Good Cancer Control Research Articles

Long-term Results of Hypofractionated Radiotherapy With Intra-prostatic Boosts in Men With Intermediate- and High-risk Prostate Cancer: A Phase II Trial

AimsIn the conventionally fractionated phase III FLAME prostate trial, focal boosts improved local control and biochemical disease-free survival (bDFS). We explored the toxicity and effectiveness of a moderately hypofractionated schedule with focal boosts. Material and methodsBIOPROP20 is a phase II single-arm non-randomised trial for intermediate- to very high-risk localised prostate cancer patients with bulky tumour volumes. Multi-parametric magnetic resonance imaging (MRI) and 18F-choline positron emission tomography-computed tomography (PET-CT) scans were used for staging and boost volume definition. Patients were treated with 60Gy in 20 fractions with a boost dose up to 68Gy. Five patients with positive lymph nodes on the PET-CT scan received radiotherapy to pelvic lymph nodes (45Gy to elective nodes, boosted up to 50Gy to involved nodes). Primary outcomes were acute (≤18 weeks) and late urinary and gastrointestinal toxicity, prospectively recorded up to 5 years with Common Terminology Criteria for Adverse Events v4 (CTCAE). Secondary outcomes were biochemical or clinical progression, metastasis-free survival (MFS), and overall survival (OS). Results61 patients completed radiotherapy with hormone therapy (range: 6–36 months). Cumulative acute and late gastrointestinal toxicity was low at 6.6% and 5.0%, respectively. Cumulative acute and late urinary toxicity was 49.2% and 30.1%, respectively; the prevalence reduced to 5.9% at 5 years. At 5 years: 6 patients had biochemical progression (bDFS: 88.5%; 95% CI: 80.2–97.6%), the MFS was 82.4% (95% CI: 73.0–92.9%), 5 patients died (OS: 91.2%; 95% CI: 84.1–98.9%), one with prostate cancer. The prostate, boost, nodal planning volumes, and the organs at risk (rectum, bowel, urethra, and bladder) met the optimal protocol dose constraints. There was a trend to increased urinary toxicity with increasing urethral (RR: 1.95, 95% CI: 0.73–5.22, p = 0.18), but not bladder dose. ConclusionFocal boosts with a 20 fraction hypofractionated prostate radiotherapy schedule are associated with an acceptable risk of gastrointestinal and urinary toxicity and achieve good cancer control. ClinicalTrials.gov identifierNCT02125175.

Outcomes of Targeted Therapy Plus Immunotherapy and High-Dose Stereotactic Ablative Body Radiotherapy (SABR) for Metastatic Renal Cell Cancer Patients.

Stereotactic ablative body radiotherapy (SABR) is one of the treatment options for metastatic renal cell carcinoma (mRCC) but is limited by a lack of data to evaluate targeted therapy plus immunotherapy concurrently with high-dose SABR to multiple sites. We evaluated the safety and disease control for mRCC patients who concurrently received the above tri-modality treatment. Patients were treated with SABR (40-70 Gy/5-10 fractions) for small lesions or partial-SABR (tumor center boosted with 6-8 Gy/3-5 fractions with 50-60 Gy/20-25 fractions to the whole tumor volume) for bulky tumors or tumors adjacent to critical organs. When SABR/partial-SABR was not feasible, a moderate fractionated radiotherapy plan, usually 60Gy/20 fractions were applied. of Targeted therapy plus immunotherapy (PD-1 inhibitor) was not interrupted during or after radiotherapy (RT). Adverse events (AEs) were evaluated. Disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were calculated. The PFS1 was defined as the first progression since the start of RT. The PFS2 was defined as the second progression after the second RT course, if new metastases occurred after first RT were all re-irradiated, and the systemic therapy was not changed. The Kaplan-Meier method was used for time-to-event endpoints. A total of 51 patients, with a median age of 57 yr, were enrolled. The median follow-up was 12 months. There were 75% of patients with intermediate-risk and 18% with favorable-risk disease. 61% of the patients were oligometastatic. 71% had clear cell renal cancer. There were 241 metastases while 161 (67%) were irradiated. 80% of the lesions received SABRP/partial SABR. 1 patient with 14 lesions irradiated received proton therapy. All the surviving patients are continuing using targeted therapy while 81% patients complete at least 1-year PD-1 therapy. 10 patients (20%) had grade 3 drug-related AEs: pneumonitis (n = 2), elevated alanine transaminase (n = 4), myositis (n = 1), hand-foot syndrome myositis (n = 1), enteritis (n = 1), fatigue (n = 1). There were 1 grade 4 AEs of upper gastrointestinal bleeding. No grade 3-5 RT-related AEs was found. ORR and DCR for irradiated lesion were 51% and 98%. Median OS and PFS2 was not reached. Median PFS1 was 14(6-22) months. Estimated 1- and 2-yr OS, PFS1 and PFS2 were 90% and 90%, 56% and 38%, 74% and 51% respectively. Univariate analysis showed that an PFS1 benefit was found in patients who received radiation before systemic therapy failure (p = 0.038). We investigated the high-dose RT in combination of concurrent targeted and immunotherapy in patients with metastatic RCC. We found that this treatment regimen was well tolerated, with good cancer control. Early use of high-dose RT to multi-lesions may improve PFS. Partial-SABR for bulky lesions close to critical organs could be safely and effectively applied under certain circumstances. These encouraging findings warrant further investigation.

