Prostatic Neoplasms: Greenberg RE

Montie JE, Clark PE, Eisenberger MA, El-Galley R, Greenberg RE, Herr HW, Hudes GR, Kuban DA, Kuzel TM, Lange PH, Lele SM, Michalski J, Patterson A, Pohar KS, Richie JP, Sexton WJ, Shipley WU, Small EJ, Trump DL, Walther PJ, Wilson TG, Anonymous00046. · University of Michigan Comprehensive Cancer Center. · J Natl Compr Canc Netw. · Pubmed #19176203 No free full text.

This publication has no abstract.

Kaplan DJ, Crispen PL, Greenberg RE, Chen DY, Viterbo R, Buyyounouski MK, Horwitz EM, Uzzo RG. · Department of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. · Urology. · Pubmed #18289645 No free full text.

Abstract: OBJECTIVES: The incidence of histologic prostate cancer (CaP) after definitive radiation therapy (RT) for localized disease is rarely quantitated. We investigated the relationship between prostate-specific antigen (PSA) and histologically residual CaP after definitive RT in patients undergoing radical cystoprostatectomy (RCP) for unrelated indications. METHODS: We reviewed our prostate cancer database to identify patients undergoing RCP who previously received definitive RT for localized CaP. Pre-radiation variables examined include PSA, Gleason score, radiation modality, and dose. Post-radiation variables reviewed include PSA, time to RCP, the presence of histologically proven prostate cancer, and Gleason score. RESULTS: We identified 21 patients who underwent RCP at a median of 60 months after RT for localized CaP. Pre-radiation Gleason scores were low (6 or less) to intermediate risk (3+4) in 82% (14 of 17), intermediate (4+3) to high (8 or greater) in 18% (3 of 17), and unavailable in 4 patients. Median pre-radiation PSA was 9 ng/mL. Median PSA before RCP in all patients was 0.8 ng/mL. A total of 52% (11 of 21) of patients demonstrated active CaP in the RCP specimen. Although 89% (16 of 18) of patients met the Phoenix definition of biochemical freedom from disease, 50% (8 of 16) of these patients had histologically residual CaP at the time of RCP. Median PSA was not significantly different between patients with and without active CaP. CONCLUSIONS: Histologic evidence of CaP was noted in 50% of patients demonstrating biochemical freedom from disease at the time of RCP. Although the biological significance of active CaP in this select population is uncertain, our findings demonstrate the limitations of PSA in monitoring CaP disease activity after definitive RT.

Crispen PL, Uzzo RG, Golovine K, Makhov P, Pollack A, Horwitz EM, Greenberg RE, Kolenko VM. · Fox Chase Cancer Center, Philadelphia, PA 19111, USA. · Prostate. · Pubmed #17262802 No free full text.

Abstract: BACKGROUND: NF-kappaB and AP-1 transcriptional factors contribute to the development and progression of prostate malignancy by regulating the expression of genes involved in proliferation, apoptosis, angiogenesis, and metastasis. METHODS: NF-kappaB and AP-1 activities were examined by TransAm assay. Cytokines levels were assessed by ELISA. ICAM-1 and gp130 expression was examined by flow cytometry. Cell adhesion was examined by the ability of cells to adhere to fibronectin-coated plates. Cell viability was determined by propidium iodide staining. RESULTS: Treatment with alpha-tocopherol succinate (VES) inhibits NF-kappaB but augments AP-1 activity, reduces expression of IL-6, IL-8, and VEGF, suppresses cell adhesion, ICAM-1 and gp130 expression in androgen-independent PC-3, DU-145, and CA-HPV-10 cells. VES supplementation also decreases the expression of anti-apoptotic XIAP and Bcl-X(L) proteins and sensitizes androgen-dependent LNCaP cells to androgen deprivation. CONCLUSIONS: Our findings propose a potential mechanism of VES-mediated anti-tumor activity and support the role of vitamin E analogs as potential chemopreventative agents against prostate cancer.

