Determinants of Long-term Survival of Patients With Locally Advanced Prostate Cancer

The Role of Extensive Pelvic Lymph Node Dissection

M Moschini; N Fossati; F Abdollah; G Gandaglia; V Cucchiara; P Dell'Oglio; S Luzzago; SF Shariat; F Dehò; A Salonia; F Montorsi; A Briganti

Disclosures

Prostate Cancer Prostatic Dis. 2016;19(1):63-67.

Results

Baseline Patient Characteristics

Clinical and pathological demographics of the cohort are reported in Table 1. The average PSA value was 20.5 ng ml⁻¹ (median: 9.6 ng ml⁻¹; IQR: 6.3–18.6 ng ml⁻¹). Considering pathological GS, 595 (37%) patients had 8–10 GS. Average number of RLNs and positive LNs was 19.0 (median: 17; IQR: 11–23) and 1.7 (median: 0; IQR: 0–1), respectively. Overall, 547 (34.5%) and 865 (54.5%) patients were treated with adjuvant hormonotherapy and RT, respectively.

Cox Regression Analyses and Survival Estimates

At univariable analyses, GS 8–10 (hazard ratio (HR): 4.3), positive surgical margin (HR: 1.8), number of positive nodes (HR: 1.03) and number of RLNs (HR: 1.02) were the only predictors of CSM rate (all P≤0.01). At multivariable analyses, GS 8–10 (HR: 2.5), aRT (HR: 0.5) and a higher number of positive LNs (HR: 1.06) were independently associated with higher CSM rate (all P≤0.05). Conversely, higher number of RLNs (HR: 0.94) was an independent predictor of a lower CSM rate (P≤0.03) (Table 2). Survival estimates were calculated based on the multivariable model. Mean and median follow-up were 80 and 72 months, respectively. Patients were stratified according to the number of RLNs using the points of maximum separation (Figure 1a). The predicted CSM-free rate increased consistently with rising number of RLNs, from 93% for patients with 10 RLNs to 98% for patients with 60 RLNs (Figure 2a). Similar trends were observed when patients were stratified according to GS and aRT status (Figure 2b and c).

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Figure 1.

Kaplan–Meier survival estimates based on multivariable analysis, assessing cancer-specific survival rate in 1586 pT3-T4 prostate cancer patients treated with surgery and pelvic lymph node dissection. Patients were stratified according to the total number of lymph nodes removed.

(Enlarge Image)

Figure 2.

The multivariable analyses 10-yr cancer specific survival rate predicted (a) by the total number of lymph nodes removed for the entire cohort, (b) after stratification according to Gleason score, and (c) by adjuvant radiotherapy (aRT) status.

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Table 1. Descriptive statistics of the cohort of 1586 patients with non-metastatic pT3-pT4 prostate cancer treated with radical prostatectomy and extended pelvic lymph node dissection between 1987 and 2014 at one tertiary care center
Variables	Entire cohort (n=1586, 100%)
Age at surgery, years
Mean	65.8
Median (IQR)	66.1 (61.1–70.9)
PSA, ng ml⁻¹
Mean	20.5
Median (IQR)	9.6 (6.3–18.6)
Type of surgery
Robotic-assisted radical prostatectomy	253 (16.0%)
Open radical prostatectomy	1333 (84.0%)
D'amico risk group
Low risk	132 (8.3%)
Intermediate risk	589 (37.1%)
High risk	717 (45.2%)
Unknown	148 (9.3%)
Removed lymph nodes
Mean	19.0
Median (IQR)	17 (11–23)
Positive lymph nodes
Mean	1.7
Median (IQR)	0 (0–1)
Pathological Gleason score
2–6	184 (11.6%)
7	807 (50.9%)
8–10	595 (37.5%)
PSM	656 (41.4%)
LNI	655 (41.3%)
Adjuvant HT	547 (34.5%)
Adjuvant RT	865 (54.5%)
Salvage HT	79 (5.0%)
Salvage RT	119 (7.5%)

Abbreviations: HT, hormonotherapy; IQR, interquartile range; LNI, lymph node invasion; PSM, positive surgical margin; RT, radiotherapy.

Table 2. Univariable and multivariable Cox regression analyses predicting cancer-specific mortality and overall mortality in 1586 pT3-pT4 prostate cancer patients treated with radical prostatectomy
Variables	Cancer-specific mortality
	Univariate analysis		Multivariate analysis
	HR (95% CI)	P	HR (95% CI)	P
Age, years	1.02 (1.00–1.04)	0.07	1.08 (1.04–1.13)	<0.001
PSA, ng ml⁻¹	1.00 (1.00–1.00)	0.01	1.00 (1.00–1.00)	0.7
Positive surgical margin	1.84 (1.25–2.72)	0.002	1.76 (0.87–3.57)	0.1
Number of positive nodes	1.03 (1.02–1.05)	<0.001	1.06 (1.01–1.12)	0.03
Number of nodes removed	1.02 (1.00–1.03)	0.01	0.94 (0.90–0.99)	0.02
Type of surgery
Open surgery	Ref.	0.6	Ref.	0.6
Robotic surgery	0.82 (0.40–1.70)		0.80 (0.33–1.92)
GS pathological
2–6	Ref.	<0.001	Ref.	<0.001
7	1.08 (0.62–1.89)	0.8	0.72 (0.44–1.66)	0.3
8–10	4.28 (2.60–7.05)	<0.001	2.46 (1.29–4.80)	0.02
ADJ RT	0.69 (0.47–1.02)	0.06	0.54 (0.42–0.81)	0.02
ADJ HT	2.82 (1.87–4.26)	<0.001	1.59 (0.48–5.27)	0.4