose-escalated external beam radiotherapy for localized prostate cancer.

5 Background: We present a large retrospective analysis comparing rectal toxicity following high dose rate (HDR) brachytherapy as monotherapy relative to dose-escalated external beam radiotherapy (EBRT) for patients with localized prostate cancer. Methods: 2683 patients treated with HDR or EBRT between 1994 and 2017 were included. 545 (20.3%) received HDR and 2138 (79.7%) EBRT. HDR fractionation was 38 Gy/4 fractions (n=321), 24 Gy/2 (n=96), or 27 Gy/2 (n=128). EBRT patients received a median dose of 75.6 Gy in 1.8 Gy fractions [range 70.2-82.8 Gy], using either 3D conformal or intensity modulated radiotherapy (IMRT). All EBRT patients underwent 3D image guidance via an off-line adaptive process. Treatment was directed to prostate only (n=780) or prostate and seminal vesicles (n=1351). No nodal therapy was given. Target volume for HDR patients included the prostate with no expansion. Acute and chronic gastrointestinal (GI) toxicity was defined as occurring ≤ 6 and &gt; 6 months, respectively, after radiotherapy and was graded per CTCAE version 3.0. Toxicity variables were analyzed with χ2 test. Results: Median follow-up was 7.5 years (7.4 years for EBRT and 7.9 years for HDR). 69.1% of EBRT patients received IMRT with the remainder treated using 3D conformal technique. Compared to EBRT, HDR was associated with decreased rates of acute grade ≥ 2 diarrhea (0.7% vs. 4.5%, p &lt; 0.001), rectal pain/tenesmus (0.6% vs. 7.9%, p &lt; 0.001), and rectal bleeding (0% vs. 1.6%, p=0.001). Rates of chronic grade ≥ 2 rectal bleeding (1.3% vs. 8.7%, p &lt; 0.001) and radiation proctitis (0.9% vs. 3.3%, p=0.001) favored HDR over EBRT. Rates of any chronic rectal toxicity grade ≥ 2 were 2.4% vs. 10.5% (p &lt; 0.001) for HDR vs. EBRT, respectively. For the 1478 EBRT patients treated with IMRT, acute and chronic rates of any grade ≥ 2GI toxicity were 4.2% and 5.6%, respectively, compared to 1.5% (p=0.002) and 2.4% (p=0.002), respectively, for HDR patients. Conclusions: In appropriately selected patients with localized prostate cancer undergoing definitive radiation therapy, HDR brachytherapy as monotherapy is an effective strategy for reducing acute and chronic rectal toxicity.

Moderately hypofractionated radiotherapy for localized prostate cancer: Long-term outcomes for 854 consecutive patients treated over 10 years (70 Gy in 2.5 Gy/fraction).

78 Background: Moderately hypofractionated radiotherapy has been increasingly adopted in the management of localized prostate cancer (PCa). We report 10-year outcomes for patients treated with intensity modulation radiation therapy (IMRT) for localized PCa with 70 Gy in 28 fractions at 2.5 Gy/fraction. Methods: This retrospective study included 854 consecutive patients with localized PCa treated with image-guided moderately hypofractionated IMRT at a single institution between 1998 and 2012. Patients with a single intermediate-risk factor were considered to have favorable intermediate-risk (FIR) disease; multiple intermediate-risk factors were considered unfavorable (UIR). Biochemical relapse free survival (bRFS), clinical relapse free survival (cRFS), overall survival (OS) and PCa specific mortality (PCSM) were analyzed used Kaplan-Meier analysis. Grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicities were recorded (CTCAE v4.03). Results: The median follow-up was 11.3 years (Max. 19 years). For patients with low-risk (LR, 31%), FIR (28%), UIR (12.5%), and high-risk (HR, 28.5%) disease the 10 year bRFS rates were 88%, 78%, 71% and 42%, respectively (p &lt; 0.0001). The number of patients receiving no ADT, 1-6 months, or &gt; 6 months of ADT were 39%, 50%, and 11%, respectively, reflecting practice patterns during this treatment period. The 10-year cRFS were 95%, 91%, 85% and 72% for patients with LR, FIR, UIR, and HR, respectively (p &lt; 0.0001). The 10-year actuarial OS rate was 69% (95% CI 66-73%) and the 10-year PCSM was 6.8% (95% CI 5.1-8.6%) overall. For patients with LR, FIR, UIR and HR disease, the 10 year PCSM rates were 2%, 5%, 5% and 15%. 10-year cumulative incidence of grade ≥3 GU and GI toxicity was 2% and 1%, respectively. Multivariate analysis identified associations between clinical variables (ADT use, PSA nadir &lt; 0.5ng/ml, and ISUP Grade Group) and bRFS, cRFS, and PCSM. Conclusions: Moderately hypofractionated IMRT with daily image guidance for localized PCa demonstrates favorable 10-year oncologic outcomes with a low incidence of toxicity for patients across all risk groups.