Pollack A, Hanlon AL, Horwitz EM, Feigenberg SJ, Konski AA, Movsas B, Greenberg RE, Uzzo RG, Ma CM, McNeeley SW, Buyyounouski MK, Price RA. · Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #16242256 links to  free full text

Abstract: PURPOSE: The alpha/beta ratio for prostate cancer is postulated to be between 1 and 3, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. The dosimetry and acute toxicity are described in the first 100 men enrolled in a randomized trial. PATIENTS AND METHODS: The trial compares 76 Gy in 38 fractions (Arm I) to 70.2 Gy in 26 fractions (Arm II) using intensity modulated radiotherapy. The planning target volume (PTV) margins in Arms I and II were 5 mm and 3 mm posteriorly and 8 mm and 7 mm in all other dimensions. The PTV D95% was at least the prescription dose. RESULTS: The mean PTV doses for Arms I and II were 81.1 and 73.8 Gy. There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity acutely. However, there was a slight but significant increase in Arm II GI toxicity during Weeks 2, 3, and 4. In multivariate analyses, only the combined rectal DVH parameter of V65 Gy/V50 Gy was significant for GI toxicity and the bladder volume for GU toxicity. CONCLUSION: Hypofractionation at 2.7 Gy per fraction to 70.2 Gy was well tolerated acutely using the planning conditions described.

McDermott RS, Anderson PR, Greenberg RE, Milestone BN, Hudes GR. · Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. · Cancer. · Pubmed #15468187 links to  free full text

Abstract: BACKGROUND: Cranial nerve lesions due to metastases from prostate carcinoma to the skull base are an uncommon yet clinically significant finding. METHODS: The authors report the clinical features, treatment, and outcomes for 15 patients who presented with cranial nerve palsies complicating metastatic prostate carcinoma. Patient charts identified from a Fox Chase Cancer Center treatment data base were reviewed. RESULTS: All patients had hormone-refractory disease at the time of symptom onset. Twelve of 15 patients had received prior chemotherapy, and 13 of 15 patients had received prior radiation therapy to areas of bony pain. Symptoms varied from recognized clinical syndromes involving multiple cranial nerves to isolated cranial nerve lesions. All patients had lesions at the skull base that were visualized on computed tomography scans or magnetic resonance images. All patients were treated with palliative radiation therapy to either the whole brain or the skull base. Fourteen of 15 patients had a clinical (either partial or complete) response to radiation therapy. All responding patients subsequently died of prostate carcinoma without worsening of residual or development of new cranial nerve symptoms. Ten of 15 patients (67%) died within 3 months of developing symptoms, and the remaining 5 patients lived between 9 months and 31 months from onset of symptoms. CONCLUSIONS: The authors concluded that palliative radiation therapy should be considered in this heterogeneous group of patients given the potential for significant symptom improvement.

Uzzo RG, Brown JG, Horwitz EM, Hanlon A, Mazzoni S, Konski A, Greenberg RE, Pollack A, Kolenko V, Watkins-Bruner D. · The Department of Urology, Fox Chase Cancer Centre, Temple University School of Medicine, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA. · BJU Int. · Pubmed #15142142 No free full text.

