Explainable Analytics to Predict the Quality of Life in Patients with Prostate Cancer from Longitudinal Data

Figures & data

Table 1. Summary of papers describing predicting tools relating to pros (September 2016 – July 2019). ng (not given), pros (patient-reported outcomes).

Author/year	Recruited	Country	Population	Outcome	Study Type	Setting	Tool Developed
Wouter Schaake et al. 2018 (Schaake et al. 2018)	2005–2009	Netherlands	243 patients with PCa confined to the prostatic capsule (stage T1-3). All patients were treated with radiotherapy	UI, hematuria, pain and increased voiding frequency;	Prospective	Multicenter	No
Tienza et al. 2018(Tienza et al. 2018)	2002–2012	Spain	787 consecutive patients that underwent RP	UI	Retrospective	Single center	Nomogram
Jean-Bernard Delobel et al. 2017 (Delobel et al. 2017)	2000–2012	France	972 patients undergoing definitive radiotherapy for localized prostate adenocarcinoma	Rectal bleeding, urgency/tenesmus, diarrhea, and fecal incontinence	Retrospective (487 patients) Prospective (485 patients)	Multicenter	Nomogram
Nikolaos Grivas et al. 2018 (Grivas et al. 2018)	January 2012-March 2016	NG	439	Postoperative incontinence, defined as any involuntary urine loss irrespective of inlay use or amount of urine loss, according to ICIQ‐SF	Retrospective	NG	Calculator
Mauro Carrara et al. 2018 (Carrara et al. 2018)	2002–2004 and 2010–2014	Italy Switzerland	598	Late Fecal Incontinence (LFI)	Prospective	Multicenter	graphical classification tools (GCTs)
Linda Rossi et al. 2018 (Rossi et al. 2018)	NG	NG	820	Rectal bleeding, fecal and UI, and nocturia	NG	Multicenter	No
Takuya Sadahira et al. 2019 (Sadahira et al. 2019)	2010–2017	Japan	571	UI	Retrospective	Single center	NG
Mylona et al. 2019 (Mylona et al. 2019)	May 2008 and July 2018	France	272	Incontinence, retention, dysuria, hematuria, and frequency	Prospective	Multicentric	No
Lawrence H.C. Kim et al. 2020 (Kim et al. 2020)	2015–2016	NG	190	UI	Retrospective	Single center	No
Robert T. Dess et al. 2018 (Dess et al. 2018)	2008–2013	NG	373	Functional erections	Prospective	Single center	No

Table 2. Explanations of the models for predictive tools in pros. ng (not given), pros (patient-reported outcomes).

Author	Model Type	Variables	Validation (I/E)	Accuracy	N(events)
Wouter Schaake et al. (Schaake et al. 2018)	Multivariable NTCP (Normal Tissue Complication Probability); R	Dosimetric predictors of all bladder structures, pre-treatment variables diabetes, age, cardiovascular disease, abdominal surgery, adjuvant hormonal treatment and TURP.	InternaL	AUC = 0.66, R-square = 0.10	243
Antonio Tienza et al. (Tienza et al. 2018)	Multivariable logistic regression; SPSS and Orange 2.7	Age, urethral wall thickness, history of transurethral resection of the prostate, and membranous urethral length	No	AUC = 71.7	746
Jean-Bernard Delobel et al. (Delobel et al. 2017)	Regression logistic; SPSS V18 and R	Total dose, dose per fraction, RT technique	Internal	C-index = 60%	972
Nikolaos Grivas et al. (Grivas et al. 2018)	Cox multivariate analysis and multivariate binary logistic regression; SPSS V22.0	FP score, ILD and MUL	Internal; bootstrap	AUC = 0.779	439
Mauro Carrara et al. (Carrara et al. 2018)	ANN;	Mean dose, previous abdominal surgery, use of anticoagulants, use of antihypertensive drugs, use of neoadjuvant and adjuvant hormone therapy	Internal; 4-fold cross validation	AUC = 0.78	664
Linda Rossi et al. (Rossi et al. 2018)	Multivariate logistic regression; MATLAB, SPSS V21 and R (R 3.3.2)	Age, Baseline, Turp, GI Comorbidity, LRHGE, ContrastNGTDM	Internal; bootstrap	AUC = 0.73	820
Takuya Sadahira et al. (Sadahira et al. 2019)	Multivariate logistic regression	MUL and LAM	Internal	NG	571
Eugenia Mylona (Mylona et al. 2019)	Multivariate logistic; Python and R	Whole bladder region and SRS	Internal	AUC = 0.73	272
Lawrence H.C. Kim et al. (Kim et al. 2020)	Binary logistic regression SPSS version V22.0	MRI variables: age and coronal MUL	Internal	AUC = 0.78	190
Robert T. Dess et al. (Dess et al. 2018)	Logistic regression	Baseline sexual HRQoL Age	NG	AUC = 0.81	373

Table 3. Statistical characteristics of patients for all the epic-26 domains score quartiles in 1-year follow-up. epic-26 domains are UI, UIO, b (bowel), s (sexual) and h (hormonal).