MP73-03 THE PROPORTION OF PATIENTS ELIGIBLE FOR FOCAL THERAPY OF NON-METASTATIC PROSTATE CANCER IN THE MODERN MRI-DIRECTED DIAGNOSTIC PATHWAY

You have accessJournal of UrologyCME1 Apr 2023MP73-03 THE PROPORTION OF PATIENTS ELIGIBLE FOR FOCAL THERAPY OF NON-METASTATIC PROSTATE CANCER IN THE MODERN MRI-DIRECTED DIAGNOSTIC PATHWAY Deepika Reddy, David Eldred-Evans, Mathias Winkler, Taimur Shah, and Hashim Ahmed Deepika ReddyDeepika Reddy More articles by this author , David Eldred-EvansDavid Eldred-Evans More articles by this author , Mathias WinklerMathias Winkler More articles by this author , Taimur ShahTaimur Shah More articles by this author , and Hashim AhmedHashim Ahmed More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003341.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Medium-term outcomes following focal therapy for non-metastatic prostate cancer demonstrate good cancer control. There is uncertainty about what proportion of patients might be eligible for focal therapy, given the shift to an upfront MRI in the diagnostic pathway. Using four large prospective studies (PICTURE, PROMIS, IP1-PROSTAGRAM and RAPIDOnline), we evaluated how many newly diagnosed patients might be suitable for focal therapy. METHODS: Suitability was determined in a stepwise nature according to the Delphi Consensus criteria on focal therapy: PSA≤20 ng/ml, ≤rT3aN0M0, Gleason Grade Group (GGG) ≤3, if highest (GGG) was 1 then cancer length must be ≥6 mm, and treatment pattern must intend to spare at least 1 neurovascular bundle. Each study obtained local or external Research and Ethics approval. RESULTS: 201/330 (61%) recruited into PICTURE were diagnosed with≤rT3aN0 prostate cancer with PSA≤20 ng/ml of whom 119/201 (59%) were deemed suitable for focal treatment. None would have D’Amico low risk disease, 105 (88%) and 14 (12%) would have D’Amico intermediate and high-risk disease, respectively. Within PROMIS 406/740 (55%) patients had≤rT3aN0 prostate cancer and PSA≤20 ng/ml. 196/406 (48%) were focal suitable. 4 (2%), 76 (39%) and 116 (59%) had low, intermediate, and high-risk. 534/2372 (23%) in RAPID were diagnosed with≤rT3aN0 disease and PSA≤20 ng/ml. 364/534 (68%) were focal suitable. 3 (1%), 296 (82%) and 65 (18%) had low, intermediate, and high-risk. 37/411 (9%) patients recruited to IP1-PROSTAGRAM had≤rT3aN0 disease with PSA<20 ng/ml. 17/37 (46%) were focal suitable. 2 (12%) and 15 (88%) had low and intermediate-risk disease. CONCLUSIONS: Independent of varying incidence of prostate cancer within each cohorts, once diagnosed with localised disease between 5 and 7 patients out of 10 were eligible for focal treatment. Source of Funding: n/a © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1035 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Deepika Reddy More articles by this author David Eldred-Evans More articles by this author Mathias Winkler More articles by this author Taimur Shah More articles by this author Hashim Ahmed More articles by this author Expand All Advertisement PDF downloadLoading ...

Prostate Cancer in Renal Transplant Recipients: Results from a Large Contemporary Cohort.

Objectives: The aim of this study was to assess the natural history of prostate cancer (PCa) in renal transplant recipients (RTRs) and to clarify the controversy over whether RTRs have a higher risk of PCa and poorer outcomes than non-RTRs, due to factors such as immunosuppression. Patients and Methods: We performed a retrospective multicenter study of RTRs diagnosed with cM0 PCa between 2001 and 2019. Primary outcomes were overall (OS) and cancer-specific survival (CSS). Secondary outcomes included biochemical recurrence and/or progression after active surveillance (AS) and evaluation of variables possibly influencing PCa aggressiveness and outcomes. Management modalities included surgery, radiation, cryotherapy, HIFU, AS, and watchful waiting. Results: We included 166 men from nine institutions. Median age and eGFR at diagnosis were 67 (IQR 60−73) and 45.9 mL/min (IQR 31.5−63.4). ASA score was >2 in 58.4% of cases. Median time from transplant to PCa diagnosis was 117 months (IQR 48−191.5), and median PSA at diagnosis was 6.5 ng/mL (IQR 5.02−10). The biopsy Gleason score was ≥8 in 12.8%; 11.6% and 6.1% patients had suspicion of ≥cT3 > cT2 and cN+ disease. The most frequent management method was radical prostatectomy (65.6%), followed by radiation therapy (16.9%) and AS (10.2%). At a median follow-up of 60.5 months (IQR 31−106) 22.9% of men (n = 38) died, with only n = 4 (2.4%) deaths due to PCa. Local and systemic progression rates were 4.2% and 3.0%. On univariable analysis, no major influence of immunosuppression type was noted, with the exception of a protective effect of antiproliferative agents (HR 0.39, 95% CI 0.16−0.97, p = 0.04) associated with a decreased risk of biochemical recurrence (BCR) or progression after AS. Conclusion: PCa diagnosed in RTRs is mainly of low to intermediate risk and organ-confined at diagnosis, with good cancer control and low PCa death at intermediate follow-up. RTRs have a non-negligible risk of death from causes other than PCa. Aggressive upfront management of the majority of RTRs with PCa may, therefore, be avoided.

