Conditional Survival Of Patients Research Articles

Mortality risk and life years lost in young patients with heart failure according ejection fraction. Data from the Swedish Heart failure, National Patient, Cause of Death and Population Registers

Abstract Background There is a lack of data evaluating excess mortality risk (over that of the general population) and life-years lost in young patients with different heart failure (HF) phenotypes. Purpose To study excess risk for all-cause mortality in patients <55 years by their ejection fraction (EF) categories and estimate lost “life years” compared to the general population in Sweden. Methods All patients ≥18 years registered in the national quality register SwedeHF from 2003 to 2014 were included. Patients were divided into ≥55 years and <55 years. For each patient two controls without a HF diagnosis, matched for age, sex and county, were identified from the Swedish Population Register. The use of personal identification number enabled linkage to other registers. All somatic hospital discharge diagnoses are recorded in the National Patient Register (NPR). Time of death and causes of death were obtained from the Cause of Death Register. International Classification of Disease ICD 9 and ICD 10-codes for all co-morbidities were identified in NPR and for underlying causes of death during the observation period from the 1st January 2003 to 31st December 2015. Life expectancy tables from Statistics Sweden were used as reference to the conditional life expectancy for controls calculated at the age 20, 25, 30, 35 and 40 years. Life-years lost were calculated as the difference between conditional life expectancy and conditional survival for patients with HF <55 years presented as median. Results In total 60,962 patients, out of whom 3752 <55 years and 7425 controls <55 years were identified. Total observation time was 12 years; median 4.89 years. There were 2549 (67.9%) patients with ejection fraction (EF) <40% and 357 (9.5%) with EF >50%. Patients with HF<40% were more likely to be men (78.2% vs. 56.3%), to have ischemic heart disease (16.9% vs. 2.3%) and dilated cardiomyopathy (38.1% vs. 29.7%) whereas patients with EF >50% more often had hypertension (40.6% vs. 29.8%), hypertrophic cardiomyopathy (11.5% vs. 0.7%) and congenital heart disease (7.6% vs. 2.7%), all p>0.001. Cardiovascular death was the most common cause of death in all EF categories (about 55%). In a Cox proportional hazard model, patients with EF >50% had hazard ratio (HR) (95% CI) 10.6 (5.71–19.8), those with EF 40–49% 6.83 (4.43–10.5) and patients with EF<40% 7.97 (6.45–9.85) for all-cause mortality (NS). According to the conditional survival analysis patients aged 20, 25, 30, 35 and 40 years with EF<40% lost a median of 28.5, 26.6, 24.7, 22.2 and 20.1 “life years” whereas patients with EF>50% lost 32.3, 28.7, 26.1, 26.3 and 21.6 “life years” as presented in figure 1. Conclusion HF patients <55 years with EF>50% had different coexisting conditions and higher mortality risk, although not significant when compared to patients with EF <40%. Moreover, compared to the general population patients with EF>50% lost more life years than patients with EF<40%. Figure 1 Funding Acknowledgement Type of funding source: None

Conditional Survival of Patients Who Underwent Curative Resection for Esophageal Squamous Cell Carcinoma

Objective:To analyze conditional survival estimates of patients with esophageal cancer who underwent curative resection.Summary Background Data:Conditional survival reflects dynamic prognosis updated to the current status and is a more relevant indicator for current healthcare and life decisions.Methods:This study included 1883 patients who underwent complete resection for esophageal squamous cell carcinoma at a tertiary cancer center from 1994 to 2016. We calculated 5-year (5Y) conditional overall survival (COS), conditional recurrence-free survival (CRFS), and conditional relative survival (CRS) estimates from diagnosis to 5 years of survival.Results:The 5Y COS, CRFS, and CRS increased from 63.7%, 65.2%, and 70.2% at diagnosis to 75.8%, 91.9%, and 86.4 at 5 years after diagnosis, respectively. While there were large differences with different stages (stage I, II, III) at diagnosis (81.2%, 64.9%, and 37.3% for COS; 85.1, 65.1%, and 67.9% for CRFS; 89.2%, 72.1%, and 41.1% for CRS), the gap decreased with time; rates were similar after 5 years (77.1%, 75.7%, and 72.6% for COS; 91.7%, 90.6%, and 94.5% for CRFS, and 89.3%, 85.4%, and 78.3% in CRS, respectively). The 5Y COS, CRFS, and CRS were persistently lower in older patients even after 5 years.Conclusions:Conditional survival estimates generally increase over time, and the largest improvements were observed for patients with advanced stage. Availability of updated prognosis at various time points allows clinicians to better guide their patients. Our results also imply substantial residual risk of recurrence and sustained excess mortality compared to the general population even after 5 years.

