Prognostic factors influencing survival rates in elderly patients with metastatic renal cell carcinoma

Dmitry V. Semenov; Rashida V. Orlova; Valery I. Shirokorad; Stanislav V. Kostritsky; Pavel V. Kononets

South Russian Journal of Cancer. 2024. Vol. 5, No. 3. P. 31-38

https://doi.org/10.37748/2686-9039-2024-5-3-3

https://elibrary.ru/gskqjk

ORIGINAL ARTICLE

Prognostic factors influencing survival rates in elderly patients with

metastatic renal cell carcinoma..

��-��

��

South Russian

Journal of Cancer..

Vol. 5

No. 3, 2024

D. V. Semenov1,2 , R. V. Orlova1,2, V. I. Shirokorad3, S. V. Kostritsky3, P. V. Kononets4

1 St. Petersburg State University, St. Petersburg, Russian Federation

2 City Clinical Oncological Dispensary, St. Petersburg, Russian Federation

3 Moscow City Oncological Hospital No. 62 of the Moscow City Health Department, Moscow, Russian Federation

4 N. N. Blokhin National Medical Research Center of Oncology, Moscow, Russian Federation

sema.69@mail.ru

ABSTRACT

Purpose of the study. To determine the influence of prognostic factors on survival rates

in patients

with mRCC aged . 75

years.

Materials and methods. A retrospective study included 77 mRCC patients aged . 75 years who received systemic therapy

at the Municipal Oncologic Hospital No. 62 in Moscow and the Municipal Oncologic Dispensary in St. Petersburg from 2006

to 2019. Clinical data from medical records were obtained and analyzed retrospectively, all patients underwent clinical, laboratory,

and pathomorphological examination. Patients' survival rates were evaluated using the statistical method of survival

time analysis (Survival Analysis). Descriptive characteristics of survival time were calculated in the form of life tables, and

Kaplan-Meier curves were constructed.

Results. In the present study, a favorable prognosis according to International Metastatic Renal Cell Carcinoma Database

Consortium (IMDC)was noted in 20.8

% of patients with mRCC aged . 75 years; 6.5

% had solitary metastases. The 3- and

5-year survival rates were 35.8 % and 21.2 %.

In single-factor analysis in mRCC patients . 75 years of age, it was found that ECOG status (p < 0.001), histological subtype

(p = 0,01), Fuhrman grade of tumour differentiation (p = 0.003), type of metastases (p = 0.045), liver metastases (p < 0.001),

IMDC prognosis (p = 0.042) and nephrectomy (p = 0.014).

Conclusion. In

a multivariate

analysis, factors

affecting survival

in

patients

with

mRCC aged . 75

years

included sex, histologic

subtype, number of metastases, bone and lymph node metastases, IMDC prognosis, and radiation therapy and nephrectomy.

Further studies are needed to identify additional personalized prognostic factors in elderly patients with metastatic renal cell

carcinoma (mRCC).

Keywords: metastatic renal cell carcinoma, overall survival rate, elderly patients

For citation: Semenov D. V., Orlova R. V., Shirokorad V. I., Kostritskiy S. V., Kononets P. V. Prognostic factors influencing survival rates in elderly patients with

metastatic renal cell carcinoma. South Russian Journal of Cancer. 2024;

5(3): 31-38. https://doi.org/10.37748/2686-9039-2024-5-3-3, https://elibrary.ru/gskqjk

For correspondence: Dmitry V. Semenov � Cand. Sci. (Med.), Associate Professor of the Department of Oncology, Faculty of Medicine, Saint Petersburg

State University, Saint Petersburg, Russian Federation; Physician in the Oncourology Department, City Clinical Oncologic Dispensary, Saint Petersburg, Saint

Petersburg, Russian Federation

Address: 7/9 Universitetskaya Embankment, Saint Petersburg 199034, Russian Federation

