Therapy For Localized Prostate Cancer Research Articles

Current evidence for focal laser ablation and vascular-targeted photodynamic therapy for localized prostate cancer: review of literature published in the last 2 years.

Currently, a significant number of patients are diagnosed with unilateral and apparently unifocal low or intermediate-risk prostate cancer (PCa). These patients are suitable for focal therapy, thus preventing radical treatment side effects without affecting cancer control. Among focal therapy energy sources, laser-based technologies have shown promising outcomes. We aimed to summarize recent data on focal laser ablation (FLA) and vascular-targeted photodynamic therapy (VTP) for PCa. We selected eight studies reporting data on 1155 patients with PCa who underwent laser-based focal therapy. Five studies were on FLA and three on VTP (six prospective and two retrospective series); four reported both oncologic and functional outcomes whereas in three only oncologic and one only functional outcomes were discussed. Follow-up protocols and durations varied widely among the studies. PCa recurrence rates ranged between 20 and 56%. Urinary and erectile function were preserved after treatment, and complications were mild and transient. A lack of high-quality data on long-term oncological outcomes still remains, thus further highlighting the need for prospective controlled studies. FLA and VTP are well tolerated procedures with excellent functional outcomes. However, both procedures showed a significant rate of PCa recurrence, thus demonstrating a certain grade of oncologic control failure of the procedure and/or nonoptimal patients' selection.

Prostate-specific antigen kinetics and metastasis-free survival in patients treated with external beam radiotherapy combined with high-dose-rate brachytherapy boost and androgen deprivation therapy for localized prostate cancer.

PurposeSerum prostate-specific antigen (PSA) kinetics has been linked to prognosis in prostate cancer (PCa) patients. Our goal was to analyze the association between PSA kinetics and metastasis-free survival (MFS) in patients with localized PCa treated with high-dose-rate (HDR) brachytherapy (BT) boost combined with external beam radiotherapy (EBRT).Material and methodsWe retrospectively analyzed multiple PSA kinetics related to PSA nadir (nPSA), PSA bouncing, and biochemical recurrence (BCR) in 186 PCa patients treated with neoadjuvant androgen deprivation therapy (ADT), followed by EBRT combined with HDR-BT boost. Uni- and multivariate Cox regression models were calculated to assess the value of PSA-related parameters for the prediction of MFS.Results5- and 10-year MFS were 95% and 84%, respectively. Median nPSA was 0.011 (IQR, 0.007-0.057) ng/ml and predicted MFS in multivariable analysis. Implementation of nPSA improved c-index of baseline model from 0.8 to 0.68. nPSA of 0.2 ng/ml offered the most optimal discriminatory ability for identifying patients with better prognoses. Time to nPSA (median, 11 months; IQR, 8-18 months) and PSA bounce, which occurred in 12.4% of patients, were not significantly associated with MFS.ConclusionsLower values of nPSA are significantly associated with decreased risk of developing metastases in patients treated with EBRT combined with HDR-BT boost and ADT, and improve the accuracy of a clinical model for MFS.

Focal therapy for localized prostate cancer - Current status.

Focal therapy (FT) has recently gained popularity for the treatment of localized prostate cancer (PCa). FT achieves cancer control by targeting the lesions or the regions of the cancer and avoids damage to the surrounding tissues thus minimizing side effects which are common to the radical treatment, such as urinary continence and sexual function, and bowel-related side effects. Various ablative methods are used to deliver energy to the cancerous tissue. We review the different modalities of treatment and the current state of FT for PCa.

