Predictors of Cancer-specific Mortality After Disease Recurrence in Patients with Squamous Cell Carcinoma of the Penis

Disease recurrence occurs frequently after surgical treatment for squamous cell carcinoma of the penis (SCCp). We sought to determine prognostic factors that influence cancer-specific mortality (CSM) after disease recurrence in patients with SCCp. We performed a retrospective analysis of 314 patients who experienced disease recurrence after surgical treatment for SCCp between 1949 and 2012. Competing risk regression analysis addressed factors associated with CSM after SCCp recurrence. Median time from surgery to disease recurrence was 10.5 mo (interquartile range [IQR]: 5.9–21.3). Of the recurrences, 165 (53%), 118 (38%), and 31 (9.9%) were local, regional, or distant, respectively. Within a median follow-up of 4.5 yr (IQR: 2.0–6.5), 108 patients died of SCCp and 41 patients died of causes other than SCCp. Shorter time to disease recurrence was found to be significantly associated with a higher risk of CSM (p = 0.0006). Lymph node metastasis at the time of initial treatment (subdistribution hazard ratio [SHR]: 1.96; 95% confidence interval [CI] 1.23– 3.11; p = 0.005) and regional recurrence (SHR: 4.14; 95% CI, 2.16–7.93; p < 0.0001) or distant recurrence (SHR: 5.75; 95% CI, 2.59–12.73; p < 0.0001) were associated with increased risk of CSM after disease recurrence. Inclusion of time to recurrence into risk stratification may help patient counseling and treatment planning.     

Prospective Evaluation of a Molecular Marker Panel for Prediction of Recurrence and Cancer-specific Survival After Radical Cystectomy

Background

Retrospective studies demonstrated that cell cycle–related and proliferation biomarkers add information to standard pathologic tumor features after radical cystectomy (RC). There are no prospective studies validating the clinical utility of markers in bladder cancer.

Objective

To prospectively determine whether a panel of biomarkers could identify patients with urothelial carcinoma of the bladder (UCB) who were likely to experience disease recurrence or mortality.

Design, setting, and participants

Between January 2007 and January 2012, every patient with high-grade bladder cancer, including 216 patients treated with RC and lymphadenectomy, underwent immunohistochemical staining for tumor protein p53 (Tp53); cyclin-dependent kinase inhibitor 1A (p21, Cip1) (CDKN1A); cyclin-dependent kinase inhibitor 1B (p27, Kip1); antigen identified by monoclonal antibody Ki-67 (MKI67); and cyclin E1.

Intervention

Every patient underwent RC and lymphadenectomy, and marker staining.

Outcome measurements and statistical analysis

Cox regression analyses tested the ability of the number of altered biomarkers to predict recurrence or cancer-specific mortality (CSM).

Results and limitations

Pathologic stage among the study population was pT0 (5%), pT1 (35%), pT2 (19%), pT3 (29%), and pT4 (13%); lymphovascular invasion (LVI) was seen in 34%. The median number of removed lymph nodes was 23, and 60 patients had lymph node involvement (LNI). Median follow-up was 20 mo. Expression of p53, p21, p27, cyclin E1, and Ki-67 were altered in 54%, 26%, 46%, 15%, and 75% patients, respectively. In univariable analyses, pT stage, LNI, LVI, perioperative chemotherapy (CTx), margin status, and number of altered biomarkers predicted disease recurrence. In a multivariable model adjusting for pathologic stage, margins, LNI, and adjuvant CTx, only LVI and number of altered biomarkers were independent predictors of recurrence and CSM. The concordance index of a baseline model predicting CSM (including pathologic stage, margins, LVI, LNI, and adjuvant CTx) was 80% and improved to 83% with addition of the number of altered markers.

Conclusions

Molecular markers improve the prediction of recurrence and CSM after RC. They may identify patients who might benefit from additional treatments and closer surveillance after cystectomy.     

