Oncological and functional results of robotic salvage radical prostatectomy after permanent brachytherapy implants

Purpose

To evaluate the feasibility of robotic salvage prostatectomy for local recurrence after permanent brachytherapy implants for prostate cancer.

Medical treatment for biochemical relapse after radiotherapy

This article's purpose was to review the medical data justifying the use of a medical treatment for biochemical relapse after external beam radiotherapy. The MEDLINE database was searched to identify relevant information with the following medical subject headings: “prostate cancer”, “radiotherapy” and “biochemical relapse”. Prognostic factors affecting the overall survival of patients with a biochemical relapse after external beam radiotherapy have been identified: short prostate specific antigen (PSA)-doubling time (< 12 months), high PSA value (> 10 ng/mL) and short interval between treatment and biochemical relapse (< 18 months). If a second local treatment is not feasible, timing to initiate a salvage medical treatment is not defined. Particularly, randomized trials did not demonstrate a significant benefit of an early initiation of androgen deprivation treatment. Some retrospective studies suggest that an early androgen deprivation is justified if poor prognostic factors are found. However, if an androgen deprivation treatment is prescribed, intermittent schedule is non-inferior to a continuous administration and seems to offer a better quality of life. Many non-hormonal treatments have also been evaluated in this setting: only 5-alpha-reductase inhibitors could be proposed in some specific situations. In conclusion, the judicious use of a medical treatment for biochemical relapse is still debated. Given the natural history of this clinical situation, a simple surveillance is justified in many cases.     

Hyaluronic acid spacer in focal prostate reirradiation: A single centre experience

PurposeThe optimal management of locally recurrent prostate cancer after curative radiotherapy is still unknown. In this study, we evaluated the preliminary results of reirradiation using stereotactic body radiotherapy for locally recurrent prostate cancer after initial definitive local radiotherapy.Materials and methodsBetween April 2016 and February 2019, 11 patients with recurrent disease at the previously irradiated prostate were treated. Local recurrence was detected by radiological with or without functional imaging modalities including prostate multiparametric/pelvic MRI or positron-emission tomography–computerised tomography with (⁶⁸Ga)-labelled prostate-specific membrane antigen performed after rising prostate specific antigen serum level during follow-up. All patients received stereotactic body radiotherapy to the recurrent nodule to a total dose of 30 Gy in five fractions. Hyaluronic acid spacer was injected between prostate and rectum in seven patients to decrease the rectal dose. Acute toxicity was evaluated by using Common Terminology Criteria for Adverse Events version 4.0, and late toxicity was evaluated by using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring schema.ResultsAt the diagnosis, the median age was 64 years, and the mean prostate specific antigen serum concentration was 17.7 ng/mL. The median interval time between local recurrence and initial definitive radiotherapy was 63 months. Mean prostate specific antigen concentration nadir value during follow-up was 0.43 ng/mL. With a median follow up of 19 months, three patients developed either local or distant relapse. One patient had grade 3 acute rectal toxicity, and one patient had grade 2 late urinary toxicity. We did not observe any acute or late toxicity due to hyaluronic acid spacer injection.ConclusionReirradiation after local recurrence following initial definitive radiotherapy together with hyaluronic acid spacer use seems to be effective and safe.     

Diagnostic performance of imaging techniques for detecting of local recurrence after prostate brachytherapy