Moderate hypofractionated radiotherapy vs conventional fractionated radiotherapy in localized prostate cancer: a systemic review and meta-analysis from Phase III randomized trials.

PurposeTo determine the efficacy and late toxicities of moderate (2.5–4 Gy) hypofractionated radiotherapy (H-RT) in localized prostate cancer, a meta-analysis of published randomized clinical trials comparing moderate H-RT with conventional fractionated RT (C-RT) was performed.Materials and methodsSystematic search on published randomized clinical trials in English according to Cochrane review guidelines in databases of Pubmed, Embase, Cochrane, web of science, and Wiley Online Library was carried out. Outcomes of interests were biochemical and clinical disease failure (BCDF), biochemical failure (BF), overall survival (OS), and late toxicities.ResultsSeven of the 365 studies fulfilled inclusion criteria with 8,156 participants. Compared with C-RT, moderate H-RT showed a lower BF rate (risk ratio [RR] =0.80, 95% CI: 0.68–0.95, P=0.009), while did not improve OS (RR =0.68, 95% CI: 0.78–1.02, P=0.10). There was no significant difference in BCDF rates between H-RT and C-RT (RR =0.92, 95% CI: 0.82–1.02, P=0.12). The H-RT was deeply grouped into dose-escalated H-RT (with a higher biologically effective dose [BED1.5] than C-RT) and no dose-escalated H-RT; dose-escalated H-RT significantly decreased BCDF rate compared with C-RT (RR =0.84, 95% CI: 0.73–0.96, P=0.01). Regarding late toxicities, there is no significant difference in late gastrointestinal (GI; RR =0.97, 95% CI: 0.71–1.33, P=0.85) and genitourinary (GU) toxicities (RR =1.04, 95% CI: 0.87–1.24, P=0.69). When subgrouped into dose-escalated H-RT (with a higher BED5 compared with C-RT) and no dose-escalated H-RT, dose-escalated H-RT increased GI toxicity (RR =1.62, 95% CI: 1.26–2.09, P=0.0002) and GU toxicity (RR =1.28, 95% CI: 1.05–1.55, P=0.01), while no dose-escalated H-RT significantly lowered GI toxicity (RR =0.81, 95% CI: 0.70–0.94, P=0.005) and placed no influence on GU toxicity (RR =1.02, 95% CI: 0.88–1.20, P=0.77).ConclusionThis meta-analysis provides reliable evidence that moderate H-RT decreases BF rate, while does not improve OS. Compared with C-RT, H-RT with an increase in BED1.5 improved BCDF rates significantly, and accordingly, an increase in BED5 will result in elevated late GI and GU toxicities.

