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OBJECTIVE: To evaluate acute and late gastrointestinal (GI) and genitourinary (GU) toxicities after moderately hypofractionated (HF) or conventionally fractionated (CF) primary whole-pelvis radiotherapy (WPRT). METHODS: Primary prostate-cancer patients treated between 2009 and 2021 with either 60â¯Gy at 3â¯Gy/fraction to the prostate and 46â¯Gy at 2.3â¯Gy/fraction to the whole pelvis (HF), or 78â¯Gy at 2â¯Gy/fraction to the prostate and 50/50.4â¯Gy at 1.8-2â¯Gy/fraction to the whole pelvis (CF). Acute and late GI and GU toxicities were retrospectively assessed. RESULTS: 106 patients received HF and 157 received CF, with a median follow-up of 12 and 57 months. Acute GI toxicity rates in the HF and CF groups were, respectively, grade 2: 46.7% vs. 37.6%, and grade 3: 0% vs. 1.3%, with no significant difference (pâ¯= 0.71). Acute GU toxicity rates were, respectively, grade 2: 20.0% vs. 31.8%, and grade 3: 2.9% vs. 0%, (pâ¯= 0.04). We compared prevalence of late GI and GU toxicities between groups after 3, 12, and 24 months and did not find any significant differences (respectively, pâ¯= 0.59, 0.22, and 0.71 for GI toxicity; pâ¯= 0.39, 0.58, and 0.90 for GU toxicity). CONCLUSION: Moderate HF WPRT was well tolerated during the first 2 years. Randomized trials are needed to confirm these findings.
Subject(s)
Gastrointestinal Diseases , Prostatic Neoplasms , Radiotherapy, Intensity-Modulated , Male , Humans , Prostate , Retrospective Studies , Treatment Outcome , Prostatic Neoplasms/radiotherapy , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/etiology , Pelvis , Radiotherapy, Intensity-Modulated/adverse effectsABSTRACT
PURPOSE: Local recurrences after radical prostatectomy (RP) and postoperative radiotherapy (RT) are challenging for salvage treatment. Retrospective analysis of own experiences with salvage re-irradiation was performed. METHODS: The study included all consecutive patients treated with salvage stereotactic body radiotherapy (sSBRT) for prostate bed recurrence following RP and postoperative RT at a single tertiary center between 2014 and 2021. Treatment toxicity defined as the occurrence of CTCAE grade ≥â¯2 genito-urinary (GU) or gastro-intestinal (GI) adverse events (AEs) was assessed. A PSA response, biochemical control (BC) and overall survival (OS) were also evaluated. RESULTS: The study group included 32 patients with a median age of 68 years and a median follow-up of 41 months, treated with CyberKnife (53%) or Linac (47%) sSBRT. Total dose of 33.75-36.25â¯Gy in five fractions (72%) was applied in the majority of them. Approximately 19% patients reported grade ≥â¯2â¯GU AEs both at baseline and at three months, and grade ≥â¯2â¯GI toxicity increased from 0% at baseline to 6% at three months after sSBRT. There was some clinically relevant increase in late toxicity with 31% patients reporting late ≥â¯2â¯GU, and 12.5% late ≥â¯2â¯GI AEs. Two grade 3 AEs were recorded: recto-urinary fistulas. The majority of patients showed a PSA response (91% at one year post-sSBRT). The 3year BC was 40% and 3year OS was 87%. CONCLUSIONS: Manageable toxicity profile and satisfactory biochemical response suggest that SBRT in patients with local recurrence following RP and postoperative RT might be a salvage option for selected patients.
Subject(s)
Prostatic Neoplasms , Radiosurgery , Re-Irradiation , Male , Humans , Aged , Radiosurgery/adverse effects , Prostate , Prostate-Specific Antigen , Re-Irradiation/adverse effects , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Prostatic Neoplasms/drug therapy , Retrospective Studies , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Recurrence, Local/surgery , Neoplasm Recurrence, Local/etiology , Prostatectomy , Salvage Therapy/adverse effectsABSTRACT
BACKGROUND AND PURPOSE: Comparing oncological outcomes and toxicity after primary treatment of localized prostate cancer using HDR- or LDR-mono-brachytherapy (BT), or conventionally (CF) or moderately hypofractionated (HF) external beam radiotherapy. MATERIALS AND METHODS: Retrospectively, patients with low- (LR) or favorable intermediate-risk (IR) prostate cancer treated between 03/2000 and 09/2022 in two centers were included. Treatment was performed using either CF with total doses between 74 and 78â¯Gy, HF with 2.4-2.6â¯Gy per fraction in 30 fractions, or LDR- or HDR-BT. Biochemical control (BC) according to the Phoenix criteria, and late gastrointestinal (GI), and genitourinary (GU) toxicity according to RTOG/EORTC criteria were assessed. RESULTS: We identified 1293 patients, 697 with LR and 596 with IR prostate cancer. Of these, 470, 182, 480, and 161 were treated with CF, HF, LDR-BT, and HDR-BT, respectively. For BC, we did not find a significant difference between treatments in LR and IR (pâ¯= 0.31 and 0.72). The 5year BC for LR was between 93 and 95% for all treatment types. For IR, BC was between 88% in the CF and 94% in the HF group. For CF and HF, maximum GI and GU toxicity grade ≥â¯2 was between 22 and 27%. For LDR-BT, we observed 67% grade ≥â¯2 GU toxicity. Maximum GI grade ≥â¯2 toxicity was 9%. For HDR-BT, we observed 1% GI grade ≥â¯2 toxicity and 19% GU grade ≥â¯2 toxicity. CONCLUSION: All types of therapy were effective and well received. HDR-BT caused the least late toxicities, especially GI.
