Histopathologic growth patterns as prognostic factor for survival in patients with colorectal liver metastases

Sarkis Drejian; Mehdi Sadat Akhavi; Krzyztof Grzyb; Airazat Kazaryan; Åsmund Avdam Fretland; Bjørn Edwin; Davit Aghayan

doi:10.2478/raon-2026-0002

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Histopathologic growth patterns as prognostic factor for survival in patients with colorectal liver metastases

Radiology and Oncology

Volume 60 (2026): Issue 1 (March 2026)

By: Sarkis Drejian, Mehdi Sadat Akhavi, Krzyztof Grzyb, Airazat Kazaryan, Åsmund Avdam Fretland, Bjørn Edwin and Davit Aghayan

Open Access

|Feb 2026

Figures & Tables

Haematoxylin and eosin (H & E) evaluation of the three growth patterns of colorectal liver metastasis. **(A1)** Desmoplastic pattern (fibrotic tissue as a barrier between tumor and liver parenchyma), 4x, **(A2)** Desmoplastic pattern, 10x, **(B1)** Pushing pattern (hepatocytes compressed by tumor), 4x, **(B2)** Pushing pattern, 10x, **(C1)** Replacement pattern (liver parenchyma is infiltrated by tumor cells), 4x, **(C2)** Replacement pattern, 10x. The photos are from OSLO-COMET RCT archive.
D = Desmoplastic; L = Liver; P = Pushing; R = Replacement; RCT = randomized controlled trial; T = tumor

Table 1.

Baseline characteristics

Variable	Total n = 239	Desmoplastic HGP n = 104	Pushing HGP n = 54	Replacement HGP n = 32	Mixed HGP n = 49	P-value
Male	141 (59%)	68 (65%)	34 (62%)	14 (44%)	25 (51%)	0.091
Median age (IQR), years^*	67 (60–74)	66 (58–73)	70 (63–76)	62.5 (58–71)	68 (64–73)	0.028
Median BMI (IQR), kg/m²	24.8 (22.53–28.03)	24.89 (22.85–28.6)	24.68 (23.0–26.56)	24.93 (21.71–27.68)	24.8 (21.85–28.41)	0.585
ECOG score
0	197 (82%)	85 (82%)	46 (85%)	26 (81%)	40 (82%)
1	40 (17%)	18 (17%)	8 (15%)	5 (16%)	9 (18%)	0.843
2	2 (1%)	1 (1%)	0	1 (3%)	0
ASA score
1	27 (11%)	13 (13%)	6 (11%)	7 (22%)	2 (4%)
2	120 (50.5%)	49 (47%)	25 (46%)	16 (50%)	30 (61%)	0.151
3	90 (38%)	42 (40%)	22 (41%)	9 (28%)	17 (35%)
4	1 (0.5%)	0	1 (2%)	0	0
Primary tumor in the rectum	99 (41%)	44 (42%)	22 (41%)	14 (44%)	19 (39%)	0.968
Primary tumor lymph node metastasis	158 (66%)	5 (57%)	41 (76%)	26 (81%)	32 (65%)	0.021
Primary tumor
AJCC stage
T1	5 (2%)	3 (3%)	0	0	2 (4%)
T2	14 (6%)	2 (2%)	5 (9%)	2 (6%)	5 (10%)	0.116
T3	164 (69%)	79 (76%)	31 (58%)	21 (66%)	33 (67%)
T4	56 (23%)	20 (19%)	18 (33%)	9 (28%)	9 (19%)
Synchronous	140 (59%)	56 (54%)	34 (63%)	18 (56%)	32 (65%)	0.499
Chemotherapy within 6 months prior to surgery	121 (51%)	55 (53%)	27 (50%)	17 (53%)	22 (45%)	0.815
Median CEA level (IQR), μg/L	4.3 (2.35–9.5)	4.0 (2.45–8.4)	3.9 (1.8–10.5)	5.65 (2.47–6.25)	5.0 (2.6–8.05)	0.731
Previous liver resection	29 (12%)	13 (13%)	6 (11%)	5 (16%)	5 (10%)	0.896
Median tumor size (IQR), cm	2.4 (1.50–3.50)	2.1 (1.30–3.40)	2.5 (2.08–4.08)	1.8 (1.40–3.15)	2.5 (1.95–4.00)	0.003
Minimum/maximum	0.6–16	0.7–9	0.6–8	0.8–7.5	0.8–16
Open liver resection	126 (53%)	55 (53%)	28 (52%)	17 (53%)	26 (53%)	1.000
Multiple lesions	95 (40%)	37 (36%)	26 (48%)	10 (31%)	22 (45%)	0.278
Right colon	39 (16%)	15 (14%)	10 (19%)	4 (13%)	10 (20%)	0.704

1 AJCC = American Joint Committee on Cancer; ASA = American Society of Anesthesiologists; BMI = body mass index; CEA = carcinoembryonic antigen; ECOG = Eastern Cooperative Oncology Group; HGP = histopathologic growth pattern; IQR = interquartile range.