Leukotoxicity after moderately Hypofractionated radiotherapy versus conventionally fractionated dose escalated radiotherapy for localized prostate Cancer: a secondary analysis from a randomized study

BackgroundTo compare WBC counts during treatment of localized prostate cancer with either conventionally fractionated (CF) or moderately hypofractionated (HYPO) radiotherapy.MethodsWeekly blood test results were extracted from the charts of patients treated within a phase III study comparing HYPO to CF. In order to compare WBC counts at the same nominal dose in both arms and thus to tease out the effect of fractionation, for each recorded WBC value the corresponding cumulative total dose was extracted as well. WBC counts were binned according to percentiles of the delivered dose and three dose levels were identified at median doses of 16, 34.1 and 52 Gy, respectively. A General Linear Model based on mixed design Analysis Of Variance (ANOVA) was used to test variation of WBC counts between the two treatment arms.ResultsOut of 168 randomized patients, 140 (83.3%) had at least one observation for each one of the selected dose levels and were included in the analysis. Mean counts were lower in the CF than the HYPO arm at all selected dose levels, reaching a statistically significant difference at dose level #3 (5397/mm3 vs 6038/mm3 for CF and HYPO, respectively, p = 0.004). The GLM model confirms that the impact of dose on WBC counts is significantly lower in the HYPO arm over the CF one (Greenhouse-Geisser test, p = 0.04). Interestingly, while WBC counts tend to drop throughout all dose levels in the CF arm, this is the case only in the earlier part of treatment in the HYPO arm.ConclusionThis secondary analysis of a phase III study shows that dose fractionation is correlated to WBC drop during treatment of localized prostate cancer, favoring HYPO over CF.

National practice patterns for lymph node irradiation in 197,000 men receiving external beam radiotherapy for localized prostate cancer

PurposeControversy surrounds the benefit of pelvic lymph node irradiation (PLN-RT) in localized prostate cancer (CaP). Our objective was to determine the practice patterns and predictors of PLN-RT in a national cohort. Materials and methodsThe National Cancer Data Base (2005–2015) was leveraged to obtain men diagnosed with nonmetastatic CaP treated with external beam radiotherapy (n = 197,378). Multivariable logistic regressions were used to assess temporal trends and factors associated with PLN-RT. ResultsPLN-RT occurred in 37% of patients overall, which increased to 41% by 2015. When stratified by risk group, there was no significant difference in PLN-RT over time in low, favorable intermediate, unfavorable intermediate, or high-risk CaP. PLN-RT increased for men with very high-risk disease (51%–60%; odds ratio per year 1.34, 95% confidence inrerval 1.06–1.70, P = 0.013). Increased odds of PLN-RT was associated with higher risk disease, addition of hormone therapy, treatment at community hospitals, and shorter patient travel distance to treatment facilities. Surprisingly, 26% and 34% of low and favorable intermediate risk CaP received PLN-RT, respectively. Predictors of PLN-RT among these patients included treatment at a community practice and use of brachytherapy or hormone therapy. ConclusionsPLN-RT occurred in about one-third of men receiving external beam radiotherapy and increased over time, mostly in men with very high-risk CaP for unclear reasons. Of concern, over one-quarter of low-risk men receive PLN-RT. Further work is needed to understand the heterogeneity in PLN-RT use. We await the completion of RTO G 09-24 to better understand the role of PLN-RT for men with localized CaP.

Clinical implementation of magnetic resonance imaging guided adaptive radiotherapy for localized prostate cancer.

Background and purposeMagnetic resonance-guided radiation therapy (MRgRT) has recently become available in clinical practice and is expected to expand significantly in coming years. MRgRT offers marker-less continuous imaging during treatment delivery, use of small clinical target volume (CTV) to planning target volume (PTV) margins, and finally the option to perform daily plan re-optimization.Materials and methodsA total of 140 patients (700 fractions) have been treated with MRgRT and online plan adaptation for localized prostate cancer since early 2016. Clinical workflow for MRgRT of prostate cancer consisted of patient selection, simulation on both MR- and computed tomography (CT) scan, inverse intensity-modulated radiotherapy (IMRT) treatment planning and daily plan re-optimization prior to treatment delivery with partial organs at risk (OAR) recontouring within the first 2 cm outside the PTV. For each adapted plan online patient-specific quality assurance (QA) was performed by means of a secondary Monte Carlo 3D dose calculation and gamma analysis comparison. Patient experiences with MRgRT were assessed using a patient-reported outcome questionnaire (PRO-Q) after the last fraction.ResultsIn 97% of fractions, MRgRT was delivered using the online adapted plan. Intrafractional prostate drifts necessitated 2D-corrections during treatment in approximately 20% of fractions. The average duration of an uneventful fraction of MRgRT was 45 min. PRO-Q’s (N = 89) showed that MRgRT was generally well tolerated, with disturbing noise sensations being most commonly reported.ConclusionsMRgRT with daily online plan adaptation constitutes an innovative approach for delivering SBRT for prostate cancer and appears to be feasible, although necessitating extended timeslots and logistical challenges.

