Therapy For Localized Prostate Cancer Research Articles

886 - Focal therapy for localized prostate cancer with mpMRI/US fusion-guided radiofrequency ablation: Oncologic and functional outcomes

886 - Focal therapy for localized prostate cancer with mpMRI/US fusion-guided radiofrequency ablation: Oncologic and functional outcomes

Prostate specific antigen testing as disease surveillance and monitoring five years after definitive therapy for localized prostate cancer.

e17602 Background: The National Comprehensive Cancer Network, in 2007, recommends prostate specific antigen (PSA) testing every 6-12 months for the first 5 years following definitive treatment for localized prostate cancer. We compared guideline-concordant PSA testing, as disease surveillance and monitoring, in African-American (AA) and Caucasian (CA) men 5-years after definitive therapy. Methods: A total of 19,377 CA and 1,995 AA men from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database diagnosed with prostate cancer and received definitive treatments from 2007 through 2016 were included. Multivariate log-binomial regression model were used to examine the effect of demographic and clinical characteristics on the likelihood of not receiving at least one PSA surveillance test annually for the first 5 years following definitive treatment. Results: Overall, receipt of surveillance testing and monitoring was high, with 97% of CA men and 94% of AA men receiving at least one test the first year after treatment and approximately 81% of CA men and 77% of AA men receiving at least one test in the fifth year after treatment. Risk of not receiving a test in AA men declined with time compared to CA men, in the first year (Relative Risk [RR], 1.68, 95% CI, 1.37-2.07) and the fifth year (RR, 1.07, 95% CI, 0.98-1.18) since treatment. Further, non-married men and men with intermediate risk had a higher risk of not receiving a surveillance test. Conclusions: Most men received guideline-concordant PSA testing 5-years after definitive therapy. The decline in PSA surveillance overtime reflects the need for continued long-term survivorship care planning and coordination. [Table: see text]

Short-term adjuvant versus neoadjuvant hormone therapy in localized prostate cancer: A pooled individual patient analysis of two phase III trials.

5584 Background: The timing of systemic therapy in relation to radiotherapy (RT) is important in most malignancies. In contrast, androgen deprivation therapy (ADT) has largely been investigated in relation to its duration rather than its sequencing with RT. Herein, we conduct the first combined individual patient analysis of two phase III randomized trials to determine the optimal timing of ADT with RT in localized prostate cancer (PCa). Methods: Individual patient data was obtained from the Malone et al trial (JCO 2019), which randomized patients to receive neoadjuvant/concurrent or concurrent/adjuvant ADT for 6 months with prostate only RT. This was combined with the prostate only RT arms of RTOG 9413 that randomized patients to 4 months of neoadjuvant/concurrent or adjuvant ADT. The neoadjuvant/concurrent arms of both trials were combined into the “neoadjuvant” group, and the concurrent/adjuvant (Malone) and adjuvant arm (RTOG 9413) were combined in the “adjuvant” group. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Cumulative incidence of distant metastasis (DM), PCa-specific mortality (PCSM) and biochemical failure (BF) were calculated using the Fine-Gray method with non-PCa deaths as competing events. Late genitourinary (GU) and gastrointestinal (GI) toxicity are also reported. Results: The median follow-up was 14.9 years (yrs) and 1065 patients were included (n=531 neoadjuvant, 534 adjuvant). Groups were well balanced for all baseline characteristics. Adjuvant ADT was superior to neoadjuvant ADT in terms of BF (15yr: 33% vs 43%, HR: 1.37 (95%CI: 1.12-1.68), p=0.002), DM (15yr: 12% vs 18%, HR: 1.40 (95%CI: 1.00-1.95), p=0.04), and PFS (15yr: 36% vs 29%, HR: 1.25 (95%CI: 1.07-1.47), p=0.01). Adjuvant ADT yielded lower PCSM (15yr: 15% vs 20%, HR: 1.29 (95%CI: 0.95-1.75), p=0.10), but did not reach statistical significance. This approached statistical significance in high risk PCa (HR 1.39 (95%CI 1.00-1.93), p=0.053). OS was not significantly different between arms (15yr: 39% vs 34%, HR: 1.11 (95%CI: 0.95-1.30), p=0.20). There was no significant difference in either late grade ≥3 GI (p=0.21) or GU (p=0.98) toxicity. Conclusions: We demonstrate for the first time that sequencing of ADT with RT significantly impacts long-term oncologic outcomes in localized PCa, favoring an adjuvant rather than neoadjuvant approach, without increasing late toxicity. This data has important implications to ongoing and future clinical trial design. Clinical trial information: NCT00769548 .