Conditional Survival in Uveal Melanoma

To investigate conditional survival in patients with uveal melanoma in the United States. Cohort study. Patients were identified using International Classification of Disease for Oncology, Third Edition, codes for both morphologic features (melanoma, 8720-8790) and site (retina, C69.2; choroid, C69.3; and ciliary body, C69.4) from 1975 through 2011 using the Surveillance, Epidemiology, and End Results (SEER) database SEER18. Observed metastasis-free survival (MFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Conditional metastasis-free survival (cMFS) and conditional overall survival were calculated based on the observed MFS and OS. Relative survival also was calculated using the actuarial method. Survival to 5 and 10 years after diagnosis were calculated, conditioned on various numbers of years already survived. Conditional MFS, conditional OS, and conditional relative survival. A total of 6863 cases of uveal melanoma were identified. Median follow-up among survivors was 11 years. During follow-up, 3883 patients died of any cause, and of these, 2131 deaths were the result of metastatic uveal melanoma. The nonconditional 5-year MFS was 80%. After surviving 1, 2, 3, or 4 years after diagnosis, the 5-year cMFS estimates increased to 82%, 87%, 92%, and 96%, respectively. The nonconditional MFS at 10 years was estimated to be 69%. After having survived 5, 6, 7, 8, or 9 years after diagnosis, the 10-year cMFS estimates increased to 87%, 90%, 93%, 96%, and 98%, respectively. This result pattern was confirmed with estimates of relative survival. Conditional survival estimates of uveal melanoma improve with time since primary diagnosis. Among patients who already have survived for at least 5 years, 10-year conditional survival rates are high. Conditional survival analysis can provide specific guidance for counselling patients.

Risk of disease recurrence and survival in patients with multiple myeloma: A German Study Group analysis using a conditional survival approach with long-term follow-up of 815 patients.

Unlike the traditional method of overall survival prediction in patients with cancer, conditional survival predicts the survival of patients dynamically throughout the course of disease, identifying how a prognosis evolves over time. The authors assessed 815 consecutive patients with multiple myeloma through the German Study Group on Multiple Myeloma (Deutsche Studiengruppe Multiples Myelom; DSMM) incentive. Over 10 variables, including patient-specific and multiple myeloma-specific parameters, were analyzed at the time of initial diagnosis and repeatedly during follow-up. The probability of survival for another 5years was calculated according to disease-related and host-related risks. Multivariate Cox models were used to determine baseline and updated prognostic factors for survival. The median follow-up and overall survival were 10.3years and 5.1years, respectively. When comparing 5-year conditional survival probabilities from the data derived at the time of initial diagnosis with those updated over time, substantially differing prognoses were observed when follow-up data were used. Multivariate Cox regression models for cohorts surviving 0 to 5years demonstrated hazard ratios (HRs) for patients aged <60years, 60 to 69years, and >70years of 1, 1.68, and 3.17, respectively. These HRs for age were found to decline for patients surviving 5years, as well as for those with advanced stages of disease (II/III) and unfavorable cytogenetics, whereas progressive disease remained an important factor in patients surviving 1year, 3years, and 5years, with HRs of 1.85, 2.11, and 2.14, respectively. To the authors' knowledge, the current study is the first analysis of conditional survival in patients with multiple myeloma using both baseline and follow-up risk parameters, demonstrating that regular risk assessment throughout the course of disease and complete follow-up provide a more reliable conditional survival estimation than baseline assessment alone.

Conditional survival of patients with nonmetastatic bone osteosarcoma.

e23511 Background: Conditional survival provides a dynamic prediction of prognosis for patients surviving a defined period of time after diagnosis. This study aimed to determine the conditional survival and prognostic factors over time among patients with non-metastatic bone osteosarcoma. Methods: We reviewed 714 bone osteosarcoma patients treated from 1985 to 2016. Patients with metastatic disease at diagnosis or limited follow up were excluded, resulting in 587 cases for analysis. Clinical and pathological variables were recorded. Predictive variables included age at diagnosis, gender, previous radiation history, tumor site, tumor size, histologic subtype, histologic grade, resection margin, chemotherapy, and radiation therapy. The multivariate Cox proportional hazards regression was used to analyze prognostic factors of conditional overall survival and progression-free survival at baseline and 5 years after diagnosis. Results: The estimated 5-year conditional overall survival increased from 71.0% (95% CI: 67.5%-75.0%) at baseline to 86.9% (95% CI: 82.6%-90.5%) at 5 years, which means if a patient with non-metastatic bone osteosarcoma survived 5 years, the chance of surviving another 5 years was 86.9%. If the patient was progression-free for 5 years, the 5-year conditional overall survival was even higher, 93.2% (95% CI: 89.5%-96.4%), and the 5-year conditional progression-free survival improved from 57.1% (95% CI: 53.3%-61.0%) at baseline to 91.2% (95% CI: 87.5%-94.6%) at 5 years. Prognostic factors for mortality and disease progression change as survival time increases. At baseline, age (p &lt; 0.001 and p = 0.003), histologic subtype (p &lt; 0.001 and p = 0.001), grade (p &lt; 0.001 and p &lt; 0.001), tumor size (p = 0.002 and p = 0.002), resection margin (p &lt; 0.001 and p &lt; 0.001) and chemotherapy (p = 0.001 and p = 0.001) were predictive of both overall survival and progression-free survival. However, only age (p &lt; 0.001) and histologic subtype (p = 0.015) remained significant for mortality and resection margin (p = 0.001) for disease progression at 5 years. Conclusions: The survival probability of osteosarcoma improves as survival time increases. Estimates of conditional survival can provide useful information for individualized surveillance strategies, risk evaluation, patient counseling, and making clinical decisions.

