Gleason Scoring at a Comprehensive Cancer Center: What’s The Difference?

This study attempted to determine whether the Gleason score (GS) assigned at a comprehensive cancer center better predicts risk of biochemical failure (BF) after prostate radiotherapy compared with the GS of the referring institution (RI). Between 1994 and 2007, 1649 men received radiotherapy for prostate cancer at Fox Chase Cancer Center (FCCC). The Cox proportional hazard regression was used for inferences about the relationship of time to BF and GS. Harrell’s C-index (HCI) was used to assess concordance in the Cox regression between predicted and observed events. The discordance rate was 26% for any change in either major or minor Gleason pattern. In the RI GS 2 through 6 group, 79 (8%) patients were upgraded to GS 7. Twenty percent of patients with RI GS 7 were downgraded and 2% were upgraded. In the RI GS 8 through 9 group, 58% were downgraded to GS 6 (12%) or GS 7 (88%). The FCCC GS altered the NCCN risk group assignment in 144 men (9%): 92 (64%) men to lower risk and 52 (36%) to higher risk. FCCC GS was a stronger predictor of BF; the hazard ratios for GS 2 through 6 (ref), 3+4, 4+3, and 8 through 9 were 1.00 (ref), 1.82, 4.14, and 2.92, respectively. In contrast, the hazard ratios for the RI GS were 1.00 (ref), 1.53, 2.44, and 1.76, respectively. FCCC GS (HCI=0.76) had improved performance compared with RI GS (HCI=0.74). Changes in GS were common and the GS assigned by a comprehensive cancer center provided better BF risk stratification and prognostication for patients. Changes in GS may impact treatment recommendations in 9% to 26% of patients.

Abstract

This study attempted to determine whether the Gleason score (GS) assigned at a comprehensive cancer center better predicts risk of biochemical failure (BF) after prostate radiotherapy compared with the GS of the referring institution (RI). Between 1994 and 2007, 1649 men received radiotherapy for prostate cancer at Fox Chase Cancer Center (FCCC). The Cox proportional hazard regression was used for inferences about the relationship of time to BF and GS. Harrell’s C-index (HCI) was used to assess concordance in the Cox regression between predicted and observed events. The discordance rate was 26% for any change in either major or minor Gleason pattern. In the RI GS 2 through 6 group, 79 (8%) patients were upgraded to GS 7. Twenty percent of patients with RI GS 7 were downgraded and 2% were upgraded. In the RI GS 8 through 9 group, 58% were downgraded to GS 6 (12%) or GS 7 (88%). The FCCC GS altered the NCCN risk group assignment in 144 men (9%): 92 (64%) men to lower risk and 52 (36%) to higher risk. FCCC GS was a stronger predictor of BF; the hazard ratios for GS 2 through 6 (ref), 3+4, 4+3, and 8 through 9 were 1.00 (ref), 1.82, 4.14, and 2.92, respectively. In contrast, the hazard ratios for the RI GS were 1.00 (ref), 1.53, 2.44, and 1.76, respectively. FCCC GS (HCI=0.76) had improved performance compared with RI GS (HCI=0.74). Changes in GS were common and the GS assigned by a comprehensive cancer center provided better BF risk stratification and prognostication for patients. Changes in GS may impact treatment recommendations in 9% to 26% of patients.

The Gleason histopathologic grading system is 1 of 3 determinants of prostate cancer stage and is an important indicator of the biologic behavior and outcome after radical prostatectomy, external-beam radiation therapy, and brachytherapy.1-4 Based on the study from the Veterans Administration Cooperative Urological Research Group, the Gleason Grading System, initially developed by Dr. Donald Gleason in 1966, is the dominant prostate cancer grading system used worldwide.5 Since its development, several revisions in guidelines of pathological reporting have occurred, the most recent being from 2005.6 The Gleason grading system is a measure of histologic architectural differentiation of prostate cancer cells, from 1, being the most differentiated, to 5, being undifferentiated. The most prevalent and second most prevalent patterns are added together to yield a Gleason score (GS) with values between 2 and 10. A GS of 2 through 6 is considered well to moderately well differentiated, a GS of 7 is considered moderately to poorly differentiated, and a GS of 8 through 10 is considered poorly differentiated to undifferentiated.7 GS is an important prognostic factor, independent of initial prostate-specific antigen (PSA) level or T stage, used in the AJCC staging system8 and NCCN risk grouping, which are used to make treatment recommendations.9