Effect of Nodal Metastases on Cancer-specific Mortality After Cytoreductive Nephrectomy

Background

Relatively few reports have described the outcomes of patients with node-positive renal cell carcinoma (RCC) in the presence of distant metastases. We examined the outcomes of these patients in a large population-based cohort and examined the ability of standard risk factors to predict cancer-specific mortality (CSM).

Methods

Using the Surveillance, Epidemiology, and End Results database, 1415 RCC patients with distant metastases undergoing cytoreductive nephrectomy (CNT) were identified. Univariable and multivariable analyses addressed CSM to identify independent predictors of CSM. First, the effect of nodal disease on CSM and overall mortality (OM) was estimated in patients with metastatic disease (N0M1 vs. N1M1). Then, we examined the effect of the number of removed nodes and the number of positive nodes on CSM to quantify the effect on mortality, if any, of the increasing burden of nodal disease.

Results

Actuarial survival estimates demonstrated that for patients with nodal disease 40.2, 23.5 and 11.5 % of patients survived at 12, 24 and 60 months after nephrectomy. In Kaplan–Meier analyses, patients with N1M1 disease had a significantly worse CSM when compared to patients with N0M1 disease (log rank p < 0.001). In multivariable analyses, N1M1 had a 68 and 69 % increase in CSM and OM (vs. N0M1 disease) while, for every additional positive node, CSM and OM increased by 5.1 and 5.6 %.

Conclusions

In patients undergoing CNT, the burden of nodal disease is an independent predictor of CSM, with an incremental effect of every additional positive node.     

Multi-institutional Validation of the CAPRA-S Score to Predict Disease Recurrence and Mortality After Radical Prostatectomy

Background

The University of California, San Francisco, Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score uses pathologic data from radical prostatectomy (RP) to predict prostate cancer recurrence and mortality. However, this clinical tool has never been validated externally.

Objective

To validate CAPRA-S in a large, multi-institutional, external database.

Design, setting, and participants

The Shared Equal Access Regional Cancer Hospital (SEARCH) database consists of 2892 men who underwent RP from 2001 to 2011. With a median follow-up of 58 mo, 2670 men (92%) had complete data to calculate a CAPRA-S score.

Intervention

RP.

Outcome measurements and statistical analysis

The main outcome was biochemical recurrence. Performance of CAPRA-S in detecting recurrence was assessed and compared with a validated postoperative nomogram by concordance index (c-index), calibration plots, and decision curve analysis. Prediction of cancer-specific mortality was assessed by Kaplan-Meier analysis and the c-index.

Results and limitations

The mean age was 62 yr (standard deviation: 6.3), and 34.3% of men had recurrence. The 5-yr progression-free probability for those patients with a CAPRA-S score of 0–2, 3–5, and 6–10 (defining low, intermediate, and high risk) was 72%, 39%, and 17%, respectively. The CAPRA-S c-index was 0.73 in this validation set, compared with a c-index of 0.72 for the Stephenson nomogram. Although CAPRA-S was optimistic in predicting the likelihood of being free of recurrence at 5 yr, it outperformed the Stephenson nomogram on both calibration plots and decision curve analysis. The c-index for predicting cancer-specific mortality was 0.85, with the caveat that this number is based on only 61 events.

Conclusions

In this external validation, the CAPRA-S score predicted recurrence and mortality after RP with a c-index >0.70. The score is an effective prognostic tool that may aid in determining the need for adjuvant therapy.     

Late Recurrence After Radical Resection of Esophageal Cancer

Background

Approximately 10–20 % of esophageal cancer patients in whom recurrence is diagnosed experience late recurrence beyond 2 years after esophagectomy. However, the risk of late recurrence is still unclear. The aim of this study was to identify the risk factors of late recurrence for appropriate postoperative surveillance.

