Friedrich Dessauer (1881-1963): the forgotten medical physicist, politician, and philosopher.

Today, the name Friedrich Dessauer is almost forgotten; however, his scientific, social, and political works should not be. Dessauer's professional career began at a young age as a professor of physics in Frankfurt am Main. It is said that he published 400 papers and 65 book chapters and pamphlets. He was a technical inventor who established laws that dealt with theories to explain the limited understanding of the effects of radiation on cells. He advocated for methods to improve the therapeutic ratio. As a devout Catholic politician, Dessauer was an early opponent of National Socialism. This led to him being thrown into prison for political reasons in 1933. He did not leave until 1934, and then for Istanbul, largely thanks to Turkish efforts and his appointment as director of a large new institution. While he was already a well-known physicist in Germany, he had to start from scratch in order to build a modern institute. A recent article in the journal Radiotherapy and Oncology celebrated his important contributions to radiology from Turkey. After his contract in Istanbul expired in 1937, he left for the small University of Fribourg in Switzerland, where he was unfortunately unable to continue his scientific productivity. Dessauer wrote textbooks as well as political and philosophical books, and attempted to bridge the gap between Catholicism and science. Additionally, after the war, he began to teach again in Frankfurt. In photos of Dessauer, radiation-induced skin changes on his face and hands were clearly visible. Towards the end of his life, he received many medals and honors for his achievements in Germany, some of them posthumously.

The Crosstalk between Nerves and Cancer-A Poorly Understood Phenomenon and New Possibilities.

INTRODUCTION: Crosstalk occurs between nerve and cancer cells. These interactions are important for cancer homeostasis and metabolism. Nerve cells influence the tumor microenvironment (TME) and participate in metastasis through neurogenesis, neural extension, and axonogenesis. We summarized the past and current literature on the interaction between nerves and cancer, with a special focus on pancreatic ductal adenocarcinoma (PDAC), prostate cancer (PCa), and the role of the nerve growth factor (NGF) in cancer. MATERIALS/METHODS: We reviewed PubMed and Google Scholar for the relevant literature on the relationship between nerves, neurotrophins, and cancer in general and specifically for both PCa and PDAC. RESULTS: The NGF helped sustain cancer cell proliferation and evade immune defense. It is a neuropeptide involved in neurogenic inflammation through the activation of several cells of the immune system by several proinflammatory cytokines. Both PCa and PDAC employ different strategies to evade immune defense. The prostate is richly innervated by both the sympathetic and parasympathetic nerves, which helps in both growth control and homeostasis. Newly formed autonomic nerve fibers grow into cancer cells and contribute to cancer initiation and progression through the activation of ß-adrenergic and muscarinic cholinergic signaling. Surgical or chemical sympathectomy prevents the development of prostate cancer. Beta-blockers have a high therapeutic potential for cancer, although current clinical data have been contradictory. With a better understanding of the beta-receptors, one could identify specific receptors that could have an effect on prostate cancer development or act as therapeutic agents. CONCLUSION: The bidirectional crosstalk between the nervous system and cancer cells has emerged as a crucial regulator of cancer and its microenvironment. Denervation has been shown to be promising in vitro and in animal models. Additionally, there is a potential relationship between cancer and psychosocial biology through neurotransmitters and neurotrophins.

Tracing the Evolution of Prostate Brachytherapy in the 20th Century.

BACKGROUND: Prostate brachytherapy (BT) techniques have evolved over the past century. This paper aimed to preserve our collective memory of history and the early development of its technique. We searched articles in PubMed and Google Scholar using keywords referring to authors, dates, and BT technical details, including different radioactive sources and country-specific publications. We reviewed the work published by Holm and Aronowitz. The digital library Internet Archives was used to retrieve original journal articles, science newspaper printings, and government reports, which allowed us to situate the development of BT in its sociopolitical context in Europe and the USA. Our search was conducted in English, French, and German languages. SUMMARY: Early BT methods were developed by European physicians with early access to radium. Technical advancements were made by HH Young, who brought this practice to the USA, where Barringer pioneered the use of radon seeds and low-dose interstitial brachytherapy. While centralized radiotherapy centers, such as Memorial Hospital in New York, emerged for training and research, the high cost of radium and opposing interests made brachytherapy harder to implement in Germany. After World War II, the introduction of man-made radioisotopes allowed experiments with colloidal solutions and new seeds, including I-125. In the 1980s, transrectal ultrasound allowed for more accurate radioactive seed insertion and replaced the transrectal finger guidance.