Incidence of genitourinary complications following radiation therapy for localised prostate cancer

PurposeStudies of genitourinary toxicity following radiotherapy for prostate cancer are mainly from high volume single institutions and the incidence and burden of treatment remain uncertain. Hence we determine the cumulative incidence of treatment-related genitourinary toxicity in patients with localised prostate cancer treated with primary external beam radiotherapy (EBRT) at a state population level.MethodsWe analysed data from a prospective population-based cohort, including hospital admission and cancer registry data, for men with localised prostate cancer who underwent primary EBRT without nodal irradiation between 1998 and 2019 in South Australia. The 10-year cumulative incidence of genitourinary toxicity requiring hospitalisation or procedures was determined. Clinical predictors of toxicity and the volume of admissions, non-operative, minor operative and major operative procedures were determined.ResultsAll the included patients (n = 3350) had EBRT, with a median (IQR) of 74 Gy (70–78) in 37 fractions (35–39). The 10-year cumulative incidence of was 28.4% (95% CI 26.3–30.6) with a total of 2545 hospital admissions, including 1040 (41%) emergency and 1893 (74%) readmissions. The 10-year cumulative incidence of patients in this cohort requiring a urological operative procedure was 18% (95% CI 16.1–19.9), with a total of 106 (4.2%) non-operative, 1044 (41%) minor operative and 57 (2.2%) major operative urological procedures.ConclusionsGenitourinary toxicity after radiotherapy for prostate cancer is common. Although there continue to be advancements in radiotherapy techniques, patients and physicians should be aware of the risk of late toxicity when considering EBRT.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00345-022-04124-x.

Lesion-targeted focal therapy for localized prostate cancer, using cryoablation and microwave ablation : Case presentation and tips for successful treatment

Lesion-targeted focal therapy for localized prostate cancer, using cryoablation and microwave ablation : Case presentation and tips for successful treatment

High-Intensity Focused Ultrasound (HIFU) Focal Therapy for Localized Prostate Cancer with MRI-US Fusion Platform.

Objective The study aimed at investigating the outcome of prostate HIFU focal therapy using the MRI-US fusion platform for treatment localization and delivery. Methods It is a prospectively designed case series of HIFU focal therapy for localized prostate cancer. The inclusion criteria include clinical tumor stage ≤T2, visible index lesion on multiparametric MRI less than 20 mm in diameter, absence of Gleason 5 pattern on prostate biopsy, and PSA ≤ 20 ng/ml. HIFU focal therapy was performed in the conventional manner in the beginning 50% of the series, whereas the subsequent cases were performed with MRI-US fusion platform. The primary outcome was treatment failure rate which is defined by the need of salvage therapy. Secondary outcomes included tumor recurrence in follow-up biopsy, PSA change, perioperative complications, and postoperative functional outcomes. Results Twenty patients underwent HIFU focal ablation. HIFU on an MRI-US fusion platform had a trend of a longer total operative time than the conventional counterpart (124.2 min vs. 107.1 min, p=0.066). There was no difference in the mean ablation volume to lesion volume ratio between the two. The mean PSA percentage change from baseline to 6-month is more significant in the conventional group (63.3% vs. 44.6%, p=0.035). No suspicious lesion was seen at 6-month mpMRI in all 20 patients. Two patients, one from each group, eventually underwent radical treatment because of the presence of clinically significant prostate cancer in the form of out-of-field recurrences during follow-up biopsy. No significant difference was observed before and after HIFU concerning uroflowmetry, SF-12 score, and EPIC-26 score. It was observed that energy used per volume was positively correlated with PSA density of the patient (r = 0.6364, p=0.014). Conclusion In conclusion, HIFU with conventional or MRI-US fusion platform provided similar oncological and functional outcomes.

P046 - External validation of biochemical definition to predict oncologic outcomes following focal therapy for localized prostate cancer using high intensity focused ultrasound

P046 - External validation of biochemical definition to predict oncologic outcomes following focal therapy for localized prostate cancer using high intensity focused ultrasound

PJY02 - The proportion of potential candidates for focal therapy in localized prostate cancer in a real-life cohort and their final pathologic results

PJY02 - The proportion of potential candidates for focal therapy in localized prostate cancer in a real-life cohort and their final pathologic results

Outcomes of intensity-modulated radiation therapy for intermediate- or high-risk prostate cancer: a single-institutional study.