Can Transurethral Resection of the Prostate (TURP) Be Another Gateway to the Focal Therapy of Localized Prostate Cancer?

Background and Objectives Minimally invasive methods are expected to avoid the risk of overtreatment and overtreatment of radical therapy to manage the increased number of patients with low-volume, low-grade localized prostate cancer. Based on our experience of radical transurethral resection of prostate cancer (TURPCa) as a radical treatment, we studied the efficacy and safety of focal TURPCa as a focal therapy for patients with localized prostate cancer. Materials and Methods We performed focal TURPCa in 49 patients during the period from July 2007 to August 2016 and followed them with prostate-specific antigen (PSA) testing for the mean period of 68.0 months. We selected the patient as a candidate for the study if the biopsy revealed that cancer foci were limited in one lobe, or the foci were several or less even found in both lobes. Standard TURP was followed by further resection and fulguration of the peripheral zone where cancer was considered to exist. We selected one of our three methods of focal TURPCa as follows: one lobe radical TURPCa, radical resection of the affected lobe with unaffected lobe being resected less vigorously; nerve-sparing radical TURPCa, radical resection of both lobes except for the posterolateral part of the prostate; target radical TURPCa, radical resection of the cancer focus and the surrounding prostate when the target is suggested single. Results Twelve patients were in the low-risk group (D’Amico), 29 in the intermediate-risk group, and 8 in the high-risk group. Pathological stages were as follows: pT0, three cases; pT2a-b, 17 cases; pT2c, 29 cases. The preoperative PSA of 6.15±2.73 ng/mL (mean±SD) dropped to 0.172±0.283 ng/mL postoperatively. PSA failure occurred in only two patients (4.1%). Incontinence did not develop and erectile function was preserved in eight (44.4%) of the 18 potent patients. The most frequent complication was bladder neck contracture (20.4%). Other complications included acute epididymitis (8.1%), bladder tamponade (2.0%). No patients died of prostate cancer. Conclusions Though the final assessment of efficacy will require long-term follow-up results with more cases, we may think focal TURPCa can be another treatment option as a focal therapy for localized prostate cancer.

Ultrahypofractionated versus hypofractionated and conventionally fractionated radiation therapy for localized prostate cancer: A systematic review and meta-analysis of phase III randomized trials

IntroductionTo characterize the efficacy (5-year disease-free survival [DFS]) and safety (incidence of grade 2+ late gastrointestinal or genitourinary toxicity) of ultrahypofractionated radiation therapy (UHRT) versus hypofractionated radiation therapy (HFRT) and conventionally fractionated radiation therapy (CFRT) by comparing patients treated on phase III protocols. MethodsA PICOS/PRISMA/MOOSE protocol was used to identify eligible studies. Weighted random effects meta-analyses were conducted using the DerSimonian and Laird method. Wald-type tests were used to compare treatment modalities for each outcome, where the null hypothesis was rejected for p < 0.05. ResultsSeven studies were included that consisted of 6795 patients (2849 CFRT, 3357 HFRT, and 589 UHRT). Median age was 68 years. Summary effect sizes for 5-year DFS were 85.1% (95% CI: 82.1%–87.8%) for CFRT, 86% (95% CI: 83%–88.7%) for HFRT, and 85% (95% CI: 80%–87%) for UHRT (p = 0.66 and p = 0.8 for CFRT vs. HFRT and CFRT versus UHRT, respectively). Summary effect sizes for late grade 2+ gastrointestinal toxicity were 12.1% (95% CI: 9.2%–15.4%) for CFRT, 14.6% (95% CI: 9.9%–20%) for HFRT, and 10% (95% CI: 7%–13%) for UHRT (p = 0.41 and p = 0.09 for CFRT versus HFRT and CFRT versusus UHRT, respectively). Summary effect sizes for late grade 2+ genitourinary toxicity were 19.4% (95% CI: 10.7–29.9%) for CFRT, 20.4% (95% CI: 10.2%–32.9%) for HFRT, and 18% (95% CI: 15%–22%) for UHRT (p = 0.89 and p = 0.92 for CFRT versus HFRT and CFRT versus UHRT, respectively). ConclusionUltrahypofrationated regimens appear to offer similar levels of safety and efficacy to CFRT and HFRT. These findings are hypothesis-generating and require further validation by ongoing prospective trials.