Charles Brenton Huggins: A historical review of the Nobel laureate's pioneering discoveries.

Androgen deprivation therapy for prostate cancer was pioneered by Charles Huggins, laureate of the Nobel Prize in Medicine in 1966. The authors tried to understand the scientific context and how previous findings paved Huggins way to his discoveries. With the help of summary or review articles on androgen deprivation therapy, the authors identified key publications and used his Nobel Prize speech as a basis to understand his discoveries. Furthermore, they used a recording of the laboratory-talk interview he gave about his findings to guide them to relevant publications. The authors found that the basis for Huggins' discoveries was the isolation of testosterone in 1935, not long before Huggins' 1941 hallmark publication. Huggins' work follows major experiments in the 19th century in orchiectomy done as a treatment for prostate hypertrophy. Researching the etiology of idiopathic hydrocele, Huggins analyzed the composition of prostate fluid. Further research led to the discovery of the influence of castration, testosterone, and estrogen on acid phosphatase. Recently developed methods facilitated the measurement of the phosphatases. He, therefore, had a biomarker for metastatic prostate cancer to measure treatment response. Very early on, he reported clinical improvements after castration in metastatic patients. Although the effect of orchiectomy on prostate hypertrophy was already known, Huggins was the first to show that testosterone stimulated and estrogen decreased the activity of prostate cancer. Huggins also established phosphatases as a tumor marker to measure disease response.

A Literature Review of Racial Disparities in Prostate Cancer Research.

BACKGROUND: Despite recent awareness of institutional racism, there are still important racial disparities in prostate cancer medical research. We investigated the historical development of research on racial disparities and bias. METHODS: PubMed was searched for the term 'prostate cancer race' and added key terms associated with racial disparity. As an indicator of scientific interest in the topic, we analyzed whether the number of publications increased linearly as an indicator of growing interest. The linearity is expressed as R2. RESULTS: The general search term "prostate cancer race" yielded 4507 publications. More specific search terms with ≥12 publications showing a higher scientific interest were found after 2005. The terms with the most publications when added to the general term were "genetic" (n = 1011), "PSA" (n = 995), and "detection" (n = 861). There was a linear increase in publications for "prostate cancer race" (R2 = 0.75) since 1980. Specific terms added to the general terms with a high linear increase (R2 ≥ 0.7) were "screening" (R2 = 0.82), "detection" (R2 = 0.72), "treatment access" (R2 = 0.71), and "trial underrepresentation" (R2 = 0.71). However, only a few studies have investigated its association with sexual activity. A combination with "sexual" showed 157 publications but only two years with ≥12 publications/year. CONCLUSION: The terms "genetic", "PSA", and "detection" have been the focus of recent research on racial differences in prostate cancer. We found that old stereotypes are still being mentioned but seem to find little interest in the current literature. Further research interest was found in "treatment access". Recently, interest in socioeconomic factors has decreased.

Can PSMA PET/CT help in dose-tailoring in post-prostatectomy radiotherapy?

There are few randomized trials to evaluate the use of PSMA-PET in the planning of post-prostatectomy radiotherapy. There are two unresolved questions 1) should we increase the dose to lesions visible on PSMA-PET 2) can we reduce dose in the case of a negative PSMA-PET. In this review, we summarize and discuss the available evidence in the literature. We found that in general, there seems to be an advantage for dose-increase, but ta large recent study from the pre-PSMA era didn't show an advantage for dose escalation. Retrospective studies have shown that conventional doses to PSMA-PET-positive lesions seem sufficient. On the other hand, in the case of a negative PSMA-PET, there is no evidence that dose-reduction is possible. In the future, the combination of PSMA-PET with genomic classifiers could help in better identify patients who might benefit from either dose- de-or -increase. We further need to identify intraindividual references to help identify lesions with higher aggressiveness.

IgG4-related disease and prostate cancer: A case report and review of the literature.

