Before the introduction of modern imaging techniques and the recent developments in molecular diagnosis, tumor markers (TMs) were among the few available diagnostic tools for the management of cancer patients. Easily obtained from serum or plasma samples, TMs are minimally invasive and convenient, and the associated costs are low. Single TMs were traditionally used but these have come under scrutiny due to their low sensitivity and specificity when used, for example, in a screening setting. However, recent research has shown superior performance using a combination of multiple TMs as a panel for assessment, or as part of validated algorithms that also incorporate other clinical factors. In addition, newer TMs have been discovered that have an increased sensitivity and specificity profile for defined malignancies. The aim of this review is to provide a concise overview of the appropriate uses of both traditional and newer TMs and their roles in diagnosis, prognosis, and the monitoring of patients in current clinical practice. We also look at the future direction of TMs and their integration with other diagnostic modalities and other emerging serum based biomarkers, such as circulating nucleic acids, to ultimately advance diagnostic performance and improve patient management.

Purpose

Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is an aggressive malignancy associated with a poor prognosis. Although existing literature focuses on patients presenting with metastatic disease, characteristics and outcomes for patients with localized disease are not well described. We aimed to evaluate postnephrectomy characteristics, outcomes, and predictors of survival in patients with sRCC who presented with clinically localized disease.

Patients and methods

An institutional review board-approved review from 1986 to 2011 identified 77 patients who presented with clinically localized disease, underwent nephrectomy, and had sRCC in their primary kidney tumor. Clinical and pathologic variables were captured for each patient. Overall survival (OS) and recurrence-free survival (RFS) were calculated for all patients and those who had no evidence of disease (NED) following nephrectomy, respectively. Comparisons were made with categorical groupings in proportional hazards regression models for univariable and multivariable analyses.

Results

OS for the entire cohort (n = 77) at 2 years was 50%. A total of 56 (77%) patients of the 73 who has NED following nephrectomy experienced a recurrence, with a median time to recurrence of 26.2 months. On multivariable analysis, tumor stage, pathologically positive lymph nodes, and year of nephrectomy were significant predictors of both OS and recurrence-free survival. Limitations include the retrospective nature of this study and relatively small sample size.

Conclusions

Long-term survival for patients with sRCC, even in clinically localized disease, is poor. Aggressive surveillance of those who have NED following nephrectomy is essential, and further prospective studies evaluating the benefit of adjuvant systemic therapies in this cohort are warranted.

Purpose

Men with metastatic castration-resistant prostate cancer (mCRPC) have limited treatment options after progressing on hormonal therapy and chemotherapy. Here, we evaluate the safety and efficacy of atezolizumab (anti-PD-L1) + radium-223 dichloride (radium-223) in men with mCRPC.

Patients and methods

This phase Ib study evaluated atezolizumab + radium-223 in men with mCRPC and bone and lymph node and/or visceral metastases that progressed after androgen pathway inhibitor treatment. Following safety assessment of concurrent dosing, 45 men were randomized 1:1:1 to concurrent or one of two staggered dosing schedules with either agent introduced one cycle before the other. This was followed by a safety-efficacy expansion cohort (randomized 1:1:1). The primary endpoints were safety and objective response rate (ORR) by RECIST 1.1. Secondary endpoints included radiographic progression-free survival (rPFS), PSA responses, and overall survival (OS).

Results

As of October 4, 2019, 44 of 45 men were evaluable. All 44 had ≥1 all-cause adverse event (AE); 23 (52.3%) had a grade 3/4 AE. Fifteen (34.1%) grade 3/4 and 3 (6.8%) grade 5 AEs were related to atezolizumab; none were related to radium-223. Confirmed ORR was 6.8% [95% confidence interval (CI), 1.4-18.7], median rPFS was 3.0 months (95% CI, 2.8-4.6), median PSA progression was 3.0 months (95% CI, 2.8-3.3), and median OS was 16.3 months (95% CI, 10.9-22.3).

Conclusions

This phase Ib study demonstrated that atezolizumab + radium-223, regardless of administration schedule, had greater toxicity than either drug alone, with no clear evidence of additional clinical benefit for patients with mCRPC and bone and lymph node and/or visceral metastases.

Squamous cell carcinoma of the penis represents approximately 0.5% of all cancers among men in the United States and other developed countries. Although rare, it is associated with significant disfigurement, and only half of the patients survive beyond 5 years. Proper evaluation of both the primary lesion and lymph nodes is critical, because nodal involvement is the most important factor of survival. The NCCN Clinical Practice Guidelines in Oncology for Penile Cancer provide recommendations on the diagnosis and management of this devastating disease based on evidence and expert consensus.