Address: 56 Veterans Ave., Saint Petersburg 198255, Russian Federation

E-mail: sema.69@mail.ru

ORCID: https://orcid.org/0000-0002-4335-8446

SPIN: 2342-6530, AuthorID: 202214

ResearcherID: KQU-5717-2024

Scopus Author ID: 58596081800

Compliance with ethical standards: the study adhered to the ethical principles outlined in the World Medical Association Declaration of Helsinki (1964,

revised in 2013). The research was approved by the Ethics Committee of the Saint Petersburg City Clinical Oncological Dispensary (protocol No. 2356 dated

May 20, 2022). Informed consent was obtained from all study participants

Funding: this work was not funded

Conflict of interest: the authors declare that there are no obvious and potential conflicts of interest associated with the publication of this article

The article was submitted 02.03.2024; approved after reviewing 31.05.2024; accepted for publication 24.07.2024

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INRODUCTION

Over the past decade, the incidence of RCC has

been increasing annually. RCC occurs in 25 % of patients

with newly diagnosed RCC over the age of 75

([1]. Currently, the majority of patients with metastatic

renal cell carcinoma (mRCC) receive various

options for systemic therapy, due to which the median

overall

survival

(s)

increased to 4

years

[2, 3]. It

is known that in elderly patients, the activity of the

tumor process

is

lower due to a slowdown in

metabolic

processes in the body. The implementation of

modern drug therapy contributes to an increase in

Table 1. Characteristics of patients

��

the indicators of OS in patients with mRCC, includ

ing in

elderly patients

[4]. But

aggressive

systemic

therapy in patients over 75

years of age is associated

with an increased risk of undesirable side effects

that worsen the quality of life. In our study, we

studied prognostic factors in patients with mRCC

aged . 75 years, affecting survival rates.

MATERIALS AND METHODS

A retrospective analysis of 77 patients aged

. 75 years who received systemic therapy at the

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Moscow City Oncological Hospital No. 62 and

Characteristic . 75 �� (n = 77)

n (%)

Gender:

male

51 (66.2)

female

26 (33.8)

ECOG status:

0 1 (1.3)

1 29 (37.7)

2 35 (45.5)

3 12 (15.6)

Histological type:

clear-cell carcinoma 64 (83.1)

non-clear-carcinoma 13 (16.9)

Differentiation grade:

G1 18 (23.4)

G2 27 (35.1)

G3 32 (41.6)

Metastasis type:

metachronous 53 (68.8)

synchronous 24 (31.2)

Number of metastases:

solitary 5 (6.5)

single 27 (35.1)

multiple 45 (58.4)

IMDC prognosis:

favorable 16 (20.8)

intermediate 32 (41.6)

poor 29 (37.7)

Metastatic site:

lungs 48 (62.3)

bones 26 (33.8)

liver 6 (7.8)

lymph nodes 21 (27.3)

Prior nephrectomy:

71 (92.2)

Metastasectomy:

11 (14.3)

Radiation therapy: 10 (13)

South Russian Journal of Cancer 2024. Vol. 5, No. 3. P. 31-38

Semenov D. V. , Orlova R. V., Shirokorad V. I., Kostritskiy S. V., Kononets P. V. Prognostic factors influencing survival rates in elderly patients with metastatic renal

cell carcinoma

the St. Petersburg City Oncological Dispensary

from 2006 to 2019 was carried out. All patients re

ceived systemic antitumor therapy. The influence

of clinical and morphological factors on overall

survival(s) was assessed. Detailed characteristics

of patients are given in Table 1.

Survival curves for Overall

Based on Kaplan-Meier estimates

1.00

Probability

0.75

0.50

0.25

0

0 12 24 36 48 60

Number

at risk

Time (months)

AII 77 62 48 28 18 15

3-year OS: 35.8 % 5-year OS: 21.2 %

Fig. 1. Overall survival (OS) of patients . 75 years of mRCC (n = 77)

Survival curves for Histology

Based on Kaplan-Meier estimates

1.00

Patient data was consolidated in the form of

spreadsheets and analyzed using the Statistica

12 for Windows program. Life expectancy was calculated

from the date of diagnosis to the date of

last observation or death. Survival was assessed

using the Kaplan-Mayer method, survival differences

were determined using a log-rank test; Cox

regression analysis was used to exclude factors

that

do not

have

independent

prognostic significance.