Abstract: OBJECTIVE: To define the prevalence and patterns of self-initiated herbal and vitamin supplementation among men at high risk of developing prostate cancer, as there is increasing public awareness of prostate cancer screening, risk-factor assessment and prevention, leading to increasing interest in the use and systematic study of nutritional therapies for prostate cancer prevention. SUBJECTS AND METHODS: Since 1996 our institution has prospectively maintained a prostate cancer-risk registry through its Prostate Cancer Risk Assessment Program (PRAP). Eligibility includes African-American men, any man with at least one first-degree relative or two or more second-degree relatives with prostate cancer, or men who tested positively for the BRCA1 gene mutation. A 420-item self-administered questionnaire was completed and included the use of nutritional supplements and complementary therapies. We divided men into groups who used supplements to lessen their cancer risk and those who did not. The prevalence and patterns of use were evaluated and the two groups then compared for differences in demographic, socio-economic and risk-perception variables. RESULTS: In all, 345 high-risk men were enrolled in the PRAP over a 5-year period. Data on the use of dietary or herbal supplements were available on 333 men (97%), of whom over half (170) reported taking one or more supplements to prevent prostate cancer. Supplement use was divided into eight categories, including vitamins, minerals, extracts from fruits/seeds, organic compounds, flowers/bulbs, leaves/bark, roots, or animal products. Most commonly used for self-initiated chemoprevention were vitamins (95%), minerals (28%), and fruit/seed extracts (18%). More than a quarter of men (27%) took three or more agents. Men taking proactive preventative measures were statistically more likely to be Caucasian and aged > 60 years (P < 0.05). African-Americans were less likely to self-initiate preventative steps. Men taking supplements tended to return more often for follow-up and participate in PRAP longer, while those not taking supplements tended to earn less and report less self-perceived risk. CONCLUSIONS: A significant proportion of men at risk of developing prostate cancer initiate measures they perceive to reduce their risk. Although the chemopreventative efficacy of many of these supplements remains unsubstantiated, they are widely perceived by the public to reduce the risk of developing prostate cancer. These data provide an insight into patient perceptions and misconceptions of chemopreventative strategies, and may help to refine recruitment efforts in multi-institutional prostate cancer prevention trials.

Horwitz EM, Uzzo RG, Hanlon AL, Greenberg RE, Hanks GE, Pollack A. · Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. · J Urol. · Pubmed #12771738 No free full text.

Abstract: PURPOSE: Adoption of the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definition has been critical for evaluating and comparing outcome following treatment with radiation. However, since its almost universal adoption, several points have remained controversial, notably backdating the date of failure to the point midway between the posttreatment prostate specific antigen (PSA) nadir and the first increase. We evaluated the impact of backdating on no biochemical evidence of disease (bNED) control and suggest changes in the definition. MATERIALS AND METHODS: Between April 1, 1989 and November 30, 1998, 1,017 patients with nonmetastatic prostate cancer were treated with 3-dimensional conformal radiation therapy alone. bNED control was defined using the ASTRO consensus definition. bNED failure was calculated from the time midway between the posttreatment PSA nadir and the first of the 3 consecutive increases in PSA (date of failure A). Four alternate failure time points were chosen, including backdating to the date of the first increase in PSA after the nadir, the date between the first and second consecutive PSA increases, the date between the second and third consecutive PSA increases, and the date of the third increase in PSA after the nadir (dates of failure 1 to 4). Kaplan-Meier estimates were calculated for all definitions of failure as well as hazard functions with time. Subset analyses based on prognostic group and followup time were also performed. RESULTS: The 10-year Kaplan-Meier bNED control rates were 64%, 52%, 47%, 42% and 39% using dates of failure A and 1 to 4, respectively. These differences persisted when patients were stratified by prognostic group. These same differences in bNED control were observed for the long-term followup subset, in which 10-year bNED control rates were 48%, 47%, 44%, 41% and 39% using dates of failure A and 1 to 4, respectively. CONCLUSIONS: Adoption of the ASTRO consensus definition has been crucial for evaluating outcome in the radiation oncology community. However, the date of failure should be moved from the current point to one closer to the point at which failure is declared. Additional analysis with large numbers of patients from multiple institutions is necessary to determine the point.

Uzzo RG, Pinover WH, Horwitz EM, Parlanti A, Mazzoni S, Raysor S, Mirchandani I, Greenberg RE, Pollack A, Hanks GE, Watkins-Bruner D. · Department of Department of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. · Urology. · Pubmed #12670560 No free full text.