There are few reports from Japan about the outcomes of intensity-modulated radiation therapy for localized prostate cancer. This study was aimed at assessing the efficacy and toxicity of intensity-modulated radiation therapy in patients with intermediate- or high-risk prostate cancer. We conducted a review of the data, retrieved from our institutional database, of patients who had received intensity-modulated radiation therapy for localized prostate cancer at a radiation dose of 78Gy in 39 fractions. Data of 201 patients with intermediate-risk prostate cancer and 311 patients with high-risk prostate cancer were analyzed. The median follow-up period after the completion of intensity-modulated radiation therapy was 100months (range, 24-154). The rates of cause-specific survival, overall survival, metastasis-free survival and biochemical recurrence-free survival in the intermediate-risk patients were 99, 95, 95 and 94% at 5years and 99, 91, 90 and 86% at 8years, respectively; the corresponding rates in the high-risk patients were 100, 97, 91 and 84% at 5years and 96, 92, 84 and 76% at 8years, respectively. The crude incidence of late grade 2-3 genitourinary toxicity was 28.1%, and that of late grade 3 genitourinary toxicity was 2.0%. The crude incidence of late grade 2 gastrointestinal toxicity was 5.1%, and there were no cases of late grade 3 gastrointestinal toxicity. Our data demonstrated that intensity-modulated radiation therapy is effective for patients with localized intermediate-risk or high-risk prostate cancer while having minimal toxicity.

Body Composition and Risk of All-Cause Mortality in Men Treated With Radiation Therapy for Prostate Cancer: A Pooled Analysis of NRG/RTOG 9406 and NRG/RTOG 0126

To validate the association between body composition and all-cause mortality in men treated with radiation therapy for localized prostate cancer (PCa). Secondarily, to integrate body composition as a factor to help classify patients by risk of all-cause mortality.All participants of NRG/RTOG 9406 and NRG/RTOG 0126 with archived computed tomography that extended cranially to include the L4-L5 interface were included. Muscle mass and muscle density were estimated by measuring the cross-sectional area and average attenuation of the paired psoas muscles on a single slice at the level of L4-L5. Bone density was estimated by measuring the average attenuation of the vertebral body cancellous bone on a single slice at mid-L5. Adipose tissue density was estimated by measuring the average attenuation of the subcutaneous adipose tissue on a single slice at L4-L5. Survival analyses, including Cox proportional hazards models, were performed to assess the relationship between body composition variables and all-cause mortality. Recursive partitioning (RPA) was utilized to create a classification tree to classify NRG/RTOG 0126 participants by risk of death, and the discriminant ability of the classification model was validated using the NRG/RTOG 9406 data set.Data from 2,066 men was included in this study (864 from NRG/RTOG 9406 and 1,202 from NRG/RTOG 0126). A total of 648 men died in the follow-up period and 51 (7.9%) were due to PCa. Psoas area, psoas density, and vertebral body density were individually associated with overall survival. In the final multivariable model, psoas area, comorbidity score, and age were associated with overall survival (Table). The RPA yielded a classification tree with 4 prognostic groups determined by age, comorbidity, and psoas cross-sectional area. When the RPA classification was applied to the NRG/RTOG 9406 validation set the discriminant ability was preserved (P < 0.001 groupwise log-rank).The results of this study strongly support that body composition is related to all-cause mortality in men with localized PCa, with most deaths due to causes other than PCa. The inclusion of psoas cross-sectional area in the RPA classification tree suggests that body composition provides additive information to age and comorbidity status for mortality prediction. This study also confirms the feasibility of performing body composition analysis using archived CT scans using NRG Oncology clinical trial data sets. These methods can be applied to other NRG Oncology data sets to further explore how body composition is related to patient outcomes.