Comparative Effectiveness of Radiation Versus Radical Cystectomy for Localized Muscle-Invasive Bladder Cancer

Radical cystectomy (RC) with neoadjuvant chemotherapy is the most commonly recommended treatment for muscle-invasive bladder cancer (MIBC), yet RC with urinary diversion remains an invasive treatment. Although some patients with MIBC gain good cancer control with radiation therapy (RT), its effectiveness remains under discussion. Therefore, we aimed to reveal the effectiveness of RT compared with RC for MIBC. Using cancer registry and administrative data from 31 hospitals in our prefecture, we recruited patients with bladder cancer (BC) initially registered between January 2013 and December 2015. All patients received RC or RT, and none had metastases. Prognostic factors for overall survival (OS) were analyzed by Cox proportional hazards model and log-rank test. Propensity score matching between the RC and RT groups was performed to examine the association of each factor with OS. Among the patients with BC, 241 received RC and 92 received RT. Median ages of the patients receiving RC and RT were 71.0 and 76.5 years, respectively. Five-year OS rates were 44.8% for patients receiving RC and 27.6% for patients receiving RT (P < .001). Multivariate analysis for OS showed that older age, poorer functional disability, clinical node positive, and pathology of nonurothelial carcinoma were significantly associated with worse prognosis. A propensity score-matching model identified 77 patients with RC and 77 with RT. In this arranged cohort, there were no significant differences in OS between the RC and RT groups (P=.982). Prognostic analysis with matched characteristics showed that patients with BC receiving RT were not significantly different from those receiving RC. These findings could contribute to proper treatment strategies for MIBC.

Stereotactic Ablative Radiotherapy in the Treatment of Early-Stage Lung Cancer – A Done Deal?

Stereotactic ablative radiotherapy (SABR) is an important curative-intent treatment option for early-stage non-small cell lung cancer. It offers good cancer control without invasive surgery and has become the standard of care for medically inoperable patients. The literature on SABR for early-stage non-small cell lung cancer is substantial and continues to grow. However, there remain areas of controversy where data are limited – notably the use of SABR in medically operable patients. Other areas of some debate include the treatment of central/ultra-central and large (>5 cm) lesions, as well as treatment with co-existing interstitial lung disease. This review article provides an overview of the current literature together with a discussion of future directions.

Magnetic Resonance Imaging and Targeted Biopsies Compared to Transperineal Mapping Biopsies Before Focal Ablation in Localised and Metastatic Recurrent Prostate Cancer After Radiotherapy

