Neoadjuvant Chemohormonal Therapy before Radical Prostatectomy for Japanese Patients with High-Risk Localized Prostate Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Patients
2.2. Statistical Analysis
3. Results
3.1. Patients Characteristics
3.2. Analysis of Biochemical Progression-Free Survival and Overall Survival
3.3. Analysis of Factors Predicting Biochemical Progression-Free Survival
3.4. Analysis of Peri-Operative Toxicities during NCHT
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Number of Patients | 21 |
---|---|
Median age (years) (range) | 65.3 (55–73) |
Median initial PSA (ng/mL) (range) | 11.4 (4.3–97.0) |
Median PSA density (ng/mL/mL) (range) | 0.40 (0.14–4.95) |
Clinical T stage at diagnosis (%) | |
T2b T2c T3a T3b | 1 (5) 3 (15) 16 (75) 1 (5) |
Median maximum tumor diameter before NCHT by MRI (mm) (range) | 20.0 (13.2–37.7) |
Grade group (%) | |
1 2 3 4 5 | 1 (5) 4 (19) 1 (5) 8 (37) 7 (34) |
NCCN criteria (%) | |
High risk, but not very high risk (PSA > 20 or Grade Group 4 or 5 or T3a with no very high-risk features) | 13 (62) |
Very high-risk (T3b-4 or Primary Gleason pattern 5 or multiple high-risk features or >4 cores with Grade Group 4 or 5) | 8 (38) |
Median PSA after NCHT (ng/mL) (range) | 1.28 (0.08–7.66) |
Pathological T stage (%) | |
T2a T2b T2c T3a T3b | 8 (37) 2 (10) 7 (33) 2 (10) 2 (10) |
Pathological N stage (%) | |
0 1 | 20 (95) 1 (5) |
Extraprostatic extension (%) | |
Negative Positive | 18 (85) 3 (15) |
Resection margin (%) | |
Negative Positive | 16 (76) 5 (24) |
Median number of resected lymph nodes (range) | 10 (2–28) |
Pathologic changes after chemohormonal therapy (%) | |
Grade 0 Grade 1 Grade 2 Grade 3 | 9 (43) 5 (24) 7 (33) 0 (0) |
Factors | Univariate Hazard Ratio [95% CI] (p-Value) |
---|---|
Age (<65 vs. ≥65) | 1.07 [0.30–3.82] (p = 0.91) |
Initial PSA (≥20 vs. <20) | 0.96 [0.25–3.73] (p = 0.95) |
PSA density (≥ 0.4 vs. < 0.4) | 0.53 [0.15–1.91] (p = 0.33) |
cT (≥3 vs. <3) | 0.80 [0.20–3.16] (p = 0.75) |
Maximum tumor diameter before NCHT by MRI (≥20 mm vs. <20 mm) | 1.41 [0.39–5.06] (p = 0.59) |
Grade group (4, 5 vs. 1, 2, 3) | 5.69 [0.71–45.4] (p = 0.10) |
NCCN criteria (very high vs. high risk but not very high) | 4.07 [1.11–14.9] (p = 0.03) |
PSA after NCHT (≥1.28 vs. <1.28) | 1.30 [0.37–4.62] (p = 0.69) |
pT (≥3 vs. <3) | 1.05 [0.22–4.98] (p = 0.95) |
Extraprostatic extension (positive vs. negative) | 0.53 [0.06–4.23] (p = 0.55) |
Resection margin (positive vs. negative) | 1.47 [0.38–5.72] (p = 0.57) |
Resected lymph node number (<10 vs. ≥10) | 1.68 [0.48–5.81] (p = 0.42) |
Largest cross-section tumor diameter (≥20 mm vs. <20 mm) | 3.77 [0.94–15.0] (p = 0.059) |
Grade (NCI-CTC) | 0 | 1 | 2 | 3 | 4 |
---|---|---|---|---|---|
Neutropenia | 0 | 1 | 2 | 6 | 12 |
Febrile neutropenia | 19 | 0 | 0 | 2 | 0 |
Mucositis oral | 20 | 0 | 0 | 1 | 0 |
Malaise | 18 | 3 | 0 | 0 | 0 |
Anorexia | 14 | 7 | 0 | 0 | 0 |
Diarrhea | 18 | 2 | 1 | 0 | 0 |
Aspartate aminotransferase increased | 17 | 3 | 1 | 0 | 0 |
Peripheral sensory neuropathy | 19 | 2 | 0 | 0 | 0 |
Study | Patients | Treatment Regimens | Results | Median Follow-Up Time (Months) |
---|---|---|---|---|
Prayer-Galetti et al., 2007 [6] | n = 22, ≥PSA 15 ng/mL or ≥Gleason score 8 or ≥cT3 | q3 weeks × 4 cycles docetaxel (70 mg/m2) plus triptorelin plus estramustine | 15% CR, 80% PR, 5% PD. Five-year rate of bPFS was 42%. | 53 |