Dynamic evaluation of conditional survival in patients with oral squamous cell carcinoma after surgical resection: A large-scale prospective study.

To dynamically estimate conditional survival (CS) probabilities for patients with oral squamous cell carcinoma (OSCC) after surgical resection. A large-scale prospective study was performed involving 1147 eligible OSCC patients from December 2002 to June 2018. Follow-up was completed on January 8, 2019. Cox proportional hazards models were utilized to assess prognostic factors related to overall survival (OS). Three-year CS (CS3) of patients who had already survivedxyears was calculated as the formula CS3=OS(x+3)/OS(x). CS3 estimates at the time of 0, 1, 3, 5-year survival demonstrated a tendency increase over time, and improved from 78.47% to 82.25%, while the postoperative actuarial OS decreased from 78.47% at 3years to 57.12% at 8years. Moreover, the differences between CS3 and actuarial OS were more obvious among patients with unfavorable tumor characteristics. Disparities in CS3 across all subgroups of tumor features illustrated more prominent at baseline (d range: 0.24 to 0.40), while the gaps would narrow if those patients have already survived 5years (d range: -0.01 to 0.18). Our findings suggest that survival profiles of OSCC patients evolve and increase over time following resection, especially for those with unfavorable tumor features at initial diagnosis. CS estimates may provide more accurate prediction and guide surveillance schedules.

Conditional Survival in Heart Transplantation: An Organ Procurement and Transplantation Network Database Analysis

Survival after heart transplantation is typically reported only in terms of overall survival. Conditional survival may provide prognostic information for patients after surviving a given period. This study sought to provide an analysis of conditional survival in heart transplantation. Data from 29,000 patients who underwent heart transplantation between 2002 and 2016 were analyzed from the Organ Procurement and Transplantation Network database, and 5-year conditional survival rates were calculated according to age, sex, race, renal function, and hepatic function at transplantation. As time from transplantation increased from 0 to 5 years, the 5-year observed conditional survival changed from 74% to 82% for ages younger than 40 years, 79% to 82% for ages 40 to 49, 79% to 78% for ages 50 to 60, and 75% to 70% for ages older than 60 at transplantation. Conditional survival peaked at 1 and 2 years after transplantation for most subgroups. In recipients younger than 40 years, men had slightly higher conditional survival than women (absolute difference, 3%-4%). In recipients older than 60 years, women had slightly higher conditional survival (absolute difference, 1%-4%). Black recipients had lower survival than white and Hispanic recipients for nearly all time points. Recipients younger than 40 years with the worst renal (65% to 88%) and hepatic function (66% to 83%) at transplantation experienced the largest increase in conditional survival. The conditional survival of patients who undergo heart transplantation changes substantially over time. The largest increases in conditional survival are in young patients with impaired renal and hepatic function. Conditional survival can provide more accurate prognostic information for heart recipients who survive a given period after transplantation.

Conditional survival after neoadjuvant chemoradiotherapy and surgery for oesophageal cancer.