Abstract: OBJECTIVES: Uncertainty exists regarding optimal prostate cancer screening parameters for high-risk populations. The purpose of this study is to report the use of percent free prostate-specific antigen (PSA) as an indication for biopsy in men at increased risk for developing prostate cancer who have a normal digital rectal examination (DRE) and total PSA level between 2 and 4 ng/mL. METHODS: African-American men and men with at least one first-degree relative with prostate cancer are eligible for enrollment into the Prostate Cancer Risk Assessment Program (PRAP) at our institution. Between October 1996 and April 2002, 310 asymptomatic high-risk men with no history of prostate cancer, benign prostatic hyperplasia (BPH), or prostatic intraepithelial neoplasia (PIN) were screened in the PRAP with DRE and total PSA. Percent free PSA was obtained in men with a total PSA between 2 and 10 ng/mL. Men with a normal DRE and total PSA between 2 and 4 ng/mL were advised to undergo transrectal ultrasound-guided (TRUS) biopsies of the prostate if the percent free PSA was less than 27%. Other indications for biopsy included an abnormal DRE or a total PSA greater than 4 ng/mL. The primary endpoint evaluated was prostate cancer detection in high-risk men with a benign prostate examination, a normal total PSA between 2 and 4 ng/mL, and percent free PSA less than 27%. RESULTS: Of the 310 men, 174 (56%) were African American and 202 (65%) had at least one first-degree relative with prostate cancer. Sixty-two of the 310 men were referred for prostate biopsy, and 40 of 62 had biopsy performed. Twenty-one of 40 men were diagnosed with prostate cancer for a cancer detection rate of 53% in all men undergoing biopsy and an overall cancer detection rate of 6.8% in this high-risk population. Thirty-seven high-risk men (median age 54 years) with a total PSA level between 2 and 4 ng/mL (median 2.7 ng/mL) and a normal DRE were found to have a percent free PSA level of less than 27% (median 16%, range 8% to 25%). Twenty-three of these 37 men (62%) proceeded with the recommended prostate biopsy. Prostatic adenocarcinoma was diagnosed in 12 of 23 men for a cancer detection rate of 52% in men undergoing biopsy and 32% in all men with a normal DRE, a total PSA between 2 and 4 ng/mL, and a percent free PSA less than 27%. All positive biopsies demonstrated clinically significant Gleason score 6 or 7 disease. In all men electing radical prostatectomy, bilateral organ-confined disease (pT2bN0M0) was confirmed. CONCLUSIONS: In this unique population of men at high risk for prostate cancer, a percent free PSA of less than 27% was found to be useful for detecting early-stage but clinically significant cancers in men with a total PSA value between 2 and 4 ng/mL and normal DRE findings.

Movsas B, Chapman JD, Hanlon AL, Horwitz EM, Greenberg RE, Stobbe C, Hanks GE, Pollack A. · Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. · Urology. · Pubmed #12385924 No free full text.

Abstract: OBJECTIVES: To investigate whether low partial pressure of oxygen (PO2) in prostate cancer (CaP) predicts for biochemical outcome after radiotherapy. We previously reported that hypoxic regions exist in human CaP. METHODS: Custom-made Eppendorf PO2 microelectrodes were used to obtain approximately 100 PO2 readings from both pathologically involved regions of the prostate (as determined by sextant biopsies) and normal muscle (as an internal control). Fifty-seven patients with localized disease were prospectively studied; all received brachytherapy implants (48 low dose rate and 9 high dose rate) under spinal anesthesia. Nine patients had received prior hormonal therapy. Biochemical failure was defined as two consecutive rises in prostate-specific antigen level, without a return to baseline. Cox proportional hazards regression analysis was used to evaluate the influence of hypoxia on biochemical control, while adjusting for prostate-specific antigen, Gleason score, stage, implant type (low dose rate versus high dose rate), perineural invasion, hemoglobin level, use of hormonal therapy, average (mean) of the median prostate PO2, average median muscle PO2, and prostate/muscle PO2 (P/M) ratio. RESULTS: With a median follow-up of 19 months (range 4 to 31), 9 patients developed biochemical failure. A threshold analysis of the P/M ratio demonstrated that biochemical control at 2 years differed significantly at a ratio of less than 0.05 versus 0.05 or greater (31% versus 92%, P <0.0001). However, the classic prognosticators were similar in these two groups. On multivariate analysis, the P/M ratio was the only predictor of biochemical control (P = 0.0002). CONCLUSIONS: To our knowledge, this is the first study to correlate the degree of hypoxia in CaP with treatment outcome after radiotherapy. The P/M PO2 ratio was the strongest predictor for biochemical control on stepwise multivariate analysis. Longer follow up with more patients is planned to confirm this result.

