Radiotherapy (RT) for prostate cancer (PC) has steadily evolved over the last decades, with improving biochemical disease-free survival. Recently population based research also revealed an ...association between overall survival and doses ≥ 75.6 Gray (Gy) in men with intermediate- and high-risk PC. Examples of improved RT techniques are image-guided RT, intensity-modulated RT, volumetric modulated arc therapy, and stereotactic ablative body RT, which could facilitate further dose escalation. Brachytherapy is an internal form of RT that also developed substantially. New devices such as rectum spacers and balloons have been developed to spare rectal structures. Newer techniques like protons and carbon ions have the intrinsic characteristics maximising the dose on the tumour while minimising the effect on the surrounding healthy tissue, but clinical data are needed for confirmation in randomised phase III trials. Furthermore, it provides an overview of an important discussion issue in PC treatment between urologists and radiation oncologists: the comparison between radical prostatectomy and RT. Current literature reveals that all possible treatment modalities have the same cure rate, but a different toxicity pattern. We recommend proposing the possible different treatment modalities with their own advantages and side-effects to the individual patient. Clinicians and patients should make treatment decisions together (shared decision-making) while using patient decision aids.
To investigate the association between prostate specific antigen (PSA) bounce and disease outcome after prostate brachytherapy.
We analyzed 975 patients treated with 125I implantation monotherapy ...between 1992 and 2006. All patients had tumor Stage ≤2c, Gleason score ≤7 prostate cancer, a minimum follow-up of 2 years with at least four PSA measurements, and no biochemical failure in the first 2 years. Median follow-up was 6 years. Bounce was defined as a PSA elevation of +0.2 ng/mL with subsequent decrease to previous nadir. We used the Phoenix +2 ng/mL definition for biochemical failure. Additional endpoints were disease-specific and overall survival. Multivariate Cox regression analysis was performed to adjust for potential confounding factors.
Bounce occurred in 32% of patients, with a median time to bounce of 1.6 years. More than 90% of bounces took place in the first 3 years after treatment and had disappeared within 2 years of onset. Ten-year freedom from biochemical failure, disease-specific survival, and overall survival rates were, respectively, 90%, 99%, and 88% for the bounce group and 70%, 93%, and 82% for the no-bounce group. Only 1 patient (0.3%) died of prostate cancer in the bounce group, compared with 40 patients (6.1%) in the no-bounce group. Adjusted for confounding, a 70% biochemical failure risk reduction was observed for patients experiencing a bounce (hazard ratio 0.31; 95% confidence interval 0.20–0.48).
A PSA bounce after prostate brachytherapy is strongly related to better outcome in terms of biochemical failure, disease-specific survival, and overall survival.
To assess the risk of second primary cancer (SPC) after (125)Iiodine prostate cancer brachytherapy compared with prostatectomy and the general population.
In a cohort consisting of 1,888 patients ...with prostate cancer who received monotherapy with brachytherapy (n = 1,187; 63%) or prostatectomy (n = 701; 37%), SPC incidences were retrieved by linkage with the Dutch Cancer Registry. Standardized incidence rates (SIRs) and absolute excess risks (AERs) were calculated for comparison.
A total of 223 patients were diagnosed with SPC, 136 (11%) after brachytherapy and 87 (12%) after prostatectomy, with a median follow-up of 7.5 years. The SIR for all malignancies, bladder cancer, and rectal cancer were 0.94 (95% CI, 0.78 to 1.12), 1.69 (95% CI, 0.98 to 2.70), and 0.90 (95% CI, 0.41 to 1.72) for brachytherapy and 1.04 (95% CI, 0.83 to 2.28), 1.82 (95% CI, 0.87 to 3.35), and 1.50 (95% CI, 0.68 to 2.85) for prostatectomy, respectively. Bladder SPC risk was significantly increased after brachytherapy for patients age 60 years or younger (SIR, 5.84; 95% CI, 2.14 to 12.71; AER, 24.03) and in the first 4 years of follow-up (SIR, 2.14; 95% CI, 1.03 to 3.94; AER, 12.24). Adjusted for age, the hazard ratio (brachytherapy v prostatectomy) for all SPCs combined was 0.87 (95% CI, 0.64 to 1.18).