Subject(s)
Brachytherapy , Prostatic Neoplasms , Radiation Injuries , Male , Humans , Prostatic Neoplasms/radiotherapy , Brachytherapy/adverse effects , Brachytherapy/methods , Aged , Radiation Injuries/etiology , Middle Aged , Retrospective Studies , Aged, 80 and over , Radiation Dose Hypofractionation , Radiotherapy Dosage , Treatment OutcomeABSTRACT
PURPOSE: External beam radiotherapy (EBRT) with or without brachytherapy boost (BTB) has not been compared in prospective studies using guideline-recommended radiation dose and recommended androgen-deprivation therapy (ADT). In this multicenter retrospective analysis, we compared modern-day EBRT with BTB in terms of biochemical control (BC) for intermediate-risk (IR) and high-risk (HR) prostate cancer. METHODS: Patients were treated for primary IR or HR prostate cancer during 1999-2019 at three high-volume centers. Inclusion criteria were prescribed ≥â¯76â¯Gy EQD2 (α/ßâ¯= 1.5â¯Gy) for IR and ≥â¯78â¯Gy EQD2 (α/ßâ¯= 1.5â¯Gy) for HR as EBRT alone or with BTB. All HR patients received ADT and pelvic irradiation, which were optional in IR cases. BC between therapies was compared in survival analyses. RESULTS: Of 2769 initial patients, 1176 met inclusion criteria: 468 HR (260 EBRT, 208 BTB) and 708 IR (539 EBRT, 169 BTB). Median follow-up was 49 and 51 months for HR and IR, respectively. BTB patients with ≥â¯113â¯Gy EQD2Gy experienced a stable, good BC outcome compared with BTB at lower doses. Patients treated with ≥â¯113â¯Gy EQD2Gy also experienced significantly improved BC compared with EBRT (10-year BC failure rates after ≥â¯113â¯Gy BTB and EBRT: respectively 20.4 and 41.8% for HR and 7.5 and 20.8% for IR). CONCLUSIONS: In patients with IR and HR prostate cancer, BTB with ≥â¯113â¯Gy EQD2Gy offered a BC advantage compared with dose-escalated EBRT and lower BTB doses.
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PURPOSE: To describe a local radio-oncological treatment for patients with prostate cancer that metastasized to either the lymph nodes or distant regions. METHODS AND MATERIALS: We included 133 patients with prostate cancer that displayed either distant metastases (DM) or lymph node metastases alone (NM) and were treated between 2004 and 2019. All patients underwent computed tomography and a bone scan or 18F- or prostate-specific membrane antigen-targeted positron emission tomography. Patients received local external beam radiation therapy to the prostate to achieve local control (60-81.4â¯Gy to the prostate, and 45-50.4â¯Gy to pelvic lymph nodes), with either the 3D conformal (4-field box) or volumetric modulated arc therapy technique. A urologist prescribed additional therapy. RESULTS: We included 51 patients with DM and 82 patients with NM. The mean follow-up was 42 months for all patients. The groups were similar in T stage, initial prostate-specific antigen, histology, androgen deprivation therapy, age, treatment techniques, and prescribed doses, but different in lymph node inclusion and follow-up times. In the NM and DM groups, the 5year biochemical recurrence-free rates were 52% and 24%, respectively (pâ¯< 0.0001); the 5year disease-specific survival rates were 92% and 61%, respectively (pâ¯= 0.001); and the 5year OS rates were 77% and 48%, respectively (pâ¯= 0.01). The groups had similar acute and late gastrointestinal and genitourinary side effects, except that late genitourinary side effects occurred significantly more frequently in the NM group (pâ¯= 0.01). CONCLUSIONS: DM was associated with significantly worse outcomes than NM. The long-term survival of patients with metastatic prostate cancer was low.