BackgroundRecurrent prostate cancer after radiotherapy occurs in one in five patients. The efficacy of prostate magnetic resonance imaging (MRI) in recurrent cancer has not been established. Furthermore, high-quality data on new minimally invasive salvage focal ablative treatments are needed. ObjectiveTo evaluate the role of prostate MRI in detection of prostate cancer recurring after radiotherapy and the role of salvage focal ablation in treating recurrent disease. Design, setting, and participantsThe FORECAST trial was both a paired-cohort diagnostic study evaluating prostate multiparametric MRI (mpMRI) and MRI-targeted biopsies in the detection of recurrent cancer and a cohort study evaluating focal ablation at six UK centres. A total of 181 patients were recruited, with 155 included in the MRI analysis and 93 in the focal ablation analysis. InterventionPatients underwent choline positron emission tomography/computed tomography and a bone scan, followed by prostate mpMRI and MRI-targeted and transperineal template-mapping (TTPM) biopsies. MRI was reported blind to other tests. Those eligible underwent subsequent focal ablation. An amendment in December 2014 permitted focal ablation in patients with metastases. Outcome measurements and statistical analysisPrimary outcomes were the sensitivity of MRI and MRI-targeted biopsies for cancer detection, and urinary incontinence after focal ablation. A key secondary outcome was progression-free survival (PFS). Results and limitationsStaging whole-body imaging revealed localised cancer in 128 patients (71%), with involvement of pelvic nodes only in 13 (7%) and metastases in 38 (21%). The sensitivity of MRI-targeted biopsy was 92% (95% confidence interval [CI] 83–97%). The specificity and positive and negative predictive values were 75% (95% CI 45–92%), 94% (95% CI 86–98%), and 65% (95% CI 38–86%), respectively. Four cancer (6%) were missed by TTPM biopsy and six (8%) were missed by MRI-targeted biopsy. The overall MRI sensitivity for detection of any cancer was 94% (95% CI 88–98%). The specificity and positive and negative predictive values were 18% (95% CI 7–35%), 80% (95% CI 73–87%), and 46% (95% CI 19–75%), respectively. Among 93 patients undergoing focal ablation, urinary incontinence occurred in 15 (16%) and five (5%) had a grade ≥3 adverse event, with no rectal injuries. Median follow-up was 27 mo (interquartile range 18–36); overall PFS was 66% (interquartile range 54–75%) at 24 mo. ConclusionsPatients should undergo prostate MRI with both systematic and targeted biopsies to optimise cancer detection. Focal ablation for areas of intraprostatic recurrence preserves continence in the majority, with good early cancer control. Patient summaryWe investigated the role of magnetic resonance imaging (MRI) scans of the prostate and MRI-targeted biopsies in outcomes after cancer-targeted high-intensity ultrasound or cryotherapy in patients with recurrent cancer after radiotherapy. Our findings show that these patients should undergo prostate MRI with both systematic and targeted biopsies and then ablative treatment focused on areas of recurrent cancer to preserve their quality of life.This trial is registered at ClinicalTrials.gov as NCT01883128.

Cancer Control Outcomes Following Focal Therapy Using High-intensity Focused Ultrasound in 1379 Men with Nonmetastatic Prostate Cancer: A Multi-institute 15-year Experience

BackgroundFocal therapy aims to treat areas of cancer to confer oncological control whilst reducing treatment-related functional detriment. ObjectiveTo report oncological outcomes and adverse events following focal high-intensity focused ultrasound (HIFU) for treating nonmetastatic prostate cancer. Design, setting, and participantsAn analysis of 1379 patients with ≥6 mo of follow-up prospectively recorded in the HIFU Evaluation and Assessment of Treatment (HEAT) registry from 13 UK centres (2005–2020) was conducted. Five or more years of follow-up was available for 325 (24%) patients. Focal HIFU therapy used a transrectal ultrasound-guided device (Sonablate; Sonacare Inc., Charlotte, NC, USA). Outcome measurements and statistical analysisFailure-free survival (FFS) was primarily defined as avoidance of no evidence of disease to require salvage whole-gland or systemic treatment, or metastases or prostate cancer–specific mortality. Differences in FFS between D’Amico risk groups were determined using a log-rank analysis. Adverse events were reported using Clavien-Dindo classification. Results and limitationsThe median (interquartile range) age was 66 (60–71) yr and prostate-specific antigen was 6.9 (4.9–9.4) ng/ml with D’Amico intermediate risk in 65% (896/1379) and high risk in 28% (386/1379). The overall median follow-up was 32 (17–58) mo; for those with ≥5 yr of follow-up, it was 82 (72–94). A total of 252 patients had repeat focal treatment due to residual or recurrent cancer; overall 92 patients required salvage whole-gland treatment. Kaplan-Meier 7-yr FFS was 69% (64–74%). Seven-year FFS in intermediate- and high-risk cancers was 68% (95% confidence interval [CI] 62–75%) and 65% (95% CI 56–74%; p = 0.3). Clavien-Dindo >2 adverse events occurred in 0.5% (7/1379). The median 10-yr follow-up is lacking. ConclusionsFocal HIFU in carefully selected patients with clinically significant prostate cancer, with six and three of ten patients having, respectively, intermediate- and high-risk cancer, has good cancer control in the medium term. Patient summaryFocal high-intensity focused ultrasound treatment to areas of prostate with cancer can provide an alternative to treating the whole prostate. This treatment modality has good medium-term cancer control over 7 yr, although 10-yr data are not yet available.

Nerve-sparing Robot-assisted Retroperitoneal Lymph Node Dissection: The Monoblock Technique