We present a case of a patient with recurrent prostate cancer after treatment for favorable intermediate risk cancer. There was an exceptionally steep increase in PSA from <0.5 to 130ng/mL in 27 months accompanied with the development of bone metastasis. The PSA increase was unexpected. We suspect that this unusual development of metastases must have been caused by an impairment of the immune system caused by his IgG4 disease, and this may have allowed residual prostate cancer cells in the prostate to spread quickly. The influence of IgG4 on cancer is debated.

PSMA-PET/CT-Guided Intensification of Radiation Therapy for Prostate Cancer (PSMAgRT): Findings of Detection Rate, Effect on Cancer Management, and Early Toxicity From a Phase 2 Randomized Controlled Trial.

PURPOSE: Prostate-specific membrane antigen (PSMA) ligand positron emission tomography (PET) is increasingly integrated in prostate cancer management because of its diagnostic performance. We sought to evaluate the effect of PSMA-PET/computed tomography (CT)-guided intensification of radiation therapy (PSMAgRT) on patient outcomes. Here, we report secondary trial endpoints including the rate of new lesion detection, effect on prostate cancer management, and treatment-related toxicities. METHODS AND MATERIALS: In this phase 2 cohort multiple randomized controlled trial across 2 institutions, men with prostate cancer planned for RT were randomly selected for PSMAgRT across 4 strata: oligometastatic, high risk (Cancer of the Prostate Risk Assessment ≥6 or cN1), salvage post-RT, and salvage postprostatectomy (RP). Primary endpoint was failure-free survival at 5 years, with analysis pending further follow-up. Secondary endpoints included new lesion detection yield of PSMA-PET/CT, acute and delayed toxicities, effect on prostate cancer management, and health-related quality-of-life outcomes. This trial is registered with ClinicalTrials.gov, identifier NCT03525288, companion to registry NCT03378856. RESULTS: Between May 2018 and February 2021, 262 patients were enrolled and randomized. Nine patients were later excluded (5 control, 4 PSMAgRT), leaving 253 patients for analysis (23 oligometastatic, 86 high risk, 16 salvage post-RT, and 128 salvage post-RP). New lesions were detected in 45.5% of oligometastatic, 39.5% of high risk, 14.3% of salvage post-RT, and 51.6% of salvage post-RP. Overall, PSMA-PET/CT led to intensification of RT in over half of patients (52.0%), with minimal intensification of systemic therapy (4.0%). With a median follow-up of 12.9 months, this intensification was associated with 3 attributable grade 3+ events (2.5% of patients undergoing PSMAgRT) but no difference in the rate of grade 2+ events attributable to RT compared with controls (43%, both arms). CONCLUSIONS: In this randomized trial, PSMA-PET/CT led to intensification of RT in more than half of patients. Longer follow-up is required to determine whether this intensification translates to effect on cancer control and long-term toxicity and health-related quality-of-life outcomes.

Findings on Diagnostic Magnetic Resonance Imaging Before Radiotherapy for Prostate Cancer.

PURPOSE: Pre-treatment diagnostic magnetic resonance imaging (MRI) is used in prostate cancer detection and staging; however, little is known about its potential for radiotherapy treatment decision, or its prognostic value. We investigated the findings on pre-treatment MRI and its potential influence on treatment decisions, and its ability to predict biochemical recurrence in patients treated with radiotherapy. METHODS: Files of patients treated by radiotherapy from 2014 to 2022 were searched for if they had had an MRI within 12 months before radiotherapy. Prostate Imaging Reporting & Data System (PI-RADS) score, index lesion diameter and the presence of organ confined disease or extra-prostatic extension were correlated with their Cancer of the Prostate Risk Assessment (CAPRA) score. Distribution of radiological and clinical features between groups were estimated using a chi-squared test. RESULTS: Out of 1280 patients, 314 (24.5%) had an MRI. The distribution depended on the treatment received: 22.5% who received low-dose rate (LDR) brachytherapy as monotherapy, 24.0% treated with high-dose rate (HDR) boost and 32.0% treated with external-beam radiotherapy (EBRT) (P = .017). The CAPRA score significantly correlated with the PI-RADS score (r = .342, P < .01) and the diameter of the index lesion (r = .473, P < .01). A clinically significant number of 22% patients with CAPRA ≤ 3 disease presented with lesions ≥15 mm and were less likely to be treated with LDR monotherapy (P < .01). 39 patients had a recurrence, only 5 had an MRI: 4 had a lesion of ≥20 mm and 3 a seminal vesicle invasion. CONCLUSION: More than twenty percent of patients with CAPRA ≤3 presented on MRI a ≥15 mm lesion. An MRI could potentially affect treatment choice, and although exploratory our results suggest an important prognostic potential.