1* Post-hoc test for variables with significant differences

1 Age: Desmoplastic vs. Pushing (p-value 0.036), Pushing vs. Replacement (p-value 0.010), Replacement vs. Mixed (p-value 0.032).

1 Primary tumor lymph node metastasis: Desmoplastic vs. Pushing (p-value 0.018), Desmoplastic vs. Replacement (p-value 0.012)

1 Median tumor size: Desmoplastic vs. Pushing (p-value 0.04), Desmoplastic vs. Mixed (p-value 0.020), Pushing vs. Replacement (p-value 0.007), Replacement vs. Mixed (p-value 0.022)

Kaplan-Meier curve of recurrence-free survival in the groups.

Kaplan-Meier curve of overall survival in the groups.

Table 2.

Chemotherapy administration and long-term oncologic outcomes

Variable	All types 239	Desmoplastic 104	Pushing 54	Replacement 32	Mixed 49	P-value
Neoadjuvant chemotherapy, n (%)	95 (40%)	46 (44%)	19 (35%)	12 (38%)	18 (37%)	0.660
Adjuvant chemotherapy, n (%)	122 (51%)	53 (51%)	25 (46%)	12 (38%)	32 (65%)	0.078
Recurrence-free survival
1 y, %	54%	69%	39%	41%	47%
3y, %	38%	49%	31%	27%	31%
5y, %	33%	45%	21%	23%	31%
Median (95% CI), mo	16 (11 to 21)	31 (12 to 50)	10 (5 to 15)	9 (6 to 12)	11 (6 to 16)	0.002
Disease recurrence, n (%)	155 (65%)	55 (53%)	42 (78%)	24 (75%)	34 (70%)	0.006
Liver, n	84 (35%)	33 (32%)	22 (42%)	9 (29%)	20 (41%)	0.415
Isolated liver recurrence	58 (24%)	24 (23%)	15 (28%)	6 (19%)	13 (27%)	0.750
Recurrence in resection bed	9 (4%)	5 (5%)	3 (6%)	1 (3%)	0	0.433
Lung, n	60 (25%)	18 (17%)	17 (31%)	12 (38%)	13 (27%)	0.066
Other Extrahepatic, n	37 (16%)	15 (14%)	9 (17%)	5 (16%)	8 (16%)	0.982
Treatment of the first disease recurrence
Repeated liver surgery, n (%)	56 (23%)	20 (19%)	16 (30%)	7 (22%)	13 (27%)	0.500
LLR	29 (12%)	13 (13%)	5 (9%)	3 (9%)	8 (16%)
OLR	20 (8%)	7 (7%)	6 (11%)	2 (6%)	5 (10%)
RFA	6 (3%)	0	5 (9%)	1 (3%)	0
Transplant	1 (0.5%)	0	0	1 (3%)	0
Lung resection, n (%)	13 (5%)	4 (4%)	1 (2%)	6 (20%)	2 (4%)	0.005
Other surgical procedure, n (%)	9 (4%)	5 (5%)	2 (4%)	2 (6%)	0	0.428
Only palliative chemotherapy, n (%)	43 (18%)	13 (13%)	13 (24%)	5 (16%)	12 (25%)	0.172
Radiotherapy and radio-chemotherapy, n (%)	24 (10%)	9 (9%)	7 (13%)	4 (13%)	4 (8%)	0.768
No treatment, n (%)	10 (4%)	5 (5%)	4 (7%)	1 (3%)	0	0.292
Overall survival
1 y, %	97%	95%	96%	97%	98%
3 y, %	74%	75%	72%	84%	69%
5 y, %	55%	62%	39%	59%	55%
Median (95% CI), months	74 (58 to 90)	94	49 (39 to 59)	86 (43 to 129)	82 (43 to 121)	0.036
Alive patients, n (%)	103 (43%)	52 (50%)	16 (30%)	14 (44%)	22 (45%)	0.064

1 HR = hazard ratio; IQR = interquartile range; CI = confidence interval; n= number; mo = month; LLR = laparoscopic liver resection; OLR = open liver resection; RFA = radiofrequency ablation; Y = year

1* Post-hoc test for variables with significant differences –

1 Recurrence-free survival: Desmoplastic vs. Pushing (p-value < 0.001), Desmoplastic vs. Replacement (p-Value 0.007),

1 Desmoplastic vs. Mixed (p-Value 0.023)

1 Disease recurrence: Desmoplastic vs. Pushing (p-value 0.002), Desmoplastic vs. Replacement (p-value 0.027)

1 Lung resection: Desmoplastic vs. Replacement (p-value 0.05), Pushing vs. Replacement (p-value 0.006), Replacement vs. Mixed (p-value 0.031)

1 Overall survival: Desmoplastic vs. Pushing (p-value 0.005), Pushing vs. Replacement (p-value 0.049

Table 3.