3 Single shot stereotactic body radiotherapy for localized prostate cancer: Case report

Introduction We report on the quality assurance (QA) and treatment management of the first patient included in the ONE SHOT trial. ONE SHOT, single shot stereotactic body radiotherapy (SBRT) for localized prostate cancer, is a multicenter single arm phase I/II trial which will enrolled 45 patients in total. Its main objective is to determine the safety and efficacy of a single SBRT fraction at a dose of 19 Gy in patients with localized prostate cancer. Indeed, recent data showed good tolerance and biochemical control after single interstitial application of 19/20 Gy to the prostate or after SBRT in five fractions, so that ultra-hypofractionated single-dose SBRT employing imaged-guided radiotherapy and real-time tumour tracking with implanted electromagnetic transponders (Calypso® with DynamicEdge™ gating) may be feasible with a safe toxicity profile and an optimal long-term tumor control. Methods Three Calypso beacons were implanted in the patient prostate 4 days before the planning CT scan. The patient was imaged with empty rectum and full bladder with 1 mm slices thickness. For urethra contouring and visualization during treatment, a non-radiopaque catheter was inserted during CT simulation and before the treatment delivery. The prescription dose was 19 Gy in a single fraction to the whole prostate gland ±proximal seminal vesicles and 17 Gy to the urethra planning-risk volume (PRV). The plan consisted into 2 full VMAT arcs using 10MV FFF beam from the TrueBeam linac with 6 degrees of freedom couch. It was optimized on Eclipse TPS (Varian) with Rapidplan™, a knowledge-based planning software, and the dose was calculated with AAA v13026 algorithm. QA controls included portal dosimetry (PD) (Varian, PDIP v13026), absolute dose measurements with Diamond detector (PTW) inserted in Lucy 3D QA phantom (Standard Imaging) and Gafchromic film measurements (EBT-XD films). Results The treatment plan of the first ONE SHOT patient satisfied the dose-volume constraints for all OARs and the coverage requirement for the PTV and PRV. The total number of monitor units for the two arcs was 7125. The results of the PD QA were within the tolerance, with Gamma index 1%/1 mm = 98.7%. For absolute dose measurement, the difference between expected and measured dose was 1.7% inside PRV and 3% in the PTV region. Film gamma index with 4%/1 mm criteria was 97.4%. Patient positioning before treatment required two cone-beam CT (CBCT) before the first arc, because Calypso detected a 2 mm shift in the longitudinal direction after the couch adjustment made after the 1st CBCT. The first arc was treated without interruption and a third CBCT was acquired between the arcs. However, no shift was observed and the second arc was treated without patient realignment. Conclusions QA results were all within the tolerance for SBRT treatment and the first ONE SHOT patient was treated successfully as planned.