PurposeThe purpose of this study was to evaluate MRI and fluorocholine PET/CT diagnostic performances for the detection of local recurrence following prostate brachytherapy for localised prostate cancer.Material and methodsIn this single-centre study, we retrospectively reviewed data from 21 patients treated by brachytherapy for localised prostate cancer and diagnosed with biochemical recurrence according to Phoenix Criteria, who underwent MRI and fluorocholine PET/CT. We included patients with local relapse suspicion according to imaging exams, with biopsy for the final assessment of local recurrence. Patient analysis data were supplemented by segment analysis using an 8-segment model.ResultsThe fluorocholine PET/CT was positive for 81% and negative for 19% of patients. The sensitivity and specificity were 92% and 33% with diagnosis accuracy of 67%. The MRI was positive for 57% and negative for 43% of patients. The sensitivity and specificity were 67% and 56% with diagnosis accuracy of 62%. There was no statistically significant difference between fluorocholine PET/CT and MRI accuracy (P = 0.63). On a segment-based analysis, the sensitivity and specificity were 44% and 82% for fluorocholine PET/CT with diagnosis accuracy of 78%. For MRI, specificity was 91% diagnosis accuracy was 82%.ConclusionBoth MRI and fluorocholine PET/CT permit to highlight local recurrence sites after prostate brachytherapy. Confirmation biopsies are, however, necessary since this accuracy is insufficient.     

Expérience monocentrique de la tomographie par émission de positons à la (18F)-fluorocholine : analyse de son impact sur les indications de traitement local de rattrapage dans la prise en charge des adénocarcinomes prostatiques

PurposeTo assess usefulness of (¹⁸F)-fluorocholine positron emission tomography (PET) for localizing relapse in patients with biochemical relapse from prostate adenocarcinoma and its impact on indications of salvage local therapy.Patients and methodsAn (¹⁸F)-fluorocholine PET coupled with computed tomography was performed in 28 patients with biochemical progression from prostate adenocarcinoma. At the time of (¹⁸F)-fluorocholine PET, median prostate specific antigen (PSA) was 3.0 ng/mL (from 0.34 to 93 ng/mL) and 17 patients (60.7%) received hormone therapy. Eighteen patients from this cohort were potentially candidates to salvage radiotherapy.ResultsA pathologic uptake was shown in 11 patients (39.3%) and 17 patients (60.7%) had no pathologic uptake. Median PSA was 2.4 ng/mL (0.33 to 36 ng/mL) in case of negative (¹⁸F)-fluorocholine PET, versus 6.75 ng/mL (1.21 to 93 ng/mL) in case of pathologic uptake (P = 0.04). Among the 17 patients candidates to salvage radiotherapy, (¹⁸F)-fluorocholine PET helped deciding for salvage radiotherapy in five patients, since it showed only centropelvic pathologic uptake (27.7%). In one patient, it showed metastatic and radiotherapy was contraindicated. After prostatectomy, (¹⁸F)-fluorocholine PET was positive in only one patient candidate to salvage radiotherapy (9.1%), showing anastomotic relapse.Conclusion(¹⁸F)-fluorocholine was positive in about a third of patients with biochemical progression. Its clinical impact is being prospectively investigated.     

Baseline prostate-specific antigen measurements and subsequent prostate cancer risk in the Danish Diet,Cancer and Health cohort

AimAlthough prostate-specific antigen (PSA) screening reduces mortality from prostate cancer, substantial over-diagnosis and subsequent overtreatment are concerns. Early screening of men for PSA may serve to stratify the male population by risk of future clinical prostate cancer.Methods and materialCase–control study nested within the Danish ‘Diet, Cancer and Health’ cohort of 27,179 men aged 50–64 at enrolment. PSA measured in serum collected at cohort entry in 1993–1997 was used to evaluate prostate cancer risk diagnosed up to 14 years after. We identified 911 prostate cancer cases in the Danish Cancer Registry through 31st December 2007 1:1 age-matched with cancer-free controls. Aggressive cancer was defined as ?T3 or Gleason score ?7 or N1 or M1. Statistical analyses were based on conditional logistic regression with age as underlying time axis.ResultsTotal PSA and free-to-total PSA ratio at baseline were strongly associated with prostate cancer risk up to 14 years later. PSA was grouped in quintiles and free-to-total PSA ratio divided in three risk groups. The incidence rate ratio for prostate cancer was 150 (95% confidence interval, 72–310) among men with a total PSA in the highest quintile (>5.1 ng/ml) compared to the lowest (<0.80 ng/ml). The risk of aggressive cancer was highly elevated in men with a PSA level in the highest quintile. The results indicate that one-time measurement of PSA could be used in an individualised screening strategy, sparing a large proportion of men from further PSA-based screening.     