BackgroundRetroperitoneal lymph node dissection (RPLND) is a treatment option for men with stage 1 or 2 testis cancer and the standard of care for men with postchemotherapy retroperitoneal residual disease. Given the morbidity of RPLND, four important surgical modifications have been proposed: minimally invasive access, nerve-sparing resection, template resection, and en-bloc resection. ObjectiveTo describe the surgical steps and perioperative outcomes of robotic nerve-sparing unilateral template RPLND with en-bloc resection (roboRPLND-NS+). Design, setting, and participantsFrom 2017 to 2019, five patients with suspicion of retroperitoneal metastatic testicular cancer on abdominopelvic computed tomography underwent roboRPLND-NS+ at a single referral center. All surgeries were carried out by a single surgeon who has performed more than 500 extended and more than 50 super-extended robot-assisted lymph node dissections. Surgical procedureA lateral transperitoneal robotic approach with a da Vinci Xi Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) in six-arm configuration was used. The sympathetic chains, postganglionic sympathetic fibers, and hypogastric plexus were preserved as much as possible to ensure a nerve-sparing procedure. The template borders consisted of the renal vein cranially, the ureter laterally, the interaortocaval space medially, the common iliac artery caudally, and the psoas muscle dorsally for the right and left modified RPLND templates. Lymph nodes and the surrounding fatty tissue were progressively resected from the common iliac vessels and the abdominal aorta using the split-and-roll technique, and all of the template tissue was resected as a single specimen. Intraoperative and postoperative complications were recorded. MeasurementsLymph node yield and perioperative and postoperative oncological and functional outcomes were measured. Results and limitationsThe median patient age was 38 yr (interquartile range [IQR] 32–41) and the median operative time was 274 min (IQR 238–280). Node metastases were pathologically confirmed in three patients. The median number of lymph nodes removed was 19 (IQR 18–21), and the median number of positive lymph nodes was 2 (IQR 1–3). No patient experienced intraoperative or postoperative complications. The postoperative hospital stay was either 3 or 4 d. Maintenance of antegrade ejaculation was achieved in all patients. After median follow-up of 15 mo (IQR 14–30), all patients were alive and no recurrence was observed. Limitations include the low number of patients and the single surgeon experience. ConclusionsRoboRPLND-NS+ is a safe and feasible technique that allows removal of a high number of lymph nodes with good functional outcomes. Short-term survival outcomes were excellent, with no recurrences or deaths recorded. Patient summaryWe describe a feasible and safe robot-assisted surgical procedure for removal of lymph nodes in patients with testicular cancer. Our technique has potential to decrease the medical problems arising as side effects of the surgery while achieving good cancer control.

MRI and targeted biopsies compared to transperineal mapping biopsies for targeted ablation in recurrent prostate cancer after radiotherapy: Primary outcomes of the FORECAST trial.

5009 Background: Radiotherapy is a common and effective treatment for localised prostate cancer. However, recurrence of cancer can occur in 10-15% of men in the following 5 years. Most patients with recurrence are managed using hormonal therapy with associated systemic side-effects and subsequent development of castrate resistance. Salvage prostatectomy confers a high risk of urine incontinence and rectal injury. Accurately localising and ablating only areas of recurrence within the prostate might be effective with fewer side-effects. The FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial assessed this diagnostic and treatment pathway for men with radiorecurrent cancer (NCT01883128). Methods: We first compared the accuracy of multi-parametric MRI (mp-MRI) and MRI-targeted biopsy in identifying areas of recurrent cancer to a transperineal template prostate mapping (TTPM) biopsy (Apr/2014-Jan/2018) in 181 patients from 6 UK centres. We then assessed the functional and cancer control outcomes of focally ablating areas of intraprostatic recurrence in 93 patients with localised or metastatic cancer (using cryotherapy or HIFU). Primary outcomes were sensitivity of mpMRI and MRI-targeted biopsies and urinary continence after focal ablation. A key secondary outcome was progression free survival (PFS) defined as no new metastases or hormone use (localised group only), or chemotherapy or further local treatment. Results: Of 181 men with suspicion of recurrence following radiotherapy, re-staging whole-body imaging (Choline PET and Bone Scan) showed localised disease in 128 (71%), nodal disease only in 13 (7%) and 38 (21%) metastatic. The sensitivity of MRI-targeted biopsy was 92% (95%CI 83-97%). Specificity, and positive and negative predictive values, were 75% (95%CI 45-92%), 94% (95%CI 86-98%) and 65% (95%CI 38-86%). 4/72 (6%) cancers were missed on TTPM biopsies alone and 6/72 (8%) were missed on MRI-targeted biopsies alone. Overall sensitivity of mpMRI was 81% (95%CI 73-88%) using Likert score 4-5 to denote a positive test. Specificity, and positive and negative predictive values, were 88% (95%CI 73-98%), 96% (95%CI 90-99%) and 57% (95%CI 42-70%). In the 93 men undergoing focal ablation, urinary continence was preserved in 78/93 (84%); 5/93 (5%) had a CTCAE grade 3+ adverse events. There were no rectal injuries. With a median follow-up of 27.8 [SD 1.3] months, PFS was 66% [54-75] at 24-months. Metastases-free survival in the 73 men with localised disease was 80% [95%CI 68–88] at 24-months. There were no cancer specific deaths. Conclusions: Prostate mpMRI and MRI-targeted biopsies can accurately detect and localise recurrent prostate cancer following radiotherapy. Focal ablation to areas of intra-prostatic recurrence preserves continence in the majority of men with good cancer control. Clinical trial information: NCT01883128.