Disagreement between individual readings of a single prostate biopsy slide has been reported.10-12 However, no official recommendations have been made regarding the need for a second confirmatory pathology review (SPR) before beginning treatment. Furthermore, no reported series have examined the impact of an SPR for men receiving external-beam radiotherapy. Of the 2 series that examine SPR for patients undergoing brachytherapy, the GS change resulted in alterations of clinical risk level in 15% to 19% of their patient cohort.13,14 The goal of this study was to retrospectively evaluate the impact of an SPR in men treated with external-beam radiotherapy at an academic comprehensive cancer center.

Materials and Methods

The authors examined 1649 men diagnosed with prostate cancer based on a transrectal ultrasound-guided prostate biopsy at a referring institution (RI). An RI was defined as any institution other than Fox Chase Cancer Center (FCCC). Patients were definitively treated between 1994 and 2007 with either 3-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) alone (no androgen deprivation therapy). The 3D-CRT and IMRT techniques were reported on previously.15-17

Pathologic slides of all patients diagnosed at an RI were reviewed at FCCC by an oncologic pathologist with special expertise in urologic pathology. Each slide was assigned a GS, which is a measure of aggressiveness of prostate cancer.5 During this review, pathologic specimens of prostate tissue are viewed under the microscope and graded based on the degree of differentiation of primary and secondary morphologic patterns of the tumor, each graded from 1 to 5. The GS is calculated by summing the major and minor Gleason grade patterns from each biopsied site, with the total score ranging from 2 to 10 (with a GS of 2 representing least aggressive and a GS of 10 representing most aggressive with highest potential to spread). Per the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer, GSs were grouped according to the prognostic category as follows: a score of 2 through 6 is considered low grade, a score of 7 (3+4 and 4+3) is intermediate grade, and 8 or 9 (4+4, 4+5, and 5+4) is high grade.9 A panel of oncologic pathologists further reviewed cases with a discrepancy in GS diagnosis with the RI (a total of 429 cases [26%]) until a consensus diagnosis was reached.

Follow-up generally consisted of serial PSA determinations every 6 months and digital rectal examinations annually. Biochemical failure (BF) was determined using the American Society for Radiation Oncology (ASTRO) consensus definition (ie, Phoenix or PSA nadir plus 2 ng/mL definition).

Statistical Methods

Agreement between pathologists at FCCC and the RI was measured with the Kappa statistic, wherein a value of 0 indicates no agreement and 1 indicates perfect agreement. The Cox proportional hazard regression was used for inferences about the relationship of time to BF and GS for FCCC and the RI separately, each model adjusting for T stage (T1/2 vs T3), initial PSA (continuous), and radiotherapy dose (continuous). A separate model examined the impact of FCCC GS review (upgrading or down-grading) on time to BF while adjusting for the initial GS from the RI, T stage, initial PSA level, and dose. Harrell’s C-index (HCI) was used to assess concordance in the Cox regression between predicted and observed events. An HCI of 1 indicates a perfect ability to rank the outcomes in the order they actually occurred, and an HCI of 0.5 indicates a purely random ranking; this value is comparable to the area under the receiver operator characteristic curve. Statistical analyses were performed using SAS software (version 9.2). Tests were 2-sided using a 0.05 level of significance. Kaplan-Meier plots were generated using R, version 2.10.1.

Results

The median follow-up was 64 months (range, 4.0-176.0 months) and the median follow-up PSA interval was 6.2 months (range, 0.5-95.0 months). The median patient age was 68 years (range, 36-88 years). Most patients (79.4%) had T1/2 prostate cancer and a PSA level less than 10 (Table 1). The median radiotherapy dose was 76 Gy given in 2-Gy fractions (range, 70-80 Gy). Table 2 illustrates the distribution of patients by year of treatment.