Urinary function and quality of life after radiotherapy for prostate cancer in patients with prior history of surgical treatment for benign prostatic hyperplasia

BackgroundTo evaluate long-term IPSS score and urinary quality of life after radiotherapy for prostate cancer, in patients with prior history of surgical treatment for benign prostatic hyperplasia (BPH).MethodsIn this retrospective study, we reviewed medical records of patients treated in our department, between 2007 and 2013 with surgery for BPH followed by radiotherapy for localized prostate cancer. Patients were contacted to fill in IPSS questionnaire and they were also asked for urinary quality of life. Predictive factors known to be associated with bad urinary function were also analysed.ResultsFifty-nine patients were included in our study. Median age was 70 years. Median follow-up was 4.6 years. Median radiotherapy dose was 78 Gy (5 × 2 Gy/week). Thirty patients (48.5%) received hormone therapy in combination with RT. Main surgery indications were urinary symptoms (65%) and urinary retention (20%). Five-year biochemical-disease free survival was 75% and 5-year clinical relapse free survival was 84%. At the time of the study, the IPSS after radiotherapy was as follows: 0–7: 77.6%; 8–19:20.7%; 20–35: 1.7%. Urinary quality of life was satisfactory for 74.2% of patients. After multivariate analysis, a high dose of RT and a medical history of hypertension were associated with a poorer quality of urinary life (p = 0.04).ConclusionExternal radiotherapy remains an appropriate treatment option without a major risk for deterioration in urinary function in patient with antecedent surgery for BPH. High dose of RT and a medical history of hypertension were associated with a poorer quality of urinary life.

SALVAGE CRYOABLATION TARGETING RECURRENT LESIONS AFTER DEFINITIVE RADIOTHERAPY FOR PROSTATE CANCER: IMPACT OF POST CRYOABLATION CHANGE IN URINARY AND SEXUAL FUNCTION

(Purpose) To describe our initial experience in salvage cryoablation targeting recurrent lesions after definitive irradiation for prostate cancer. (Methods) Eligible patients for this treatment were those who developed biochemical failure after definitive radiotherapy for localized prostate cancer, but without distant metastasis, and with solid lesions identifiable on multiparametric magnetic resonance imaging (mpMRI). Histological proof of recurrence with mapping biopsy covering corresponding sites was obtained. Two to four cryoprobes were inserted transperineally into the prostate under general anesthesia with extensive lithotomy position. The rapid expansion of argon gas cryogen through a small opening within the cryoprobe cools itself to make an ice ball and the quick exchange to helium gas induces an active thawing phase. Entire procedure is monitored and guided with the use of transrectal ultrasonography. Postoperative follow-up included patient interview, digital rectal examination, prostate specific antigen (PSA) testing and quality of life (QOL) monitoring using IPSS and IIEF-5 at 1, 3, 6 and 12 months postoperatively. Changes of mpMRI findings with time, particularly at one month, were used to judge immediate treatment impact. (Results) Five patients underwent salvage cryoablation between October 2015 and September 2016. No grade 3/4 complications such as rectal fistula or urethral stenosis were experienced. Mean and maximal percent decline of PSA from baseline levels at 1, 3, 6 and 12 months following cryoablation were 72.2 and 94.7%, 79.4% and 93.9%, 78.2% and 92.1%, 79.6% and 90.9%, respectively. Posttreatment IPSS showed temporary worsening with average changes in score of 1.8, 1.5, 1.6, and 1.0 times over baseline levels, respectively. IPSS score returned to the baseline in one at six months and two at 12 months. Two of 5 patients were sexually active prior to therapy and thus evaluable. Both showed significant decline in IIEF score by 95% at 12 months. No patients showed any signs of recurrence. mpMRI at one month following cryoablation confirmed complete disappearance of visible lesions in all cases. (Conclusions) Salvage cryoablation for recurrent lesions of prostate cancer after definitive radiotherapy is feasible with minimal morbidity. Both oncological outcome and adverse events should be monitored carefully with longer follow up.