BackgroundConditional survival accounts for the time already survived after surgery and may be of additional informative value. The aim was to assess conditional survival in patients with oesophageal cancer and to create a nomogram predicting the conditional probability of survival after oesophagectomy.MethodsThis retrospective study included consecutive patients with oesophageal cancer who received neoadjuvant chemoradiation followed by oesophagectomy between January 2004 and 2019. Conditional survival was defined as the probability of surviving y years after already surviving for x years. The formula used for conditional survival (CS) was: CS(x|y) = S(x + y)/S(x), where S(x) represents overall survival at x years. Cox proportional hazards models were used to evaluate predictors of overall survival. A nomogram was constructed to predict 5‐year survival directly after surgery and given survival for 1, 2, 3 and 4 years after surgery.ResultsSome 660 patients were included. Median overall survival was 44·4 (95 per cent c.i. 37·0 to 51·8) months. The probability of achieving 5‐year overall survival after resection increased from 45 per cent directly after surgery to 54, 65, 79 and 88 per cent given 1, 2, 3 and 4 years already survived respectively. Cardiac co‐morbidity, cN category, ypT category, ypN category, chyle leakage and pulmonary complications were independent predictors of survival. The nomogram predicted 5‐year survival using these predictors and number of years already survived.ConclusionThe probability of achieving 5‐year overall survival after oesophagectomy for cancer increases with each additional year survived. The proposed nomogram predicts survival in patients after oesophagectomy, taking the years already survived into account.

Conditional survival of patients with rectal cancer undergoing Watch and Wait: The risk of recurrence over time.

30 Background: Patients with rectal cancer and complete clinical response (cCR) after neoadjuvant chemoradiation (nCRT) have been offered non-operative management (W&amp;W). Risk factors for local regrowth (RG) include baseline cT and type of nCRT. However, the influence of risk factors for RG over time and the extent in time that patients need to be followed with the rectum in situ after a cCR are unknown. Objective: Analyze the risk of recurrence over time through conditional survival (cDFS/cLRFS) estimates for rectal cancer patients under W&amp;W. Methods: Retrospective analysis of all patients from the largest multicenter database of patients managed non-operatively (International Watch and Wait Database–IWWD). Only patients with cCR after nCRT and W&amp;W with a median of &gt;3 years of follow-up were included. cDFS was used to investigate the evolution of recurrence-odds, as patients remain disease-free after nCRT. 2-year cDFS was estimated at “x” years after nCRT based on the formula cDFS2=DFS(x+2)/DFS(x). Results: 768 patients treated between 1991-2015 were included. Using cDFSestimates, the probability of remaining disease-free for 2 additional years once cCR was achieved and sustained for 1, 3, and 5 years, were 85%, 97%, and 95%, respectively. These contrast with the actuarial DFS for similar intervals of 70%, 68% and 65% respectively. Baseline cT was associated with the risk of RG at 1 year after a cCR (cT2 aLRFS 89% vs. cT3 82%; p=0.004). However, after sustaining a cCR for 1 year, baseline cT becomes irrelevant at 2 years (cLRFS; 94% vs. 90%; |d| 0.14). Also, total dose of RT (≤50 vs &gt;50Gy) was associated with the risk of RG (aLRFS 76% vs 85%; p=0.03) at 1 year. Dose of RT becomes irrelevant (at 2 years; cLRFS 93% vs. 90%; |d| 0.10) once patients sustained a cCR for 1 year. Conclusions: Conditional survival estimates suggests that patients have significantly lower risks (≤5%) of developing late RG (at 5 years) after sustaining cCR for 3 years. A sustained cCR over time may be more relevant for long-term risk of RG than cT-stage or RT dose. The present data can have significant consequences for the recommendation of intensive surveillance after sustaining 3ys of cCR.

Conditional Survival of Patients With Nonmetastatic Renal Cell Carcinoma: How Cancer-Specific Mortality Changes After Nephrectomy.

Conditional survival (CS) may reveal important differences in cancer-specific mortality (CSM) among patients with nonmetastatic renal cell carcinoma (nmRCC). This study assessed CS according to T and N stages in patients treated surgically for nmRCC. Within the SEER database (2001-2015), all patients with nmRCC treated with either partial or radical nephrectomy were identified. CSM-free estimates according to T and N stage and substage groupings (pT1aN0-pT4N0 and pTanyN1) and multivariable Cox regression models with adjustment for Fuhrman grade and histologic subtype were assessed. According to T and N stage and substage groupings, the following patients were included in the study: 35,966 (46.2%) with pT1aN0 disease; 18,858 (24.2%) with pT1bN0; 5,977 (7.7%) with pT2aN0; 2,511 (3.2%) with pT2bN0; 11,839 (15.2%) with pT3aN0; 1,037 (1.3%) with pT3b-cN0; 402 (0.5%) with pT4N0; and 1,302 (1.7%) with pTanyN1. Conditional CSM-free survival estimates were 98.2% at 1 year versus 98.0% at 10 years of event-free follow-up for patients with pT1aN0 disease, relative to baseline. Conversely, pT4N0/pTanyN1 conditional CSM-free survival estimates were 55.8% at 1 year versus 77.9% at 8 years of event-free follow-up. Attrition due to mortality was highest in patients with pT4N0/pTanyN1 disease. In multivariable Cox regression analyses, T stage, tumor grade, and histologic subtype represented independent predictors, but no interactions were identified. Tumor stage and its substages represent extremely important determinants of prognosis after lengthy event-free follow-up. The recorded observations have critical importance for physicians regarding patient follow-up and counseling.