Diefenbach MA, Dorsey J, Uzzo RG, Hanks GE, Greenberg RE, Horwitz E, Newton F, Engstrom PF. · Department of Population Science, Fox Chase Cancer Center, Philadelphia, PA 19422, USA. · Semin Urol Oncol. · Pubmed #11828358 No free full text.

Abstract: Patients diagnosed with early-stage prostate cancer not only have to cope with the impact of the cancer diagnosis, but also need to interpret complicated medical information to make an informed treatment decision. We report initial results from an ongoing longitudinal investigation examining treatment decision making among men diagnosed with early stage prostate cancer. Men (N = 654) were recruited into the assessment study after an initial treatment consultation with a urologic surgeon or radiation oncologist. Patients were, on average, 66 years old, married (85%), had at least a high school education (45%), were retired (58%), and were Caucasian (91%) or African American (7%). Guided by a cognitive-affective theoretical framework, we assessed treatment and disease-relevant beliefs and affects in addition to clinical variables. The majority of patients decided on external beam radiation therapy (52%), followed by brachytherapy (25%), prostatectomy (17%), and watchful waiting (6%). Patients who decided on prostatectomy were significantly younger (mean age, 58 yr) than patients who received radiation therapy (mean age, 67 yr) and brachytherapy (mean age, 66 yr). When asked for the most important reason influencing their treatment decision, patients indicated physician recommendation (51%), advice from friends and family (19%), information obtained from books and journals (18%), or the Internet (7%). Among cognitive variables, patients who decided on surgery perceived prostate cancer as being significantly more serious (P <.001), and had greater difficulties in making a treatment decision (P <.005) compared with patients receiving radiation therapy or brachytherapy. Surgical patients were also more distressed about their treatment decision (P <.001) and concerned that the cancer might spread (P <.005). To date, patients followed-up after treatment have not indicated significant regrets about their therapeutic choice. These data suggest that unique treatment-related beliefs and affects need to be taken into account during the treatment counseling process. Implications for the development of decision aids are discussed.

Movsas B, Chapman JD, Hanlon AL, Horwitz EM, Pinover WH, Greenberg RE, Stobbe C, Hanks GE. · Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. · Am J Clin Oncol. · Pubmed #11586096 No free full text.

Abstract: The purpose of this study was to characterize the extent of hypoxia in human prostate carcinoma using the Eppendorf PO2 microelectrode. Custom-made Eppendorf PO2 microelectrodes were used to obtain PO2 measurements from the pathologically involved region of the prostate (as determined by the pretreatment sextant biopsies), as well as from a region of normal muscle for comparison. Fifty-nine patients with localized prostate cancer were studied, all of whom received brachytherapy implants under spinal anesthesia. A multivariate mixed effects analysis for prediction of tumor oxygenation was performed including the following covariates: type of tissue (prostate versus muscle), prostatic-specific antigen, disease stage, patient age and race, tumor grade, volume, perineural invasion, and hormonal therapy. Because of differences in patient characteristics, control measurements were obtained from normal muscle in all patients. This internal comparison showed that the oxygen measurements from the pathologically involved portion of the prostate were significantly lower (average median PO2 = 2.4 mm Hg) compared with the measurements from normal muscle (average median PO2 = 30.0 mm Hg), p < 0.0001. A multivariate, linear, mixed analysis demonstrated that the only significant predictor of oxygenation was the type of tissue (prostate versus muscle). This study, using in vivo electrode oxygen measurements, suggests that hypoxia exists in human prostate carcinoma. More patients will be accrued to this study to ultimately correlate the oxygenation status in prostate carcinoma tumors with treatment outcome.

Cvetkovic D, Movsas B, Dicker AP, Hanlon AL, Greenberg RE, Chapman JD, Hanks GE, Tricoli JV. · Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. · Urology. · Pubmed #11306422 No free full text.

