Keywords
early detection of cancer - alternate medicine - behavioral sciences - epidemiology
- delayed diagnosis - cancer care facility
Introduction
Cancer is one of the leading causes of death in most developing countries and when
presenting in advanced stage, the response of the disease to treatment is reported
to be suboptimal, which can inadvertently result in poor outcome[1]
[2]
[3] and with questionable efficacy in treatment of malignancy, use of alternate medicine
in the initial phase of the disease has been shown to cause delay in diagnosis and
advancement of stage, thus worsening its prognosis.[4] The objectives of this study were to estimate the delay of presentation to a cancer
care facility from the initiation of symptoms of malignancy and to evaluate this delay
with respect to the use of alternate medicine and advanced stage (stage III and IV)
of presentation.
Materials and Methods
Study Design and Population
A single institutional hospital based cross-sectional study was undertaken in the
radiation oncology department of a government medical college in eastern India, between
August 2023 and December 2023. A convenience sampling method was used for enrolling
the subjects.
Patients with cytological or histological proof of malignancy, giving written signed
consent after proper information and explanation regarding this study (in case of
minor, consent of parent was considered), were enrolled. Inability to recall the period
of delay between onset of symptoms and time at presenting to hospital and unavailability
of adequate documents regarding important details of disease led to exclusion.
Sample Size Calculation
Approximately 1,800 patients were encountered per month for 5 months (August–December
2023). So, population size, N = 1800*5 = 9000.
Now, using the formula, sample size = 
the sample size was estimated to be 1061. Details of calculation are enclosed in the
[Supplementary Material], available in the online version.
Study Technique
A questionnaire consisting of questions assessing the sociodemographic factors, the
disease related parameters, the delay between onset of symptoms and reporting to hospital
and usage of alternate medicine before initial treatment was prepared. Initially,
the questionnaire was pretested among a group of 15 subjects. It was validated and
after few amendments, the final version was attained. Study proposal was submitted
to institutional ethical committee and after getting written clearance, interview
of the subjects by trained physicians was started. Data thus collected was compiled
and subjected to statistical analysis.
Statistical Analysis
The data was analyzed using Statistical Package for Social Sciences (SPSS) Statistics
Version 26.0 (IBM Inc., Chicago, Illinois, United States) and Microsoft Excel (Microsoft
Corp., Redmond, Washington, United States). Comparative analysis was done with cross
tables along with Kruskal–Wallis test for association between delay and the independent
variables (demographic parameters and alternate medicine usage). Predictors for delay
were assessed with logistic regression analysis. Spearman's rank test was used to
measure the direction and strength of correlation of delay and alternate medicine
use against stage at presentation. P value less than 0.05 was considered as statistically
significant.
Results
Among the patients attending the outpatient department of our institution, 1,089 fulfilled
the inclusion criteria and were selected. Out of them, 67 were rejected as per the
exclusion criteria. Ultimately, 1,022 subjects were interviewed.
Demographic Parameters
The subjects were aged between 7 and 87 years with a median age of 55 years (interquartile
range: 47–62 years) with majority (589 [57.6%]) of them being females. Most of them
(903 [88.3%]) belonged to rural background with 477 (46.7%) subjects having completed
primary education, 508 (49.7%) being homemakers and majority (581 [56.8%]) having
monthly family income ranging between 10,000 and 19,999 INR. Details are presented
in [Supplementary Table 1].
Disease Related Parameters
Most common primary site of diagnosis was breast (242 [23.6%]) followed by head and
neck (213 [20.8%]) and uterine cervix (191 [18.6%]). Commonest stage at presentation
was stage III {455 (44.5%)} followed by stage II (360 [35.2%]) and stage IV (173 [16.9%]).
Six-hundred twenty-eight (52.1%) subjects had an advanced stage (either stage III
or IV) at presentation. Details are presented in [Supplementary table 2].
Parameters Related to Delay in Presentation
Majority of the subjects (574 [56.1%]) presented to a cancer care facility after an
interval of 4 to 6 months from the onset of symptoms. Seven-hundred sixty-nine (75.2%)
subjects had a delay of more than 3 months and 196 (19.1%) subjects had a delay of
more than 6 months. Only 21 (0.2%) subjects reported within 1 month.