Subject(s)
Prostatic Neoplasms , Radiotherapy, Intensity-Modulated , Male , Humans , Prostatic Neoplasms/pathology , Androgen Antagonists/therapeutic use , Radiotherapy, Intensity-Modulated/methods , Prostate-Specific Antigen , Urogenital System/pathologyABSTRACT
PURPOSE: Hypofractionated radiotherapy for prostate cancer is well established for definitive treatment, but not well defined in the postoperative setting. The purpose of this analysis was to assess oncologic outcomes and toxicity in a large cohort of patients treated with conventionally fractionated three-dimensional (3D) conformal radiotherapy (CF) and hypofractionated volumetric modulated arc therapy (HF) after radical prostatectomy. METHODS: Between 1994 and 2019, a total of 855 patients with prostate carcinoma were treated by postoperative radiotherapy using CF (total dose 65-72â¯Gy, single fraction 1.8-2â¯Gy) in 572 patients and HF (total dose 62.5-63.75â¯Gy, single fraction 2.5-2.55â¯Gy) in 283 patients. The association of treatment modality with biochemical control, overall survival (OS), and gastrointestinal (GI) and genitourinary (GU) toxicity was assessed using logistic and Cox regression analysis. RESULTS: There was no difference between the two modalities regarding biochemical control rates (77% versus 81%, respectively, for HF and CF at 24 months and 58% and 64% at 60 months; pâ¯= 0.20). OS estimates after 5 years: 95% versus 93% (pâ¯= 0.72). Patients undergoing HF had less frequent grade 2 or higher acute GI or GU side effects (pâ¯= 0.03 and pâ¯= 0.005, respectively). There were no differences in late GI side effects between modalities (hazard ratio 0.99). Median follow-up was 23 months for HF and 72 months for CF (pâ¯< 0.001). CONCLUSION: For radiation therapy of resected prostate cancer, our analysis of this largest single-centre cohort (nâ¯= 283) treated with hypofractionation with advanced treatment techniques compared with conventional fractionation did not yield different outcomes in terms of biochemical control and toxicities. Prospective investigating of HF is merited.
Subject(s)
Prostatic Neoplasms , Radiotherapy, Intensity-Modulated , Humans , Male , Prospective Studies , Prostate/pathology , Prostatectomy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Radiation Dose Hypofractionation , Radiotherapy, Intensity-Modulated/methodsABSTRACT
PURPOSE: To retrospectively evaluate the biochemical no evidence of disease (bNED) and late side effects after adjuvant radiotherapy in prostate cancer patients. METHODS: Patients (nâ¯= 85) treated with external beam radiotherapy between 1997 and 2013 following radical prostatectomy (RPE) with pathological tumour stage pT2c with positive surgical margins or pT3 and pT4 tumours with or without positive margins who presented with a postoperative and a preradiation prostate-specific antigen (PSA) level below 0.1â¯ng/ml. The mean dose applied was 66â¯Gy with conventional fractionation (4 field box-technique). No androgen deprivation therapy was administered, and patients with incomplete data (missing Gleason score, pT stage, or PSA values postoperatively and/or prior to radiation at the presentation at our department) have been excluded from the analysis. Biochemical recurrence was defined as reaching a PSA level >â¯0.2â¯ng/ml during follow-up and bNED rates were assessed. In addition, patients were divided into two groups according to the Roach formula for predicting the risk of pelvic node involvement at a cut-off value of 15%. Late urogenital and gastrointestinal side effects (EORTC/RTOG) were assessed. RESULTS: After a median follow-up of 60 months the bNED rate was 88% at 5 years and 72% at 10 years for all patients. Patients with low risk of lymph node involvement (group <â¯15%) had a 5 year and 10 year bNED of 97% and 85%, while patients with high risk of positive lymph node involvement (group >â¯15%) showed corresponding bNED rates of 77% and 52%, respectively. A significant difference according to the Roach stratification was detected (pâ¯≤â¯0.002). Late urogenital (UG) and gastrointestinal (GI) grade ≥â¯2 side effects were detected in 10% and 15%, respectively. CONCLUSION: Postoperative radiotherapy with an average dose of 66â¯Gy to the prostatic fossa following RPE provides excellent tumour control rates with acceptable side effects. Patients with a higher risk of positive lymph nodes (>â¯15%) according to the Roach formula show significant worse tumour control rates.