Conditional survival and recurrence of remnant gastric cancer after surgical resection: A multi-institutional study.

The present study was designed to evaluate the dynamic survival and recurrence of remnant gastric cancer (RGC) after radical resection and to provide a reference for the development of personalized follow‐up strategies. A total of 298 patients were analyzed for their 3‐year conditional overall survival (COS3), 3‐year conditional disease‐specific survival (CDSS3), corresponding recurrence and pattern changes, and associated risk factors. The 5‐year overall survival (OS) and the 5‐year disease‐specific survival (DSS) of the entire cohort were 41.2% and 45.8%, respectively. The COS3 and CDDS3 of RGC patients who survived for 5 years were 84.0% and 89.8%, respectively. The conditional survival in patients with unfavorable prognostic characteristics showed greater growth over time than in those with favorable prognostic characteristics (eg, COS3, ≥T3: 46.4%‐83.0%, Δ36.6% vs ≤T2: 82.4%‐85.7%, Δ3.3%; P < 0.001). Most recurrences (93.5%) occurred in the first 3 years after surgery. The American Joint Committee on Cancer (AJCC) stage was the only factor that affected recurrence. Time‐dependent Cox regression showed that for both OS and DSS, after 4 years of survival, the common prognostic factors that were initially judged lost their ability to predict survival (P > 0.05). Time‐dependent logistic regression analysis showed that the AJCC stage independently affected recurrence within 2 years after surgery (P < 0.05). A postoperative follow‐up model was developed for RGC patients. In conclusion, patients with RGC usually have a high likelihood of death or recurrence within 3 years after radical surgery. We developed a postoperative follow‐up model for RGC patients of different stages, which may affect the design of future clinical trials.

Conditional Survival in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab.

BackgroundNivolumab is approved for the treatment of advanced renal cell carcinoma (RCC). However, traditional overall survival (OS) or progression-free survival (PFS) do not reflect patient prognosis after initial management. Therefore, this study aimed to evaluate conditional overall survival (COS) and conditional progression-free survival (CPFS) in patients with advanced RCC treated with nivolumab.Material/MethodsThere were 847 patients with advanced RCC treated with first-line nivolumab plus ipilimumab (n=425) and sunitinib (n=422), and 821 patients were treated with second-line nivolumab (n=410) and everolimus (n=411). Primary endpoints were COS and CPFS. Individual patient data of PFS and OS were digitally reconstructed from two large randomized controlled trials (CheckMate 025 and CheckMate 214).ResultsIn first-line treatment, compared with sunitinib, improvement of one-year CPFS for the nivolumab plus ipilimumab group after living for 0.5 and 0.75 years were 14% (from 53.0% to 67.0%) and 16% (from 57.0% to 73.0%) higher than the one-year PFS of 6.5% (from 42.9% to 49.4%), with similar results for one-year COS following first-line treatment. For second-line treatment, compared with everolimus, the improvement of one-year CPFS for the nivolumab group after living for 0.5 and 0.75 years were 19% (from 25.0% to 44.0%) and 19% (from 27.0% to 46.0%) and significantly higher than the one-year PFS of 4.5% (from 18.5% to 23.0%).ConclusionsSurvival benefit for patients with advanced RCC from nivolumab (plus ipilimumab) compared with sunitinib was more evident from conditional survival (CS) analysis of first-line treatment.

Conditional survival of patients with stage I-III squamous cell carcinoma of the penis: temporal changes in cancer-specific mortality.

To test the conditional survival that examined the effect of event-free survival on cancer-specific mortality after primary tumour excision (PTE) in patients with squamous cell carcinoma of the penis (SCCP). Within the SEER database (1998-2015), 2282 stage I-III SCCP patients were identified. Conditional survival estimates were used to calculate cancer-specific mortality (CSM) after event-free survival intervals of 1, 2, 3, and 5years. Multivariable Cox regression models predicted CSM according to event-free survival. After PTE, 5-year CSM-free rate was 78.0% and increased to 84.6%, 88.1%, 92.0%, and 94.2% in patients who survived ≥ 1, ≥ 2, ≥ 3, and ≥ 5years. After stratification according to tumour characteristics, 5-year CSM-free rates increased from 85.9 to 95.4%, 79.0 to 97.1%, 78.9 to 90.0%, and from 54.5 to 86.0% in those survived ≥ 5years, respectively, in T1N0, T2N0, T3N0, and N1-2 patients. In multivariable analyses, T2N0 [hazard ratio (HR) 1.68; p value < 0.001], T3N0 (HR 1.94; p value 0.001), and N1-2 (HR 6.61; p value < 0.001) were independent predictors of higher CSM rate at baseline, relative to T1N0. A decrease in all HRs was assessed over time in patients who survived. Attrition due to CSM was highest in N1-2 cohort and lowest in T1N0. Conditional survival models showed a direct relationship between event-free survival duration and subsequent CSM in SCCP patients. Even patients with non-organ-confined disease may achieve survival probabilities similar to those with organ-confined disease after at least 5years of event-free survival since PTE.