Evaluation of Visualizing the Prostatic Urinary Tract in MRI With a Super Resolution Deep Learning Model for Urethra Sparing Radiotherapy

<h3>Purpose/Objective(s)</h3> In the treatment planning for urethra-sparing radiation therapy in localized prostate cancer, it is important to visualize the prostatic urinary tract to reduce the risk of urinary symptoms linked to the urethral dose. We developed a methodology for visualizing the prostatic urinary tract by post-urination magnetic resonance imaging (PU-MRI) without using a urethral catheter for urethra-sparing radiotherapy. Several super-resolution (SR) deep learning models were proposed for improving image quality. This study investigated whether these SR deep learning models improve the visibility of the prostatic urinary tract in PU-MRI. <h3>Materials/Methods</h3> We enrolled 30 patients who had previously undergone real-time-image-gated spot scanning proton therapy (RGPT) by inserting fiducial markers at our institution from October 2019 to October 2020. PU-MRI was performed using a non-contrast high-resolution two-dimensional T2-weighted turbo spin-echo (TSE) imaging sequence. Four different SR deep learning models were constructed: the EDSR (enhanced deep SR network), WDSR (widely activated SR network), SRGAN (SR generative adversarial network), and RDN (residual dense network). All models were trained using a diverse 2K resolution high-quality image dataset. We imported PU-MRIs as low-resolution images and exported four SR images that were enlarged using one of the models each. To assess the performance of the proposed SR image compared to PU-MRI, we used the complex wavelet structural similarity index measure (CW-SSIM) as the quantitative metric. A 1-to-5 scale was used to subjectively evaluate the visibility of the prostatic urinary tract by two radiation oncologists. <h3>Results</h3> The mean (± standard deviation) of the CW-SSIM in the EDSR, WDSR, SRGAN, and RDN were 0.999 ± 0.001, 0.999 ± 0.002, 0.993 ± 0.002, and 0.997 ± 0.002, respectively. The mean prostatic urinary tract visibility scores for oncologist 1 and 2 were 3.70 ± 0.64 and 3.53 ± 0.99 for PU-MRI, 3.67 ± 0.60 and 2.70 ± 0.82 for EDSR, 3.70 ± 0.53 and 2.73 ± 0.81 for WDSR, 3.67 ± 0.65 and 2.73 ± 0.81 for SRGAN, and 4.37 ± 0.61 and 3.73 ± 0.93 for RDN, respectively. <h3>Conclusion</h3> This study investigated whether the combination of PU-MRI and SR deep learning models improves visibility of the prostatic urinary tract. The results suggest that SR images using RDN are highly similar to the original image and subjectively improve the visibility of the prostatic urinary tract.

Tumor irradiation combined with minimally invasive surgery (vascular-targeted photodynamic therapy) enhances anti-tumour effects in preclinical prostate cancer

Hanna T Sjoberg, Yiannis Philippou, Anette L Magnussen, Iain DC Tullis, Esther Bridges, Andrea Chatrian, Joel Loefebvre, Ka Ho Tam, Emma A Murphy, Jens Rittscher, Dina Preise, Lilach Agemy, Tamar Yechezkel, Sean C Smart, Paul Kinchesh, Stuart Gilchrist, Danny P Allen, David A Scheiblin, Stephen J Lockett, David A Wink, Alastair D Lamb, Ian G Mills, Adrian Harris, Ruth J Muschel, Boris Vojnovic, Avigdor Scherz, Freddie C Hamdy, Richard J Bryant.&#x0D; &#x0D; Introduction There is an important clinical need to improve the treatment of high risk localised and locally advanced prostate cancer (PCa), and to reduce the side effects of these treatments. We hypothesised that multi-modality therapy combining radiotherapy and vascular-targeted photodynamic therapy (VTP) could PCa tumour control compared against monotherapy with each of these treatments alone. This could provide proof-of-concept to take to the clinic. VTP is a minimally invasive focal surgical therapy for localised PCa, which rapidly destroys targeted tumours through vascular disruption. Tumour vasculature is characterised by vessel immaturity, increased permeability, aberrant branching and inefficient flow. Fractionated radiotherapy (FRT) alters the tumour microenvironment and promotes transient vascular normalisation.&#x0D; Materials and Methods We investigated whether sequential delivery of FRT followed by VTP 7 days later improves PCa tumour control compared to monotherapy with FRT or VTP alone.&#x0D; Results FRT induced vascular normalisation changes in PCa flank tumour allografts, improving vascular function as demonstrated using dynamic contrast enhanced magnetic resonance imaging. FRT followed by VTP significantly delayed tumour growth in flank PCa allograft pre-clinical models, compared with monotherapy with FRT or VTP alone, and improved overall survival.&#x0D; Conclusion Taken together, these results suggest that combining FRT and VTP could become a promising multimodal clinical strategy in PCa therapy. This provides proof-of-concept for this multi-modality therapy approach to take forward to early phase clinical trials.