Subject(s)
Prostate-Specific Antigen , Prostatic Neoplasms , Humans , Male , Neoplasm Staging , Prostatectomy , Prostatic Neoplasms/pathology , Radiotherapy, Adjuvant , Retrospective StudiesABSTRACT
PURPOSE: The goal of our study was comparison of external beam radiotherapy (EBRT) and I125 seeds brachytherapy in terms of biochemical control and development of late gastrointestinal and genitourinary side effects. PATIENTS AND METHODS: 477 low-risk prostate cancer patients treated between 2000 and 2019 at our department using either I125 seeds brachytherapy or EBRT with a dose of 74 or 78â¯Gy were reviewed for our analysis. 213 patients were treated with EBRT and 264 with seeds. RESULTS: Patients were followed up yearly with a median follow-up of 70 (3-192) months. The biochemical no evidence of disease (bNED) rates after 5 years were 95% for both EBRT and seeds, and after 10 years 87% for EBRT and 94% for seeds using the Phoenix criteria, although no significant difference was observed. Concerning gastrointestinal side effects, EBRT showed significantly higher rates of RTOG grade ≥2 toxicity compared to seeds, but at no point in follow-up more than 15% of all patients. On the other hand, genitourinary side effects were significantly more prevalent in patients treated with seeds, with 40% RTOG grade ≥2 toxicity 12 months after treatment. Nevertheless, both types of side effects decreased over time. CONCLUSION: Both EBRT and seeds provide excellent biochemical control with bNED rates after 10 years of about 90%. In terms of side effects, patients treated with seeds show higher grades of genitourinary side effects, while patients treated with EBRT show higher grades of gastrointestinal side effects.
Subject(s)
Prostatic Neoplasms/radiotherapy , Aged , Aged, 80 and over , Brachytherapy/adverse effects , Brachytherapy/methods , Disease-Free Survival , Humans , Iodine Radioisotopes/adverse effects , Iodine Radioisotopes/therapeutic use , Male , Middle Aged , Radiotherapy/adverse effects , Radiotherapy/methods , Radiotherapy Dosage , Retrospective Studies , RiskABSTRACT
PURPOSE: This study's objective was the comparison of external beam radiotherapy (EBRT) and I125 seed brachytherapy regarding clinical outcome and development of side effects. PATIENTS AND METHODS: In all, 462 localized intermediate-risk prostate cancer patients treated between 2000 and 2019â¯at our department using either I125 seed brachytherapy or EBRT with a dose of 74 or 78â¯Gy were included: 297 patients were treated with EBRT and 165 with seeds. Biochemical no evidence of disease (bNED) rates according to Phoenix definition as well as late gastrointestinal and urogenital side effects (EORTC/RTOG) were assessed. RESULTS: Patients were followed up yearly with a median follow-up of 54 (3-192) months. Observed bNED rates for 74â¯Gy, 78â¯Gy and seeds were 87, 92, and 88% after 5 years and 71, 85, and 76% after 9 years, respectively. No significant differences were found comparing seeds with 74â¯Gy (pâ¯= 0.81) and 78â¯Gy (pâ¯= 0.19), as well as between 74 and 78â¯Gy (pâ¯= 0.32). Concerning gastrointestinal side effects, EBRT showed significantly higher rates of RTOG grade ≥â¯2 toxicity compared to seeds, but at no point of the follow-up more than 10% of all patients. However, genitourinary side effects were significantly more prevalent in patients treated with seeds, with 33% RTOG grade ≥â¯2 toxicity 12 months after treatment. Nevertheless, both types of side effects decreased over time. CONCLUSION: Favorable intermediate-risk prostate cancer patients can be treated either by external beam radiotherapy (74/78â¯Gy) or permanent interstitial seed brachytherapy.
Subject(s)
Brachytherapy , Prostatic Neoplasms , Brachytherapy/adverse effects , Humans , Iodine Radioisotopes/adverse effects , Male , Prostate-Specific Antigen , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/radiotherapy , Radiotherapy DosageABSTRACT
PURPOSE: The aim of this work was to characterise actuarial incidence and prevalence of early and late side effects of local versus pelvic three-dimensional conformal postoperative radiotherapy for prostate cancer. MATERIALS AND METHODS: Based on a risk-adapted protocol, 575 patients received either local (n = 447) or local-plus-pelvic (n = 128) radiotherapy. Gastrointestinal (GI) and genitourinary (GU) side effects (≥grade 2 RTOG/EORTC criteria) were prospectively assessed. Maximum morbidity, actuarial incidence rate, and prevalence rates were compared between the two groups. RESULTS: For local radiotherapy, median follow-up was 68 months, and the mean dose was 66.7 Gy. In pelvic radiotherapy, the median follow-up was 49 months, and the mean local and pelvic doses were 66.9 and 48.3 Gy respectively. Early GI side effects ≥ G2 were detected in 26% and 42% of patients respectively (p < 0.001). Late GI adverse events were detected in 14% in both groups (p = 0.77). The 5year actuarial incidence rates were 14% and 14%, while the prevalence rates were 2% and 0% respectively. Early GU ≥ G2 side effects were detected in 15% and 16% (p = 0.96), while late GU morbidity was detected in 18% and 24% (p = 0.001). The 5year actuarial incidence rates were 16% and 35% (p = 0.001), while the respective prevalence rates were 6% and 8%. CONCLUSIONS: Despite the low prevalence of side effects, postoperative pelvic radiotherapy results in significant increases in the actuarial incidence of early GI and late GU morbidity using a conventional 4field box radiotherapy technique. Advanced treatment techniques like intensity-modulated radiotherapy (IMRT) or volumetric modulated arc radiotherapy (VMAT) should therefore be considered in pelvic radiotherapy to potentially reduce these side effects.