Associations of sexual dysfunction symptoms with PSA-detected localised and advanced prostate cancer: A case-control study nested within the UK population-based ProtecT (Prostate testing for cancer and Treatment) study

BackgroundSexual dysfunction might be symptomatic of cancer spreading beyond the prostate by local invasion, a mechanism of tumour progression associated with prognosis. Conversely, among men with raised prostate-specific antigen (PSA) levels, a negative association might be expected if sexual dysfunction was symptomatic of benign, rather than malignant, prostatic disease.Patients and methodsCases and controls were selected from among men recruited to the UK population-based ProtecT (Prostate testing for cancer and Treatment) study. Men aged 50–69 years were invited for PSA testing and those with a PSA level ?3.0 ng/ml were invited for biopsy. We investigated whether symptoms of sexual dysfunction, determined by self-completed questionnaire prior to biopsy, were associated with prostate cancer.ResultsOf the 8924 men who had a PSA level ?3.0 ng/ml (11% of the men who had a PSA test), 6585 underwent biopsy of whom 2813 and 421, respectively, were subsequently diagnosed with localised and advanced prostate cancer and 3351 had a negative biopsy result. No individual symptom of sexual dysfunction was associated with risk of prostate cancer. The symptom score was associated with advanced (odds ratio (OR) per one unit increase in score = 1.06; 1.00–1.12; P = 0.07) but not with localised (OR = 1.00; 0.97–1.02; P = 0.9) prostate cancer (P = 0.05 for heterogeneity).ConclusionsOur study provides weak evidence that sexual dysfunction may be associated with PSA-detected advanced, but not localised, prostate cancer among men with raised PSA levels.     

Image-guided high-dose-rate interstitial brachytherapy boost in the radical radiotherapy for a huge metastatic carcinoma of cervical lymph nodes from an unknown primary site

The purpose of this article was to report the treatment effect of image-guided high-dose-rate interstitial brachytherapy boost in the radical radiotherapy for a huge metastatic carcinoma of cervical lymph nodes from an unknown primary site. The patient was a 75-year-old male. A diagnostic biopsy showed metastatic squamous cell carcinoma and the tumour size was 7.5 × 6.5 × 11.5 cm³ before treatment (N3; AJCC 7th). After external beam radiotherapy with a dose of 60 Gy in 30 fractions, the residual tumour (6.2 × 4.7 × 6.0 cm³) was treated with image-guided high-dose-rate interstitial brachytherapy boost under ultrasound guidance. The brachytherapy dose was 16 Gy in four fractions of 4 Gy each. Removal of the huge metastatic tumour was securely achieved by high dose rate interstitial brachytherapy guided with ultrasound scanning. The refractory tumour in the patients healed uneventfully after image-guided high-dose-rate interstitial brachytherapy without recurrence during the 24 months of follow-up. The image-guided high-dose-rate interstitial brachytherapy boost may be a proposed treatment strategy for metastatic carcinoma of cervical lymph nodes from an unknown primary site with radical radiotherapy, especially for huge residual tumour.     

Basal cell hyperplasia (BCH) versus high grade prostatic intraepithelial neoplasia (HGPIN) in tiny prostatic needle biopsies: Unusual diagnostic dilemma