Corrigendum: MRI-guided focal or integrated boost high dose rate brachytherapy for recurrent prostate cancer.

[This corrects the article DOI: 10.3389/fonc.2022.971344.].

Change of the Neutrophil-to-Lymphocyte Ratio during Treatment: A Potential Prognostic Biomarker in Metastatic Prostate Cancer Treated with Radium-223 Dichloride.

The neutrophil to lymphocyte ratio (NLR) at baseline has been shown to have prognostic value in metastatic prostate cancer. Little is known about the importance of a change in the NLR during treatment in patients treated with Radium-223 (223Ra). We investigated the prognostic value of the NLR at baseline and during therapy in patients with metastatic prostate cancer treated with 223Ra and also in patients treated with Docetaxel. We reviewed all patients treated with 223Ra in our center and randomly chosen patients treated with Docetaxel. Patients were stratified according to NLR ≤ 5 and >5 at baseline and at 12 weeks of therapy. The relationship between NLR measured at baseline and at 12 weeks and overall survival (OS) were evaluated. A total of 149 patients treated with 223Ra and 170 with Docetaxel were evaluated. For patients treated with 223Ra, overall survival was significantly better in patients that had both an NLR ≤ 5 at baseline and at 12 weeks. No such effect of NLR was found in patients treated with Docetaxel. In the present study, NLR at baseline and after 12 weeks of therapy was found to be prognostic factor in patients treated with 223Ra but not in those treated with Docetaxel.

MRI-guided focal or integrated boost high dose rate brachytherapy for recurrent prostate cancer.

Background and purpose: Locally recurrent prostate cancer after radiotherapy merits an effective salvage strategy that mitigates the risk of adverse events. We report outcomes of a cohort enrolled across two institutions investigating MRI-guided tumor-targeted salvage high dose rate brachytherapy (HDR-BT). Materials and methods: Analysis of a prospective cohort of 88 patients treated across two institutions with MRI-guided salvage HDR-BT to visible local recurrence after radiotherapy (RT). Tumor target dose ranged from 22-26 Gy, using either an integrated boost (ibBT) or focal technique (fBT), delivered in two implants over a median of 7 days. Outcome metrics included cancer control and toxicity (CTCAE). Quality of life (QoL-EPIC) was analyzed in a subset. Results: At a median follow-up of 35 months (6 -134), 3 and 5-year failure-free survival (FFS) outcomes were 67% and 49%, respectively. At 5 years, fBT was associated with a 17% cumulative incidence of local failure (LF) outside the GTV (vs. 7.8% ibBT, p=0.14), while LF within the GTV occurred in 13% (vs. 16% ibBT, p=0.81). Predictors of LF outside fBT volumes included pre-salvage PSA>7 ng/mL (p=0.03) and interval since RT less than 5 years (p=0.04). No attributable grade 3 events occurred, and ibBT was associated with a higher rate of grade 2 toxicity (p<0.001), and trend towards a larger reduction in QoL sexual domain score (p=0.07), compared to fBT. Conclusion: A tumor-targeted HDR-BT salvage approach achieved favorable cancer control outcomes. While a fBT was associated with less toxicity, it may be best suited to a subgroup with lower PSA at later recurrence. Tumor targeted dose escalation may be warranted.

Impact of Statin Use on Localized Prostate Cancer Outcomes after Radiation Therapy: Long-Term Follow-Up.