Oncological Long-term Outcome After Whole-gland High-intensity Focused Ultrasound for Prostate Cancer—21-yr Follow-up

BackgroundOwing to the morbidity of established radical treatment options for prostate cancer, alternative whole-gland and focal treatment strategies have emerged. High-intensity focused ultrasound (HIFU) is one of the most studied sources for tissue ablation and has been used since the 1990s. ObjectiveTo provide 21-yr oncological long-term follow-up data of an unselected series of patients who underwent whole-gland HIFU for nonmetastatic prostate cancer. Design, setting, and participantsA total of 674 patients were treated between November 1997 and November 2012 in one university center. Outcome measurements and statistical analysisThe oncological outcome was assessed by biopsy failure–free survival (BFFS), salvage treatment–free survival (STFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Multivariable Cox proportional hazard regression analyses were performed to estimate the prognostic relevance of clinical variables. Results and limitationsIn total, 560 patients were included into the evaluation and the median follow-up was 15.1 yr, with a range up to 21.4 yr. At 15 yr, CSS rates for low-, intermediate-, and high-risk patients were 95%, 89%, and 65%, respectively; MFS, STFS-1 (salvage treatment other than HIFU), STFS-2 (salvage treatment including repeat HIFU), and BFFS rates were 91%, 85%, and 58%; 77%, 63%, and 29%; 67%, 52%, and 28%; and 82%, 73%, and 47%, respectively. Preoperative high-risk category was an independent predictor of inferior OS, CSS, MFS, STFS, and BFFS. ConclusionsAlthough whole-gland HIFU achieved good long-term cancer control in low- and intermediate-risk patients, high-risk patients should not be treated routinely by HIFU. Intermediate-risk patients achieve high CSS and MFS rates, but a relevant salvage treatment rate has to be reckoned with. Long-term data after whole-gland therapy might help derive implications for focal treatment sources and patient selection. Patient summaryLong-term data after whole-gland high-intensity focused ultrasound (HIFU) therapy are crucial to prove its oncological efficacy, and may help derive implications for focal treatment strategies and patient selection. In this context, whole-gland HIFU achieved good long-term cancer control up to 21 yr in low- and intermediate-risk prostate cancer (PCa) patients. Owing to considerably inferior long-term cancer control, it should not routinely be used in high-risk PCa patients.

Interplay of long non-coding RNAs and HIF-1α: A new dimension to understanding hypoxia-regulated tumor growth and metastasis.

Hypoxia is a feature of the solid tumor microenvironment that is associated with poor clinical outcomes in multiple tumor types. Hypoxia-induced factor-1 alpha (HIF-1α) is a master regulator of hypoxic adaption, has been demonstrated to modulate hypoxic gene expression profiling and signaling transduction networks, and is thus a potential therapeutic target. Despite hypoxic response signaling having being extensively studied, the involvement of long non-coding RNAs (lncRNAs) in the hypoxic response has become a new focus of attention. Emerging evidence has documented complex interactions between HIF-1α and lncRNAs, which contribute to the acquisition of multiple hallmarks of cancer. In this review, we focus on recent advances in the study of hypoxia and HIF-1α-regulated lncRNAs, and summarize the molecular mechanisms and functional outcomes of the interplay between lncRNAs and HIF-1α, which may provide important insights into cancer diagnosis and prognosis, enabling better control of cancer.

Erratum to: Oncological outcome of neoadjuvant low-dose estramustine plus LHRH agonist/antagonist followed by extended radical prostatectomy for Japanese patients with high-risk localized prostate cancer: a prospective single-arm study.

Background Patients with advanced high-risk prostate cancer (PCa) are prone to have worse pathological diagnoses of positive surgical margins and/or lymph node invasion, resulting in early biochemical recurrence (BCR) despite having undergone radical prostatectomy (RP). Therefore, it is controversial whether patients with high-risk PCa should undergo RP. The purpose of this study was to evaluate the efficacy of neoadjuvant chemohormonal therapy (NAC) followed by RP. Methods A total of 87 patients with high-risk PCa prospectively underwent extended RP after NAC; most of the patients underwent 6 months of estramustine phosphate (EMP) 140 mg twice daily, along with a luteinizing hormone-releasing hormone agonist/antagonist. We developed our surgical technique to reduce the rate of positive surgical margins. We aimed to approach the muscle layer of the rectum by dissecting the mesorectal fascia and continuing the dissection through the mesorectum until the muscle layer of the rectum was exposed. Results More than 1 year had elapsed after surgery in all 86 patients, with a median follow-up period of 37.7 months. The 3-year BCR-free survival was 74.9%. Multivariate Cox-regression analysis revealed that a positive core ratio of 50% or greater and pathological stage of pT3 or greater were independent predictors for BCR. About 17 of 23 cases received salvage androgen deprivation therapy and concurrent external beam radiotherapy, and showed no progression after the salvage therapies. Conclusions NAC concordant with extended RP is feasible and might provide good cancer control for patients with high-risk PCa.