A treatment planning study of urethra-sparing intensity-modulated proton therapy for localized prostate cancer.

Urethra-sparing radiation therapy for localized prostate cancer can reduce the risk of radiation-induced genitourinary toxicity by intentionally underdosing the periurethral transitional zone. We aimed to compare the clinical impact of a urethra-sparing intensity-modulated proton therapy (US-IMPT) plan with that of conventional clinical plans without urethral dose reduction. This study included 13 patients who had undergone proton beam therapy. The prescribed dose was 63 GyE in 21 fractions for 99% of the clinical target volume. To compare the clinical impact of the US-IMPT plan with that of the conventional clinical plan, tumor control probability (TCP) and normal tissue complication probability (NTCP) were calculated with a generalized equivalent uniform dose-based Lyman-Kutcher model using dose volume histograms. The endpoints of these model parameters for the rectum, bladder, and urethra were fistula, contraction, and urethral stricture, respectively. The mean NTCP value for the urethra in US-IMPT was significantly lower than that in the conventional clinical plan (0.6% vs. 1.2%, p<0.05). There were no statistically significant differences between the conventional and US-IMPT plans regarding the mean minimum dose for the urethra with a 3-mm margin, TCP value, and NTCP value for the rectum and bladder. Additionally, the target dose coverage of all plans in the robustness analysis was within the clinically acceptable range. Compared with the conventional clinically applied plans, US-IMPT plans have potential clinical advantages and may reduce the risk of genitourinary toxicities, while maintaining the same TCP and NTCP in the rectum and bladder.

Early Experience with Salvage Robotic-Assisted Radical Prostatectomy in Proton Beam Radiotherapy Failures.

Aims: To assess the perioperative and short-term functional and oncologic outcomes of the salvage robot-assisted radical prostatectomy (sRARP), after recurrence following primary proton beam therapy for clinically localized prostate cancer.Methods: Ten patients undergoing sRARP after failure of the prior definitive proton beam therapy for localized prostate cancer were included. BCR is defined as a prostate-specific antigen (PSA) value of 2.0 ng/mL greater than the absolute nadir. All of the individuals had a diagnosis of prostate cancer via biopsy after proton beam therapy, with negative findings on magnetic resonance imaging/computer tomography of the pelvis and abdomen, and a bone scan. The sRARP procedure with pelvic lymph node dissection was performed by a single surgeon in all patients.Results: The median age of the cohort at sRARP was 66.8 years, and the mean BMI was 29.2 kg/m2. The mean duration from proton beam therapy to sRARP was 58.4 months; the mean preoperative PSA level was 5.5 ng/mL, the mean operative time was 230 minutes, and the approximate blood loss was 745 mL. Anastomotic leakage occurred in half of the individuals, and bladder neck contracture developed in 6 patients. For 8 patients, the continence results within 6 months follow-up were available. Overall, 24 complications occurred in 9 patients. At follow-up in the 32nd month, the overall survival rate was 80%, and the BCR-free survival rate was 90%.Conclusion: sRARP after proton beam therapy is an applicable procedure, but has a high risk of serious complications.