BackgroundHistopathological differentiation between BCH and HGPIN in prostatic needle biopsies is a diagnostic challenge. The gold standard for detection of HGPIN and BCH is histopathological examination; however subjectivity in interpretation and tiny volume of obtained tissue hamper reliable diagnosis.AimsThe aim of this study was to assess usefulness of using the p63 and p504s to solve this problem. Although the use of p63 and p504s is now well established in differentiation between preneoplastic and neoplastic prostatic lesions, their usefulness in tiny tissue material is, however, not fully studied.MethodsThe study included a spectrum of 30 prostatic needle biopsies (5 BCH, 10 HGPIN, 10 indefinite luminal proliferations where BCH and HGPIN could not be distinguished from each other and 5 adenocarcinomas). H&E stained sections were examined for histopathological features. Other sections were stained immunohistochemically with p63 and p504s.ResultsThe mean age of patients was 69 (SD = 7.6) years. PSA range was 1.3–2.7 ng/ml. Ultrasongraphic findings were unremarkable. All BCH showed p504s−/p63+ pattern, All HGPIN had p504s+/p63+ pattern while carcinomas were p504s+/p63−. After immunostaining combined with histopathological features; the 10 indefinite specimens could be diagnosed as 4 BCH and 6 HGPIN. The article explains how applying this staining pattern on the challenging specimens, combined with histopathological features, can be helpful in proper identification of prostatic proliferations.     

Radiothérapie de rattrapage après prostatectomie radicale : que faire en cas de concentration de PSA postopératoire élevée persistante ou de récidive locale macroscopique ?

The management of the postoperative biological relapse of prostate cancer is most often based on salvage radiotherapy (RT) and a variable duration of hormone therapy (HT) in addition. The indications for RT ± HT become more consensual for the adjuvant postoperative situation or in the event of a rising PSA level after a period where an undetectable PSA level was achieved. On the other hand, in the event of detectable PSA immediately postoperatively or in the event of a biological recurrence with macroscopic relapse in the prostate bed seen on conventional imaging assessment, the treatment options are still being evaluated. This article will describe these 2 situations and their current management but also will come through assessments with the contribution of modern imaging and new treatment options in terms of RT dose and RT ± HT combination.     

Five-fraction HDR brachytherapy in locally advanced cervical cancer: A monocentric experience

PurposeThe 5-fraction scheme (5 × 5–5.5 Gy) is a common High-Dose Rate (HDR) intracavitary brachytherapy regimen for locally advanced cervical cancer (LACC). Yet, its equivalence with Pulse-Dose rate (PDR) schemes remains unproved. The present study aimed at reporting on the outcome of LACC patients treated with 5-fraction HDR brachytherapy.Materials and methodsThe medical records of all consecutive patients treated with curative-intent HDR brachytherapy for a LACC in a French Cancer Center were retrospectively reviewed.ResultsThirty-eight LACC patients underwent a 5-fraction intracavitary HDR brachytherapy between 2015 and 2019 (median dose = 25 Gy/5 fractions, following external-beam radiotherapy). Median age at diagnosis was 60 (range: 29–87). Thirty-one patients (81.5%) underwent concurrent chemotherapy. Tumor stages ranged from 3 IB2 (7.8%), 4 IB3 (10.5%), 4 IIA2 (10.5%), 12 IIB (31.7%), 1 IIIA (2.6%), 2 IIIB (5.3%), 7 IIIC1 (18.5%), 4 IIIC2 (10.5%), 1 IVA (2.6%) (2018 FIGO). Median D90% to CTV_HR reached 79.5 Gy (EQD2). Median D90% to CTV_IR reached 59.5 Gy (EQD2). Median Bladder D2cc was 69.8 Gy (EQD2). Median Rectum D2cc was 58.3 Gy (EQD2). Acute/late grade 3 toxicity was reported in one patient (2.6%). No grade 4–5 toxicity occurred. At a median 38 months follow-up, 10 patients (26.3%) had local (n = 7, 18.4%), nodal (n = 6, 15.7%) and/or distant (n = 7, 18.4%) relapse. Three-year overall survival rate was of 81.6%.ConclusionThe 5-fraction HDR scheme was well tolerated even in frail patients. Three-year local control was lower than expected. Treatment (absence of parametrial interstitial implants and use of cervical EBRT boost) and patients’ characteristics (age, comorbidities) may explain such results.     