Subject(s)
Combined Modality Therapy/statistics & numerical data , Gastrointestinal Tract/radiation effects , Prostatectomy , Prostatic Neoplasms/radiotherapy , Radiation Injuries/epidemiology , Radiotherapy, Adjuvant/statistics & numerical data , Adult , Aged , Aged, 80 and over , Cohort Studies , Follow-Up Studies , Humans , Incidence , Lymph Node Excision , Lymphatic Irradiation/adverse effects , Male , Middle Aged , Pelvis/radiation effects , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Radiation Injuries/etiology , Radiotherapy, Conformal/adverse effects , Survival RateABSTRACT
BACKGROUND: For several tumor entities, automated treatment planning has improved plan quality and planning efficiency, and may enable adaptive treatment approaches. Whole-pelvic prostate radiotherapy (WPRT) involves large concave target volumes, which present a challenge for volumetric arc therapy (VMAT) optimization. This study evaluates automated VMAT planning for WPRT-VMAT and compares the results with manual expert planning. METHODS: A system for fully automated multi-criterial plan generation was configured for each step of sequential-boost WPRT-VMAT, with final "autoVMAT" plans being automatically calculated by the Monaco treatment planning system (TPS; Elekta AB, Stockholm, Sweden). Configuration was based on manually generated VMAT plans (manualVMAT) of 5 test patients, the planning protocol, and discussions with the treating physician on wishes for plan improvements. AutoVMAT plans were then generated for another 30 evaluation patients and compared to manualVMAT plans. For all 35 patients, manualVMAT plans were optimized by expert planners using the Monaco TPS. RESULTS: AutoVMAT plans exhibited strongly improved organ sparing and higher conformity compared to manualVMAT. On average, mean doses (Dmean) of bladder and rectum were reduced by 10.7 and 4.5 Gy, respectively, by autoVMAT. Prostate target coverage (V95%) was slightly higher (+0.6%) with manualVMAT. In a blinded scoring session, the radiation oncologist preferred autoVMAT plans to manualVMAT plans for 27/30 patients. All treatment plans were considered clinically acceptable. The workload per patient was reduced by > 70 min. CONCLUSION: Automated VMAT planning for complex WPRT dose distributions is feasible and creates treatment plans that are generally dosimetrically superior to manually optimized plans.
Subject(s)
Pelvis/radiation effects , Prostatic Neoplasms/radiotherapy , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Aged , Algorithms , Humans , Lymphatic Metastasis/radiotherapy , Male , Middle Aged , Organs at Risk/radiation effects , Radiotherapy Dosage , Tumor Burden/radiation effectsABSTRACT
To further personalise treatment in metastatic cancer, the indications for metastases-directed local therapy (MDT) and the biology of oligometastatic disease (OMD) should be kept conceptually apart. Both need to be vigorously investigated. Tumour growth dynamics - growth rate combined with metastatic seeding efficiency - is the single most important biological feature determining the likelihood of success of MDT in an individual patient, which might even be beneficial in slowly developing polymetastatic disease. This can be reasonably well assessed using appropriate clinical imaging. In the context of considering appropriate indications for MDT, detecting metastases at the edge of image resolution should therefore suggest postponing MDT. While three to five lesions are typically used to define OMD, it could be argued that countability throughout the course of metastatic disease, rather than a specific maximum number of lesions, could serve as a better parameter for guiding MDT. Here we argue that the unit of MDT as a treatment option in metastatic cancer might best be defined not as a single procedure at a single point in time, but as a series of treatments that can be delivered in a single or multiple sessions to different lesions over time. Newly emerging lesions that remain amenable to MDT without triggering the start of a new systemic treatment, a change in systemic therapy, or initiation of best supportive care, would thus not constitute a failure of MDT. This would have implications for defining endpoints in clinical trials and registries: Rather than with any disease progression, failure of MDT would only be declared when there is progression to polymetastatic disease, which then precludes further options for MDT.