How cancer-specific mortality changes over time after radical cystectomy: Conditional survival of patients with nonmetastatic urothelial carcinoma of the urinary bladder

ObjectivesWe studied the effect of conditional survival on 5-year cancer-specific mortality (CSM) probability in a contemporary North-American population-based nonmetastatic urothelial carcinoma of urinary bladder cohort treated with radical cystectomy. Methods and materialsWithin the SEER database (2004–2015), we identified pTa/pTis/pT1N0 high grade, pT2 to pT4N0 and pTanyN1-3 patients treated with radical cystectomy for nonmetastatic urothelial carcinoma of urinary bladder. Conditional 5-year CSM-free estimates were assessed after event-free follow-up duration. Multivariable Cox regression models predicted CSM according to event-free follow-up duration. ResultsAccording to T and N stages, 1,079 (7.9%) pTa/pTis/pT1N0, 5,058 (37.2%) pT2N0, 2,865 (21.1%) pT3N0, 1,211 pT4N0 (8.9%) and 3,382 (24.9%) pTanyN1-3 patients were included. Conditional CSM-free estimates increased from 90.1 to 91.8%, 80.6 to 92.5%, 62.5 to 90.7%, 53.1 to 84.5%, and 37.5 to 84.0% after 5 years of event-free follow-up, in respectively pTa/pTis/pT1N0, pT2N0, pT3N0, pT4N0, and pTanyN1-3 patients. Attrition due to mortality was highest in pTanyN1-3 cohort and lowest in pTa/pTis/pT1N0. In Multivariable Cox regression analyses, pT2N0 (hazard ratio [HR] 1.9 P< 0.001), pT3N0 (HR 4.3 P< 0.001), pT4N0 (HR 5.8 P< 0.001) and pTanyN1-3 (HR 9.1 P< 0.001) were independent predictors of higher CSM at baseline, relative to pTa/pTis/pT1N0. A decrease in all conditional HRs to nonsignificant levels was recorded at 60 months for pT4N0 and pTanyN1-3 and at 48 months for pT2N0 and pT3N0. Conclusions Conditional survivalshowed a direct relationship between event-free follow-up duration and survival probability. Conditional CSM-free estimates increased in proportion with event-free follow-up but also resulted in equally proportional increase in attrition rates.

Conditional survival and changing risk profile in patients with chordoma: a population-based longitudinal cohort study

ObjectiveTo evaluate the conditional survival of patients with chordoma to potentially help physician planning of optimal cancer surveillance and guide better clinical decisions.MethodsIn total, 1942 patients with chordoma were identified and extracted from Surveillance, Epidemiology, and End Results (SEER) databases (1973–2015). The cumulative survival estimates were used to calculate the conditional survival rate, and the Greenwood formula was used to estimate the 95% CI. In addition, multivariable Cox regression analyses were used to calculate hazard ratios, according to the duration of survival.ResultsThe conditional 5-year disease-specific survival in patients with regional or localized chordoma was relatively stable over time, whereas in patients with distant chordoma, there was a gradual improvement. The conditional 5-year disease-specific survival (DSS) of patients older than 60 years old and patients with a tumor size between 5 and 10 cm improved. Interestingly, for patients with a tumor larger than 10 cm, the conditional 5-year DSS decreased over time. After surviving 5 years, the hazard ratio (HR) of patients older than 60 years old decreased from 1.33 to 1.24, that of patients with a tumor size between 5 and 10 cm decreased from 1.61 to 1.52 and that of patients with distant metastasis decreased from 3.30 to 1.09. However, after surviving 5 years, the HR of patients with a tumor size larger than 10 cm increased from 2.33 to 3.77, that of patients who underwent surgical resection increased from 0.37 to 0.58 and that of patients who received radiation therapy increased from 0.81 to 1.04.ConclusionAge at diagnosis, tumor size and disease stage can influence conditional survival for patients with chordoma. The HR of different factors will change over the survival time. Therefore, understanding the changing risk profile and conditional 5-year DSS of chordoma is critical for accurate clinical treatment guidance.