Two-year outcomes of moderately hypofractionated 70 Gy in 28 fractions, intensity-modulated radiotherapy and volumetric modulated arc therapy for localised prostate cancer

AbstractIntroduction:Standard external beam radiotherapy is a treatment option for patients with localised prostate cancer and is used in patients with low-, intermediate- and high-risk disease with androgen deprivation according to the risk of the disease. In the last few years, hypofractionated radiotherapy has been demonstrated to be as safe as standard radiotherapy if given over a shorter time than standard radiotherapy with larger doses per fraction. External radiotherapy for localised prostate cancer typically delivers 37–42 fractions of 1·8–2·0 Gy per fraction given 5 days per week over 7·5–8·5 weeks. Hypofractionated radiotherapy delivers 20–28 fractions of 2·5–2·6 Gy per fraction given 5 days per week over 4–5·6 weeks.Methods:A retrospective analysis of assessment of 30 patients was undertaken from 2016 to 2018. The aim of this study was to evaluate the 2-year outcomes of 30 patients with prostate cancer treated with hypofractionated radiotherapy 70 Gy in 28 fractions.Results:Biochemical failure with hypofractionated radiotherapy was found in a total of 20% of patients. In the classification by risk groups, there were no biochemical failures in low-risk patients; in the low intermediate course, 3·3% of patients; in the high intermediate group, 3·3% patients; and in the high-risk group, the largest documented biochemical failure was in 13·3% of patients. For acute urinary toxicity, grade I was 56·6%; grade II, 6·6%. For acute rectal toxicity, grade I was 46·6%; grade II, 3·3%.Conclusion:This is one of the first studies of hypofractionated radiotherapy in prostate cancer in Latin America, and the results of this study demonstrated that the outcomes were similar to the standard regimen in all risk groups.

Rates of rectal toxicity in patients treated with high dose rate brachytherapy as monotherapy compared to dose-escalated external beam radiation therapy for localized prostate cancer

BackgroundUsing a prospectively collected institutional database, we compared rectal toxicity following high dose rate (HDR) brachytherapy as monotherapy relative to dose-escalated external beam radiotherapy (EBRT) for patients with localized prostate cancer. Methods2683 patients treated with HDR or EBRT between 1994 and 2017 were included. 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). EBRT patients underwent 3D image guidance via an off-line adaptive process. ResultsMedian follow-up was 7.5 years (7.4 years for EBRT and 7.9 years for HDR). 545 patients (20.3%) received HDR brachytherapy and 2138 (79.7%) EBRT. 69.1% of EBRT patients received IMRT. Compared to EBRT, HDR was associated with decreased rates of acute grade ≥2 diarrhea (0.7% vs. 4.5%, p < 0.001), rectal pain/tenesmus (0.6% vs. 7.9%, p < 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 < 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 < 0.001) for HDR versus EBRT, respectively. In those treated with IMRT, acute and chronic rates of any grade ≥2 GI toxicity were significantly reduced but remained significantly greater than those treated with HDR. ConclusionsIn appropriately selected patients with localized prostate cancer undergoing radiation therapy, HDR brachytherapy as monotherapy is an effective strategy for reducing rectal toxicity.

A prospective comparison of MRI-planned versus CT-planned radiotherapy for prostate cancer.