Univariable and multivariable analysis of prognostic factors for recurrence free and overall survival

Variable	Recurrence-free survival			Overall survival
	Univariable	Multivariable Cox regression analysis		Univariable	Multivariable Cox regression analysis
	P Value	Hazard ratio (95% CI)	P-Value	P-value	Hazard ratio (95% CI)	P-value
Age (per year)	0.463			< 0.001	1.027 (1.007–1.047)	0.008
Male sex	0.579			0.193	1.432 (0.993–2.065)	0.055
BMI	0.126	1.029 (0.989–1.070)	0.156	0.697
ECOG score	0.130	1.273 (0.868– .869)	0.217	0.005	1.659 (1.129–2.437)	0.010
ASA score	0.108	1.119 (0.858–1.458)	0.408	0.192
*Primary tumor*
Rectum	0.195	0.885 (0.624–1.256)	0.494	0.403
Right colon	0.75			0.134	1.238 (0.798–1.919)	0.341
AJCC T- stage (1,2–3,4)	0.176	0.547 (0.291–1.029)	0.061	0.597
Lymph node involvement	< 0.001	1.610 (1.075–2.412)	0.021	0.041	1.349 (0.921–1.976)	0.124
*Liver metastasis*
Synchronous	0.023	1.302 (0.914–1.856)	0.144	0.129
Previous liver resection	0.791			0.256
Multiple lesions	0.310			0.798
Lobar distribution	0.621			0.494
Tumor size (per cm)	0.017	1.084 (0.992–1.185)	0.076	< 0.001	1.014 (1.005–1.022)	0.002
Chemo within 6 mo prior surgery	0.109	1.140 (0.814–1.597)	0.446	0.997
Preoperative CEA (> 5 ng/mL)	0.155	1.255 (0.896–1.757)	0.186	0.750
Extrahepatic disease	< 0.001	2.834 (1.766–4.548)	< 0.001	0.011	1.690 (1.028–2.779)	0.039
*Liver resection*
Laparoscopy	0.489			0.515
Blood loss	0.486			0.863
Blood transfusion	0.353			0.243
Operative time	0.896			0.684
Post operative severe complications	0.900			0.216
R1 resection (<1 mm)^*	0.094	0.831 (0.504–1.370)	0.468	0.120	1.075 (0.663–1.741)	0.77
Involved resection margin	0.002	1.625 (0.841–3.141)	0.148	0.156	1.390 (0.730–2.648)	0.316
No adjuvant chemotherapy	0.401			0.555
*Growth patterns*
Desmoplastic vs. none desmoplastic	< 0.001	1.446 (1.005–2.081)	0.047	0.073	0.912 (0.633–1.313)	0.619

1 AJCC = American Joint Committee on Cancer; ASA = American Society of Anesthesiologists; BMI = body mass index; CEA = carcinoembryonic antigen; ECOG = Eastern Cooperative Oncology Group; mo = month

1* R1 resection - presence of tumor cells within 1 mm from the resection margin

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DOI: https://doi.org/10.2478/raon-2026-0002 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099

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Language: English

Page range: 114 - 123

Submitted on: Aug 18, 2025

Accepted on: Nov 19, 2025

Published on: Feb 6, 2026

Published by: Association of Radiology and Oncology

In partnership with: Paradigm Publishing Services

Publication frequency: 4 issues per year

Keywords:

histopathologic growth pattern,

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© 2026 Sarkis Drejian, Mehdi Sadat Akhavi, Krzyztof Grzyb, Airazat Kazaryan, Åsmund Avdam Fretland, Bjørn Edwin, Davit Aghayan, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution 4.0 License.

Volume 60 (2026): Issue 1 (March 2026)

Histopathologic growth patterns as prognostic factor for survival in patients with colorectal liver metastases

Figures & Tables

FIGURE 1.

Figure 2.

Table 1.

Figure 3.

Figure 4.

Table 2.

Table 3.

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