Evaluation of adjuvant vaginal vault brachytherapy in early stage cervical cancer patients

PurposeAdjuvant external beam radiotherapy (EBRT) was shown to decrease pelvic relapses in patients with an early stage cervical cancer and intermediate-risk histopathological prognostic factors, at the cost of increased bowel morbidity. We examined the feasibility and results of adjuvant brachytherapy alone as an alternative to EBRT in this situation.Patients and methodsMedical records of consecutive patients receiving adjuvant brachytherapy between 1991 and 2018 for an early stage cervical cancer were examined. Patients were included if they presented a pT1a2N0 or pT1b1N0 disease following radical colpohysterectomy. Adjuvant vaginal wall brachytherapy (without EBRT) was indicated because of a tumor size ≥ 2 cm and/or presence of lymphovascular space invasion (LVSI). Patients received 60 Gy to 5 mm of the vaginal wall, through low-dose or pulse-dose rate technique. Patients’ outcome was examined for disease control, toxicities and prognostic factors.ResultsA total of 40 patients were included. Eight patients (20%) had LVSI, 26 patients (65%) had a tumor size ≥ 2 cm. With median follow-up time of 42.0 months, 90% of patients were in complete remission and four patients (10%) experienced tumor relapse, all in the peritoneal cavity, and associated with synchronous pelvic lymph node failure in 2/4 patients. No vaginal or isolated pelvic nodal failure was reported. At 5 year, overall survival was 83.6% (CI95%: 67.8–100%) and disease-free survival was 85.1% (CI95%: 72.6–99.9%). In univariate analysis, probability of relapse correlated with tumor size ≥ 3 cm (P = 0.004). No acute or late toxicity grade more than 2 was reported.ConclusionBrachytherapy alone was a well-tolerated adjuvant treatment for selected patients with intermediate risk factors. The risk of relapse in patients with tumor size ≥ 3 cm was however high, suggesting that EBRT is more appropriate in this situation.     

Survival benefit of early androgen receptor inhibitor therapy in locally advanced prostate cancer: Long-term follow-up of the SPCG-6 study

BackgroundThe optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate.MethodsA randomised, double-blind, parallel-group trial comparing bicalutamide 150 mg once daily with placebo in addition to standard care in patients with hormone-naïve, non-metastatic PCa. Kaplan–Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death).FindingsA total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised to receive bicalutamide in addition to their standard care and 611 to receive placebo. Median follow-up was 14.6 years. Overall, 866 (71.1%) patients died, 428 (70.5%) in the bicalutamide arm and 438 (71.7%) in the placebo arm, p = 0.87. Bicalutamide significantly improved OS in patient with locally advanced disease (hazard ratios (HR) = 0.77 (95% confidence interval (CI): 0.63–0.94, p = 0.01), regardless of baseline prostate-specific antigen (PSA), with a survival benefit which was apparent throughout the study period. In contrast, survival favoured randomisation to the placebo arm in patients with localised disease (HR = 1.19 (95% CI: 1.00–1.43), p = 0.056). However, a survival gain from bicalutamide therapy was present in patients with localised disease and a baseline PSA greater than 28 ng/mL at randomisation. In multivariate Cox proportional hazard model, only including patients managed on watchful waiting as their standard of care (n = 991) OS depended on age, World Health Organisation (WHO) grade, baseline PSA, clinical stage and randomised treatment.InterpretationThroughout the 14.6 year follow-up period the addition of early bicalutamide to standard of care resulted in a significant OS benefit in patients with locally advanced PCa. In contrast, patients with localised PCa and low PSA derived no survival benefit from early bicalutamide. The optimal timing for initiating bicalutamide in non-metastatic PCa patients is dependent on disease stage and baseline PSA.     