Table 3 summarizes changes in patient’s GS on FCCC pathology review. Agreement between FCCC GS and RI GS was moderate (kappa = 0.53; 95% CI, 0.50-0.57). Overall, compared with RI GS (ie, 6 vs 7 vs 8-9), FCCC GS was upgraded in 8% of patients and downgraded in 6% of patients. In the RI GS 6 (3+3) group, 79 (8%) patients were upgraded to the intermediate category: 62 patients (6%) upgraded to GS 3+4, and 17 (2%) upgraded to GS 4+3. A greater impact of the FCCC SPR was observed in the RI GS 7 group where 20% were downgraded to FCCC GS 6 and 2% upgraded to FCCC GS 8 through 9. Regarding changes within the GS 7 group, 12% of men with RI GS 3+4 were reassigned FCCC GS 4+3 and 14% of men with RI GS 4+3 were reassigned FCCC GS 3+4. The greatest impact of the FCCC SPR was seen in the RI GS 8 through 9 group, wherein most men (58%) were downgraded to FCCC GS 6 (12%) or 7 (88%). The FCCC GS altered the NCCN risk group assignment in 144 men (9%): 92 (64%) men to lower risk and 52 (36%) to higher risk.

Table 1

Patient Characteristics for the Study Population (N=1649)

Table 1

Cox proportional hazards regression analysis was used for inferences about time to BF based on the RI GS and FCCC GS. Three different Cox multi-variable analyses (MVA) were completed. The first 2 analyze RI GS and FCCC GS separately (Table 4), adjusting for T stage (T1/2 vs T3), initial PSA, and radiotherapy dose. The MVA model with FCCC GS shows the hazard ratio (HR) for BF was greater than that for RI GS, which suggests the risk of BF based on FCCC GS was greater compared with RI GS. The HR was 1.82 for FCCC GS 3+4 (vs GS 2-6; 95% CI, 1.25-2.65; P=.002), 4.14 for GS 4+3 (95% CI, 2.87-5.96; P<.0001), and 2.92 for GS 8 through 9 (95% CI, 1.45-5.87; P=.003). Comparatively, the HR was 1.53 for the RI GS 3+4 (vs GS 2-6; 95% CI, 1.05-2.24; P=.03), 2.44 for GS 4+3 (95% CI, 1.71-3.49; P<.0001), and 1.76 for GS 8 through 9 (95% CI, 0.96-3.24; P=.07). The FCCC GS was also highly predictive of BF for GS 3+4 versus 4+3, with a lower HR compared with the RI GS, suggesting that changes in primary Gleason pattern were also important (Table 4).

Table 2

Distribution of Patients by Year of Radiotherapy Initiation (N=1649)

Table 2

Regarding the concordance estimates of the 2 models, the HCI was 0.76 for the model with FCCC GS, slightly higher than the HCI of 0.74 for the model with RI GS. In summary, these data show that FCCC GS was better at assigning and discriminating risk of BF between GS groups compared with RI GS.

The Kaplan-Meier estimates of BF based on RI versus FCCC GS are shown in Figure 1. This figure further illustrates that estimates of BF according to the FCCC GS were generally higher for GS 7 and GS 8 through 9 compared with RI. The favorable GS 2 through 6 group had lower estimates of BF according to the FCCC GS versus RI GS.

Table 5 shows the predictive value of a change (upgrading or downgrading) in GS based on FCCC SPR. Examining BF based on the change in GS, Table 5 shows that independent of the initial RI GS, upgrading of the score was associated with poorer BF (P=.01) compared with the group whose GS stayed the same or was lowered (P=.0004).

Discussion

In this study, which is the largest retrospective analysis of the impact of an SPR of GS and only report on the impact of an SPR of GS in patients treated with radiotherapy, the authors found that overall, an SPR impacted approximately 13% of patients when considering a change in the overall GS (ie, 6 vs 7 vs 8-9). The FCCC GS altered the NCCN risk group assignment in 144 men (9%): 92 (64%) men were reclassified as lower risk and 52 (36%) as higher risk. In general, the risk of BF was higher for FCCC GS 7 and GS 8 through 9 groups compared with the RI GS. However, a smaller proportion of men were in the GS 7 and GS 8 through 9 groups according to the FCCC GS, suggesting that FCCC pathologists were very good at identifying men at higher risk of BF. Within the often-controversial intermediate risk group, changes in GS 3+4 versus 4+3 were more prognostic according to the FCCC GS compared with the RI GS. When considering any change in either major or minor Gleason pattern, the discordance rate was 26%. With a median follow-up of 64 months, the data show an improvement in overall prediction of BF with FCCC GS compared with RI GS. Overall, these data support a routine SPR, preferably at a dedicated comprehensive cancer center with a pathologist specialized in the diagnosis of prostate cancer.