Overall, we found no difference in SPC incidence between patients with prostate cancer treated with prostatectomy or brachytherapy. Furthermore, no increased tumor incidence was found compared with the general population. We observed a higher than expected incidence of bladder SPC after brachytherapy in the first 4 years of follow-up, probably resulting from lead time or screening bias. Because of power limitations, a small increased SPC risk cannot be formally excluded.
The use of healthcare insurance claims data for urinary incontinence (UI) pads has the potential to serve as an objective measure for assessing post-radical prostatectomy UI rates, but its validity ...for this purpose has not been established. The aim of this study is to correlate claims data with Patient Reported Outcome Measures (PROMs) for UI pad use. Patients who underwent RP in the Netherlands between September 2019 and February 2020 were included. Incontinence was defined as the daily use of ≥1 pad(s). Claims data for UI pads at 12-15 months after RP were extracted from a nationwide healthcare insurance database in the Netherlands. Participating hospitals provided PROMS data. In total, 1624 patients underwent RP. Corresponding data of 845 patients was provided by nine participating hospitals, of which 416 patients were matched with complete PROMs data. Claims data and PROMs showed 31% and 45% post-RP UI (≥1 pads). UI according to claims data compared with PROMs had a sensitivity of 62%, specificity of 96%, PPV of 92%, NPV of 75% and accuracy of 81%. The agreement between both methods was moderate (κ = 0.60). Claims data for pads moderately align with PROMs in assessing post-prostatectomy urinary incontinence and could be considered as a conservative quality indicator.
Therapeutic efficacy of cisplatin-based treatment of late stage urothelial carcinoma (UC) is limited by chemoresistance. To elucidate underlying mechanisms and to develop new approaches for ...overcoming resistance, we generated long-term cisplatin treated (LTT) UC cell lines, characterised their cisplatin response, and determined the expression of molecules involved in cisplatin transport and detoxification, DNA repair, and apoptosis. Inhibitors of metallothioneins and Survivin were applied to investigate their ability to sensitise towards cisplatin. Cell growth, proliferation, and clonogenicity were examined after cisplatin treatment by MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, EdU (5-ethynyl-2'-deoxyuridine) incorporation assay, and Giemsa staining, respectively. Cell cycle distribution and apoptosis were quantified by flow cytometry. mRNA and protein expressions were measured by real-time quantitative (qRT)-PCR, western blot, or immunofluorescence staining. LTTs recovered rapidly from cisplatin stress compared to parental cells. In LTTs, to various extents, cisplatin exporters and metallothioneins were induced, cisplatin adduct levels and DNA damage were decreased, whereas expression of DNA repair factors and specific anti-apoptotic factors was elevated. Pharmacological inhibition of Survivin, but not of metallothioneins, sensitised LTTs to cisplatin, in an additive manner. LTTs minimise cisplatin-induced DNA damage and evade apoptosis by increased expression of anti-apoptotic factors. The observed diversity among the four LTTs highlights the complexity of cisplatin resistance mechanisms even within one tumour entity, explaining heterogeneity in patient responses to chemotherapy.
Prostate biopsy, an invasive examination, is the gold standard for diagnosing prostate cancer (PCa). There is a need for a novel noninvasive diagnostic tool that achieves a significantly high pretest ...probability for PCa, reducing unnecessary biopsy numbers. Recent studies have shown that volatile organic compounds (VOCs) in exhaled breath can be used to detect different types of cancers via training of an artificial neural network (ANN).
To determine whether exhaled-breath analysis using a handheld electronic nose device can be used to discriminate between VOC patterns between PCa patients and healthy individuals.
