Ants Toi

Positioning errors and prostate motion during conformal prostate radiotherapy using on-line isocentre set-up verification and implanted prostate markers.

PURPOSE To evaluate treatment errors from set-up and inter-fraction prostatic motion with port films and implanted prostate fiducial markers during conformal radiotherapy for localized prostate cancer. METHODS Errors from isocentre positioning and inter-fraction prostate motion were investigated in 13 men treated with escalated dose conformal radiotherapy for localized prostate cancer. To limit the effect of inter-fraction prostate motion, patients were planned and treated with an empty rectum and a comfortably full bladder, and were instructed regarding dietary management, fluid intake and laxative use. Field placement was determined and corrected with daily on-line portal imaging. A lateral portal film was taken three times weekly over the course of therapy. From these films, random and systematic placement errors were measured by matching corresponding bony landmarks to the simulator film. Superior-inferior and anterior-posterior prostate motion was measured from the displacement of three gold pins implanted into the prostate before planning. A planning target volume (PTV) was derived to account for the measured prostate motion and field placement errors. RESULTS From 272 port films the random and systematic isocentre positioning error was 2.2 mm (range 0.2-7.3 mm) and 1.4 mm (range 0.2-3.3 mm), respectively. Prostate motion was largest at the base compared to the apex. Base: anterior, standard deviation (SD) 2.9 mm; superior, SD 2.1 mm. Apex: anterior, SD 2.1 mm; superior, SD 2.1 mm. The margin of PTV required to give a 99% probability of the gland remaining within the 95% isodose line during the course of therapy is superior 5.8 mm, and inferior 5.6 mm. In the anterior and posterior direction, this margin is 7.2 mm at the base, 6.5 mm at the mid-gland and 6.0 mm at the apex. CONCLUSIONS Systematic set-up errors were small using real-time isocentre placement corrections. Patient instruction to help control variation in bladder and rectal distension during therapy may explain the observed small SD for prostate motion in this group of patients. Inter-fraction prostate motion remained the largest source of treatment error, and observed motion was greatest at the gland base. In the absence of real-time pre-treatment imaging of prostate position, sequential portal films of implanted prostatic markers should improve quality assurance by confirming organ position within the treatment field over the course of therapy.

Assessing individual risk for prostate cancer.

PURPOSE To construct a clinical nomogram instrument to estimate individual risk for having prostate cancer (PC) for patients undergoing prostate specific antigen (PSA) screening, using all risk factors known for PC. PATIENTS AND METHODS We conducted a cross-sectional study of 3,108 men who underwent a prostate biopsy, including a subset of 408 volunteers with normal PSA levels. Factors including age, family history of PC (FHPC), ethnicity, urinary symptoms, PSA, free:total PSA ratio, and digital rectal examination (DRE) were incorporated in the model. A nomogram was constructed to assess risk for any and high-grade PC (Gleason score >or= 7). RESULTS Of the 3,108 men, 1,304 (42.0%) were found to have PC. Among the 408 men with a normal PSA (< 4.0 ng/mL), 99 (24.3%) had PC. All risk factors were important predictors for PC by multivariate analysis (P, .01 to .0001). The area under the curve (AUC) for the nomogram in predicting cancer, which included age, ethnicity, FHPC, urinary symptoms, free:total PSA ratio, PSA, and DRE, was 0.74 (95% CI, 0.71 to 0.81) and 0.77 (95% CI, 0.74 to 0.81) for high-grade cancer. This was significantly greater than the AUC that considered using the conventional screening method of PSA and DRE only (0.62; 95% CI, 0.58 to 0.66 for any cancer; 0.69; 95% CI, 0.65 to 0.73 for high-grade cancer). From receiver operating characteristic analysis, risk factors including age, ethnicity, FHPC, symptoms, and free:total PSA ratio contributed significantly more predictive information than PSA and DRE. CONCLUSION In a PC screening program, it is important to consider age, family history of PC, ethnicity, urinary voiding symptoms, and free:total PSA ratio, in addition to PSA and DRE.

'Prostatic evasive anterior tumours': the role of magnetic resonance imaging.

Study Type – Diagnosis (case series)
Level of Evidence 4

Evidence for a biopsy derived grade artifact among larger prostate glands.