To the authors’ knowledge, no national guidelines advise an SPR at a comprehensive cancer center. Gupta and Layfield18 reported on the prevalence of interinstitutional anatomic pathology slide review for diagnosis confirmation before surgical interventions. Their survey requests with regard to requirements and/or performance of SPR from 300 academic and community-based hospitals revealed 126 usable surveys. The results showed that approximately 50% of surveyed hospitals used a mandatory second review of outside pathology specimens, and approximately 38% encouraged it. Academic centers were more likely to have a mandatory policy in place. This study reported the prevalence of discrepancies up to 30%, with most between 2% and 5%, for both oncologic and nononcologic histology specimens.

Several studies have examined the impact of a SPR for patients with cancer. A study from the University of Iowa College of Medicine examined 5629 second-opinion surgical oncologic and nononcologic pathology specimens for most organ systems and found major disagreements concerning 132 (2.3%) cases19; 14 of these cases involved genitourinary histology. Although specifics of Gleason scoring were not discussed, the authors did state that 6 (43%) of the 14 cases resulted in major alterations of treatment or prognosis. Kronz et al20 reported their findings from a prospective review of mandatory pathology second opinion at the Johns Hopkins Hospital. Of the 6171 reviewed cases, they found that the overall rate of discrepant cases, resulting in a major modification of therapy or prognosis, was 1.4% overall and 1.2% for genitourinary cancers. Most discrepant cases involved a change between benign and malignant or a major change in tumor classification, whereas changes involving a modification of tumor grade or stage were not discussed.

Table 3

Detailed Changes of GS Between RI and FCCC Pathology Review

Table 3

More specific to prostate cancer and GS, Brimo et al21 evaluated 855 biopsy specimens of patients diagnosed elsewhere and referred to Johns Hopkins Hospital for radical prostatectomy. They found a GS discrepancy in 124 cases (15%), of which 57 (46%) were upgraded and 67 (54%) were downgraded to a different risk category (ie, GS 6 vs 7 vs 8-10).21 Of the total 204 cases with GS 7, the score was changed from 3+4 to 4+3 in 13 (6%) cases and from 4+3 to 3+4 in 12 (6%) cases. A recent study by Kuroiwa et al22 reported on a discrepancy between local and central pathologic review of prostatectomy specimens. Their review of data from 50 institutions and 2015 radical prostatectomy specimens revealed undergrading and overgrading of GS in 25.9% and 19.2% cases, respectively. The exact concordance rate for GS 8 through 10 was significantly lower than that of GS 5 through 6, 3+4, and 4+3. They found that high-volume institutions showed significantly higher exact concordance rates between local and central review for radical prostatectomy GS (P<.001). A separate report from the same institution investigated the significance of dedicated central pathologic review for GS correlation between the biopsy and radical prostatectomy specimens and the prediction of high-grade GS for 1629 patients.23 The authors found that central review significantly increased the exact concordance rate between the biopsy and radical prostatectomy specimens compared with local review. With regard to high-grade GS in the radical prostatectomy specimens, central review showed significantly greater sensitivity, positive predictive value, and negative predictive value than local review. A study from Canada evaluated the agreement of nonspecialist and genitourinary pathologists in grading prostate cancer.24 The authors retrospectively evaluated 151 cases and found that 28% (42 of 151) had a change in risk category after expert review, thereby altering treatment options. The authors concluded that all referred patients should continue to have their pathology centrally reviewed before making final treatment decisions. Another report from the British Columbia Cancer Agency examined 1323 men treated with prostate brachytherapy and found that in patients who had an SPR, the GS increased in 21.6% and decreased in 2.4%, and a change in diagnosis from benign to prostate cancer occurred in 1.2%.13 As a consequence, the authors reported a change in treatment, such as androgen deprivation therapy use, for 196 patients (14.8%; those upgraded from GS 6 to 7). Patients with GS 8 through 10 were not brachytherapy candidates, and were therefore not included in this study, nor were patients whose GS changed from 7 or less to 8 or higher. The authors also did not elaborate on Gleason grading changes from 3+4 to 4+3 and vice versa. In the current study, an SPR resulted in a change in Gleason category in 14% (ie, 6 vs 7 vs 8-9), which affects treatment recommendations. When considering any change in the primary or secondary Gleason pattern, such as 3+4 versus 4+3, the discordance rate increases to 26%.