The impact of age at the time of radiotherapy for localized prostate cancer on the development of second primary malignancies

PurposeThere is a known increased risk of second primary malignancy (SPM) in patients with prostate cancer (CaP) treated with radiotherapy (RT). It is unclear how age at diagnosis influences the risk of SPMs. Materials and methodsUsing the 1973 to 2013 Surveillance, Epidemiology, and End Results Program, we studied the impact of age on SPMs (defined as a bladder or rectal tumor) after localized CaP treatment with radical prostatectomy (RP) or RT. SPM risk was compared using inverse probability of treatment weighting (IPTW)-adjusted cumulative incidence function and competing-risk proportional hazard models. Overall survival (OS) in patients with SPM was compared using Kaplan Meier and Cox regression analyses. ResultsA total of 579,608 patients met inclusion criteria, and 51.8% of the cohort was treated with RT. The 10- and 20-year cumulative incidences of competing risk (IPTW adjusted) of SPMs were 1.9% (95%CI = 1.8–1.9%) and 3.6% (95%CI = 3.4–3.7%) after RP vs. 2.7% (95%CI = 2.6–2.8%) and 5.4%(95%CI = 5.3–5.6%) after RT. IPTW-adjusted competing risk hazard ratio (HR) of SPM after RT compared to RP was increased in the entire cohort (HR 1.46; 95%CI = 1.39–1.53, P < 0.001) and was highest in the youngest patients: Age <55 HR = 1.83 (95% confidence interval [CI] = 1.49–2.24, P<0.001), Age 55 to 64 HR = 1.66 (95%CI = 1.54–1.79, P < 0.001), Age 65–74 HR = 1.41 (95%CI = 1.33–1.48, P < 0.001), Age ≥75 HR = 1.14 (95%CI = 0.97–1.35, P = 0.112). At 10 years, SPM-specific mortality occurred in 28.9% of patients treated with RT, though OS with SPM was worse in the youngest patients: Age <55 HR = 1.88 (95%CI = 1.25–2.81, P = 0.002), Age 55–64 HR = 1.60 (95%CI = 1.42–1.81, P < 0.001), Age 65–74 HR = 1.40 (95%CI = 1.30–1.52, P < 0.001), Age ≥ 75 HR = 1.27 (95%CI = 1.06–1.53, P = 0.009). All of the age categories had similar median follow-up times. ConclusionAt 10 years there is a 1.8% increased incidence of SPM after RT compared to RP, of which <30% of RT-treated patients with an SPM die as a result of a SPM. However, the risk of SPMs was greatest among younger men treated with RT for localized CaP, and this relationship could not be explained solely by follow-up time, latency time, or life expectancy. An improved understanding of those at the highest risk of SPMs may help tailor treatment and surveillance strategies.

ONE SHOT - single shot radiotherapy for localized prostate cancer: study protocol of a single arm, multicenter phase I/II trial

BackgroundStereotactic body radiotherapy (SBRT) is an emerging treatment alternative for patients with localized prostate cancer. Promising results in terms of disease control and toxicity have been reported with 4 to 5 SBRT fractions. However, question of how far can the number of fractions with SBRT be reduced is a challenging research matter. As already explored by some authors in the context of brachytherapy, monotherapy appears to be feasible with an acceptable toxicity profile and a promising outcome. The aim of this multicenter phase I/II prospective trialis to demonstrate early evidence of safety and efficacy of a single-fraction SBRT approach for the treatment of localized disease.MethodsPatients with low- and intermediate-risk localized prostate cancer without significant tumor in the transitional zone will be treated with a single SBRT fraction of 19 Gy to the whole prostate gland with urethra-sparing (17 Gy). Intrafractional motion will be monitored with intraprostatic electromagnetic transponders. The primary endpoint of the phase I part of the study will be safety as assessed by CTCAE 4.03 grading scale, while biochemical relapse-free survival will be the endpoint for the phase II. The secondary endpoints include acute and late toxicity, quality of life, progression-free survival, and prostate-cancer specific survival.DiscussionThis is the first multicenter phase I/II trial assessing the efficacy and safety of a single-dose SBRT treatment for patients with localized prostate cancer. If positive, results of ONE SHOT may help to design subsequent phase III trials exploring the role of SBRT monotherapy in the exclusive radiotherapy treatment of localized disease.Trial registrationClinicaltrials.gov identifier: NCT03294889; Registered 27 September 2017.