Adaptive magnetic resonance-guided neurovascular-sparing radiotherapy for preservation of erectile function in prostate cancer patients.

Erectile dysfunction is a common adverse effect of external beam radiation therapy for localized prostate cancer (PCa), likely as a result of damage to neural and vascular tissue. Magnetic resonance-guided online adaptive radiotherapy (MRgRT) enables high-resolution MR imaging and paves the way for neurovascular-sparing approaches, potentially lowering erectile dysfunction after radiotherapy for PCa. The aim of this study was to assess the planning feasibility of neurovascular-sparing MRgRT for localized PCa. Twenty consecutive localized PCa patients, treated with standard 5×7.25Gy MRgRT, were included. For these patients, neurovascular-sparing 5×7.25Gy MRgRT plans were generated. Dose constraints for the neurovascular bundle (NVB), the internal pudendal artery (IPA), the corpus cavernosum (CC), and the penile bulb (PB) were established. Doses to regions of interest were compared between the neurovascular-sparing plans and the standard clinical pre-treatment plans. Neurovascular-sparing constraints for the CC, and PB were met in all 20 patients. For the IPA, constraints were met in 19 (95%) patients bilaterally and 1 (5%) patient unilaterally. Constraints for the NVB were met in 8 (40%) patients bilaterally, in 8 (40%) patients unilaterally, and were not met in 4 (20%) patients. NVB constraints were not met when gross tumor volume (GTV) was located dorsolaterally in the prostate. Dose to the NVB, IPA, and CC was significantly lower in the neurovascular-sparing plans. Neurovascular-sparing MRgRT for localized PCa is feasible in the planning setting. The extent of NVB sparing largely depends on the patient's GTV location in relation to the NVB.

Bleeding Risk Following Stereotactic Body Radiation Therapy for Localized Prostate Cancer in Men on Baseline Anticoagulant or Antiplatelet Therapy

PurposePatients on anticoagulant/antiplatelet medications are at a high risk of bleeding following external beam radiation therapy for localized prostate cancer. SBRT may reduce the bleeding risk by decreasing the volume of bladder/rectum receiving high doses. This retrospective study sought to evaluate the rates of hematuria and hematochezia following SBRT in these patients.MethodsLocalized prostate cancer patients treated with SBRT from 2007 to 2017 on at least one anticoagulant/antiplatelet at baseline were included. The minimum follow-up was 3 years with a median follow-up of 72 months. Patients who had a rectal spacer placed prior to SBRT were excluded. Radiotherapy was delivered in 5 fractions to a dose of 35 Gy or 36.25 Gy utilizing the CyberKnife system. Hematuria and hematochezia were prospectively assessed before and after treatment using the Expanded Prostate Cancer Index Composite (EPIC-26). Toxicities were scored using the CTCAE v4. Cystoscopy and colonoscopy findings were retrospectively reviewed.ResultsForty-four men with a median age of 72 years with a history of taking at least one anticoagulant and/or antiplatelet medication received SBRT. Warfarin (46%), clopidogrel (34%) and rivaroxaban (9%) were the most common medications. Overall, 18.2% experienced hematuria with a median time of 10.5 months post-SBRT. Altogether, 38.6% experienced hematochezia with a median time of 6 months post-SBRT. ≥ Grade 2 hematuria and hematochezia occurred in 4.6% and 2.5%, respectively. One patient required bladder neck fulguration and one patient underwent rectal cauterization for multiple non-confluent telangiectasia. There were no grade 4 or 5 toxicities. Cystoscopy revealed bladder cancer (40%) and benign prostatic bleeding (40%) as the most common hematuria etiology. Colonoscopy demonstrated hemorrhoids (54.5%) and radiation proctitis (9.1%) as the main causes of hematochezia. There was no significant change from the mean baseline EPIC-26 hematuria and hematochezia scores at any point during follow up.ConclusionIn patients with baseline anticoagulant usage, moderate dose prostate SBRT was well tolerated without rectal spacing. High grade bleeding toxicities were uncommon and resolved with time. Baseline anticoagulation usage should not be considered a contraindication to prostate SBRT.