Conditional Survival in Patients With Rectal Cancer and Complete Clinical Response Managed by Watch and Wait After Chemoradiation: Recurrence Risk Over Time.

Analyze conditional recurrence-free survival (cRFS) for rectal cancer patients with complete clinical response (cCR) after neoadjuvant chemoradiation (nCRT) managed nonoperatively after each year without recurrence. Select patients with cCR after nCRT have been managed nonoperatively. Risk factors for local recurrence, the need for prolonged follow-up, and the risk of recurrence over time are not well defined. Retrospective review of patients with rectal cancer cT2-4N0-2M0 treated with nCRT. Mean follow-up was 64 months. Patients who achieved cCR were managed nonoperatively. cRFS was used to investigate the evolution of recurrence-odds, as patients remain recurrence-free after completion of nCRT. Three-year cRFS was estimated at "x" years after completion of nCRT based on the formula cRFS3 = RFS(x+3)/RFS(x). One hundred ninety-seven patients with cCR after nCRT were included. Overall survival and recurrence-free survival (RFS) at 5 years were 81.9% (95% CI 74.0%-87.6%) and 60.4% (95% CI 52.5%-67.4%) respectively. Using cRFS estimates, the probability of remaining disease-free for an additional 3 years if the patient survived without disease at 1, 3, and 5 years, was 77.4% (95% CI 68.8%-83.8%), 91.0% (95% CI 81.9%-95.7%), and 94.3% (95% CI 82.9%-98.2%), respectively. In contrast, actuarial RFS rates for similar intervals were 79.1% (95% CI 72.5%-84.2%), 64.2% (95% CI 56.5%-70.8%), and 60.4% (95% CI 52.5%-67.4%). After 2 years disease-free, 3 year cRFS became similar for T2 and T3 cancers. In contrast, patients undergoing extended nCRT became less likely to develop recurrences only after initial 2 years of successful organ-preservation. Conditional survival suggests that patients have significantly lower risks (≤10%) of developing recurrences after 2 years of achieving cCR following nCRT.

The Impact of Cisplatin- or Non-Cisplatin-Containing Chemotherapy on Long-Term and Conditional Survival of Patients with Advanced Urinary Tract Cancer.

The impact of cisplatin use on long-term survival of unselected patients with advanced urinary tract cancer (aUTC) has not been adequately investigated. We used a multinational database to study long-term survival and the impact of treatment type in unselected patients with aUTC. A total of 1,333 patients with aUTC (cT4bN0M0, cTanyN+M0, cTanyNanyM+), transitional-cell, squamous, or adenocarcinoma histology who received systemic chemotherapy and had available survival data were selected. Long-term survival was defined as alive at 3 years following initiation of first-line chemotherapy. Conditional overall survival (COS) analysis was employed to study change in prognosis given time survived from initiation of first-line chemotherapy. Median follow-up was 31.7 months. The combination of cisplatin use and cisplatin eligibility accurately predicted long-term survival. Eligible patients treated with cisplatin conferred a 31.6% probability of 3-year survival (95% confidence interval [CI]: 25.1-38.3), and 2-year COS for patients surviving 3 years after initiation of cisplatin-based chemotherapy was 83% (95% CI: 59.7-93.5). The respective probabilities for patients who were ineligible for cisplatin or not treated with cisplatin despite eligibility were 14% (95% CI: 10.8-17.6) and 49.3% (95% CI: 28.2-67.4). Two-year COS remained significantly different between these two groups up to 3 years after chemotherapy initiation. Cisplatin-based therapy was associated with the highest likelihood of long-term survival in patients with aUTC and should be used in patients who fulfill the established eligibility criteria. Novel therapies are necessary to increase long-term survival in cisplatin-ineligible patients. Long-term, disease-free survival is possible in one in four eligible-for-cisplatin patients with advanced urinary tract cancer (aUTC) treated with cisplatin-based combination chemotherapy. Therefore, deviations from eligibility criteria should be avoided. Consolidation surgery should be considered in responders. These data provide benchmarks for the study of novel therapies in aUTC.