PURPOSE The PCPT has demonstrated a higher incidence of high grade (Gleason pattern 4 or greater) prostate cancers among men randomized to finasteride. One plausible explanation for this finding is that tumor grade as assigned by TRUS guided biopsy is artifactually associated with prostate volume. MATERIALS AND METHODS We evaluated our institutional data set of TRUS guided biopsies in the last 3 years and identified 369 cases of prostate cancer that fit the criteria of PSA less than 10 ng/ml, biopsy at our center and RP at our center. We identified risk factors for Gleason pattern 4 or greater on biopsy and then on RP specimens from the same patients using univariate and multiple logistic regression analyses. Assessed covariates included patient age, PSA and TRUS volume. RESULTS Risk factors for Gleason pattern 4 or greater in the biopsy specimens included age (p = 0.01), hypoechoic lesions on TRUS (p <0.001) and TRUS volume (p = 0.008). However, among RP specimens TRUS volume (p = 0.60) became nonsignificant of Gleason pattern 4 or greater on multivariable analysis. Although prostate volume was a predictor for biopsy derived high grade disease it was not predictive of true histological grade. CONCLUSIONS These data suggest that simply having a larger prostate results in fewer high grade cancers diagnosed at biopsy. Prostatectomy results in the same men suggest sampling artifact, as the distribution of cancer grade is not associated with prostate volume. These findings provide evidence that the increase in higher grade tumors among men in the finasteride arm of PCPT may simply result from prostate volume reduction.

Tumor hypoxia predicts biochemical failure following radiotherapy for clinically localized prostate cancer

Purpose: Tumor hypoxia is an important determinant of outcome in many human malignancies and is associated with treatment resistance and metastases. The aim of this study was to determine the effect of hypoxia in patients with prostate cancer treated with radiotherapy. Experimental Design: Tumor hypoxia was measured in 247 patients with clinically localized prostate cancer before radiotherapy, with or without hormonal therapy. The median pO2 was 6.8 mm Hg and the median hypoxic percentage less than 10 mm Hg (HP10) was 63%. The median follow-up was 6.6 years. Results: The 5-year biochemical relapse-free rate (bRFR) was 78%. Prostrate-specific antigen and Gleason score were both associated with biochemical relapse and formed a baseline clinical model. The effect of hypoxia was found to vary with the duration of patient follow-up. HP10, when added to the clinical model, was an independent predictor of early bRFR (P = 0.019). The relationship between hypoxia and early bRFR was more pronounced when the analysis was restricted to 142 patients with bulk tumor at the site of the oxygen measurements (P = 0.004). Hypoxia was the only factor predictive of local recurrence in 70 patients who had biopsies conducted during follow-up (P = 0.043), again with the effect being greatest early after completing treatment. Conclusions: This is the largest clinical study of prostate cancer hypoxia with direct measurement of tumor oxygen levels. It shows that hypoxia is associated with early biochemical relapse after radiotherapy and also with local recurrence in the prostate gland. Clin Cancer Res; 18(7); 2108–14. ©2012 AACR.

POLAROGRAPHIC ELECTRODE STUDY OF TUMOR OXYGENATION IN CLINICALLY LOCALIZED PROSTATE CANCER

PURPOSE To describe the oxygenation of clinically localized prostate cancer. METHODS AND MATERIALS Intraprostatic oxygen tension was measured using the Eppendorf electrode in 55 unanesthetized men with localized prostate cancer before radiotherapy. Measurements were made along two tracks through regions of suspected tumor in the prostate, and core needle biopsies were then obtained from the same regions. RESULTS The median pO(2) ranged from 0.2 to 57.3 mm Hg, and the grand median pO(2) was 4.5 mm Hg. The percentage of oxygen readings <5 mm Hg (HP(5)) ranged from 0% to 100% (median 60%). The track 1 oxygen readings were greater than those from track 2. Statistically significant heterogeneity was found in the individual oxygen readings: the between- and within-tumor components accounted for 32% and 68% of the total variability, respectively. However, the between-tumor variability in HP(5) significantly exceeded the within-tumor variability (61% vs. 39%). No association was found between oxygen values and clinical factors, including age, T stage, Gleason score, prostate-specific antigen level, hemoglobin concentration, or prior hormonal treatment. No difference was noted in the oxygenation between regions of tumor and normal prostate tissue, as determined from the core biopsies. CONCLUSION Localized prostate cancer is characterized by marked hypoxia and significant heterogeneity in oxygenation, similar to other human tumors. The normal prostate may contain regions of low oxygen concentration. HP(5), as determined in this study, should adequately discriminate among patients with prostate cancer and allow the independent prognostic significance of oxygenation to be evaluated once the study matures.