312 Background: Chronic rectal toxicity significantly decreases the quality of life for men who receive radiotherapy for prostate cancer. The volume of rectum exposed to 70 Gy or more is a validated metric that predicts the risk of late rectal toxicity. We hypothesized that MRI as compared to CT-based prostate radiotherapy treatment planning can reduce the volume of rectum exceeding 70 Gy. Methods: This prospective study single arm study enrolled 15 men treated with external beam radiation therapy for localized prostate cancer. At the time of treatment planning a 3 Tesla T2-weighted magnetic resonance imaging examination of the prostate was obtained. A radiotherapy plan was designed by a medical physicist using identical constraints for both CT and MRI-based consensus volumes defined by a radiologist and radiation oncologist. The volume of rectum exposed to 70 Gy or more was calculated and compared using the paired Signed Rank Test. Results: The median age was 70 years (range 56-84), median PSA 7.3 ng/mL (range 3.2 – 22.1), and median prostate volume 40 mL (range 25 - 65) by transrectal ultrasound. Sixty percent (n=9) were intermediate risk and 40 percent (n=6) high risk by NCCN guidelines. The majority were either clinical stage T1c (n=7) or T2 (n=6). Two men had extracapsular extension (T3a). None of the participants had seminal vesicle invasion (T3b), rectal or bladder involvement (T4), or lymph node metastasis (N1). All 15 men enrolled on the study completed both a standard radiation planning CT and research MRI examination. For CT-based treatment plans the median volume of rectum receiving 70 Gy or more was 9.3 cubic centimeters (cc) [IQR 7.0 to 10.2] compared with 4.9 cc [IQR 4.1 to 8.7] for MRI-based plans. This resulted in a median volume reduction of 2.1 cc [IQR 0.5 to 5.3, P &lt; .001]. Conclusions: MRI-planned prostate radiotherapy can reduce the volume of rectum receiving radiation doses in excess of tolerance (70 Gy or more) and should be considered in men who are at high risk for late rectal toxicity. Clinical trial information: NCT02470910.

Focal therapy for localized prostate cancer in the era of routine multi-parametric MRI

Prostate cancer focal therapy aims to minimize the side-effects of whole gland treatments, such as radical prostatectomy and radiotherapy without compromising oncological efficacy. However, concerns exist regarding the multifocal nature of prostate cancer and the lack of long-term oncological data for this form of treatment. In recent years, the routine adoption of multi-parametric magnetic resonance imaging (mpMRI) of the prostate has improved our ability to select candidates for focal therapy and to accurately deliver this form of prostate cancer treatment. We performed a review of the literature to provide a summary of the oncological and functional outcomes of men receiving primary prostate focal therapy. Furthermore, we discuss the impact of the routine implementation of mpMRI as part of the initial prostate cancer diagnostic pathway on the selection of candidates and delivery of focal therapy. Finally, we summarize knowledge gaps in the field and highlight active clinical trials in this arena. Primary focal therapy involves the application of one of a number of energies that ablate tissue, such as cryotherapy and high intensity focused ultrasound (HIFU). Success is principally dependent on highly accurate patient selection and disease localization underpinned in large part by the routine integration of pre-biopsy mpMRI. Prospective medium-term follow-up data for primary HIFU and cryotherapy for men with intermediate-risk disease have shown acceptable cancer control with low risk of side effects and complications. Additional research is needed to clearly define an appropriate follow-up approach and to guide the management of in- and out-of-field recurrences. Multiple comparative trials with randomization against standard care are currently underway in men with intermediate- and high-risk prostate cancer. The widespread adoption of prostate mpMRI has led to improved disease localization, enabling the performance of focal therapy as a viable treatment strategy for men with low volume intermediate-risk prostate cancer.

Current status and future prospective of focal therapy for localized prostate cancer: development of multiparametric MRI, MRI-TRUS fusion image-guided biopsy, and treatment modalities.

Multiparametric magnetic resonance imaging (mpMRI) has been increasingly used to diagnose clinically significant prostate cancer (csPC) because of its usefulness in combination with anatomic and functional data. MRI-targeted biopsy, such as MRI-transrectal ultrasound (TRUS) fusion image-guided prostate biopsy, has high accuracy in the detection and localization of csPC. This novel diagnostic technique contributes to the development of tailor-made medicine as focal therapy, which cures the csPC while preserving the anatomical structures related to urinary and sexual function. In the early days of focal therapy, TRUS-guided systematic biopsy was used for patient selection, and treatment was performed for patients with low-risk PC. With the introduction of mpMRI and mapping biopsy, the treatment range is now determined based on individualized cancer localization. In recent prospective studies, 87.4% of treated patients had intermediate- and high-risk PC. However, focal therapy has two main limitations. First, a randomized controlled trial would be difficult to design because of the differences in pathological features between patients undergoing focal therapy and radical treatment. Therefore, pair-matched studies and/or historical controlled studies have been performed to compare focal therapy and radical treatment. Second, no long-term (≥ 10-year) follow-up study has been performed. However, recent prospective studies have encouraged the use of focal therapy as a treatment strategy for localized PC because it contributes to high preservation of continence and erectile function.