The impact of statin use on localized prostate cancer (PCa) remains controversial, especially for patients treated with radiation therapy. We assessed the impact of statin use on biochemical recurrence (BCR) in patients treated for PCa with different modalities of radiation therapy. We evaluated 3555 patients undergoing radiation therapy between January 2001 and January 2022. The impact of statin use on BCR was analyzed for three treatment groups: external beam radiotherapy (EBRT), low-dose-rate seed brachytherapy (LDR), and EBRT plus high-dose-rate brachytherapy (EBRT + HDR). Median follow-up was 52 months among 1208 patients treated with EBRT, 1679 patients treated with LDR, and 599 patients treated with EBRT + HDR. A total of 1544 (43%) patients were taking a statin at the time of treatment, and 497 (14%) patients were in the D'Amico high-risk group. Only intermediate-risk patients treated with LDR fared better with statin use in univariate analysis (p = 0.025). This association was not significant in multivariate analysis (HR 0.44, 95% CI 0.18-1.10, p = 0.06). Statin use was not associated with a reduced risk of BCR in patients treated with radiation therapy. In the era of precision medicine, further investigation is needed to assess the benefit of statins in well-defined patients.

Subclinical inflammation as a predictor for erectile dysfunction after brachytherapy for localized prostate cancer.

PURPOSE: Neutrophil-to-lymphocyte ratio (NLR), a marker for subclinical inflammation, has been previously shown to be associated with erectile dysfunction (ED). We studied the potential predictive value of the NLR on ED after prostate brachytherapy (PB) for PCa. METHODS AND MATERIALS: Between July 2005 and January 2021, 842 patients were included in this retrospective study of a prospectively maintained database. ED was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) physician-reported scale. ED was defined as a Grade 2 or 3 function. NLR count was determined 1-2 months before PB and separated into values PB <2 and ≥2. Patient characteristics and erectile function at last follow-up were compared for patients with a Univariate and multivariate analyses were performed to evaluate the predictive value of baseline NLR ≥2 on post-PB ED. RESULTS: Baseline NLR ≥2 was found to be a statistically significant predictor of post-PB ED on both univariate (p = 0.002) and multivariate analyses (p = 0.008). Furthermore, the difference in ED prevalence between the NLR <2 and NLR ≥2 groups became more pronounced with longer follow-up after PB. The ED rate at 5 years post-PB was 43% for the NLR ≥2 groups, compared to 29% for the NLR <2 groups. CONCLUSIONS: Subclinical systemic inflammation is a potentially important factor for predicting sexual toxicity after pelvic radiotherapy. NLR may be used as a proxy for predicting post-PB ED.

Biochemical failure-rate and preservation of erectile function after prostate seed brachytherapy in early-onset prostate cancer.

INTRODUCTION: To analyze biochemical failure-free survival and erectile dysfunction (ED) in younger men treated with prostate seed brachytherapy (PB). MATERIALS AND METHODS: Included were patients ≤ 55 years treated with PB. Erectile function at baseline and after treatment were assessed using the physician-reported CTCAE version 4.0. Biochemical failure (BF) was defined according to the Phoenix Consensus definition (PSA nadir + 2 ng/mL). The log-rank test (Kaplan-Meier method) and cox-regression analysis was used to calculate BF-free survival. RESULTS: Between July 2005 and November 2020, a total of 137 patients ≤ 55 years (range 44-55 years old) were treated with PB. Median follow up was 72 months. Twenty percent had Gleason 3+4 disease and 6% a PSA >10 ng/mL. Median prostate volume was 34 cc. Actuarial biochemical failure free survival at 5, 7, and 10 years, were 98%, 95% and 89%, respectively. Five patients received local salvage treatment. On multivariate analysis, CAPRA-score (HR 4.46, 95%CI 1.76-11.33, p = 0.002) and the dosimetric measure D90 > 130 Gy (p = 0.03) were predictive of BF. Five deaths occurred in our cohort, two due to cardiovascular reasons and three due to another malignancy. At baseline, all patients were able to have erections with or without medication. At 5 years and 7 years after PB, 80% and 64% of patients had little or no ED (erections without the need for medication) respectively. CONCLUSION: In young-onset patients treated with PB, failure rates are similar to their older counterparts. Sexual function decreases with time, even in patients with good sexual function.

A single-center, multidisciplinary experience with radium-223 dichloride in men with metastatic castrate-resistant prostate cancer.