	No. of Patients for each EPIC-26 Domain
Range of Score	UI (%)	UIO (%)	B (%)	S (%)	H (%)
[0–25)	2 (0.16)	1 (0.08)	0 (0)	204 (16.80)	2 (0.17)
[25–50)	10 (0.82)	13 (1.07)	9 (0.74)	132 (10.87)	6 (0.49)
[50–75)	78 (6.42)	134 (11.04)	35 (2.88)	120 (9.89)	38 (3.13)
[75–100]	768 (63.26)	893 (73.56)	1033 (85.09)	238 (19.61)	1006 (82.87)
Missing Values	356 (29.32)	173 (14.25)	137 (11.29)	520 (42.83)	162 (13.34)

Table 4. Top 10 important variables from baseline visit selected by CB-DNN for predicting 1-year follow-up UI along with their definitions. .

Variable	Definition	Type
eq_004	Usual activities	Ordinal
ep_012	How big the problem of Increased frequency of bowel movements, if any, has been for you?	Ordinal
ip_008	During the past month, how many times did you most typically get up to urinate from the time you went to bed at night until the time you got up in the morning?	Ordinal
ib_035	Number of positive cores biopsied from LA	Ordinal
in_029	Relation of the family member diagnosed (If anyone in your family has been diagnosed with PCa)	Nominal
ep_020	How would you describe the FREQUENCY of your erections during the last 4 weeks?	Ordinal
ip_007	In the past month, how often have you had to push or strain to urinate?	Ordinal
rx_008	Which type of medications, vitamins or herbal supplements are you taking now?	Nominal
im_001	Bone scan?	Binary
in_002	How would you classify your race?	Nominal

Table 5. Top 10 important variables from baseline visit selected by CB-DNN for predicting 1-year follow-up UIO along with their definitions. .

Variable	Definition	Type
ib_064	%of first RMZ core involved	Numerical
ib_056	Number of positive cores biopsied from RA	Ordinal
ep_015	How big the problem of Abdominal/Pelvic/Rectal pain, if any, has been for you?	Ordinal
ep_020	How would you describe the FREQUENCY of your erections during the last 4 weeks?	Ordinal
in_016	Have you ever been diagnosed with chronic liver disease?	Binary
ep_021	Overall, how would you rate your ability to function sexually during the last 4 weeks?	Ordinal
ib_011	Gleason secondary grade	Ordinal
in_012	Have you ever been diagnosed with cerebrovascular disease?	Binary
ep_019	How would you describe the usual QUALITY of your erections during the last 4 weeks?	Ordinal
in_009	Have you ever been diagnosed with congestive heart failure?	Binary

Table 6. Top 10 important variables from baseline visit selected by CB-DNN for predicting 1-year follow-up bowel along with their definitions.

Variable	Definition	Type
ib_042	Number of positive cores biopsied from LMZ	Ordinal
ib_029	Intraductal carcinoma	Binary
ib_020	High Grade PIN	Binary
ib_071	%of first RB core involved	Numerical
in_018	Have you ever been diagnosed with Hemiplegia?	Binary
ep_018	How would you describe your ability to reach orgasm (climax) during the last 4 weeks?	Ordinal
ib_013b	Total cores collected	Numerical
ep_012	How big the problem of Increased frequency of bowel movements, if any, has been for you?	Ordinal
in_029	Relation of the family member diagnosed (If anyone in your family has been diagnosed with PCa)	Nominal
ib_006	DRE findings (part of biopsy-diagnostic variables)	Binary

Table 7. Top 10 important variables from baseline visit selected by CB-DNN for predicting 1-year follow-up sexual along with their definitions.

Variable	Definition	Type
ep_018	How would you describe your ability to reach orgasm (climax) during the last 4 weeks?	Ordinal
ib_008	Gland volume	Numerical
in_011	Have you ever been diagnosed with Dementia?	Binary
in_009	Have you ever been diagnosed with congestive heart failure?	Binary
ep_017	How would you describe your ability to have an erection during the last 4 weeks?	Ordinal
in_017	Have you ever been diagnosed with Diabetes?	Binary
ep_013	How big problem of Losing control of your stools, if any, has been for you?	Ordinal
ep_024	How big the problem of Breast tenderness/enlargement, if any, has been for you during the last 4 weeks?	Ordinal
ib_064	%of first RMZ core involved	Numerical
ep_023	How big the problem of Hot flashes, if any, has been for you during the last 4 weeks?	Ordinal

Table 8. Top 10 important variables from baseline visit selected by CB-DNN for predicting 1-year follow-up hormonal along with their definitions.