Methods

A total of 447 patients underwent radical esophagectomy and reconstruction for esophageal cancer from 2005 to 2014. Patients who had recurrence beyond 2 years after esophagectomy were defined as the late recurrence group and the remaining patients with recurrence as the early recurrence group. A comparison of the clinicopathological factors and prognosis was performed between patients with early recurrence, late recurrence, and no recurrence.

Results

Recurrences were recognized in 117(26.2 %) of the 447 patients. Recurrence was diagnosed within 2 years after surgery in 103 patients (88.0 %) and after 2 years in 14 patients (12.0 %). Patients with late recurrence showed a favorable prognosis compared with those with early recurrence (P = 0.0131), and late recurrence was an independent factor associated with a favorable prognosis after recurrence (HR 0.199, P = 0.025). In the comparison between patients with late recurrence and those with no recurrence who had a minimal recurrence-free survival of 2 years, pathological lymph node metastasis at esophagectomy was found to be an independent predictor of late recurrence (HR 7.296, P = 0.043).

Conclusions

Pathological lymph node metastasis at esophagectomy is a risk factor of late recurrence for esophageal cancer, and a close, lifelong follow-up is recommended for such patients.

     

Independent Predictors for Bladder Outcomes after Treatment of Intravesical Recurrence following Radical Nephroureterectomy in Patients with Primary Upper Tract Urothelial Carcinoma

Background

Few studies have described the clinical courses and outcomes in the bladder after treatment of intravesical recurrence after radical nephroureterectomy (RNU) in patients with primary upper tract urothelial carcinoma (UTUC). We investigated the indicators for predicting subsequent bladder outcomes after treatment of intravesical recurrence after RNU.

Methods

A total of 241 patients with primary UTUC (pTa-4N0M0) who experienced intravesical recurrence after RNU were included. Of these patients, 101 (41.9 %) underwent Bacillus Calmette-Guérin treatments, whereas 49 (20.3 %) underwent intravesical chemotherapy. The median follow-up period after initial transurethral resection of the bladder tumor was 33 months. Relationships with bladder outcomes were analyzed by using multivariable analysis.

Results

Ninety-six patients experienced intravesical recurrence, and bladder progression was observed in 13. Cumulative incidence rates of intravesical recurrence at 1 and 5 years after treatment of the first intravesical recurrence were 31.0 and 48.4 %, whereas those of bladder progression at 1 and 5 years thereafter were 2.4 and 8.0 %. Multivariate analysis showed that the number of recurrent tumors and pT1 tumors at the time of the first intravesical relapse were independent risk factors for subsequent intravesical recurrence. With respect to bladder progression, multivariate analysis showed that pT1 tumors, the appearance of concomitant carcinoma-in situ at the time of the first intravesical relapse, and the absence of the Bacillus Calmette-Guérin treatment were independent risk factors.

Conclusions

This retrospective study presents a detailed picture of further bladder outcomes after intravesical recurrence after RNU in primary UTUC patients. The results may assist physicians to develop a more rational protocol in bladder surveillance.     

External Validation of the European Association of Urology Biochemical Recurrence Risk Groups to Predict Metastasis and Mortality After Radical Prostatectomy in a European Cohort

The impact of biochemical recurrence (BCR) after radical treatment of prostate cancer on oncological outcomes remains unclear. A new European Association of Urology BCR risk stratification (low and high risk) has been proposed. To validate these risk groups, we retrospectively analyzed data for 1125 post-radical prostatectomy (RP) BCR patients (surgery between 1992 and 2006). Univariable Kaplan-Meier plots and multivariable Cox regression models with time-dependent covariates were used to test the independent predictor status of the risk grouping on metastatic progression (MP) and prostate cancer-specific mortality (PCSM). The 5-yr MP-free and PCSM-free survival rates were significantly higher among patients with low BCR risk compared to their high-risk counterparts. In multivariable analyses, the BCR risk grouping reached independent predictor status for MP (hazard ratio [HR] 3.46; p < 0.001) and PCSM (HR 5.12; p < 0.001). Salvage radiation therapy, especially when delivered at prostate-specific antigen <0.5 ng/ml, was highly protective. Our findings corroborate the validity of this novel BCR risk grouping, which is easily applicable in daily practice and could be valuable in decision-making for salvage therapy and clinical trials.Patient summaryThe European Association of Urology grouping for the risk of biochemical recurrence of prostate cancer after radical prostatectomy was valid when applied in a European study cohort.     

