Combination therapy improves prostate cancer survival for patients with potentially lethal prostate cancer: The impact of Gleason pattern 5.
OBJECTIVE
To investigate the impact of Gleason pattern 5 (GP5) prostate cancer after either external beam radiotherapy (EBRT) or the combination of EBRT with low-dose rate brachytherapy boost (combo).


METHODS
Between 1998 and 2008, 467 patients with National Comprehensive Cancer Network high-risk prostate cancer were treated with EBRT (n = 326) or combo (low-dose rate to 90-108 Gy using I-125 followed by EBRT) (n = 141). Freedom from biochemical failure, freedom from metastasis (FFM), cancer-specific survival (CSS), and overall survival were evaluated.


RESULTS
Combo patients were younger (66 vs. 72 years, p < 0.001) and had fewer comorbidities (Charlson comorbidity index 3.7 vs. 4.4, p < 0.001). EBRT patients had higher tumor stages (T3-4: 30% vs. 21%, p = 0.03) and lower Gleason scores (8-10: 61% vs. 75%, p = 0.01). Androgen deprivation therapy use was similar between cohorts (85% vs. 87%, p = 0.5), but EBRT patients had longer androgen deprivation therapy use (median 14 vs. 12 months, p = 0.05). GP5 predicted worse FFM (p < 0.001, hazard ratio [HR] 3.3, 95% confidence interval [CI]1.8-6.2]) and CSS (p < 0.001, HR 5.9, 95% CI 2.7-12.9) for the EBRT group, but not for the combo group (p = 0.86, HR 0.48, 95% CI 0.1-2.4 for metastasis and p = 0.5, HR 1.6, 95% CI 0.33-8.0 for CSS). In those with GP5 (n = 143), combo was associated with improved outcomes in all endpoints. On univariate analysis, 5-year outcomes for combo vs. EBRT were as follows: freedom from biochemical failure 89% vs. 65%, FFM 89% vs. 67%, CSS 93% vs. 78%, and overall survival 88% vs. 67% (p < 0.05 for all).


CONCLUSIONS
Combo was associated with improved outcomes for men with GP5 prostate cancer. This highlights the importance of local therapy, especially in patients with the highest pathologic grade disease.
Department of Radiation Oncology, University of Michigan, Ann Arbor, MI.
Adam L
AL
Liss
Department of Radiation Oncology, Providence Hospital, Novi, MI.
Eyad I
EI
Abu-Isa
Department of Radiation Oncology, University of Michigan, Ann Arbor, MI.
Maha S
MS
Jawad
Department of Radiation Oncology, University of Michigan, Ann Arbor, MI.
Felix Y
FY
Feng
Department of Radiation Oncology, University of Michigan, Ann Arbor, MI.
Sean M
SM
Vance
Department of Urology, Providence Hospital, Novi, MI.
Raymond J
RJ
Winfield
Department of Radiation Oncology, Providence Hospital, Novi, MI.
Vrinda
V
Narayana
Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA.
Howard M
HM
Sandler
Department of Radiation Oncology, University of Michigan, Ann Arbor, MI; Department of Radiation Oncology, Providence Hospital, Novi, MI.
P William
PW
McLaughlin
Department of Radiation Oncology, University of Michigan, Ann Arbor, MI. Electronic address: dhamm@umich.edu.
Daniel A
DA
Hamstra
D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D001918:Brachytherapy / Q000379:methods*; D003131:Combined Modality Therapy / Q000379:methods; D018572:Disease-Free Survival; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000532:radiotherapy* / Q000628:therapy; D011879:Radiotherapy Dosage; D015996:Survival Rate
D000726:Androgen Antagonists; D007457:Iodine Radioisotopes; D017430:Prostate-Specific Antigen
Combination therapy; Gleason pattern 5; High-risk prostate cancer