Variable	Definition	Type
ib_008	Gland volume	Numerical
in_027	Have you ever been diagnosed with HIV infection?	Binary
eq_002	Mobility	Ordinal
ip_006	In the past month how often have you had a weak urinary stream?	Ordinal
ep_014	How big the problem of Bloody stools, if any, has been for you?	Ordinal
ep_003	Which of the following best describes your urinary control during the last 4 weeks?	Ordinal
ep_011	How big the problem of Urgency to have a bowel movement, if any, has been for you?	Ordinal
ip_007	In the past month how often have you had to push or strain to urinate?	Ordinal
ib_051	%of second LB core involved	Numerical
in_008	Have you ever been diagnosed with Myocardial infarction?	Binary

Figure 1. R-squared between predicted and actual values in EPIC-26 domains. EPIC-26 Domains are a) UI b) UIO c) Bowel d) sexual and e) Hormonal.

Table 9. The items related to each EPIC-26 domain. EPIC-26 Domains are UI, UIO, B (Bowel) and S (sexual).

EPIC-26 domain	The items related to EPIC-26 domain	Number of items in the domain
UI	ep-002, ep-003, ep-004, ep-005	4
UIO	ep-006, ep-007, ep-008, ep-009	4
B	ep-011, ep-012, ep-013, ep-014 ep-015, ep-016	6
S	ep-017, ep-018, ep-019, ep-020 ep-021, ep-022	6
H	ep-023, ep-024, ep-025, ep-026 ep-027	5

Figure 2. BNs explanation for UI. eq_004 (Usual activities?) has the following options:1, I have no problems doing my usual activities | 2, I have slight problems doing my usual activities | 3, I have moderate problems doing my usual activities | 4, I have severe problems doing my usual activities | 5, I am unable to doing my usual activities. im_001 (Bone scan?) has the following options: 1, yes | 2, No.

Figure 3. BNs explanation for UIO. ep_015 (Abdominal/Pelvic/Rectal pain?) has the following options: 1, No problem | 2, Very small problem | 3, Small problem | 4, Moderate problem | 5, Big problem. ib_064 (% of first RMZ core involved?) is a numerical variable which those less than the mean and greater than the mean are labeled with 0 and 1 respectively.

Figure 4. BNs explanation for Bowel (B). ib_042 (Number of positive cores biopsied from LMZ?) has the following options: 1, 1 | 2, 2 | 3, Fragmented core tissue. ep_012 (Increased frequency of bowel movements?) has the following options: 1, No problem | 2, Very small problem | 3, Small problem | 4, Moderate problem | 5, Big problem.

Figure 5. BNs explanation for Sexual (S). ep_017 (How would you describe your ability to have an erection during the last 4 weeks?) has the following options: 1, Very poor to none | 2, Poor | 3, Fair | 4, Good | 5, Very good. ep_018 (How would you describe your ability to reach orgasm (climax) during the last 4 weeks?) has the following options: 1, Very poor to none | 2, Poor | 3, Fair | 4, Good | 5, Very good.

Figure 6. BNs explanation for Hormonal (H). eq_002 (Mobility?) has the following options: 1, I have no problems in walking about | 2, I have slight problems in walking about | 3, I have moderate problems in walking about | 4, I have severe problems in walking about | 5, I am unable to walk about. ib_008 (Gland volume?) is a numerical variable which those less than the mean and greater than the mean are labeled with 0 and 1 respectively.

Table 10. What-If Analysis Scenarios for Five Patients.

EPIC-26 Variable	State Name	Influential Variable	Current Value	What-if	Changes in EPIC-26 Variable
UI (Patient I)	A	eq_004	2	2 – > 1	+ 12%
	B	im_001	2	2 – > 1	+ 3%
	A and B	eq_004	2	2 – > 1	+ 24%
		im_001	2	2 – > 1
Urinary Irritative /Obstructive (Patient II)	C	ib_064	3	3 – > 1	+ 45%
	D	ep_015	1	1 – > 0	+ 4%
	C and D	ib_064	3	3 – > 1	+ 56%
		ep_015	1	1 – > 0
Bowel (Patient III)	E	ib_042	3	3 – > 1	+ 3%
	F	ep_012	2	2 – > 1	+ 55%
	E and F	ib_042	3	3 – > 1	+ 99%
		ep_012	2	2 – > 1
Sexual (Patient IV)	G	ep_017	2	2 – > 3	+ 21%
	H	ep_018	2	2 – > 3	+ 33%
	G and H	ep_017	2	2 – > 1	+ 16%
		ep_018	2	2 – > 1
Hormonal (Patient V)	I	eq_002	3	3 – > 1	+ 30%
	J	ib_008	1	1 – > 0	0%
	I and J	eq_002	3	3 – > 1	+ 39%
		ib_008	1	1 – > 0

Table 11. Variable importance ranking comparisons between global algorithm CB-DNN and local BNs.

EPIC-26 Variable	Variable Importance Ranking from BNs Results. Rank 1 is:	Variable Importance Ranking by Deep Neural Network
Urinary Incontinence	im_001	Rank 9
UIO	ep_015	Rank 3
Bowel	ep_012	Rank 8
Sexual	ep_017	Rank 5
Hormonal	eq_002	Rank 3

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