Chi et al., 2008 [7] | n = 72, ≥PSA 20 ng/mL and/or ≥Gleason score 7 or ≥cT3 | Six weekly docetaxel (35 mg/m2), two weeks off × 3 cycles, plus buserelin plus nilutamide/flutamide/bicalutamide | 3% CR. bPFS was 70% at 43 months. | 42.7 |
Sella et al., 2008 [8] | n = 22, ≥PSA 20 ng/mL or ≥Gleason score 8 or ≥cT2c | q3 weeks × 4 cycles docetaxel (70 mg/m2) plus goserelin plus bicalutamide plus estramustine | 0% CR. 50% of bPFS was 30 months. | 23.6 |
Mellado et al., 2009 [9] | n = 57, ≥PSA 20 ng/mL or ≥Gleason score 4+3 or ≥cT3 | Three weekly docetaxel (36 mg/m2), one week off x 3 cycles plus goserelin plus flutamide | 6% CR, 6% near CR. 31.6% patients presented PSA relapse. | 35 |
Thalgott et al., 2014 [10] | n = 30, BCR > 40% within five years by Kattan’s preoperative nomogram [15] | q3 weeks × 3 cycles docetaxel (75 mg/m2) plus buserelin plus bicalutamide | 0% CR, pathological down-staging was observed in 48.3%. Five-year rate of bPFS was 10%. In patients defined as therapy responders, five-year rate of bPFS was 40%. | 48.6 |
Zurita et al., 2015 [11] | n = 40, Confirmed lymph node metastasis or suspected lymph node metastasis (Gleason score ≥8 plus ≥PSA 25 ng/mL, cT3 with Gleason score ≥7, cT4) | Six weekly docetaxel (35 mg/m2), two-week off × 3 cycles plus LHRH agonist plus bicalutamide | 8% CR. The median time to treatment failure was 21.6 months. | 61 |
Narita et al., 2019 [12] | n = 60, cT3 or PSA ≥ 15 ng/mL or Gleason pattern 5 (primary and/or secondary) | Six weekly docetaxel (30 mg/m2) × 1 cycle plus leuproletin/goserelin plus bicalutamide plus estramustine | 10% CR. Five-year bPFS was 60.1%. | 42.5 |
Pan et al., 2019 [13] | n = 60, cT3a or Primary Gleason pattern 5, or ≥5 cores with Gleason sum 8 to 10, or PSA ≥50 ng/mL or with pelvic metastatic lymph node involvement | q3 weeks × 4–6 cycles of docetaxel (75 mg/m2) plus goserelin plus bicalutamide | 17.31% CR. Pathological down-staging 61.5%. The median time to biochemical recurrence was 19 months. | 12.5 |
Eastham et al., 2020 [14] | n = 778, Grade Group 4 or 5, or Kattan’s preoperative nomogram [15] bPFS < 60% | q3 weeks × 6 cycles docetaxel (75 mg/m2) plus buserelin plus LHRH agonist | No difference was seen in three-year bPFS between RP with NCHT and RP alone. | 72.1 |
Present study | n = 21, >PSA 20 ng/mL or ≥Gleason score 8 or cT3a | q4 weeks × 3 cycles docetaxel (70 mg/m2) plus leuprorelin | 0% CR, 57% PR, 43% SD, 0% PD. Five-year rates of bPFS, DMFS, PCSS, and OS were 57.1%, 89.4%, 100%, and 100%, respectively. | 88.6 |
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Sasaki, T.; Nishikawa, K.; Kato, M.; Masui, S.; Yoshio, Y.; Sugimura, Y.; Inoue, T. Neoadjuvant Chemohormonal Therapy before Radical Prostatectomy for Japanese Patients with High-Risk Localized Prostate Cancer. Med. Sci. 2021, 9, 24. https://doi.org/10.3390/medsci9020024
Sasaki T, Nishikawa K, Kato M, Masui S, Yoshio Y, Sugimura Y, Inoue T. Neoadjuvant Chemohormonal Therapy before Radical Prostatectomy for Japanese Patients with High-Risk Localized Prostate Cancer. Medical Sciences. 2021; 9(2):24. https://doi.org/10.3390/medsci9020024
Chicago/Turabian StyleSasaki, Takeshi, Kouhei Nishikawa, Manabu Kato, Satoru Masui, Yuko Yoshio, Yoshiki Sugimura, and Takahiro Inoue. 2021. "Neoadjuvant Chemohormonal Therapy before Radical Prostatectomy for Japanese Patients with High-Risk Localized Prostate Cancer" Medical Sciences 9, no. 2: 24. https://doi.org/10.3390/medsci9020024