Early stratification of radiotherapy response by activatable inflammation magnetic resonance imaging

Tumor heterogeneity is one major reason for unpredictable therapeutic outcomes, while stratifying therapeutic responses at an early time may greatly benefit the better control of cancer. Here, we developed a hybrid nanovesicle to stratify radiotherapy response by activatable inflammation magnetic resonance imaging (aiMRI) approach. The high Pearson’s correlation coefficient R values are obtained from the correlations between the T1 relaxation time changes at 24–48 h and the ensuing adaptive immunity (R = 0.9831) at day 5 and the tumor inhibition ratios (R = 0.9308) at day 18 after different treatments, respectively. These results underscore the role of acute inflammatory oxidative response in bridging the innate and adaptive immunity in tumor radiotherapy. Furthermore, the aiMRI approach provides a non-invasive imaging strategy for early prediction of the therapeutic outcomes in cancer radiotherapy, which may contribute to the future of precision medicine in terms of prognostic stratification and therapeutic planning.

Oncological outcome of neoadjuvant low-dose estramustine plus LHRH agonist/antagonist followed by extended radical prostatectomy for Japanese patients with high-risk localized prostate cancer: a prospective single-arm study.

Patients with advanced high-risk prostate cancer (PCa) are prone to have worse pathological diagnoses of positive surgical margins and/or lymph node invasion, resulting in early biochemical recurrence (BCR) despite having undergone radical prostatectomy (RP). Therefore, it is controversial whether patients with high-risk PCa should undergo RP. The purpose of this study was to evaluate the efficacy of neoadjuvant chemohormonal therapy (NAC) followed by "extended" RP. A total of 87 patients with high-risk PCa prospectively underwent extended RP after NAC; most of the patients underwent 6months of estramustine phosphate (EMP) 140mg twice daily, along with a luteinizing hormone-releasing hormone agonist/antagonist. We developed our surgical technique to reduce the rate of positive surgical margins. We aimed to approach the muscle layer of the rectum by dissecting the mesorectal fascia and continuing the dissection through the mesorectum until the muscle layer of the rectum was exposed. More than 1year had elapsed after surgery in all 86 patients, with a median follow-up period of 37.7months. The 3-year BCR-free survival was 74.9%. Multivariate Cox-regression analysis revealed that a positive core ratio of 50% or greater and pathological stage of pT3 or greater were independent predictors for BCR. About 17 of 23 cases received salvage androgen deprivation therapy and concurrent external beam radiotherapy, and showed no progression after the salvage therapies. NAC concordant with extended RP is feasible and might provide good cancer control for patients with high-risk PCa.

PD23-09 CONTRAST MEDIA KINETICS IN MULTIPARAMETRIC MRI BEFORE RADICAL PROSTATECTOMY PREDICTS PROBABILITY OF POSTOPERATIVE INCONTINENCE

INTRODUCTION AND OBJECTIVES:While radical prostatectomy (RP) renders good cancer control, urinary incontinence (UI) remains a major morbidity issue and significantly influences the postoperative qu...

Extended radical prostatectomy following neoadjuvant chemohormononal therapy (low dose estrmustine + LHRH agonist/antagonist) contributes to good cancer control for patients with high risk localized prostate cancer.

185 Background: Patients with high-risk prostate cancer (PCa) according to D’Amico risk categories are prone to a pathological diagnosis of positive margins or lymph node invasion and biochemical recurrence, despite having undergone radical prostatectomy (RP). Therefore, it is controversial whether RP should be done for high risk PC patients. Methods: 87 high-risk PCa patients prospectively underwent ‘extended’ RP following neoadjuvant chemohormonal therapy (NAC); primarily 6 months of estramustine phosphate 280 mg bid, along with a LH-RH agonist/antagonist. Our surgical technique was developed to reduce the rates of positive surgical margins. The goal is to approach the muscle layer of the rectum by dissecting the mesorectal fascia and continuing the dissection through the mesorectum until the muscle layer of the rectum is exposed. The procedure was safely performed as a result of good recognition of the structure between the perineal body and the rectal surface. We also performed extended lymphadenectomy if the patients meet two or more of D’Amico risk categories Results: More than 1 year had elapsed after surgery in 69 of the 87 patients with the median follow-up period of 36.2 months. Among those 69 patients, 18 (26.1%) experienced PSA failure. Kaplan-Meier analyses revealed that significant poorer PSA progression-free survival were observed in patients with higher positive biopsy core ratio, lymph node metastasis, and higher pathological stage (pT3a/b). Multivariate Cox-regression analysis revealed that higher pathological stage (pT3a/b) was the only independent valuable for predicting PSA progression failure. These 18 cases received salvage androgen deprivation therapy followed-by external beam radiotherapy and showed no progression after the salvage therapies (median follow-up period, 34.6 months after PSA progression). Conclusions: NAC concordant with extended RP is feasible and contributes to negative surgical margins that might provide good cancer control for patients with high-risk PCa.