Rectal Hydrogel Spacer Improves Late Gastrointestinal Toxicity Compared to Rectal Balloon Immobilization After Proton Beam Radiation Therapy for Localized Prostate Cancer: A Retrospective Observational Study

Our purpose was to compare dosimetric parameters and late gastrointestinal outcomes between patients treated with proton beam therapy (PBT) for localized prostate cancer with rectal balloon immobilization versus a hydrogel rectal spacer. Patients with localized, clinical stage T1-4 prostate adenocarcinoma were treated at a single institution using conventionally fractionated, dose-escalated PBT from 2013 to 2018. Patient-reported gastrointestinal toxicity was prospectively collected, and the incidence of rectal bleeding was retrospectively reviewed from patient records. One hundred ninety-two patients were treated with rectal balloon immobilization, and 75 were treated with a rectal spacer. Rectal hydrogel spacer significantly improved rectal dosimetry while maintaining excellent target coverage. The 2-year actuarial rate of grade 2+ late rectal bleeding was 19% and 3% in the rectal balloon and hydrogel spacer groups, respectively (P = .003). In univariable analysis, the probability of grade 2+ rectal bleeding was significantly correlated with increasing rectal dose. In multivariable analysis, only receipt of spacer hydrogel (hazard ratio, 0.145; P = .010) and anticoagulation use (hazard ratio, 5.019; P < .001) were significantly associated with grade 2+ bleeding. At 2-year follow-up, patient-reported Expanded Prostate Cancer Index Composite bowel quality of life composite scores were less diminished in the hydrogel spacer group (absolute mean difference, 5.5; P = .030). Use of rectal hydrogel spacer for prostate PBT is associated with a significantly lower incidence of clinically relevant, late rectal bleeding and lower decrement in long-term, patient-reported bowel quality of life compared with rectal balloon immobilization. Our results suggest that hydrogel spacer may improve rectal sparing compared with rectal balloon immobilization during PBT for prostate cancer.

Image-guided dose-escalated radiation therapy for localized prostate cancer with helical tomotherapy.

To evaluate treatment outcomes for patients with localized prostate cancer who were treated with dose-escalated primary image-guided radiation therapy (IGRT). We retrospectively analyzed 88 consecutive patients treated using helical tomotherapy with daily megavoltage CTs (MVCT). Patients were prescribed daily doses of 1.8 Gy to the planning target volume (PTV) and 2 Gy to the clinical target volume (CTV). Low- and favorable intermediate-risk patients received aminimum total dose of 72 Gy to the PTV and up to 80 Gy to the CTV. Unfavorable intermediate-risk and high-risk patients received aminimum total dose of 75.6 Gy to the PTV and up to 84 Gy to the CTV. We assessed freedom from biochemical relapse (FFBF), 5‑year biochemical recurrence-free survival (5-bRFS), distant metastasis-free survival (5-dMFS), and cancer-specific survival (5-CSS) as well as acute and late genitourinary (GU) and gastrointestinal (GI) toxicity. Among our cohort, 11.4% were low-risk, 50% intermediate-risk, and 38.6% high-risk patients according to the D'Amico criteria. Median follow-up was 66months (range8-83months). FFBF was 100%, 97.7%, and 90.7%; 5‑bRFS was 100%, 92.8%, and 70.4%; 5‑dMFS was 100%, 92.7%, and 70.4%; and 5‑CSS was 100%, 97.4%, and 89.8% for low-, intermediate-, and high-risk patients, respectively. Grades2 and3 toxicity occurred at the following rates: acute GU toxicity 39.8% and 1.1%, acute GI toxicity 12.5% and 0%, late GU toxicity 19.3% and 4.5%, and late GI toxicity 4.5% and 1.1% of patients, respectively. No toxicity >grade3 was observed. Risk-adapted dose-escalated IGRT with helical tomotherapy of up to 84 Gy is afeasible and well-tolerable treatment scheme with promising oncological results.