This prospective pilot study was conducted in the outpatient urology clinic of the Maastricht University Medical Center, the Netherlands. Patients with histologically proven PCa were already included before initial biopsy or during follow-up, with no prior treatment for their PCa. Urological patients with negative biopsies in the past year or patients with prostate enlargement (PE) with low or stable serum prostate-specific antigen were used as controls. Exhaled breath was probed from 85 patients: 32 with PCa and 53 controls (30 having negative biopsies and 23 PE).
Patient characteristics were statistically analyzed using independent sample t test and Pearson’s chi-square test. Data analysis was performed by Aethena software after data compression using the TUCKER3 algorithm. ANN models were trained and evaluated using the leave-10%-out cross-validation method.
Our trained ANN showed an accuracy of 0.75, with an area under the curve of 0.79 with sensitivity and specificity of 0.84 (95% confidence interval CI 0.66–0.94) and 0.70 (95% CI 0.55–0.81) respectively, comparing PCa with control individuals. The negative predictive value was found to be 0.88. The main limitation is the relatively small sample size.
Our findings imply that the Aeonose allows us to discriminate between patients with untreated, histologically proven primary PCa and control patients based on exhaled-breath analysis.
We explored the possibility of exhaled-breath analysis using an electronic nose, to be used as a noninvasive tool in clinical practice, as a pretest for diagnosing prostate cancer. We found that the electronic nose was able to discriminate between prostate cancer patients and control individuals.
We explored the possibility of exhaled-breath analysis using an electronic nose, to be used as a noninvasive tool in clinical practice, as a pretest for diagnosing prostate cancer. We found that the electronic nose was able to discriminate between prostate cancer patients and control individuals.
This study aimed to assess the effects of 20 wk resistance exercise training with or without protein supplementation on body composition, muscle mass, muscle strength, physical performance, and ...aerobic capacity in prostate cancer patients receiving androgen deprivation therapy (ADT).
Sixty prostate cancer patients receiving ADT were randomly assigned to perform 20 wk of resistance exercise training with supplementation of 31 g whey protein (EX + PRO, n = 30) or placebo (EX + PLA, n = 30), consumed immediately after exercise and every night before sleep. A separate control group (CON, n = 36) only received usual care. At baseline and after 20 wk, body composition (dual-energy x-ray absorptiometry), muscle mass (computed tomography scan), muscle strength (1-repetition maximum strength tests), physical performance (Timed Up and Go Test, 30-Second Chair Stand Test, and Stair Climb Test), aerobic capacity (cardiopulmonary exercise test), and habitual dietary intake (food diary) were assessed. Data were analyzed using a two-factor repeated-measures ANOVA.
Over time, muscle mass and strength increased in EX + PRO and EX + PLA and decreased in CON. Total fat mass and fat percentage increased in EX + PRO and CON, but not in EX + PLA. Physical performance did not significantly change over time in either group. Aerobic capacity was maintained in EX + PLA, but it decreased in EX + PRO and CON. Habitual protein intake (without supplements) averaged >1.0 g·kg body weight -1 ·d -1 , with no differences over time or between groups.
In prostate cancer patients, resistance exercise training counteracts the adverse effects of ADT on body composition, muscle mass, muscle strength, and aerobic capacity, with no additional benefits of protein supplementation.
To assess long-term biochemical and survival outcome after permanent prostate brachytherapy (BT).
Data on 921 patients, treated with permanent interstitial BT monotherapy between 1989 and 2004 for ...<or=T2c Nx/0 Mx/0 prostate cancer were evaluated. All patients were treated with I-125 seeds (prescription dose 144 Gy). Eighty-five patients with a gland volume >or=50cc received 6 months of antiandrogen therapy before treatment. Patients were classified into risk groups with 232 defined as low-, 369 intermediate-, and 320 high-risk disease. The median follow-up was 69 months (range, 4-186 months); mean age was 67 years.