ABSTRACT
CONTEXT: Despite the lack of level 1 evidence, metastasis-directed therapy (MDT) is used widely in the management of metastatic prostate cancer (mPCa) patients. Data are continuously emerging from well-designed prospective studies. OBJECTIVE: To summarise and report the evidence on oncological and safety outcomes of MDT in the management of mPCa patients. EVIDENCE ACQUISITION: We searched the PubMed, Scopus, and Web of Science databases for prospective studies assessing progression-free survival (PFS), local control (LC), androgen deprivation therapy (ADT)-free survival (ADT-FS), overall survival (OS), and/or adverse events (AEs) in mPCa patients treated with MDT. A meta-analysis was performed for 1- and 2-yr PFS, LC, ADT-FS, OS, and rate of AEs. Meta-regression and sensitivity analysis were performed to account for heterogeneity and identify moderators. EVIDENCE SYNTHESIS: We identified 22 prospective studies (n = 1137), including two randomised controlled trials (n = 116). Two studies were excluded from the meta-analysis (n = 120). The estimated 2-yr PFS was 46% (95% confidence interval [CI]: 36-56%) or 42% (95% CI: 33-52%) after excluding studies using biochemical or ADT-related endpoints. The estimated 2-yr LC, ADT-FS, and OS were 97% (95% CI: 94-98%), 55% (95% CI: 44-65%), and 97% (95% CI: 95-98%), respectively. Rates of treatment-related grade 2 and ≥3 AEs were 2.4% (95% CI: 0.2-7%) and 0.3% (95% CI: 0-1%), respectively. CONCLUSIONS: MDT is a promising treatment strategy associated with favourable PFS, excellent LC, and a low toxicity profile that allows oligorecurrent hormone-sensitive patients to avoid or defer ADT-related toxicity. Integration of MDT with other therapies offers a promising research direction, in particular, in conjunction with systemic treatments and as a component of definitive care for oligometastatic PCa. However, in the absence of randomised trials, using MDT for treatment intensification remains an experimental approach, and the impact on OS is uncertain. PATIENT SUMMARY: Direct treatment of metastases is a promising option for selected prostate cancer patients. It can delay hormone therapy and is being investigated as a way of intensifying treatment at the expense of manageable toxicity.
Subject(s)
Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/drug therapy , Prospective Studies , Androgen Antagonists/adverse effects , Progression-Free Survival , HormonesABSTRACT
Background: Prostate cancer is the most common cancer in men. Several efficient treatments are available for primary prostate cancer, but an economic comparison of these modalities has not been done in Austria. Objective and setting: The current study provides an economic comparison of radiotherapy and surgery for prostate cancer in Vienna and Austria. Methods: We analyzed the catalog of medical services of the Austrian Federal Ministry of Social Affairs, Health, Care and Consumer Protection and present the treatment costs for the public health sector with an LKF-point value and monetary value in 2022. Results: External beam radiotherapy, especially ultrahypofractionated, is the least costly treatment modality for low-risk prostate cancer, with costs of 2,492 per treatment. For intermediate-risk prostate cancer, differences between moderate hypofractionation and brachytherapy are small, with costs of 4,638-5,140 . In a high-risk setting, differences between radical prostatectomy and radiotherapy with androgen deprivation therapy are small (7,087 vs. 7474.06 ). Conclusion: From a purely financial point of view, treatment of low- and intermediate-risk prostate cancer in Vienna and Austria should consist of radiotherapy as long as the current catalog of services is up to date. For high-risk prostate cancer, no major difference was found.
Subject(s)
Brachytherapy , Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/therapy , Austria/epidemiology , Androgen Antagonists , Health Care CostsABSTRACT
BACKGROUND: Evidence regarding the effects of fiducials in image-guided radiotherapy (IGRT) for tumor control and acute and late toxicity is sparse. PATIENTS AND METHODS: Patients with primary low- and intermediate-risk prostate cancer, 40 with and 21 without gold fiducial markers (GFM), and treated between 2010 and 2015 were retrospectively included. The decision for or against GFM implantation took anaesthetic evaluation and patient choice into account. IGRT was performed using electronic portal imaging devices. The prescribed dose was 78 Gy, with 2 Gy per fraction. Biochemical no evidence of disease (bNED) failure was defined using the Phoenix criteria. Acute and late gastrointestinal (GI) and genitourinary toxicity (GU) were assessed using the Radiation Therapy Oncology Group criteria. RESULTS: Most patients did not receive GFM due to contraindications for anaesthesia or personal choice (60% and 25%). Regarding tumor control, no significant differences were found regarding bNED and overall and disease-specific survival (p = 0.61, p = 0.56, and p > 0.9999, respectively). No significant differences in acute and late GI (p = 0.16 and 0.64) and GU toxicity (p = 0.58 and 0.80) were observed. CONCLUSIONS: We were unable to detect significant benefits in bNED or in early or late GI and GU side effects after GFM implantation.