Serum Human Glandular Kallikrein-2 Protease Levels Predict the Presence of Prostate Cancer Among Men With Elevated Prostate-Specific Antigen

PURPOSE We hypothesize that serum human glandular kallikrein-2 (hK2) levels predict the presence of prostate cancer among men prescreened by prostate-specific antigen (PSA). PATIENTS AND METHODS We conducted a cross-sectional study of 324 men who had no history of prostate cancer and who were referred for prostate biopsy. PSA and hK2 levels were measured using specific nonisotopic immunometric techniques. Cases were patients who were diagnosed with adenocarcinoma of the prostate from biopsy, and controls were patients who had no evidence of cancer from biopsy. The odds ratio for detection of prostate cancer was determined for hK2 measurements, controlling for age, total-PSA level, digital rectal examination, and symptoms of urinary obstruction. RESULTS Of 324 men, 159 (49.1%) had cancer. Mean hK2 levels and hK2:free-PSA ratios were significantly higher in cases than in controls (1.18 v 0.53 ng/mL, respectively, for hK2, P =.0001; 1.17 v 0.62 for hK2:free-PSA ratio, P =.0001). The crude odds ratio for prostate cancer detection for patients in the highest quartile of hK2 level was 5.83 (95% confidence interval [CI], 2.8 to 12.1; P =.0001) compared with patients in the lowest quartile. The adjusted odds ratio was 6.72 (95% CI, 2.9 to 15.6; P =.0001). Similarly, the crude and adjusted odds ratios for prostate cancer detection using the hK2:free-PSA ratio were 7.36 (95% CI, 3.6 to 15.1; P =.0001) and 8.06 (95% CI, 3. 7 to 17.4; P =.0001), respectively. These odds ratios were higher than that observed for prostate cancer detection by total-PSA level (2.73; P =.03). CONCLUSION Among men prescreened with PSA for prostate cancer, patients with high hK2 measurements have a five- to eight-fold increase in risk for prostate cancer, adjusting for PSA level and other established risk factors. hK2 measurements may be a useful adjunct to PSA in improving patient selection for prostate biopsy.

Clinical Predictors of Gleason Score Upgrading Implications for Patients Considering Watchful Waiting, Active Surveillance, or Brachytherapy

Brachytherapy, active surveillance, and watchful waiting are increasingly being offered to men with low‐risk prostate cancer. However, many of these men harbor undetected high‐grade disease (Gleason pattern ≥4). The ability to identify those individuals with occult high‐grade disease may help guide treatment decisions in this patient cohort.

How early are fetal cerebral sulci visible at prenatal ultrasound and what is the normal pattern of early fetal sulcal development

To evaluate the time of appearance and pattern of development of fetal cerebral sulci at prenatal ultrasound.

V89L polymorphism of type-2, 5-alpha reductase enzyme gene predicts prostate cancer presence and progression

OBJECTIVES The valine (V) to leucine (L) polymorphism of the SRD5A2 gene is associated with 5-alpha reductase-2 activity; patients with the V allele have high activity and patients with the L allele have low activity. We examined whether this polymorphism predicts the presence of prostate cancer in 320 men without cancer who underwent biopsy and cancer progression in 318 men who underwent radical prostatectomy. METHODS The effect of the SRD5A2 gene in predicting the presence of prostate cancer was examined using logistic regression analysis, controlling for established risk factors. The effect of the SRD5A2 gene in predicting prostate cancer progression was examined using a nested, matched, case-control design. Most of the participants were white. RESULTS Of the 320 men, 158 (49.4%) were found on biopsy to have prostate cancer. The overall distribution of the V/V, V/L, and L/L genotypes was 47.5%, 42.5%, and 10.0%, respectively. The adjusted odds ratio for having prostate cancer for patients with at least one V allele was 2.53 compared with patients with the L/L genotype (P = 0.03). Of the 318 patients with cancer, 80 had biochemically detected recurrence and 238 had no evidence of recurrence. The odds ratio for progression for patients with at least one V allele was 3.32 (95% confidence interval 1.67 to 6.62, P = 0.0006) compared with patients with the L/L genotype. CONCLUSIONS Men who have the V allele of the SRD5A2 gene have a twofold increase in the risk of prostate cancer development and an additional twofold increase in the risk of progression compared with men with the L/L genotype.