INTRODUCTION: We aimed to investigate several clinical and biochemical parameters, including palliative external beam radiation therapy (EBRT) to predict survival in patients with metastatic castrate-resistant prostate cancer (mCRPC) treated with radium-223 (223Ra). METHODS: We tested known and possible prognostic parameters, including palliative EBRT, both prior and concurrent to 223Ra. Logrank test (Kaplan-Meier method) and Cox regression analysis were used to predict overall survival (OS). RESULTS: A total of 133 patients were treated with 223Ra; median age was 72 years. Median OS was 9.0 (95% confidence interval [CI] 7.4-10.6) months. By univariate analysis (log-rank test), baseline Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 (p=0.001), ≥5 cycles of 223Ra (p<0.001), baseline hemoglobin (Hb) ≥120 g/L (p <0.001), baseline total alkaline phosphatase (tALP) <110 U/L (p=0.001), and any prostate-specific antigen (PSA) decline at week 12 (p=0.013) were associated with increased OS. EBRT prior and/or concurrent to 223Ra showed a trend (p=0.051) towards inferior OS by univariate analysis only. By multivariate analysis, significant factors were PS 0-1 (hazard ratio [HR] 1.94, 95% CI 1.3-2.9, p=0.001), Hb ≥120 g/L (HR 0.5, 95% CI 0.3-0.9, p=0.011), and absence of docetaxel use prior to 223Ra (HR 1.86, 95% CI 1.08-3.22, p=0.026). With baseline Hb, tALP, and ECOG PS, we were able to divide patients into three groups with different median OS (months): 23.0 (95% CI 12.8-33.2), 8.0 (95% CI 6.7-9.3), and 5.0 (95% CI 3.1-6.9) for low-, intermediate-, and high-risk, respectively (p<0.001). CONCLUSIONS: We found that 223Ra therapy can result in an OS of close to two years in carefully selected patients. Earlier administration of 223Ra therapy to fitter patients with mCRPC should be tested.

Prevalence and Risk Factors of QTc Prolongation in Prostate Cancer Patients Undergoing Brachytherapy.

QTc prolongation is linked to Torsade de Pointes, sudden cardiac death, and overall cardiovascular mortality. 754 prostate cancer patients undergoing brachytherapy were analyzed, prolonged QTc was defined as ≥450ms. A prolonged QTc was more frequent (10.1 vs. 5.1%, p = 0.040) in patients with high-risk cancer than in low to intermediate risk patients. The absolute QTc-time was correlated with age (r = 0.125), neutrophil count (r = 0.130) and negatively correlated with the testosterone level (r=-0.205). Treating physicians should be aware of this and monitor the QTc during ADT to possibly decrease cardiac morbidity/mortality in these patients who are more likely to require ADT.

Low Serum Testosterone in Men with Newly Diagnosed Androgen-Deprivation Therapy-Naïve Prostate Cancer and Its Relationship to Cardiovascular Risk Factors: A RADICAL-PC Substudy.

PURPOSE: Cardiovascular disease is a common cause of death in prostate cancer patients. Low testosterone is associated with increased cardiovascular risk in the general male population. We investigated the relationship between serum testosterone, cardiovascular disease and risk factors in androgen-deprivation therapy-naïve prostate cancer patients. MATERIALS AND METHODS: We performed a cross-sectional analysis of a subgroup of 1,326 androgen-deprivation therapy-naïve men from RADICAL-PC (Role of Androgen-Deprivation Therapy In CArdiovascular Disease-A Longitudinal Prostate Cancer study) in whom serum testosterone was measured at baseline. RADICAL-PC is a prospective multicenter cohort study of men (2,565) enrolled within 1 year of prostate cancer diagnosis, or within 6 months of commencing androgen-deprivation therapy for the first time. Cardiovascular risk factors, cancer characteristics and total serum testosterone were collected at baseline. Low testosterone was defined as total serum testosterone <11 nmol/L (<320 ng/dL). A Framingham cardiovascular risk score ≥15 was considered high risk for future cardiovascular events. We performed logistic regression to calculate odds ratios for the association between testosterone and cardiovascular risk. RESULTS: Among 1,326 participants (median age 67 years, range 45-93), 553 (42%) had low testosterone. Low testosterone was associated with existing cardiovascular disease, diabetes, elevated hemoglobin A1c, obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension and Framingham score >15. Among patients with low testosterone, the odds ratio for high cardiovascular risk was 1.33 (1.02-1.73) after adjusting for ethnicity, education, alcohol use, cancer characteristics, physical activity and body mass index. CONCLUSIONS: Among androgen-deprivation therapy-naïve prostate cancer patients, low testosterone is common and associated with increased cardiovascular risk factors.