An analysis of the S of patients with mRCC

.

75

years

old

was

performed, depending

on

the

histological variant of the tumor, the degree of

tumor differentiation according to Fuhrman, the

IMDC prognosis group, the number, type and localization

of metastases, cytoreductive surgery

and radiation therapy.

STUDY RESULTS

The clinical and morphological characteristics

of 77 patients are presented in Table 1. The average

age was 79 (75�95) years. Clear cell renal cell

carcinoma was detected in 64 (83.1 %) patients.

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Favorable, intermediate and unfavorable forecast

for IMDC in 16 (20,8 %), 32 (41,6 %) and 29 (37.7 %)

patients. Solitary, single and multiple metastases

Survival curves for Grade

Based on Kaplan-Meier estimates

1.00

Log-rank

p = 0.0091

0 12 24 36 48 60

Number

at risk

Time (months)

Grade -

Grade 1 18 18 16 9 7 7

Grade -

Grade 2 27 23 19 12 7 5

Grade -

Grade 3 32 21 13 7 4 3

Log-rank

p = 0.012

0.75

Probability

0.25

0.50

�

B

0

Number

at risk

Histology CKP

0

64

12

53

24 36 48

Time (months)

43 25 17

60

15

HIstology -

He CKP 13 9 5 3 1 0

3-year OS: 5-year OS:

3-year OS: 43.2 % � 25.9 %

5-year OS: 23 % � 0 %

56.2 % 46.5 % 24.5 % 43.8 % 19.4 %

Fig. 2. Overall survival (OS) in patients . 75 years of mRCC depending on histologic subtype (A) and tumor differentiation according to

Fuhrman (B) (n = 77)

��-�� 2024. �. 5, � 3. �. 31-38

�� . �. , �� . �., �� . �., �� . �., �� . �. �� , ��

��

were detected in 5 (6,5 %), 27 (35,1 %) and 45

(58.4 %) patients, respectively.

The indicators of 3- and 5-year OV in patients

with mRCC were 39.7

%

[29.8�52.76

%; 95

% CI]

and

21.2

% [13.6�33.24

%; 95

% CI], respectively,

Survival curves for Type

Based on Kaplan-Meier estimates

1.00

in patients, while the median OS was 32.4 [28.9�

38.6

%; 5

% CI] months (Fig. 1).

A single-factor analysis

in patients

with

mRCC

. 75

years

old revealed that

ECOG status

(p < 0.001), histological subtype (p = 0.01), degree

Survival curves for Hepar

Based on Kaplan-Meier estimates

1.00

Log-rank

p = 0.043

0 12 24 36 48 60

Number Time (months)

at risk

�� = Syn-

Log-rank

p < 0.0001

0 12 24 36 48 60

Number Time (months)

at risk

��r -

Probability

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0.75

Probability

0.50

0.25

�

0

B

0

chronous 24 16 11 7 2 2 Liver meta-71 60 47 28 18 15

�� (2) stases (-)

�� =

��

Metachro-53 46 37 21 16 13 Liver meta-6 2 1 0 0 0

nous ��

stases (+)

3-year OS: 5-year OS: 3-year OS: 5-year OS: 1-year OS:

43.6 % and 30.7 %

27.0 % and 8.8 % 43.1 % 223.1 % 33.3%

Fig. 3. Overall survival (OS) in patients . 75 years of mRCC according to type of metastases (A) and liver metastases (B) (n = 77)

Survival curves for IMDC Survival curves for CN

Based on Kaplan-Meier estimates Based on Kaplan-Meier estimates

1.00

Log-rank

p = 0.00032

0 12 24 36 48 60

Log-rank

p = 0.0096

0 12 24 36 48 60

Probability

0.75

0.50

Probability

0.75

0.50

0.25

�

B

0

Number

at risk

IMDC -

Favorable

�� -

Intermediate

IMDC -

Unfavorable

16

32

29

15

27

20

Time (months)