Subject(s)
Prostatic Neoplasms , Radiotherapy, Image-Guided , Male , Humans , Fiducial Markers , Gold , Retrospective Studies , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/radiotherapy , Radiotherapy, Image-Guided/adverse effects , Radiotherapy, Image-Guided/methodsABSTRACT
BACKGROUND: Deep learning-based auto-planning is an active research field; however, for some tasks a treatment planning system (TPS) is still required. PURPOSE: To introduce a deep learning-based model generating deliverable DICOM RT treatment plans that can be directly irradiated by a linear accelerator (LINAC). The model was based on an encoder-decoder network and can predict multileaf collimator (MLC) motion sequences for prostate VMAT radiotherapy. METHODS: A total of 619 treatment plans from 460 patients treated for prostate cancer with single-arc VMAT were included in this study. An encoder-decoder network was trained using 465 clinical treatment plans and validated on 77 plans. The performance was analyzed on a separate test set of 77 treatment plans. Separate L1 losses were computed for the leaf and jaw positions as well as the monitor units, with the leaf loss being weighted by a factor of 100 before being added to the other losses. The generated treatment plans were recalculated in a treatment planning system and the dose-volume metrics and gamma passing rates were compared to the original dose. RESULTS: All generated treatment plans showed good agreement with the original data, with an average gamma passing rate (3%/3 mm) of 91.9 ± 7.1%. However, the coverage of the PTVs. was slightly lower for the generated plans (D98% = 92.9 ± 2.6%) in comparison to the original plans (D98% = 95.7 ± 2.2%). There was no significant difference in mean dose to the bladder between the predicted and original plan (Dmean of 28.0 ± 13.5 vs. 28.1 ± 13.3% of prescribed dose) or rectum (Dmean of 42.3 ± 7.4 vs. 42.6 ± 7.5%). The maximum dose to bladder was only slightly higher in the predicted plans (D2% of 100.7 ± 5.3 vs. 99.8 ± 4.0%) and for the rectum it was even lower (D2% of 100.5 ± 3.7 vs. 100.1 ± 4.3). CONCLUSIONS: The deep learning-based model could predict MLC motion sequences in prostate VMAT plans, eliminating the need for sequencing inside a TPS, thus revolutionizing autonomous treatment planning workflows. This research completes the loop in deep learning-based treatment planning processes, enabling more efficient workflows for real-time or online adaptive radiotherapy.
Subject(s)
Prostate , Prostatic Neoplasms , Male , Humans , Pelvis , Rectum , Urinary Bladder , Prostatic Neoplasms/radiotherapyABSTRACT
The aim of this retrospective study was to assess the adverse effects and outcomes of salvage re-irradiation with stereotactic body radiotherapy (sSBRT) for local recurrence of prostate cancer (PCa) after definitive radiotherapy (RT). The study was focused on the adverse effects and prognostic factors for treatment toxicity, followed by an analysis of patterns of failure and survival. Patients treated with sSBRT between 2012 and 2020 at a tertiary institution were included. The exclusion criteria were a primary or salvage radical prostatectomy or a palliative sSBRT dose. Patients with oligorecurrence were eligible if all metastatic lesions were treated locally with curative intent. The Kaplan-Meier method was used to estimate time to grade ≥ 3 toxicity, local control (LC), freedom from distant metastases (FFDM), progression-free survival (PFS), biochemical control (BC) and overall survival (OS). The differences between groups (focal vs. whole-gland sSBRT) were compared using the log-rank test. The Cox proportional hazards model was used to assess prognostic factors for the listed endpoints. A total of 56 patients with a median age of 70.9 years and a median follow-up of 38.6 months were included in the analysis. The majority of them received local sSBRT only (45; 80.4%), while the rest were simultaneously treated for oligometastases (11; 19.6%). Overall, 18 (32.1%) patients experienced any grade ≥ 3 toxicity, including 1 (6.7%) patient who received focal sSBRT, and 17 (41.5%) patients treated with whole-gland sSBRT. The Planning Target Volume (per cc; HR 1.01; 95% CI 1-1.02; p = 0.025) and use of ADT (yes vs. no; HR 0.35; 95%CI 0.13-0.93; p = 0.035) were independent prognostic factors for the risk of grade ≥ 3 toxicity. The estimated rate of grade ≥ 3 adverse events was significantly higher (43.8% vs. 7.1% at 2 years; p = 0.006), and there was no improvement in the LC (92.9% vs. 85.3% at 2 years; p = 0.759) in patients treated with whole-gland sSBRT compared to focal sSBRT. The 2- and 5-year LC were 87.6% and 47.9%, respectively; the 2- and 5-year FFDM were 72.7% and 42.8%, respectively; and the 2- and 5-year PFS were 67.9% and 28.7%, respectively. The primary pattern of failure was distant metastasis. The sSBRT for local recurrence of PCa after definitive RT was associated with a high risk of severe grade ≥ 3 toxicity, which significantly increased with the volume and extent of re-irradiation.