Table 4

Cox Proportional Hazards Multivariable Analysis for Biochemical Failure

Table 4
Figure 1
Figure 1

Freedom from biochemical failure (BCF) for Fox Chase Cancer Center (FCCC) versus referring institution (RI) Gleason score (GS).

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 7; 10.6004/jnccn.2013.0102

Several other studies examining interobserver reproducibility in GS reported discordance in 19% to 64%,10-12 further supporting the need for an SPR. Studies by Alsbrook et al10,11 have shown that GS agreement among the urologic pathologists fares much better than agreement among general pathologists. A recent report by Netto et al25 published findings of the randomized, multinational TAX 3501 trial. They examined interobserver variability between central and local pathologists evaluating radical prostatectomy specimens, and found a 30% GS discordance rate, with an overall change of progression-free survival estimates for 13% of patients. In a study specifically designed to estimate the frequency of change in GS as a result of genitourinary pathologists’ review and subsequent cancer treatment recommendations, Nguyen et al26 reported on the SPR results of 602 patients initially diagnosed with prostate cancer at nonacademic institutions. The GS was changed in 44% of cases, with upgrades representing 81% of those cases. Risk categories were changed from low to intermediate or high risk in 8.2% of patients, and from intermediate or high risk to low risk in 1%, thereby altering treatment decisions for approximately 10% of the patient cohort.

Table 5

Cox Proportional Hazards Multivariable Analysis for Biochemical Failure Examining the Gleason Score Change

Table 5

A limitation of the current study is its retrospective nature and its associated caveats, including the impact of patient selection, follow-up bias, and changes in GS grading over time. Regarding the GS grading over time, for example, the authors observed that the frequency of pathologists concurring with an RI GS of less than 6 was higher earlier in the study period. This may be explained partly by the report published in 2000 by Epstein27 on the inability to accurately measure the aggressiveness of prostate cancer when a GS of 2 through 4 is assigned on prostate needle biopsy. Another limitation is the underlying assumption and broad generalization that the quality of GS categorization at RIs is equivalent. This is certainly not the case, and some RIs may use a pathologist who specializes in genitourinary cancer; however, a more detailed analysis comparing various RIs was beyond the scope of this analysis. Lastly, the assumption is that a risk stratification model based on GS seeks to achieve the greatest stratification of risk between groups. This analysis shows that FCCC GS provided greater BF risk stratification than RI GS, but at the cost of the proportion of patients assigned to the higher-risk groups. Specifically, FCCC GS had a smaller proportion of patients assigned to GS 7 and GS 8 through 9. This is ideal from a population perspective, but from a personal perspective, it may not be, because higher-risk patients may not be classified as such. The ideal distribution of patients among the various GS groups is not well established, but risk stratification models, such as the AJCC stage grouping, have radiated toward achieving the greatest risk stratification among risk groups.

Conclusions

An SPR at a dedicated comprehensive cancer center by a pathologist specializing in genitourinary malignancies resulted in a change in GS grouping in 13% and GS overall by 26%. The FCCC GS altered the NCCN risk group assignment in 144 men (9%): 92 (64%) men to lower risk and 52 (36%) to higher risk. These changes all have the potential to alter management and prognosis. The GSs assigned based on the SPR provided greater prognostication of BF risk. Patients may benefit from national standards encouraging an SPR at a comprehensive cancer center.

The authors wish to thank Dr. Gerald Hanks for his leadership in the establishment of the Fox Chase Cancer Center database for the treatment of prostate cancer reported herein, and Ruth Peter and Teri Marino-White for their dedication to its maintenance.

The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors. This publication was supported by grant number P30 CA006927 from the National Cancer Institute, NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCI or NIH.

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If the inline PDF is not rendering correctly, you can download the PDF file here.