13 9 7

23 14 7

12 5 4

7

6

2

Number

at risk

CN -��

(+)

CN -��3

(-)

71

6

59

3

Time (months)

46 27 18

2 1 0

15

0

3-year OS:

64.9 % 47.2 % 18.0 %

5-year OS:

50.5 % 20.2 % 7.2 %

3-year OS:

41.6 % 16.7 %

5-year OS:

23.1 % 0 %

Fig. 4. Overall

survival

(OS)

in

patients

. 75

years

depending on

prognosis

IMDC (A)

and nephrectomy performance

(B)

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(n = 77)

South Russian Journal of Cancer 2024. Vol. 5, No. 3. P. 31-38

Semenov D. V. , Orlova R. V., Shirokorad V. I., Kostritskiy S. V., Kononets P. V. Prognostic factors influencing survival rates in elderly patients with metastatic renal

cell carcinoma

Table 2. Prognostic factors for overall survival in patients . 75 years of age with mRCC (n = 77)

(single-factor and multivariate analysis)*

Factor

Hazard rario (95 % confidence interval)

Univariate test Multivariate test

Gender:

male

female

�

0.62 (0.37�1.05, p = 0.077)

�

0.27 (0.16�0.46, p < 0.001)

ECOG status:

0

1

2

3

�

20379783.9 (0.00-Inf, p = 0.997)

38320352.5 (0.00-Inf, p = 0.997)

82331370.5 (0.00-Inf, p = 0.996)

�

41895.8 (24218�1572477.23, p < 0.001)

69920.5 (41671.28�117320.25, p < 0.001)

112174.0(53540.28-235019.58, p < 0.001)

Histological type:

clear-cell carcinoma

non-clear-carcinoma

�

2.19 (1.17�4.09, p = 0.014)

�

1.92 (1.02�3.60, p = 0.043)

Differentiation grade:

G1

G2

G3

�

1.74 (0.90�3.36, p = 0.100)

2.71 (1.40�5.25, p = 0.003)

�

1.43 (0.86�2.36, p = 0.169)

1.38 (0.83�2.32, p = 0.218)

Metastasis type:

metachronous

synchronous

�

0.59 (0.35�0.99, p = 0.045)

�

1.22 (0.71�2.08, p = 0.478)

Number of metastases:

solitary

single

multiple

�

0.64 (0.24�1.71, p = 0.372)

1.33 (0.52�3.42, p = 0.553)

�

0.59 (0.35�1.00, p = 0.050)

1.66 (1.00�2.73, p = 0.049)

Lung metastases:

present

absent

�

1.58 (0.38-6.64, p = 0.532)

�

1.29 (0.81�2.08, p = 0.139)

Bone metastases:

present

absent

1.17 (0.69�1.98, p = 0.557) 3.09 (1.82�5.23, p < 0.001)

Liver metastases:

present

absent

�

6.68 (2.74�16.28, p < 0.001)

�

1.86 (0.74�4.69, p = 0.186)

Lymph nodes metastases:

present

absent

�

1.16 (0.68�1.97, p = 0.595)

�

0.54 (0.31�0.93, p = 0.026)

IMDC prognosis:

favorable

intermediate

poor

�

4.00 (1.93-8.29, p < 0.001)

2.07 (1.03�4.18, p = 0.042)

�

1.94 (1.13�3.33, p = 0.016)

1.93 (1.17�3.20, p = 0.010)

Radiation therapy:

no

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yes

�

0.99 (0.44-2.20, p = 0.979)

�

0.28 (0.12-0.64, p = 0.002)

Prior nephrectomy:

yes

no

�

2.95 (1.25-6.99, p = 0.014)

�

6.08 (2.54�14.58, p < 0.001)

Metastasectomy 0.41 (0.05�3.53, p = 0.419) 0.65 (0.28�1.46, p = 0.323)

Note: the table only presents factors with prognostic significance

��-�� 2024. �. 5, � 3. �. 31-38

�� . �. , �� . �., �� . �., �� . �., �� . �. �� , ��

��

of tumor differentiation according to Fuhrman

(p = 0.003), type of metastases (p = 0.045), liver

metastases

had a negative

effect

on

survival

rates

(p < 0.001), IMDC prognosis (p = 0.042) and nephrectomy

(p = 0.014) (Table 2, Fig. 2�4).