ABSTRACT
BACKGROUND AND PURPOSE: Despite several prospective trials showing a clinical benefit of combining external beam radiotherapy (EBRT) with brachytherapy boost (BTB) for the treatment of intermediate- and high-risk prostate cancer (PCa) patients, none of these trials was designed to test for a survival difference. In this study, we aimed to collect a large multi-institutional database to determine whether BT boost was associated with a statistically significant improvement in survival and a reduction of distant metastases based on real-world data. MATERIAL AND METHODS: We collected the data of patients treated for intermediate- or high-risk PCa with definitive EBRT or BTB, with or without androgen deprivation therapy (ADT), between January 2003 and December 2014 at two tertiary institutions. The statistical endpoints included overall survival (OS), freedom from distant metastases (FFDM), and metastases-free survival (MFS). The impact of treatment modality was assessed using Cox regression models and log-rank testing after one-to-one propensity score matching. RESULTS: A total of 1641 patients treated with EBRT (n = 1148) or high-dose-rate BTB (n = 493) were analyzed. The median survival and clinical follow-up were 117.8 (IQR 78-143.3) and 60.7 months, respectively. The radiotherapy modality (BTB) remained an independent prognostic factor for OS (HR 0.75; 95% CI 0.63-0.88; p < 0.001), FFDM (HR 0.54; 95% CI 0.4-0.73; p < 0.001), and MFS (HR 0.72; 95% CI 0.61-0.85; p < 0.001). After propensity score matching, the remaining 986 patients were well-balanced in terms of age, maximum PSA, ISUP grade group, and TNM T stage. OS (p < 0.001), FFDM (p = 0.001) and MFS (p < 0.001) were significantly higher in the BTB group. CONCLUSIONS: There is a strong positive association between BTB and OS, FFDM, and MFS in PCa patients treated with definitive RT for intermediate- or high-risk PCa.
Subject(s)
Brachytherapy , Prostatic Neoplasms , Male , Humans , Brachytherapy/adverse effects , Prospective Studies , Androgen Antagonists/therapeutic use , Prostatic Neoplasms/pathology , Proportional Hazards Models , Retrospective StudiesABSTRACT
BACKGROUND: De novo oligometastatic prostate cancer (omPCa) on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is a new disease entity and its optimal management remains unknown. OBJECTIVE: To analyze the outcomes of patients treated with cytoreductive radical prostatectomy (cRP) for omPCa on PSMA-PET. DESIGN, SETTING, AND PARTICIPANTS: Overall, 116 patients treated with cRP at 13 European centers were identified. Oligometastatic PCa was defined as miM1a and/or miM1b with five or fewer osseous metastases and/or miM1c with three or fewer lung lesions on PSMA-PET. INTERVENTION: Cytoreductive radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Thirty-day complications according to Clavien-Dindo, continence rates, time to castration-resistant PCa (CRPC), and overall survival (OS) were analyzed. RESULTS AND LIMITATIONS: Overall, 95 (82%) patients had miM1b, 18 (16%) miM1a, and three (2.6%) miM1c omPCa. The median prebiopsy prostate-specific antigen was 14 ng/ml, and 102 (88%) men had biopsy grade group ≥3 PCa. The median number of metastases on PSMA-PET was 2; 38 (33%), 29 (25%), and 49 (42%) patients had one, two, and three or more distant positive lesions. A total of 70 (60%) men received neoadjuvant systemic therapy, and 37 (32%) underwent metastasis-directed therapy. Any and Clavien-Dindo grade ≥3 complications occurred in 36 (31%) and six (5%) patients, respectively. At a median follow-up of 27 mo, 19 (16%) patients developed CRPC and eight (7%) patients died. The 1-yr urinary continence rate was 82%. The 2-yr CRPC-free survival and OS were 85.8% (95% confidence interval [CI] 78.5-93.7%) and 98.9% (95% CI 96.8-100%), respectively. The limitations include retrospective design and short-term follow-up. CONCLUSIONS: Cytoreductive radical prostatectomy is a safe and feasible treatment option in patients with de novo omPCa on PSMA-PET. Despite overall favorable oncologic outcomes, some of these patients have a non-negligible risk of early progression and thus should be considered for multimodal therapy. PATIENT SUMMARY: We found that patients treated at expert centers with surgery for prostate cancer, with a limited number of metastases detected using novel molecular imaging, have favorable short-term survival, functional results, and acceptable rates of complications.