Conditional survival of patients with hepatocellular carcinoma undergoing curative intent resection: Analysis of the national cancer database

Background: Hepatocellular carcinoma (HCC) is a lethal malignancy rising in both incidence and mortality worldwide. Conditional survival (CS) estimates represent the probability that a patient will survive additional number of years, because the patient has already survived a given amount of time, and better define the survival potential over time. We analyzed the CS estimates of resected patients from the time of surgical resection. Methods: A retrospective analysis of patients who had curative intent surgical resection for HCC was performed using the National Cancer Data Base (NCDB) from 2004-2014. Crude survival curves were generated using the Kaplan-Meier method. For the purposes of the CS analysis, we assessed the probability of surviving an additional 5 years (CS5), given that the patient had already survived 2 years. As such, the 5-year CS for patients who had survived (S) “X” years was computed as CS5 S(x+5)/S(x). CS estimates were also stratified by clinicopathologic variables of interest. Results: The NCDB captured 11,357 patients who underwent resection for HCC. The characteristics of the patients and tumors include: male gender (74.1%), white race (78.7%), Charlson Deyo score of 0-1 (72.5%), intermediate tumor grade (53.1%), margin-negative resection (88.5%), 30-day mortality (3.2%) and 90-day mortality (5.4%). Table 1 shows that, for example, for the OS, the unconditional 5-year survival probability is 65.9%, but given that those have survived 2 years, the additional 5-year survival probability is 84.7% (in red). Also, the unconditional 4-year survival probability is 71.0%, given that the person survived 2 or 3 years, the 4-year survival probabilities are 85.1 and 78.6% respectively (in blue). Similarly, the 5-year CS for patients who have survived 2 years is as follows for: age < 65 (92.9%), intermediate grade (85.2%), margin-negative resection (84.8%), no radiation therapy (84.6%), and no systemic therapy (81.2%). The overall survival was highly statistically significant between different groups within each of these variables (p < 0.0004). Conclusion: CS estimates following resection in HCC patients reflect an improved survival for a given length of time survived compared to the respective unconditional survival. However, the CS declines for each successive year survived reflecting other variables that (perhaps not oncologic) that impact survival in HCC. CS estimates provides more accurate prognostic information for the individual resected HCC patients, and can be used by clinical clinicians to guide further therapy and follow up years after resection.

Five‐year conditional survival for patients with hepatocellular carcinoma in Queensland, Australia

Five‐year conditional survival for patients with hepatocellular carcinoma in Queensland, Australia

Conditional Survival in Patients with Multiple Myeloma Undergoing Upfront Autologous Stem Cell Transplantation

Background Conditional survival (CS) is defined as the probability of surviving an additional x years given a patient has already survived y years since diagnosis or a time-point of interest. Although there are readily available overall survival (OS) estimates in multiple myeloma (MM) from the time of diagnosis or autologous stem cell transplantation (ASCT), data on CS in those who had already survived a landmark time since ASCT are lacking. Our objective was to investigate 5-year CS rate and standardized mortality ratio (SMR) in 1-, 3- and 5-year survivors after front-line ASCT in MM. Method We reviewed the institutional transplant database at Cleveland Clinic to identify 340 patients who underwent frontline ASCT (≤18 months from diagnosis) for MM between 1996 and 2013. OS was estimated by the Kaplan-Meier method. Relapse mortality (RM) and non-relapse mortality (NRM) were estimated with cumulative incidence. SMR was defined as the ratio of number of deaths in the study patients to that in an age, sex and race-matched healthy population. Estimates of outcomes and SMR are presented with 95% confidence intervals (CI). Results We identified 309 survivors at 1 year, 246 at 3 years, and 178 at 5 years from ASCT. The median age at ASCT was 56 years (range, 22-76) in all 3 cohorts. The median time from diagnosis to ASCT was 7.9 months in 1- and 3-year and 8.2 months in 5-year survivors. Approximately 40%, 35%, and 25% of patients had ISS stage I, II and III disease respectively at diagnosis in all cohorts. Median follow-up from ASCT in surviving patients was 88 months, 90 months and 100 months in 1-, 3- and 5-year survivors respectively. Estimated 5-year CS was 59% (53-64) in 1-year survivors, 60% (53-67) in 3-year survivors and 62% (53-70) in 5-year survivors. The respective cumulative incidence of 5-year conditional RM was 34% (28-39), 29% (23-35) and 25% (18-33) and that of NRM was 7% (5-11), 11% (7-16) and 13% (8-19). The SMR of 1-year, 3-year and 5-year survivors was 6.9 (5.8-8.2), 6.1 (5.0-7.5) and 5.6 (4.3-7.3) respectively, indicating significantly worse survival compared to demographically-matched healthy population irrespective of the duration of survival after ASCT. Survival curves for the 3 cohorts are shown in Figure I. Conclusion The probability of surviving an additional 5 years in patients with MM undergoing front-line ASCT does not improve with time, as shown in 1-, 3- and 5-year survivors, with estimated 5-year CS staying constant at around 60%. However, a decrease in the magnitude of SMR was observed with increase in the number of years already survived after ASCT. Information on CS and SMR is a pragmatic resource for long-term survivorship and beneficial at an individual level for counselling patients.