Abstract: OBJECTIVES: To test the hypothesis that increasing levels of hypoxia are associated with increased expression of vascular endothelial growth factor (VEGF) in prostate cancer by correlating the level of median tissue oxygenation in human prostate tumors with the immunohistochemically determined level of VEGF expression. METHODS: Custom-made Eppendorf oxygen microelectrodes were used to quantitate the pO(2) levels in prostate tumors of 13 men undergoing radical prostatectomy. All pO(2) measurements were performed under fluorine-based general anesthesia. Paraffin-embedded tumor tissue from these men was analyzed to measure the level of VEGF expression by immunohistochemical staining. The significance of the associations between the pO(2) levels and VEGF staining were determined by the Pearson correlations. RESULTS: The range of the median pO(2) levels (based on between 97 and 129 individual measurements) among 13 prostate tumors was 0.5 to 44.9 mm Hg. The blinded comparison of pO(2) levels and VEGF staining intensity demonstrated a significant correlation between increasing hypoxia and the percentage of cells staining positive for VEGF (r = -0.721, P = 0.005). This correlation was also significant when pO(2) levels were compared with the overall immunoreactive score, which takes into account staining intensity (r = -0.642, P = 0.018). CONCLUSIONS: To our knowledge, this is the first study demonstrating a significant association between increasing levels of hypoxia and increased expression of the angiogenesis marker VEGF in human prostate carcinoma. The results of our study further support the exploration of antiangiogenesis strategies for the treatment of human prostate cancer.

Jordan JJ, Hanlon AL, Al-Saleem TI, Greenberg RE, Tricoli JV. · Department of Radiation Oncology, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA, USA. · Cancer Genet Cytogenet. · Pubmed #11172902 No free full text.

Abstract: A change in Y chromosome number is one of the many cytogenetic abnormalities reported in human prostate tumors. However, reports in the literature have varied regarding the frequency of Y loss or gain and the significance of Y aneusomy with respect to the biology of the disease. We have conducted an analysis of the Y chromosome in malignant and benign hyperplastic human prostate epithelium in order to determine whether regional Y loss occurs in prostate cancer. To accomplish this we performed dual-color fluorescence in situ hybridization (FISH) on serial sections of paraffin-embedded prostate tumor tissues using either a Yp (SRY), Ycen (alpha-satellite) or Yq (satellite 3) probe, and an Xcen (alpha-satellite) probe that served as a control for hybridization and nuclear truncation. The results of our FISH analysis demonstrated loss of Yp in the malignant epithelium of 14/40 (35%) prostate tumor sections examined. We also found loss of Yq in 4/40 (10%) of the samples, with one of these exhibiting accompanying Yp loss. The remaining samples, 23/40 (58%), retained both Yp and Yq markers, with no evidence of either Ycen loss or Y gain in any of the tumor samples examined. In addition, Y loss was detected in the benign hyperplastic regions in nearly one-half of the tissue sections that exhibited Y loss in the malignant epithelium. These results demonstrate that regional chromosome Y loss occurs in prostate cancer, that loss of Yp is the most frequent event, and suggest that this loss may in some cases be a precursor to prostate malignancy.

Movsas B, Chapman JD, Greenberg RE, Hanlon AL, Horwitz EM, Pinover WH, Stobbe C, Hanks GE. · Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. · Cancer. · Pubmed #11064360 links to  free full text