Average 5- and 10-year biochemical no evidence of disease (bNED) rates were 79% and 57%. Average 10-year bNED rates by risk group were 88% for low-risk, 61% for intermediate-risk, and 30% for high-risk disease. The average 10-year overall and disease-specific survival rates were 59% and 82%. Ten-year overall and disease-specific survival rates by risk group were, respectively, 68% and 96% for low-risk, and 64% 87% for intermediate-risk, and 49% and 69% for high-risk disease. In multivariate Cox regression analysis, both risk group and treatment era were independent predictors of bNED and survival.
These data on long-term survival continue to support the use of I-125 monotherapy for prostate cancer in low-risk patients and, in particular, demonstrate its efficacy in intermediate-risk patients.
Tumour heterogeneity and resistance to systemic treatment in urothelial carcinoma (UC) may arise from cancer stem cells (CSC). A recent model describes cellular differentiation states within UC based ...on corresponding expression of surface markers (CD) and cytokeratins (CK) with CD90 and CK14 positive cells representing the least differentiated and most tumourigenic population. Based on the fact that this population is postulated to constitute CSCs and the origin of cisplatin resistance, we enriched urothelial carcinoma cell lines (UCCs) for CD90 and studied the tumour-initiating potential of these separated cells in vitro.
Magnetic- and fluorescence-activated- cell sorting were used for separation of CD90(+) and CD90(-) UCCs. Distribution of cell surface markers CD90, CD44, and CD49f and cytokeratins CK14, CK5, and CK20 as well as the effects of short- and long-term treatment with cisplatin were assessed in vitro and measured by qRT-PCR, immunocytochemistry, reporter assay and flow cytometry in 11 UCCs.
We observed cell populations with surface markers according to those reported in tumour xenografts. However, expression of cytokeratins did not concord regularly with that of the surface markers. In particular, expression of CD90 and CK14 diverged during enrichment of CD90(+) cells by immunomagnetic sorting or following cisplatin treatment. Enriched CD90(+) cells did not exhibit CSC-like characteristics like enhanced clonogenicity and cisplatin resistance. Moreover, selection of cisplatin-resistant sublines by long-term drug treatment did not result in enrichment of CD90(+) cells. Rather, these sublines displayed significant phenotypic plasticity expressing EMT markers, an altered pattern of CKs, and WNT-pathway target genes.
Our findings indicate that the correspondence between CD surface markers and cytokeratins reported in xenografts is not maintained in commonly used UCCs and that CD90 may not be a stable marker of CSC in UC. Moreover, UCCs cells are capable of substantial phenotypic plasticity that may significantly contribute to the emergence of cisplatin resistance.
Objective: The purpose of this review was to summarize the current literature on the assessment and treatment of radiation urethritis and cystitis (RUC) for the development of an evidenced-based ...management algorithm. Material and Methods: The PubMed/MEDLINE database was searched by a multidisciplinary group of experts in January 2021. Results: In total, 48 publications were identified. Three different types of RUC can be observed in clinical practice: inflammation-predominant, bleeding-predominant, and the combination of inflammation- and bleeding-RUC. There is no consensus on the optimal treatment of RUC. Inflammation-predominant RUC should be treated symptomatically based on the existence of bothersome storage or voiding lower urinary tract symptom as well as on pain. When bleeding-predominant RUC has occurred, hydration and hyperbaric oxygen therapy (HOT) should be used first and, if HOT is not available, oral drugs instead (sodium pentosane polysulfate, aminocaproic acid, immunokine WF 10, conjugated estrogene, or pentoxifylline + vitamin E). If local bleeding persists, focal therapy of bleeding vessels with a laser or electrocoagulation is indicated. In case of generalized bleeding, intravesical installation should be initiated (formalin, aluminium salts, and hyaluronic acid/chondroitin). Vessel embolization is a less invasive treatment with potentially less complications and good clinical outcomes. Open- or robot-assisted surgery is indicated in patients with permanent, life-threatening bleeding, or fistulae. Conclusions: Treatment of RUC, if not self-limiting, should be done according to the type of RUC and in a stepwise approach. Conservative/medical treatment (oral and topic agents) should primarily be used before invasive (transurethral) treatments.
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