Ultrahypofractionation Should be a Standard of Care Option for Intermediate-Risk Prostate Cancer

Ultrahypofractionation Should be a Standard of Care Option for Intermediate-Risk Prostate Cancer

AUTHOR REPLY

We agree with the important points raised in this commentary. There is indeed a lack of evidence as to what constitutes optimal follow-up following partial gland ablation (PGA). There can be no doubt that magnetic resonance imaging (MRI) has a significant part to play, and that it may indeed perform better than prostate specific antigen (PSA) profiles when it comes to predicting failure. 1 Dickinson L. Ahmed H.U. Hindley R.G. et al. Prostate-specific antigen vs. magnetic resonance imaging parameters for assessing oncological outcomes after high intensity-focused ultrasound focal therapy for localized prostate cancer. Urol Oncol. 2017; 35 (30 e9-30 e15) Crossref PubMed Scopus (55) Google Scholar A total of 32% of the patients undergoing PGA using high-intensity focused ultrasound (HIFU) in this study over a 9-year period were treated within a National Institute for Health Research (NIHR) portfolio study and as such prostate biopsies were mandated. Those treated outside of a trial followed a similar protocol, with the exception of routine biopsy. All patients were followed closely post-treatment with regular PSA testing and interval MRI scanning following a protocol which is very similar to that used for our current active surveillance cohort.

ESTRO ACROP consensus guideline on the use of image guided radiation therapy for localized prostate cancer

Use of image-guided radiation therapy (IGRT) helps to account for daily prostate position changes during radiation therapy for prostate cancer. However, guidelines for the use of IGRT are scarce.An ESTRO panel consisting of leading radiation oncologists and medical physicists was assembled to review the literature and formulate a consensus guideline of methods and procedure for IGRT in prostate cases. Advanced methods and procedures are also described which the committee judged relevant to further improve clinical practice. Moreover, ranges for margins for the three most popular IGRT scenarios have been suggested as examples.

Phase I study of cancer lesion-targeted microwave coagulation therapy for localized prostate cancer: A pilot clinical study protocol

BackgroundWhole-gland therapy for prostate cancer, which might cause more harm than no therapy (observation or active surveillance), might be a overtreatment. In order to avoid overtreatment as well as undertreatment of localize prostate cancer, novel strategy of organ-preserving therapies have been developed to achieve both cancer control and functional preservation. For the therapeutic techniques, microwave ablation would be an option for lesion-targeted focal therapy to eradicate biopsy-proven cancer lesion with its safety margin. Following our recent pilot clinical study of lesion-targeted focal cryotherapy, prospective clinical trial was designed to investigate the safety and therapeutic effects of lesion-targeted microwave therapy for localized prostate cancer. MethodsThis is a single-center, phase I, clinical study to evaluate primarily the safety of lesion-targeted focal microwave treatment for prostate cancer. Patients with a magnetic resonance imaging (MRI)-visible, MR-ultrasound image-fusion targeted biopsy-proven clinically significant cancer will be enrolled. The target sample size is 5. Transrectal ultrasound-guided focal microwave ablation will be performed under general anesthesia. The primary endpoint is adverse events after microwave focal therapy. Secondary endpoint includes to assess both cancer control and quality of life (functional preservation). DiscussionThis single-center, phase I, clinical study aims to evaluate the safety and efficacy of lesion-targeted focal microwave treatment for prostate cancer. The importance of this clinical trial is that it may establish new treatment for prostate cancer. Trial registrationThis study was registered with Japan Registry of Clinical Trials (jRCTs052190026).

Multimodal treatment in focal therapy for localized prostate cancer using concomitant short-term androgen deprivation therapy: the ENHANCE prospective pilot study.