The impact of time to prostate specific antigen nadir on biochemical recurrence and mortality rates after radiation therapy for localized prostate cancer.

PURPOSE: To investigate the effect of time to prostate-specific antigen (PSA) nadir (TTN) after radiation therapy (RTx) for prostate cancer (PCa) on biochemical recurrence (BCR) and overall survival (OS) rates. PATIENTS AND METHODS: We analyzed 2,506 patients treated with RTx (external beam radiotherapy, brachytherapy or combinations) between years 2000 and 2021. Kaplan Meier and multivariable Cox regression models tested BCR-free survival and OS after stratification according to TTN (≤24 vs. 24.1-60 vs. >60 months). Similar analyses were performed after stratification according to absolute PSA values at nadir (<0.01 vs. 0.01-0.1 vs. 0.11-0.4 vs. >0.4 ng/ml). Finally, we repeated analyses after setting the time point of PSA nadir as the beginning of follow up in survival analyses. RESULTS: 10-year BCR-free survival rates were 55.5, 81.7 and 91.1% and OS rates were 71.5, 79.4 and 96.1% for TTN ≤24 months, 24.1 month-60 month and >60 months, respectively. Longer TTN was an independent predictor for BCR-free survival and OS (all P<0.001). However, after accounting for lead-time bias, in multivariable analyses, this association remained only significant for BCR-free survival (P≤0.03), but not for OS (P≥0.1). Finally, compared to a PSA nadir of <0.01 ng/ml, PSA nadir of 0.01-0.1 ng/ml, 0.11-0.4 ng/ml as well as >0.4 ng/ml were independent predictors for shorter BCR-free survival (P≤0.02), but not OS (P≥0.08). CONCLUSION: Shorter time to TTN and high PSA values at nadir are indicative of early treatment failure (BCR) and OS. However, after accounting for lead-time bias, this effect only remained valid for BCR.

PSA outcomes and late toxicity of single-fraction HDR brachytherapy and LDR brachytherapy as monotherapy in localized prostate cancer: A phase 2 randomized pilot study.

PURPOSE: To evaluate the PSA outcomes and the late patient's reported health related quality of life (HRQOL) and toxicity after single-fraction High-Dose-Rate brachytherapy (HDRB) and Low-Dose-Rate brachytherapy (LDRB) for prostate cancer. METHODS: Men with low and favorable intermediate-risk prostate cancer across 3 centres were randomized between monotherapy brachytherapy with either Iodine-125 LDRB or 19 Gy single-fraction HDRB. Biochemical outcomes were evaluated using the Phoenix definition, PSA nadir and absolute PSA value <0.4 ng/mL. Toxicities and HRQOL were recorded at 24 and 36 months. RESULTS: A total of 31 patients were randomized, 15 in the LDRB arm and 16 patients in the HDRB arm. After a median follow-up of 45(36-53) months, 3 patients in the HDRB arm experienced biochemical failure (p = 0.092). Nineteen Gy single-fraction HDRB was associated with significantly higher PSA nadir compared to LDRB (1.02 ± 0.66vs 0.25 ± 0.39, p < 0.0001). Moreover, a significantly larger proportion of patients in the LDRB group had a PSA <0.4 ng/mL (13/15 vs 2/16, p < 0.0001). For late Genito-Urinary, Gastro-Intestinal, and sexual toxicities at 24 and 36 months, no significant differences were found between the 2 arms. As for HRQOL, the IPSS and EPIC-26 urinary irritative score were significantly better for patients treated with HDRB over the first 36 months post-treatment (p = 0.001 and p = 0.01, respectively), reflecting superior HRQOL. CONCLUSION: HDRB resulted in superior HRQOL in the irritative urinary domain compared to LDRB. PSA nadir was significantly lower in the LDRB group and a higher proportion of patients in the LDRB group reached PSA <0.4 ng/mL.