Clinical predictors of severe late urinary toxicity after curative intensity-modulated radiation therapy for localized prostate cancer.

Intractable late urinary toxicity is a serious complication after radiotherapy for patients with localized prostate cancer (LPC). We assessed clinical factors correlated with severe late urinary toxicity in LPC treated with curative image-guided intensity-modulated radiation therapy (IMRT). A total of 452 patients with LPC treated with IMRT between 2002 and 2016 were retrospectively analyzed. Among them, 432 patients received androgen deprivation therapy (ADT). The median total irradiated doses were 80 (range, 76-80) Gy. Each daily dose was 2 Gy per fraction. The median follow-up was 83 (range, 4-210) months. Late urinary toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03. Grade 3 late urinary toxicity was observed in 27 patients. No cases with grade ≥ 4 late urinary toxicity were observed. The 5-, 10-, and 12.5-year grade 3 late urinary toxicity-free survival rates were 97%, 91.8% and 88.1%, respectively. Age, risk classification, total irradiated dose, ADT duration, antithrombotic therapy (AT), cardiovascular disease, hypertension (HT), diabetes mellitus (DM), dyslipidemia (DL), prior transurethral resection of the prostate (TURP) and prior high-intensity focused ultrasound (HIFU) were investigated for correlations with grade 3 late urinary toxicity. In univariate analysis, AT and prior HIFU and no other studied factors, were correlated with grade 3 late urinary toxicity. AT and prior HIFU appear to be predictive of grade 3 late urinary toxicity. Patients with LPC with these relevant clinical factors should be carefully followed up by sharing detailed information with the urology department.

Radiation therapy dose and androgen deprivation therapy in localized prostate cancer: a meta-regression of 5-year outcomes in phase III randomized controlled trials

BackgroundWhile multiple randomized trials have evaluated the benefit of radiation therapy (RT) dose escalation and the use and prolongation of androgen deprivation therapy (ADT) in the treatment of prostate cancer, few studies have evaluated the relative benefit of either form of treatment intensification with each other. Many trials have included treatment strategies that incorporate either high or low dose RT, or short-term or long-term ADT (STADT or LTADT), in one or more trial arms. We sought to compare different forms of treatment intensification of RT in the context of localized prostate cancer.MethodsUsing preferred reporting items for systemic reviews and meta-analyses (PRISMA) guidelines, we collected over 40 phases III clinical trials comparing different forms of RT for localized prostate cancer. We performed a meta-regression of 40 individual trials with 21,429 total patients to allow a comparison of the rates and cumulative proportions of 5-year overall survival (OS), prostate cancer-specific mortality (PCSM), and distant metastasis (DM) for each treatment arm of every trial.ResultsDose-escalation either in the absence or presence of STADT failed to significantly improve any 5-year outcome. In contrast, adding LTADT to low dose RT significantly improved 5-year PCSM (Odds ratio [OR] 0.34, 95% confidence interval [CI] 0.22–0.54, p < 0.001) and DM (OR 0.35, 95% CI 0.20–0.63. p < 0.001) over low dose RT alone. Adding STADT also significantly improved 5-year PCSM over low dose RT alone (OR 0.55, 95% CI 0.41–0.75, p < 0.001).ConclusionWhile limited by between-study heterogeneity and a lack of individual patient data, this meta-analysis suggests that adding ADT, versus increasing RT dose alone, offers a more consistent improvement in clinical endpoints.