Curiethérapie de haut débit de dose après radiothérapie externe d’un cancer de prostate : impact de la courbe d’apprentissage sur la dosimétrie

PurposeTo analyse the influence of the learning curve on dosimetric data for high-dose-rate brachytherapy prostate cancer boost.Patients and methodsFrom February 2009 to May 2012, after a first course of external beam radiation therapy (46 Gy/23 fractions), 124 patients underwent high-dose-rate brachytherapy boost using Plato™ (Nucletron, an Elekta company, Elekta AB, Stockholm, Sweden). The impact of the learning curve on the dosimetric quality of the prostate implant was assessed. The dosimetric data have been analysed: clinical target volume (CTV), D90 (dose to 90 % of CTV), D100, V100 (part on the CTV receiving 100 % of the dose), V150, V200 and DHI (dose non-homogeneity index). The doses delivered to 0.1, 1 and 2 cm³ of the rectum and urethra were calculated.ResultsDuring the study period (39 months), a significant reduction of V150 (P < 0.001), V200 (P < 0.001), D0.1rectum (P < 0.001), D1rectum (P < 0.001), D2rectum (P < 0.001), D0.1urethra (P < 0.001), and D1urethra (P < 0.002) was observed associated with a significant degradation of the D90 (P < 0.001) but not significant for the V100 (P = 0.29) and the D100 (P = 0.3).ConclusionThis study confirms that the dosimetric quality of high-dose-rate brachytherapy prostate implant is significantly improved during the learning curve period.     

Comparison between the ICRU rectal point and modern volumetric parameters in brachytherapy for locally advanced cervical cancer

PurposeThe implementation of image-guided brachytherapy in cervical cancer raises the problem of adapting the experience acquired with 2D brachytherapy to this technique. The GEC-ESTRO (Groupe européen de curiethérapie – European Society for Radiotherapy and Oncology) has recommended reporting the dose delivered to the rectum in the maximally exposed 2 cm³ volume, but so far, the recommended dose constraints still rely on 2D data. The aim of this study was to evaluate the relationship between the doses evaluated at the ICRU rectal point and modern dosimetric parameters.Material and methodsFor each patient, dosimetric parameters were generated prospectively at the time of dosimetry and were reported. For analysis, they were converted in 2 Gy equivalent doses using an α/β ratio of 3 with a half-time of repair of 1.5 hours.ResultsThe dosimetric data from 229 consecutive patients treated for locally advanced cervical cancer was analyzed. The mean dose calculated at ICRU point (DICRU) was 55.75 Gy ± 4.15, while it was 59.27 Gy ± 6.16 in the maximally exposed 2 cm³ of the rectum (P = 0.0003). The D2 cm³ was higher than the DICRU in 78% of the cases. The mean difference between D2 cm³ and DICRU was 3.53 Gy ± 4.91. This difference represented 5.41% ± 7.40 of the total dose delivered to the rectum (EBRT and BT), and 15.49% ± 24.30 of the dose delivered when considering brachytherapy alone. The two parameters were significantly correlated (P = 0.000001), and related by the equation: D2 cm³ = 0.902 × DICRU + 0.984. The r² coefficient was 0.369.ConclusionIn this large cohort of patients, the DICRU significantly underestimates the D2 cm³. This difference probably results from the optimization process itself, which consists in increasing dwell times above the ICRU point in the cervix. Considering these findings, caution must be taken while implementing image-guided brachytherapy and dose escalation.     

Patterns of locoregional failure in women with early-stage breast cancer treated by whole breast irradiation in the lateral isocentric decubitus position: Large-scale single-centre experience