Correspondence: Mark K. Buyyounouski, MD, MS, Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111. E-mail: mark.buyyounouski@fccc.edu
  • View in gallery

    Freedom from biochemical failure (BCF) for Fox Chase Cancer Center (FCCC) versus referring institution (RI) Gleason score (GS).

  • 1.

    StephensonAJKattanMWEasthamJA. Prostate cancer-specific mortality after radical prostatectomy for patients treated in the prostate-specific antigen era. J Clin Oncol2009;27:43004305.

    • Search Google Scholar
    • Export Citation
  • 2.

    ZhouPChenMHMcLeodD. Predictors of prostate cancer-specific mortality after radical prostatectomy or radiation therapy. J Clin Oncol2005;23:69926998.

    • Search Google Scholar
    • Export Citation
  • 3.

    PottersLRoachMIIIDavisBJ. Postoperative nomogram predicting the 9-year probability of prostate cancer recurrence after permanent prostate brachytherapy using radiation dose as a prognostic variable. Int J Radiat Oncol Biol Phys2010;76:10611065.

    • Search Google Scholar
    • Export Citation
  • 4.

    PottersLPurrazzellaRBrusteinS. The prognostic significance of Gleason Grade in patients treated with permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys2003;56:749754.

    • Search Google Scholar
    • Export Citation
  • 5.

    GleasonDF. Histologic grading of prostate cancer: a perspective. Hum Pathol1992;23:273279.

  • 6.

    EpsteinJIAllsbrookWCJrAminMB. The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol2005;29:12281242.

    • Search Google Scholar
    • Export Citation
  • 7.

    EpsteinJIPotterSR. The pathological interpretation and significance of prostate needle biopsy findings: implications and current controversies. J Urol2001;166:402410.

    • Search Google Scholar
    • Export Citation
  • 8.

    EdgeSB. AJCC cancer staging manual. New York, NY: Springer; 2010.

  • 9.

    MohlerJLBahnsonRRBostonB. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. J Natl Compr Canc Netw2010;82:162200. To view the most recent version of these guidelines visit NCCN.org.

    • Search Google Scholar
    • Export Citation
  • 10.

    AllsbrookWCJrMangoldKAJohnsonMH. Interobserver reproducibility of Gleason grading of prostatic carcinoma: urologic pathologists. Hum Pathol2001;32:7480.

    • Search Google Scholar
    • Export Citation
  • 11.

    AllsbrookWCJrMangoldKAJohnsonMH. Interobserver reproducibility of Gleason grading of prostatic carcinoma: general pathologist. Hum Pathol2001;32:8188.

    • Search Google Scholar
    • Export Citation
  • 12.

    di LoretoCFitzpatrickBUnderhillS. Correlation between visual clues, objective architectural features, and interobserver agreement in prostate cancer. Am J Clin Pathol1991;96:7075.

    • Search Google Scholar
    • Export Citation
  • 13.

    ThomasCWBainbridgeTCThomsonTA. Clinical impact of second pathology opinion: a longitudinal study of central genitourinary pathology review before prostate brachytherapy. Brachytherapy2007;6:135141.

    • Search Google Scholar
    • Export Citation
  • 14.

    SooriakumaranPLovellDPHendersonA. Gleason scoring varies among pathologists and this affects clinical risk in patients with prostate cancer. Clin Oncol (R Coll Radiol)2005;17:655658.

    • Search Google Scholar
    • Export Citation
  • 15.

    BuyyounouskiMKHorwitzEMPriceRA. Intensity-modulated radiotherapy with MRI simulation to reduce doses received by erectile tissue during prostate cancer treatment. Int J Radiat Oncol Biol Phys2004;58:743749.

    • Search Google Scholar
    • Export Citation
  • 16.

    BuyyounouskiMKHorwitzEMUzzoRG. The radiation doses to erectile tissues defined with magnetic resonance imaging after intensity-modulated radiation therapy or iodine-125 brachytherapy. Int J Radiat Oncol Biol Phys2004;59:13831391.

    • Search Google Scholar
    • Export Citation
  • 17.

    HanksGEHanlonALPinoverWH. Survival advantage for prostate cancer patients treated with high-dose three-dimensional conformal radiotherapy. Cancer J Sci Am1999;5:152158.

    • Search Google Scholar
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