The median OS in clear cell and non-light

cell

cancers

was

34.4

[30.0�44.6; 95

% CI] and

21.2

[10.4�NA; 95

% CI] months, respectively, and

in G1, G2 and G3 was 46.4 [34.4�NA; 95

% CI],

33,4

[26,9�51; 95

% CI] and 21.7 [13.9�31.6; 95

%

CI] months, respectively.

The median S in metachronous and synchronous

metastases was 33 [29.1�46.9;

95

%

CI]

and

23.7 [12�44.6;

95

%

CI] months,

respectively,

and in

the absence and presence of liver metastases was

33.4

[29.1�44.6; 95

% CI] and 5.1

[3.5�NA; 95

% CI]

months, respectively.

The median OS with favorable, intermediate

and unfavorable forecasts was 65.2 [35.9�NA;

95

% CI], 35,8

[29�46,3; 95

% CI] and

21.2

[13.7�

31.1; 95

% CI] months, respectively, and in the

presence or absence of nephrectomy was

32.6

[29�44.6; 95

% CI] and 10

[5�NA; 95

% CI]

months, respectively.

In multivariate analysis,

gender

[HR = 0.27 (95

%

CI = 0.16�0.46], ECOG status [HR = 112174.0

(95

% CI

=

53540.28�235019.58], histological

subtype

[HR

=

1.92

(95

% CI = 1.02�3.60], number

of metastases

[HR

=

1.66

(95

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% CI

=

1.00�

2.73], bone metastases

[HR

= 3.09

(95

%

CI = 1.82�5.23] and lymph nodes [HR = 0.54

(95

%

CI = 0.31�0.93], IMDC prognosis [HR =

1.93 (95

%

CI = 1.17�3.20], as well as radiation

therapy [HR

=

0.28

(95

% CI =

0.12�0.64] and

nephrectomy [HR

= 6.08

(95

% CI =

2.54�14.58]

were additional factors that had an independent

negative effect on the indicators of OS in elderly

patients with mRCC (Table 2).

DISCUSSION

Currently, due to an increase in life expectancy,

the number of senile patients with renal cell carcinoma

is growing in the world, 25 % of patients over

75 years of age are diagnosed with RCC for the

first time ([1]. In a retrospective study by Kanesvaran

R et al. old age does not affect the indicators

of OS in mRCC [5]. In our

study, the rates of 3

and 5-year-olds in patients with mRCC . 75 years

were 35.8 % and 21.2 %. In the work of Ryuichi

Mizuno

et al. A

decrease in OS in senile patients

is possible due to an unbalanced distribution of

patients

in

the

IMDC prognosis

groups, a higher incidence

of anemia, as well as a higher percentage

of patients receiving symptomatic therapy instead

of second-line systemic

therapy [6]. In our

study,

anemia was noted in 35.1 % of patients, 1/5 of

patients in the group with a favorable prognosis

according to IMDC, one third of patients had bone

metastases.

The decrease in OS indicators may occur due

to ineffective therapy of senile patients and early

transfer of this category to symptomatic treatment

[7]. Modern

drug therapy over the

past

few

decades has led to

a significant increase in OS

rates in patients with mRCC. Elderly patients after

the first line of systemic

therapy are not always

transferred to the second line due to the high

risk

of adverse

events. This

is

due

to a lack

of

evidence that elderly patients can tolerate systemic

therapy of two or more lines in order to increase

the indicators of OS. Currently, in addition

to prognostic prognostic factors, personalized

therapeutic strategies

are

being

developed

[8, 9].

In our

study,

we identified additional prognostic

factors affecting survival rates in senile patients

with mRCC.

The limitations of this study are the size of the

studied group of patients and its retrospective nature.