In male subjects, delay was more pronounced in those with lung cancer than those with
head and neck cancers (29.56 vs. 24.86% at >6 months delay), whereas in the female
subjects, delay was more pronounced in those with breast cancer than those with cancer
of the uterine cervix (23.43 vs. 3.19% at >6 months delay). Variation of delay with
respect to gender specific diagnoses are detailed in [Supplementary Table 5], available in the online version.
Parameters Related to Usage of Alternate Medicine
Two-hundred eighty-one subjects (27.5%) admitted of using alternate medicine after
onset of symptoms that was chiefly homeopathy (214 [20.9%]) followed by ayurveda (43
[4.20%]) with most (156 [15.26%]) using it for a period of 4 to 6 months. About 89.67%
of those who used alternate medicine and 50.74% of those who did not use it had an
advanced stage (either stage III or IV) at presentation, respectively. [Supplementary table 2], [Supplementary Fig. S1 (A)]
Association of Cumulative Delay in Reporting to Hospital to Various Independent Variables
For the ease of understanding, the delay for the individual subjects is categorized
as period of cumulative delay as follows:
-
a) ≤1 month
-
b) >1 month (includes those with delay >1 month, >3 months, >6 months and >1 year)
-
c) >3 months (includes those with delay >3 months, >6 months and >1 year)
-
d) >6 months (includes those with delay >6 months and >1 year)
-
e) >1 year
Association of delay in presentation was assessed against age, sex, domicile, education,
occupation, monthly family income, and alternate medicine use of the subjects with
the use of cross tabulations and chi-squared test, but no consistent pattern of association
was observed. Details of association between cumulative delay period and various independent
variables are enclosed in the [Supplementary Table 5] and [6], available in the online version.
Logistic regression analysis was carried out to assess the role of demographic parameters
namely age, sex, domicile, education, occupation, and income as predicting factors
for delay. Out of all these, only having female sex had higher odds (odds ratio [OR]:
2.94, 95% confidence interval: 2.14–4.04, p = 0.000) of presenting with delay of more than 3 months, which was statistically
significant.[Supplementary Table 3]
Proportion of subjects presenting in advanced stage (stage III or IV) progressively
increased with corresponding increase in the period of delay from 627 out of 1,001
(62.63%) having more than 1 month delay to 619 out of 769 (80.48%) subjects having
more than 3 month delay to 193 out of 196 (98.47%) having more than 6-month delay
to 11 out of 11 (100%) having more than 1 year delay ([Table 1]; [Supplementary Fig. S1 (B)]).
Table 1
The relationship between delay, alternate medicine usage, and stage of disease
|
Variable
|
Category
|
Percentage of subjects for the respective period of cumulative delay
|
p-Value
|
|
≤1 month (21)
|
>1 month (1001)
|
>3 month (769)
|
>6 month (196)
|
>1 year (11)
|
|
Alternate medicine usage
|
Yes (281)
|
0 (0.00)
|
281 (100.00)
|
270 (96.08)
|
120 (42.70)
|
7 (2.49)
|
0.000
|
|
No (741)
|
21 (2.83)
|
720 (97.16)
|
499 (67.34)
|
76 (10.25)
|
5 (0.67)
|
|
Stage
|
I (34)
|
7 (33.33)
|
27 (2.70)
|
1 (0.13)
|
0 (0.00)
|
0 (0.00)
|
0.000
|
|
II (360)
|
13 (61.90)
|
347 (34.66)
|
149 (19.37)
|
4 (2.04)
|
1 (9.09)
|
|
III (455)
|
1 (4.76)
|
454 (45.35)
|
149 (58.25)
|
65 (33.16)
|
4 (36.36)
|
|
IV (173)
|
0 (0.00)
|
173 (17.28)
|
171 (22.23)
|
127 (64.79)
|
7 (63.63)
|
|
Advanced stage (III + IV) (628)
|
1 (4.76)
|
627 (62.63)
|
619 (80.48)
|
193 (98.47)
|
11 (100.00)
|
|
In 252 alternate medicine users with advanced stage disease (III + IV)
|
0 (0.00)
|
252 out of 281 (89.68)
|
249 out of 270 (92.22)
|
119 out of 120 (99.16)
|
7 out of 7 (100.00)
|
Values are presented as number (%).