Abstract: BACKGROUND: The purpose of this study was to analyze the extent of hypoxia in prostate carcinoma tumors using the Eppendorf pO(2) microelectrode and correlate this with pretreatment characteristics and prognostic factors. METHODS: Custom-made Eppendorf pO(2) microelectrodes were used to obtain pO(2) measurements from the pathologically involved region of the prostate (as determined by the pretreatment sextant biopsies) as well as from a region of normal muscle for comparison. Each set of measurements comprised approximately 100 separate readings of pO(2), for a total of 10,804 individual measurements. Fifty-five patients with localized prostate carcinoma were studied: Forty-one patients received brachytherapy implants, and 14 patients underwent radical prostatectomy. The pO(2) measurements were obtained in the operating room by using a sterile technique under spinal anesthesia for the brachytherapy group and under general anesthesia for the surgery group. The Eppendorf histograms were recorded and described by the median pO(2), mean pO(2), and percentage < 5 mm Hg and < 10 mm Hg. A multivariate mixed-effects analysis for the prediction of tumor oxygenation was performed and included the following covariates: type of tissue (prostate vs. muscle), type of treatment (implant vs. surgery) and/or anesthesia (spinal vs. general), prostate specific antigen level, disease stage, patient age and race, tumor grade, tumor volume, perineural invasion, and hormonal therapy. RESULTS: Due to differences in patient characteristics and the anesthesia employed, control measurements were obtained from normal muscle (in all but two patients). This internal comparison showed that the oxygen measurements from the pathologically involved portion of the prostate were significantly lower (average median pO(2), 9.9 mm Hg) compared with the measurements normal muscle (average median pO(2), 28.6 mm Hg; P < 0.0001). A multivariate, linear, mixed analysis demonstrated that, among all of the patients, the significant predictors of oxygenation were tissue (prostate vs. muscle) and anesthesia (spinal vs. general) or treatment (implant vs. surgery). Among the brachytherapy (spinal anesthesia) patients, the significant predictors of pO(2) were tissue type, disease stage, and patient age. There were no significant predictors of oxygenation in the surgical (general anesthesia) group. CONCLUSIONS: This study, employing in vivo electrode oxygen measurements, demonstrated that hypoxia exists in prostate carcinoma tumors. A dramatic effect of anesthesia was observed, likely due to modulation of polarography in the presence of fluorine. Within the group of brachytherapy (spinal anesthesia) patients, increasing levels of hypoxia (within prostatic tissue) correlated significantly with increasing clinical stage and patient age. More patients will be accrued to this prospective study to further correlate the oxygenation status in prostate carcinoma tumors with known prognostic factors and, ultimately, treatment outcome.

Movsas B, Chapman JD, Horwitz EM, Pinover WH, Greenberg RE, Hanlon AL, Iyer R, Hanks GE. · Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. · Urology. · Pubmed #9886581 No free full text.

Abstract: OBJECTIVES: The purpose of this study was to characterize, by use of the Eppendorf microelectrode, the extent of hypoxia (range/heterogeneity) in human prostate carcinomas. METHODS: Custom-made Eppendorf pO2 microelectrodes were used to obtain PO2 measurements from the pathologically involved side of the prostate, as well as from a region of normal muscle for comparison. Each set of measurements comprised approximately 100 separate readings of pO2, for a total of 2145 individual measurements. Twelve patients were studied, 7 of whom underwent brachytherapy, 3 a radical prostatectomy, and 2 a cystoprostatectomy. The pO2 measurements were obtained in the operating room, using sterile technique, under spinal anesthesia for the brachytherapy group patients and under general anesthesia for the surgery group patients. The Eppendorf histograms were recorded and described by the median pO2, mean pO2, and percentage of measurements less than 5 mm Hg and less than 10 mm Hg. RESULTS: Because of differences in patient characteristics and the anesthesia employed, control measurements were obtained from nearby normal muscle as an internal control in all but 2 patients. This internal comparison showed that the oxygen measurements from the pathologically involved portion of the prostate were significantly lower than those from normal muscle. Similarly, higher pO2 readings were obtained from the pathologically normal prostates (in the patients with bladder cancer) than from the prostates of patients with prostate carcinoma. Increasing levels of hypoxia were observed with increasing clinical stage. Significant predictors of oxygenation include the type of tissue (pathologically involved prostate versus normal muscle or normal prostate), clinical stage, and type of anesthesia. CONCLUSIONS: This report, to our knowledge, represents the first study to obtain in vivo electrode measurements of oxygen levels in patients with prostate cancer and suggests that hypoxic regions exist in human prostate carcinoma. More patients will be accrued to this prospective study to correlate the oxygenation status of prostate carcinoma with known prognostic factors and treatment outcome.