Further research is needed to develop personalized

approaches in elderly patients with mRCC

to improve the quality of life and increase the indicators

of OS.

CONCLUSION

The factors influencing survival rates in patients

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with mRCC aged . 75

years in multivariate analysis

were gender, histological subtype, number of

metastases, bone and lymph node metastases,

IMDC prognosis, as well as radiation therapy and

nephrectomy.

Further studies are needed to determine additional

personalized prognostic factors in senile

patients with mRCC.

South Russian Journal of Cancer 2024. Vol. 5, No. 3. P. 31-38

Semenov D. V. , Orlova R. V., Shirokorad V. I., Kostritskiy S. V., Kononets P. V. Prognostic factors influencing survival rates in elderly patients with metastatic renal

cell carcinoma

References

1. Pal SK, Vanderwalde A, Hurria A, Figlin RA. Systemic therapies for metastatic renal cell carcinoma in older adults. Drugs

Aging.

2011

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Information about authors:

Dmitry V. Semenov � Cand. Sci. (Med.), Associate Professor of the Department of Oncology, Faculty

of Medicine St. Petersburg State University,

Saint Petersburg, Russian Federation; doctor of the Oncourology department, City Clinical Oncological Dispensary, St. Petersburg, Russian Federation

ORCID: https://orcid.org/0000-0002-4335-8446, SPIN: 2342-6530, AuthorID: 202214, ResearcherID: KQU-5717-2024, Scopus

Author ID: 58596081800

Rashida

V.

Orlova

�

Dr.

Sci.

(Med.),

Professor,

Head

of

the

Department

of

Oncology,

Faculty

of

Medicine

St.

Petersburg

State

University,

Saint Petersburg, Russian Federation; Chief Specialist in Clinical Oncology, City Clinical Oncological Dispensary, St. Petersburg, Russian Federation

ORCID: https://orcid.org/0000-0002-9368-5517, SPIN: 9932-6170, AuthorID: 401170

Valery

I. Shirokorad � Dr. Sci. (Med.), Head of the Oncourological Department Moscow City

Oncological Hospital No. 62 of the Moscow City

Health

Department, Moscow, Russian Federation

ORCID: https://orcid.org/0000-0003-4109-6451, AuthorID: 481900

Stanislav V. Kostritsky

� oncourologist, Moscow City

Oncological Hospital No. 62 of the Moscow City

Health Department, Moscow,

Russian Federation

ORCID: https://orcid.org/0000-0003-4494-1489, SPIN: 1421-2469, AuthorID: 980451, ResearcherID: Y-6978-2018

Pavel V. Kononets

� Dr. Sci. (Med.), Professor, Director of the N. N. Trapeznikov Scientific Research Institute N. N. Blokhin National Medical

Research Center of Oncology, Moscow, Russian Federation

ORCID: https://orcid.org/0000-0003-4744-6141, SPIN: 9884-6940, AuthorID: 755462

Contribution of the authors:

Semenov D. V. � collection of material, analysis of the obtained data, writing the manuscript;

Orlova R. V. � analysis of the obtained data, editing of the manuscript;

Shirokorad V. I. � development of the study design, obtaining data for analysis, editing of the manuscript;

Kostritsky S. V. � collection of material, analysis of the obtained data.

Prognostic factors influencing survival rates in elderly patients with metastatic renal cell carcinoma Текст научной статьи по специальности «Клиническая медицина»

Аннотация научной статьи по клинической медицине, автор научной работы — Dmitry V. Semenov, Rashida V. Orlova, Valery I. Shirokorad, Stanislav V. Kostritsky, Pavel V. Kononets

Похожие темы научных работ по клинической медицине , автор научной работы — Dmitry V. Semenov, Rashida V. Orlova, Valery I. Shirokorad, Stanislav V. Kostritsky, Pavel V. Kononets

Прогностические факторы, влияющие на показатели выживаемости у больных старческого возраста с метастатическим почечноклеточным раком

Текст научной работы на тему «Prognostic factors influencing survival rates in elderly patients with metastatic renal cell carcinoma»