Risk Factors Influencing Recurrence, Patterns of Recurrence, and the Efficacy of Adjuvant Therapy After Radical Resection for Gallbladder Carcinoma

Backgrounds

Gallbladder carcinoma (GBC) is an aggressive neoplasm, and resection is the only curative modality. Recurrence frequently occurs after the curative resection of advanced GBC. Adjuvant treatment, particularly radiotherapy, is recommended and is used without any evidence of a beneficial effect. The aim of this study was to characterize patterns of recurrence and to identify the factors that influence recurrence and the efficacy of adjuvant therapy after the curative resection of GBC.

Methods

The records of patients that underwent surgical resection with curative intent for gallbladder carcinoma from October 1994 and August 2007 were retrospectively reviewed. Recurrence patterns, times to recurrence, and survival rates were analyzed. Sites of recurrence were identified retrospectively and categorized as locoregional or distant.

Results

One hundred sixty-six patients underwent surgical resection with curative intent for gallbladder adenocarcinoma. The 5-year recurrence rates of stages IA, IB, IIA, and IIB patients were 0%, 24.3%, 44.9%, and 58.3%, retrospectively. Positivity for lymph node metastases was found to have predictive significance for disease-free survival (p?=?0.009). Regional lymph node recurrence (27.7%) was observed most frequently. There was no significant disease-free survival rates between the no adjuvant therapy and the adjuvant therapy groups.

Conclusions

The regional lymph nodes and the liver were found to be the most common sites of recurrence after curative resection. Lymph node metastases were identified as an independent predictor of tumor recurrence by multivariate analysis. Based on the disease-free survivals observed in this study, the authors find it would be difficult to advocate the routine use of adjuvant radiotherapy and/or chemotherapy     

Prostate Cancer Biochemical Recurrence Rates After Robotic-Assisted Laparoscopic Radical Prostatectomy

Background and Objectives:

To determine prostate cancer biochemical recurrence rates with respect to surgical margin (SM) status for patients undergoing robotic-assisted laparoscopic radical prostatectomy (RALP).

Methods:

IRB-approved radical prostatectomy database was queried. Patients were stratified as low, intermediate, and high risk according to D’Amico''s risk classification. Postoperative prostate-specific antigen (PSA) values were obtained every 3 mo for the first year, then biannually and annually thereafter. Biochemical recurrence was defined as ≥0.2ng/mL. Patients receiving adjuvant or salvage treatment were included. Positive surgical margin was defined as presence of cancer cells at inked resection margin in the final specimen. Margin presence (negative/positive), margin multiplicity (single/multiple), and margin length (≤3mm focal and >3mm extensive) were noted. Kaplan-Meier curves of biochemical recurrence-free survival (BRFS) as a function of SM were generated. Forward stepwise multivariate Cox regression was performed, with preoperative PSA, Gleason score, pathologic stage, prostate gland weight, and SM as covariates.

Results:

At our institution, 1437 patients underwent RALP (2003-2009). Of these, 1159 had sufficient data and were included in our analysis. Mean follow-up was 16 mo. Kaplan-Meier curves demonstrated significant increase in BRFS in low-risk and intermediate-risk groups with negative SM. Overall BRFS at 5 y was 72%. Gleason score, pathologic stage, and SM status were significant prognostic factors in multivariate analysis.