Overall survival and oncological outcomes after partial nephrectomy and radical nephrectomy for cT2a renal tumors: A collaborative international study from the French kidney cancer research network UroCCR

Partial nephrectomy (PN) is recommended as first-line treatment for cT1 stage kidney tumors because of a better renal function and probably a better overall survival than radical nephrectomy (RN). For larger tumors, PN has a controversial position due to lack of evidence showing good cancer control. The aim of this study was to compare the results of PN and RN in cT2a stage on overall survival and oncological results. A retrospective international multicenter study was conducted in the frame of the French kidney cancer research network (UroCCR). We considered all patients aged≥18 years who underwent surgical treatment for localized renal cell carcinoma (RCC) stage cT2a (7.1-10cm) between 2000 and 2014. Cox and Fine-Gray models were performed to analyze overall survival (OS), cancer specific survival (CSS) and cancer-free survival (CFS). Comparison between PN and RN was realized after an adjustment by propensity score considering predefined confounding factors: age, sex, tumor size, pT stage of the TNM classification, histological type, ISUP grade, ASA score. A total of 267 patients were included. OS at 3 and 5 years was 93.6% and 78.7% after PN and 88.0% and 76.2% after RN, respectively. CSS at 3 and 5 years was 95.4% and 80.2% after PN and 91.0% and 85.0% after RN. No significant difference between groups was found after propensity score adjustment for OS (HR 0.87, 95% CI: 0.37-2.05, P=0.75), CSS (HR 0.52, 95% CI: 0.18-1.54, P=0.24) and CFS (HR 1.02, 95% CI: 0.50-2.09, P=0.96). PN seems equivalent to RN for OS, CSS and CFS in cT2a stage kidney tumors. The risk of recurrence is probably more related to prognostic factors than the surgical technique. The decision to perform a PN should depend on technical feasibility rather than tumor size, both to imperative and elective situation. 4.

Combined Vocal Exercises for Rehabilitation After Supracricoid Laryngectomy: Evaluation of Different Execution Times

The supracricoid partial laryngectomy allows the preservation of laryngeal functions with good local cancer control. To assess laryngeal configuration and voice analysis data following the performance of a combination of two vocal exercises: the prolonged /b/vocal exercise combined with the vowel /e/ using chest and arm pushing with different durations among individuals who have undergone supracricoid laryngectomy. Eleven patients undergoing partial laryngectomy supracricoid with cricohyoidoepiglottopexy (CHEP) were evaluated using voice recording. Four judges performed separately a perceptive-vocal analysis of hearing voices, with random samples. For the analysis of intrajudge reliability, repetitions of 70% of the voices were done. Intraclass correlation coefficient was used to analyze the reliability of the judges. For an analysis of each judge to the comparison between zero time (time point 0), after the first series of exercises (time point 1), after the second series (time point 2), after the third series (time point 3), after the fourth series (time point 4), and after the fifth and final series (time point 5), the Friedman test was used with a significance level of 5%. The data relative to the configuration of the larynx were subjected to a descriptive analysis. In the evaluation, were considered the judge results 1 which have greater reliability. There was an improvement in the general level of vocal, roughness, and breathiness deviations from time point 4 [T4]. The prolonged /b/vocal exercise, combined with the vowel /e/ using chest- and arm-pushing exercises, was associated with an improvement in the overall grade of vocal deviation, roughness, and breathiness starting at minute 4 among patients who had undergone supracricoid laryngectomy with CHEP reconstruction.

Focal cryotherapy: step by step technique description

ABSTRACTIntroduction and objective:Focal cryotherapy emerged as an efficient option to treat favorable and localized prostate cancer (PCa). The purpose of this video is to describe the procedure step by step.Materials and methods:We present the case of a 68 year-old man with localized PCa in the anterior aspect of the prostate.Results:The procedure is performed under general anesthesia, with the patient in lithotomy position. Briefly, the equipment utilized includes the cryotherapy console coupled with an ultrasound system, argon and helium gas bottles, cryoprobes, temperature probes and an urethral warming catheter. The procedure starts with a real-time trans-rectal prostate ultrasound, which is used to outline the prostate, the urethra and the rectal wall. The cryoprobes are pretested and placed in to the prostate through the perineum, following a grid template, along with the temperature sensors under ultrasound guidance. A cystoscopy confirms the right positioning of the needles and the urethral warming catheter is installed. Thereafter, the freeze sequence with argon gas is started, achieving extremely low temperatures (-40°C) to induce tumor cell lysis. Sequentially, the thawing cycle is performed using helium gas. This process is repeated one time. Results among several series showed a biochemical disease-free survival between 71-93% at 9-70 month- follow-up, incontinence rates between 0-3.6% and erectile dysfunction between 0-42% (1–5).Conclusions:Focal cryotherapy is a feasible procedure to treat anterior PCa that may offer minimal morbidity, allowing good cancer control and better functional outcomes when compared to whole-gland treatment.