PurposeThe purpose of this study was to evaluate locoregional control and describe the patterns of failure in patients with breast cancer receiving whole breast radiotherapy in the isocentric lateral decubitus position technique.Patients and methodsIn a series of 832 consecutive female patients with early-stage breast cancer including invasive and in situ tumours treated by breast-conserving surgery followed by three-dimensional conformal whole breast irradiation in the isocentric lateral decubitus position between 2005 and 2010, all patients who experienced locoregional recurrence were studied. Five-year recurrence-free and overall survival rates were calculated. Regional recurrence mapping patterns were also determined.ResultsThe median age of this series of 832 women was 61.5 years (range: 29–90 years). Various types of fractionation were used: 50 Gy in 25 fractions (17.9%), 66 Gy in 33 fractions (50 Gy in 25 fractions to breast followed by sequential boost to tumour bed to a total dose 66 Gy in 33 fractions.) (46.5%), 40 Gy in 15 fractions or 41.6 Gy in 13 fractions (26.1%) and 30 Gy in 5 fractions (9.5%). With a median follow-up of 6.4 years, only 36 patients experienced locoregional recurrence and no association with the fractionation regimen was identified (P = 0.2). In this population of 36 patients, 28 (3.3%) had “in-breast” local recurrences (77.8%), two had local recurrences and regional lymph node recurrence (5.6%), and six had regional lymph node recurrence only (in non-irradiated areas; 16.6%). The median time to recurrence was 50 months. Complete mapping of patterns of recurrences was performed and, in most cases, local recurrences were situated adjacent to the primary tumour bed. Cases of local recurrences presented a significantly lower distant metastasis rate (P < 0.001) and had a significantly longer overall survival compared to patients with regional lymph node recurrence (P < 0.001). However, multivariate Cox regression analysis showed that the site of recurrence had no significant impact on overall survival (P = 0.14).ConclusionThe results of this study indicate a low local recurrence rate. Further careful follow-up and recording of recurrences is needed to improve the understanding of patterns of recurrence.     

Optimal source distribution for focal boosts using high dose rate (HDR) brachytherapy alone in prostate cancer

PurposeTo investigate the optimal distribution of sources using high dose rate brachytherapy to deliver a focal boost to a dominant lesion within the whole prostate gland based on multi-parametric magnetic resonance imaging (mpMRI).MethodsSixteen patients with prostate cancer underwent mpMRI each of which demonstrated a dominant lesion. There were single lesions in 6 patients, two lesions in 4 and 3 lesions in 6 patients. Two dosimetric models and parameters were compared in each case. The first model used 10 mm intervals between needles, and the second model used additional needles at 5 mm intervals between each needle in the boost area.ResultsThree of thirty-two plans did not achieve the plan objectives. These three plans were in the first model. A higher median urethral volume was seen in the ‘unsuccessful’ group (2.7 cc, and 1.9 cc, respectively, p-value = 0.12). Conformity indices of the second model were also better than the first model (COIN index; 0.716 and 0.643, respectively).ConclusionsFocal monotherapy based on mpMRI achieves optimal dosimetry by individualizing the needle positions using 5 mm spacing rather than 10 mm spacing within the boost volume. A larger urethral volume may have an adverse effect on this distribution. Formal clinical evaluation of this approach is currently underway.     

Pro-inflammatory cytokines and prostate-specific antigen in hyperplasia and human prostate cancer

Background: The aim of this study was to relate the expression, analyzed by Western blot and immunohistochemistry, of several pro-inflammatory cytokines, including IL-1, IL-6 and TNF-α, with serum levels of prostate-specific antigen (PSA) in normal and pathologic (hyperplasia and cancer) prostate tissues to elucidate their possible role in tumor progression. We are also discussing the possible use of these cytokines as a potential therapeutic target. Methods: The study was carried out in 5 normal, 25 benign prostatic hyperplastic (BPH) and 17 cancerous human prostates (PC). Immunohistochemical and Western blot analysis were performed. Serum levels of PSA were assayed by an immulite autoanalyzer. Results: The most relevant results showed that in BPH, IL-1α, IL-6 and tumor necrosis factor (TNF) were only expressed in patients with PSA serum levels of 0–4 or 4–20 ng/ml, but not in the group >20 ng/ml. In PC these cytokines were only expressed in patients with PSA serum levels >4 ng/ml. Conclusions: In PC there was an association between the high expression of pro-inflammatory cytokines (TNFα, IL-6, IL-1), elevated serum levels of PSA and cancer progression. A better understanding of the biologic mechanism of this association may provide new targets for therapy in these patients.