Conclusions:

Negative surgical margins resulted in lower biochemical recurrence rates for low-risk and intermediate-risk groups. Multifocal and longer positive margins were associated with higher biochemical recurrence rates compared with unifocal and shorter positive margins. Documenting biochemical recurrence rates for RALP is important, because this treatment for localized prostate cancer is validated.     

Salvage Surgery in Patients with Local Recurrence After Radical Prostatectomy

BackgroundSince the introduction of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging, isolated local recurrence after radical prostatectomy (RP) can be delineated accurately.ObjectiveTo describe and evaluate surgical technique, biochemical response, and therapy-free survival (TFS) after salvage surgery in patients with local recurrence in the seminal vesicle bed.Design, setting, and participantsWe retrospectively assessed 40 patients treated with open salvage surgery in two centres (11/2014-02/2020). All patients presented with biochemical recurrence (BCR) after RP with a singular local recurrence at PSMA PET imaging. Thirty-three (82.5%) patients received previous salvage radiation therapy.Surgical procedureOpen salvage surgery with PSMA radioguidance.MeasurementsProstate-specific antigen (PSA) nadir and percentage of patients with complete biochemical response (cBR) without further treatment (PSA < 0.2 ng/ml) after 6–16 wk were assessed. BCR-free survival and TFS were calculated using Kaplan-Meier estimates. Clavien-Dindo complications were evaluated.Results and limitationsPrior to salvage surgery, median PSA was 0.9 ng/ml (interquartile range [IQR]: 0.5–1.7 ng/ml). Postoperatively, median PSA nadir was 0.1 ng/ml (IQR: 0–0.4 ng/ml). In 31 (77.5%) patients, cBR was observed. During the median follow-up of 24.4 months, 22 (55.0%) patients experienced BCR and 12 (30.0%) received further therapy. At 1 yr of follow-up, BCR-free survival rate was 62.2% and TFS rate was 88.3%. Three (7.5%) Clavien-Dindo grade III complications were observed. The main limitations are the retrospective design, short follow-up, and lack of a control group.ConclusionsSalvage surgery of local recurrence within the seminal vesicle bed is feasible. It may present an opportunity in selected, locally recurrent patients to prolong BCR-free survival and increase TFS. Further studies are needed to confirm our findings.Patient summaryWe looked at the outcomes from prostate cancer patients with locally recurrent disease after radical prostatectomy and radiotherapy. We found that surgery in well-selected patients may be an opportunity to prolong treatment-free survival.     

Metastatic Behavior of Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy: Association with Primary Tumor Location

Purpose

To investigate the site-specific pattern of disease recurrence and/or metastasis and the associated patient outcomes after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC).

Methods

A total of 733 patients with UTUC from a retrospective multi-institutional cohort were included, with a median follow-up of 34 months. Associated patient outcomes were analyzed by multivariate analysis. To evaluate the influence of primary tumor location, we divided it into four areas: renal pelvis, and upper, middle, and lower ureter.

Results

A total of 218 patients experienced disease recurrence, with the majority of relapses occurring within the first 3 years. Cumulative incidence rates of first disease recurrence at 1 and 3 years were 18.9 and 29.8 %, respectively. Of these patients, 38.5 % developed distant recurrence; 17.4 % experienced both local and distant recurrences; and 44.0 % developed isolated local recurrence. The predominant sites of distant metastasis were lung, liver, and bone. Multivariate analysis revealed that the prevalence of local recurrence and lung metastasis was significantly associated, with primary tumor location being independent of other clinicopathological variables. Lower/middle ureter tumors had a higher rate of local recurrence in the pelvic cavity, and renal pelvic tumors had a higher prevalence of distant relapse in the lungs. Similar results were obtained when rerunning the data set by excluding patients who received adjuvant chemotherapy (n = 131).

Conclusions

This multi-institutional study provided a detailed picture of metastatic behavior after RNU, and primary tumor locations were associated with unique patterns of metastatic spread in UTUC patients.