Focal therapy (FT) for localized prostate cancer (PCa) is emerging to reduce adverse effects of radical treatments, while maintaining comparable oncological outcomes. However, an area for improvement still exists and a gap in cancer control needs to be filled by complementing FT with additional forms of treatment to minimize failures. Part of the recurrences/persistences after FT may be related to PCa microenvironment favouring tumorigenesis of benign tissue or indolent PCa left untreated. FT-induced inflammation may alter microenvironment in a pro-tumorigenic fashion. On the contrary, androgen deprivation therapy (ADT) modifies PCa microenvironment and suppresses PCa tumorigenesis. So far, ADT has proven effective in combination with radiotherapy, has been evaluated in the context of AS and to reduce prostate volume in the context of whole-gland high-intensity focused ultrasound (HIFU). However, no prospective data exist evaluating FT/ADT combination in terms of cancer control for the treatment of localized PCa. We will perform the ENHANCE pilot study (EvaluatioN of HIFU Hemiablation and short-term AndrogeN deprivation therapy Combination to Enhance prostate cancer control). Twenty men with localized unilateral csPCa will receive HIFU hemi-ablation and concomitant short-term ADT. Oncologic efficacy will be assessed 1-year post-treatment considering the persistence/recurrence of csPCa. Complications and functional outcomes will be evaluated using internationally validated questionnaires. If the hypothesis of an oncological benefit together with no relevant additional toxicity is confirmed, the ENHANCE study will allow an evidence-based starting point for a large randomized controlled trial against the standard of care and/or HIFU hemiablation alone.

Quality of Life-Focused Decision-Making for Prostate Cancer.

Quality of life (QoL) outcomes have been reported in the literature and incorporated in decision-making in localized prostate cancer management for decades. Until recently, there was less emphasis on understanding the QoL effects of therapies for patients with advanced disease, possibly because there were fewer options for treatment. The purpose of this review is to summarize the key recent literature describing QoL outcomes for prostate cancer treatments in different disease settings. Recent data demonstrate that men who undergo local therapy for prostate cancer have worse early QoL related to therapy in sexual, urinary, and bowel function domains compared with men who choose observation, though the effects become less divergent over time. In patients receiving systemic therapy for advanced prostate cancer, more effective treatment typically delays deterioration of various aspects of QoL as assessed by patient-reported outcomes. While there are multiple management options for localized and advanced prostate cancer, different treatment modalities affect QoL in distinct ways. Particularly in settings that lack head-to-head efficacy data between treatment options, clinicians can incorporate adverse effect profiles and effects on patient-reported outcomes describing QoL to inform patients as they make treatment decisions for prostate cancer.

High efficacy of hypofractionated proton therapy with 4 fractions of 5 Gy as a boost to 50 Gy photon therapy for localized prostate cancer

PurposeWe report the outcome of hypofractionated proton boost as an alternative to high dose-rate brachytherapy boost, aimed at an equivalent dose exceeding 86 Gy in 2 Gy fractions, for patients with localized prostate cancer and all risk groups. MethodsProton boost of 20 Gy given in 4 daily fractions to the prostate was followed after a one-week rest by photon therapy to 50 Gy in 2 Gy fractions. Outcomes are presented per risk group according to both NCCN and ISUP classifications. Advanced imaging was performed for adequate staging, and at an early stage of rising PSA, to identify the relapse site. Endpoints were PSA relapse-free-, locoregional relapse-free-, and distant metastasis-free- survival. Prostate cancer-specific-, metastasis-free-, and overall survival were also estimated. Genitourinary (GU) and gastrointestinal (GI) toxicity were based on patients‘ questionnaires and physicians‘ records. ResultsWe treated 531 patients between 2002 and 2015; 504 had localized disease. The cohort included 180 patients with T3/T4 disease (36%). The majority of the 50% with high-/very high-risk disease received ADT, 9–24 months; 92 had adjuvant pelvic node treatment. Median follow-up was 113 months (43–193). For low-, intermediate-, high-, and very high-risk patients, the 5-year PSA relapse-free survival was 100%, 94%, 82%, and 72%, respectively. Prolonged ADT improved biochemical control and nodal treatment regional control. The NCCN classification had higher predictive discrimination than the ISUP classification. The 5-year prevalence grade 3+ was 2% for GU and 0% for GI toxicity in pre-treatment symptom-free patients, and not worsened by nodal treatment. ConclusionDose escalation with hypofractionated proton boost was as effective as reported with high dose-rate brachytherapy boost, and the GU and GI toxicity profile was very similar. The proton boost was also appropriate for patients with larger prostate volume, higher T-stage, and high-risk disease encompassing elective regional node photon therapy.

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.