A higher proportion of subjects who had used alternate medicine (270 out of 281 [96.08%])
presented with significant delay as compared to those who did not (499 out of 741
[67.34%] for more than 3 months delay and the difference further increased with increase
in duration of delay.[Supplementary Fig. S2 (A)]
Of those 281 subjects who had used alternate medicine, 252 (89.67%) presented in an
advanced stage. With increase in delay period, this percentage progressively escalated
in this sub population.[Supplementary Fig. S2 (B)]
Spearman's rank test demonstrated a strong positive correlation (Spearman's rho: 0.742)
between delay and stage at presentation. For those who had used alternate medicine,
a moderate positive correlation (Spearman's rho: 0.592) between the same parameters
was observed.
Discussion
Delay in cancer treatment has been classically divided into patient delay and provider
delay. Patient delay is defined as the interval between the date of initial symptom
and consultation with a physician, while provider delay is defined as the interval
from first visit to starting of medical intervention.[2] Multiple studies have suggested that patient delay, typically more than 3 months,
is strongly associated with larger tumor size, advanced stage during presentation
and inferior long-term survival.[3]
[5]
[6]
[7] With advancement in stage, the tumor cells show lesser degree of differentiation
and greater propensity for microscopic dissemination and metastasis along with decreased
response to treatment, ultimately leading to higher occurrences of mortality and morbidity.[8]
[9]
[10] It has been suggested that timely appreciation of initial symptom by the patient
acts as a trigger for seeking prompt medical attention, which forms the psychological
basis of variation in patient delay.[11] Also, it is often observed that the rate of survival and cure of cancer is higher
in those diagnosed in the initial stage, especially for those subsites, for which
symptoms develop in early stage (e.g., breast, cervix, oral cavity).
In this study, 75% subjects presented with more than 3 months of delay and 19% presented
at more than 6 months, which are alarmingly high. Delay in presentation was more pronounced
in those with lung cancer among male subjects and in those with breast cancer among
females. Of all the sociodemographic parameters assessed, only female sex had higher
odds (OR: 2) of predicting a delay more than 3 months. Progressive increase in the
period of delay was associated with corresponding increase in the percentage of subjects
presenting in advanced stage, from 62.63% in those having more than 1 month delay
to 80.48% in those having more than 3-month delay and 97.95% in those having more
than 6-month delay. This very observation adequately points toward the massive disadvantage
of delayed reporting after onset of symptoms.
Evidence from existing literature highlight the association of initial alternate medicine
usage to delay in presentation and advanced stage in diagnosis.[4]
[12]
[13]
In this study, 89.67% of those subjects who had history of alternate medicine usage
presented in advanced stage (stage III or IV) versus 50.74% of those who did not.
In this subgroup, progressive increase in the period of delay was associated with
corresponding increase in the percentage of presentation in advanced stage, from 89.68%
in those having more than 1 month delay to 92.22% in those having more than 3-month
delay to 99.16% in those having more than 6-month delay, which were greater than the
corresponding values for the total sample as a whole. Though a direct causal association
could not be inferred upon, for those who had used alternate medicine, a moderate
positive correlation between delay and stage at presentation was observed. These findings
shed light on the harm caused by loss of invaluable time after onset of symptoms due
to engagement in alternate medicine usage, ultimately leading to delayed presentation
in an advanced stage.
This study has some limitations. It could be difficult and error-prone for subjects
to correctly recall the exact date of first symptom especially in those with longer
delay, thus introducing bias in the reported findings. Also, some sex specific cancers
differ by modes of presentation. For example, breast cancer usually is reported early
with a lump, whereas prostate cancer presents late with subtle symptoms. This variation
was not taken into consideration that does not allow us to generalize the findings
of this study across sexes.
Conclusion
This study, conducted in a majorly rural part of eastern India, reveals the alarmingly
high levels of delay in presentation among cancer patients after onset of symptoms,
of which female sex was a significant predictor. This delay was significantly associated
with advanced stage at diagnosis and alternate medicine use after onset of symptoms.
This study provides substantial information in order to generate policies for maximally
curbing this delay by urgent implementation of awareness programs especially among
the rural population of low-middle income countries, focusing on the symptoms of malignancy
and the necessity of visiting a hospital promptly, right after suspicion of those
symptoms. Knowledge on benefits of early detection on reduction in mortality and cost
burden of cancer treatment also needs to be imbibed. Research works scrutinizing the
attitude among the population regarding the reasons behind their preference of alternate
medicine for cancer treatment is of utmost necessity.