Subtotal surgical therapy for localized prostate cancer: a single-center precision prostatectomy experience in 25 patients, and SEER-registry data analysis.

BackgroundWe recently described a novel form of focal therapy for prostate cancer (CaP)—the precision prostatectomy. Here we report on the first 25 consecutive patients. Further, utilizing Surveillance Epidemiology and End Results (SEER)-registry data, we assess long-term oncological efficacies of various focal therapy techniques.MethodsMen who met the criteria: (I) PSA ≤15 ng/mL, (II) stage ≤cT2, (III) dominant unilateral lesion with Gleason ≤4+3 with any number or percentage (%) of cores involved ipsilaterally on biopsy, (IV) no primary Gleason ≥4 contralaterally, and (V) preoperative erectile function score (IIEF-5/SHIM) of ≥17 with/without PDE-5i were included in this prospective, single-arm, IDEAL stage 2b study (December 2016 to July 2017). Safety of the technique, and intermediate-term urinary, sexual and oncological outcomes were studied. Descriptive statistics and Kaplan-Meier (KM) analysis were used to assess 12-month urinary continence (0–1 pad), 12-month sexual potency (SHIM ≥17), and 36-month freedom from clinically-significant CaP (grade group ≥2), radical treatment, metastatic disease and mortality. SEER-registry was queried to evaluate CaP-specific survival in patients undergoing hyperthermia, cryotherapy, or segmental prostatectomy.ResultsAt study entry, the median (IQR) age, PSA and SHIM score were 56.5 (53.1–62.3) years, 4.2 (3.8–5.9) ng/mL and 23 [20–25], respectively. Only 1 patient met the Epstein criteria for active surveillance. All patients were followed for a minimum of 2 years. At 12 months, from a functional standpoint, all patients were continent. Twenty-three (92%) patients were potent at 12 months. From an oncological standpoint, at 36 months, the KM analysis (95% CI) demonstrated a 96.2% (92.9–98.7) rate of freedom from clinically-significant CaP and a 92.7% (88.9–97.2) rate of freedom from radical treatment. All patients were alive and free of metastatic disease at the latest follow-up. Analysis of the SEER-registry data demonstrated 10-year CaP-specific survival rates of 91.6% to 97.7% among the 3 studied modalities, P=0.298.ConclusionsPrecision prostatectomy is feasible, technically safe, and offers excellent postoperative functional results. At 36 months of follow-up, the oncological outcomes and secondary procedure rates appear to be at-par with the ablative forms of focal therapy.

Androgen Deprivation Therapy Combined With Particle Therapy for Prostate Cancer: A Systematic Review

PurposeThere is high-level evidence for addition of androgen deprivation therapy to photon-based radiotherapy of the prostate in intermediate- and high-risk prostate cancer. Little is known about the value of ADT in particle therapy of prostate cancer. We are conducting a systematic review on biochemical disease-free survival, overall survival, and morbidity after combined particle therapy and ADT for prostate cancer.MethodsA thorough search in PubMed, Embase, Scopus, and Web of Science databases were conducted, searching for relevant studies. Clinical studies on prostate cancer and the treatment combination of particle therapy and androgen deprivation therapy were included. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on PROSPERO (CRD42021230801).ResultsA total of 298 papers were identified. Fifteen papers reporting on 7,202 patients after proton or carbon-ion therapy for localized prostate cancer where a fraction or all patients received ADT were selected for analysis. Three thousand five hundred and nineteen (49%) of the patients had received combined ADT and particle therapy. Primarily high-risk (87%), to a lesser extent intermediate-risk (34%) and low-risk patients (12%) received ADT. There were no comparative studies on the effect of ADT in patients treated with particles and no studies identified ADT as an independent prognostic factor related to survival outcomes.ConclusionsThe review found no evidence to support that the effects on biochemical disease-free survival and morbidity of combining ADT to particle therapy differs from the ADT effects in conventional photon based radiotherapy. The available data on the topic is limited.